Tag Archives: transplant without remission

Transplant, Haplo-Style

Standard

FullSizeRender-18FullSizeRender-34FullSizeRender-35FullSizeRender-9FullSizeRender-16FullSizeRender-15FullSizeRender-10FullSizeRender-11FullSizeRender-12FullSizeRender-11FullSizeRender-7You look out upon a field studded with rocks, rocks small that huddle together in the hand like eggs in a nest, fist-sized rocks, rocks you think if you gave them all your strength you could heave up out of that earth, hold to your chest, hugging them round with your arms.  And here and there, a few scattered boulders.  Boulders, monoliths, enormities that stand silhouetted against the sky.

How can I ever gather them all?  The task overwhelms.  Scattered all about they don’t look like much.  Yet to convey the enormity of the day, one massive boulder would never suffice.  No, all those rocks would be necessary.  And not just a great pile, no, no, an intricately designed wall.  Or better yet, something yet more complex: a dome formed with each rock set carefully in place.  Rock against rock.  Force pressing up against force.  Rocks tucked tight so that the tension could somehow hold up the curvature.

To come to this day, this day seemingly like hundreds of others, has required a hundred thousand minute steps.  How many times has a nurse “entered” her line?  Fifteen seconds of scrub time.  Fifteen seconds of dry time.  How many sets of vitals?  How many CBCs (Complete Blood Count)?  How many echos and bone marrow biopsies?  How many times have her cells gone hurtling past a laser, striking that electron off to release a burst of energy at a precise wavelength to reveal its identity?  How many transfusions of red blood and platelets?  How many emails flying back and forth between doctors, careful to consider all facets of her case, what will be best? What meds?  What protocols?  How many great hurdles overcome?  How many slim possibilities made real?

When at last the time came, when at last word came that, “the cells are here,” and the room began to flood with folk, tears came quick.  Tears of being just plain overwhelmedly grateful.  The weight of the bounty, the absolute wonder of all that has taken place to bring us to this day.  This day.  This day of transplant.  This day of hope, of an open door, of another gift, another opportunity to pull a weapon from the scabbard and thrust it into the heart of those cancer cells.  And the faces…faces dear to us, faces with whom the most difficult possible conversations have taken place.  Faces beaming with joy for having walked long segments of this road with us.  And though the faces of many were not present, I saw them still.  In my mind there I saw Dr. Pollard, Dr. Gardner, Dr. Tarlock, Dr. Cooper, Dr. Berstein, Dr. Law, Dr. Kemna, Dr. Hong, Dr. Albers, the faces of countless nurses, of pathologists, and lab techs, Mohammed and Bonnie.  The list could go on and on.  If this was a Golden Globe I’d be kicked off the stage.

And there was something so poignant about the setting.  The plan had been all along to put Allistaire in the ICU for the most crucial, dangerous portions of transplant.  The ICU has many more means of monitoring her heart and an array of cardiac meds that cannot be given on the Cancer Unit.  Allistaire cannot be handled by standard protocols alone.  Everything that happens with intense immune responses result in the potential for great fluid shifts which in turn can radically impact the heart.  The first event of concern was simply receiving her cells.  As with all blood products, there is always the risk of an allergic type reaction, but even more significant is the possibility of a “cytokine storm,” due to the large mis-match between Sten’s stem cells and her own body.  It is like two great waves crashing into one another.  This clash of contrasts can result in a cascade of immune system signally and response that can be severe enough to be fatal.

When I asked the nurse what room we would be in the ICU, my mouth dropped at her response.  Forest PICU 6 room 321.  The very room we spent 70 of the 80 days Allistaire was in the PICU last January through April.  So as the morning turned to afternoon and the cells finally began to flow into her line, and the “Happy Transplant Day,” song was ended, and someone yelled, “Speech!” – I simply could not resist.  I could not resist proclaiming the wonder that we had come full circle, that in the span of one entire year, we had returned to this very room to at long last enter this gauntlet of transplant.  As I stood there before that little throng of medical staff and family, the bare white unadorned walls of this agonizingly familiar ICU room constraining, my heart was bursting, my few words fumbling to offer up a naming of gift and thanks.  Thanks for each person present and not present who has so faithfully, and graciously and compassionately done their part.  We have each put our head into the wind and pressed forward though relentlessly buffeted, somehow forward motion has been attained and as we look back, wow, wow, who can believe we have covered such a great distance?!

In the center of the room, a bright flash of spirit.  Allistaire Kieron Anderson, a spirit whose light is like sparkling pink lemonade, giddy, curls upon curls, curls of blonde hair tinged in pink and curves of cheek and chin with light glinting out of her blue eyes.  Lord, you make a crazy claim, one hard to fathom, sometimes hard to swallow, yet simultaneously gorgeous and wondrous:  You know all of our days before one of them comes to be (Psalm 139:16).  I have sought your face, I have yearned to walk this life held in You and one year ago, you said, “Come, follow Me, take my hand and let us walk this way, down this road leading into darkness,” as alarms blared on pumps and CT scans and echocardiograms declared disaster. I don’t know the road ahead, but as I turn, craning my neck back to look down that dark road behind me, hand gripped in Yours, I am simply in awe, in awe of the dangers and sorrows, of tears that threatened to drown and always Your hand, never letting go, and always Your Word, Your quiet voice entreating me to fix my eyes on You, on You and rest child, rest, rest in Me though all around you, you feel the ground giving way and the night presses in thick and you can’t seem to catch your breath, and the teeth flash and your whole being groans.

And startlingly, here we are, we have circled back around.  The obvious question is, “Why?  Why Lord?  What was the point of all that?  I mean really, really, did we really have to take what feels like a year-long detour through treacherous territory only to come back to where we started yet more bloodied and bruised, wounds deep?”  So much lost.  So much time.  So much separation.  So much damage.  So very many tears.  The lacerations and scars are easy to see yet don’t begin to reveal the depth of ravaging.  What is harder still to see is the other-worldly beauty, the treasure often imperceptible.  Seeds in dirt don’t look like much.  Seeds sailing on winds…The Lord’s aim has never been transplant.  He aims for my heart, for all hearts and sometimes in great peril and pressing darkness we are more able to see aright, to incline our ear to His voice, to have His Word made full and pulsing with life, our stiff necks bend low and we come to worship the God of creation as never before.  Getting to transplant has never been hard for the Lord.  To say that it has been trivial in His sight sounds callous only when I fail to set it against the enormity of His heart for me, for me a child of Adam, a child of God.  But I have no doubt God smiled broad and His face beamed as we gathered in that small room and were witness to the marvel of the human body, to the tenacious brokenness of creation, to the wonders of medicine and human endeavor, and to hope, hope for a way through.

I don’t know the road ahead and there is the quiver of trepidation, knowing there are still many dangers.  But on this gray January day with rain intent on saturating, my heart feels heavy and full, full with the satiation of joy and full of yearning to keep leaning in, inclining my face to the face of my God.  I look at this little girl and marvel that I should be so blessed to call her daughter and to walk this road with her, to hold her sweet little hand along the way, and to incline my ear to the pleasure of her small sweet voice, a voice proclaiming dreams of a future and joy for the present, delight in simply putting color down on paper, color alongside color alongside color.

Allistaire has made it through five fractions of focal radiation to the chloromas in her sinuses, eight fractions of TBI (Total Body Irradiation), three doses of the chemotherapy Fludarabine, all in preparation, a “conditioning,” for transplant.  The only direct immediate result has been fatigue and a C-Diff (Clostridium Difficule) infection due to the effects of radiation on her gut for which she is now on Flagel.  On Monday, on her day of rest, Sten’s birthday, Sten received his fifth and final shot of GCSF (Granulocyte Colony Stimulating Factor).  Then, in the early afternoon over the course of several hours, his blood was pulled out, and through the action of centrifugal force, the lighter weight white blood cells including CD34 stem cells, were separated out and the remaining blood returned, a process known as apherisis.  In total, the goal of 5-6 million CD34 cells/kg was achieved in a mere 187ml of Sten’s blood.  Sten’s blood was then processed, having both the red blood cells and platelets removed because of the antibodies Allistaire has formed against them.  When that bag of orangish red blood arrived in Allistaire’s room on Transplant Day, it contained nearly 120 million CD34 stem cells within 148 ml.

Due to extreme weariness at countless plans dashed, I felt no need to explain this transplant of Allistaire’s until it actually came to fruition.  So at last it is clearly time to explain what we’re doing here because truly there are so many different types of bone marrow transplants, each specially designed and chosen to fit with the uniqueness of the patient and their disease.  In order to make any sense of what is happening in Allistaire’s transplant, a brief overview of bone marrow transplants seems necessary.  When transplants were first developed by Dr. Donnall Thomas of Fred Hutchinson Cancer Research Center in the 1960’s and 70’s, the goal was to have the ability to use extreme doses of chemotherapy and radiation to destroy a leukemia patient’s bone marrow, the source of their cancer, and then “rescue” them by giving an infusion of another person’s bone marrow.  Without this “rescue,” the obliterated marrow could never recover and the patient would die.  Only later was it discovered that a key component of a bone marrow transplant’s potential to cure comes from the immunotherapy effect of Graft Versus Leukemia (GVL).  More about that in a bit.

All bone marrow transplants  begin with “conditioning,” which primarily attempts to eradicate any remaining cancer cells and to make way for the incoming stem cells.  Patients have the highest chance of a “successful” transplant when they go into transplant in remission which is generally defined as little to no detectable disease.  In Leukemia this means 5% or less disease in the marrow and ideally no extramedullary disease (cancer cells which form tumors outside of the marrow).  Each transplant protocol has specific requirements regarding disease status which determines whether or not a patient will be approved to move forward with a transplant.  Additionally, there are numerous conditions of health, especially regarding the major organs (heart, liver, kidneys, etc).  Determining which specific transplant regimen is best for the patient requires a great deal of data gathering and consideration.  All have variable elements of benefit and risk.

The two key defining components of a bone marrow transplant are the type of conditioning and the stem cell source.  There are a number of different types and doses of chemotherapy which may be used in conditioning.  Additionally, a patient may or may not also receive radiation as part of conditioning.  Sometimes the radiation is focused only on certain areas of the body where there have been or are tumors, or only the lymph nodes may be targeted.  In Allistaire’s case, she had both focal radiation and TBI (Total Body Irradiation) which sends radiation throughout the entire body.  Depending on the patient’s health, they may or may not be able to endure full intensity conditioning.  For older transplant patients who may not be in optimal health, “mini transplants,” were developed by Dr. Rainer Storb, also of Fred Hutch Cancer Research.  In patients like Allistaire who have one or more major organ systems that have been compromised, intensity of conditioning is an enormous consideration.  While Dr. Bleakley was very hesitant to give Allistaire a full-intensity conditioning transplant given the status of her heart, the extreme aggressiveness of her disease necessitated this in order to give her any chance of a cure.

The second component that distinguishes a transplant, is the stem cell source used for “rescue” after the marrow has been decimated. This might be may very favorite part of transplant.  Rescue.  A word conjuring up vivid, dramatic images, harrowing situations, bravery, sacrifice, love.  To read specifically about about the beauty of “rescue,” as I wrote about in Allistaire’s first transplant click HERE.  Originally, all transplants used whole marrow as the stem cell source which meant all donors had bone marrow removed directly from their bones.  In time, a method was developed for harvesting stem cells from the peripheral blood with the aid of GCSF (Granulocyte Colony Stimulating Factor).  GCSF promotes the production of stem cells in the marrow and their mobilization into the peripheral blood where they are collected by apherisis.  This is the means by which Sten donated his stem cells.  Lastly, the most recently developed stem cell source is that of cord blood.  Cord blood is blood that is extracted from the umbilical cord of a newborn baby.  Mothers can opt to donate their child’s cord blood which is then registered with the National Marrow Registry and banked, awaiting a person in need of a transplant.  It should be noted that some cancer patients have their own stem cells harvested and then reinfused after conditioning.  This type of transplant is known as an Autologous transplant.  However, whenever a particular blood cell line itself is the source of a patient’s cancer, as in the case of leukemia, they cannot be “rescued,” with their own stem cells as these are the source of their cancer.  In an Allogeneic transplant, the patient receives another person’s stem cells.

Many clinical trials have been conducted exploring the risks and benefits of diverse combinations of conditioning regimens and stem cell sources.  However, a major consideration in determining what type of stem cell source to use in a patient’s transplant is simply availability.  To receive someone else’s bone marrow fundamentally means you are receiving another person’s immune system.  Our immune system is able to accomplish the extraordinary defense of our bodies in large part because of its ability to identify “self” and “other.”  This is actually why cancer is so hard to eradicate.  In essence, the immune system of a person with cancer has failed to identify their cancer cells as “other.”  This is because cancer cells develop from normal healthy cells.  The goal of virtually all cancer treatment is to discern and target the subtle differences between healthy cells and cancer cells.  Typically a prospective transplant patient is “matched” to the greatest degree possible with the incoming stem cells so that the incoming cells look as close to “self” as possible.  This is done through HLA typing.  On human’s chromosome 6, there is a grouping of genes that encode for Human Leukocyte Antigens (HLA) which are then presented on the cell surface of all cells in a person’s body.  It is like a bar code (in the form of cell surface proteins) used as a unique identifier for that person.  These HLA proteins are what distinguish one individual person from another and are what allow a person’s immune system to identify “self” from “other.”  The immune system aims to identify and destroy anything “other.”  For this reason, it is essential that there be a significant degree of HLA matching between the patient and the incoming stem cells.  Otherwise, the patient’s own immune system would heartily attack and destroy the incoming stem cells.  When this happens it is known as “graft failure.”

Another potentially severe complication of a HLA mismatch between patient and donor is known as GVHD (Graft Versus Host Disease).  In this situation, the incoming donor cells may identify the patient’s body as “other” and set about attacking the patient’s tissues, most commonly the skin, gut and liver.  GVHD can even be fatal.  The ways to prevent or reduce GVHD have typically been to select the highest degree of HLA matching and/or give the patient immune suppressants which suppress the immune fighting T-cells within the graft/donor cells.  A major down side of immune suppressants is that they also suppress the incoming immune system’s ability to fight infection which can often lead to life-threatening infections.  As research into GVHD progresses, scientists are learning more about what subsets of T-cells are responsible for the majority of GVHD.  Dr. Bleakley has been conducting a clinical trial in which the “naive T-cells” are depleted or removed from the donor cells prior to infusion into the transplant patient. This has succeeded in substantially reducing the incidence of chronic GVHD.  Click HERE to read more about this fascinating research yielding substantially better results.

The highest degree of HLA matching is a 10 out of 10 match, which means the patient’s cells share the same genetic code as the donor cells at the ten major points on Chromosome 6.  In order to accomplish this matching, patient and donor most often share very similar ethnicity.  It is more difficult to find a good match for those patients who are ethnically diverse, whose ethnicity is rarer or derives from parts of the world in which there is very low Bone Marrow Registry participation.  For example, one of our friend’s was from the indigenous tribes of Guatemala.  Her specific ethnicity is simply rare in the world.  Another friend with sickle-cell was Ugandan, a part of the world with very little registry participation.  Almost amusingly, in Allistaire’s case she may be “too white,” in that she has never had a single match within the United States.  Her matched donors have always been found through the German registry.  She was unable to participate in Dr. Bleakley’s naive t-cell depleted protocol because it requires a U.S. donor.  For this reason, patients will have better transplant options when more people join the Bone Marrow Registry, thus increasing the likelihood that the patient can find a match.  For patients who have no sufficient bone marrow matches, cord blood can be a good option because it must be matched at fewer points (max of 6 out of 6).  Again, this is why donating your newborn’s cord can literally save a life!

As noted, the two major distinguishing components of a stem cell transplant are the type of conditioning and the type of stem cell source.  There is no one right transplant as each patient comes into needing transplant in varying degrees of health, disease status and access to stem cell source.  Allistaire went into her first stem cell transplant in June 2013 with nearly 70% disease in her marrow and 9 chloromas/tumors.  Otherwise her body was “healthy.”  Nevertheless, because of the enormity of her disease, she was only able to receive a transplant because of a specific transplant clinical trial through Fred Hutch that did not require remission.  She would have been dead long ago had it not been for that clinical trial.  When Allistaire relapsed again in October 2014 and needed a second transplant, we were aiming to use the “naive T-cell depleted transplant,” which did require remission.  Fortunately remission was attained but Allistaire had no U.S. matches and Dr. Bleakley set about trying to gain permission from the FDA and the German registry to allow Allistaire to use the available matched German donor from outside the U.S.

However, last January the cumulative effect of her years of chemotherapy and the severe typhlitus infection put her into heart failure.  She no longer qualified for transplant because of the extremely poor function of her heart which nearly resulted in her death.  Even once she regained some function, for a very long time she would have only qualified for low-conditioning transplants.  However, no low-conditioning transplant could sufficiently wipe out her extremely aggressive disease.  So for the past 10-11 months the goal has been to keep her cancer under control while giving her heart the time to possibly regain enough strength to qualify for a full-intensity conditioning transplant.  This has been extremely difficult as the oncologists have had limited treatment options.  Many types of chemotherapy themselves can be hard on the heart and/or greatly assault the marrow, effectively suppressing the immune system which then allows for the possibility of life-threatening infections.  Not only can the infection itself kill you, but the body’s attempt to fight the infection often causes major fluid shifts, changes in heart rates and blood pressures, all of which can put major strain on the heart.  Even seemingly minor situations like the two instances of an ileus resulted in all her medications, fluids and sustenance being given IV which puts a great burden on the heart.  It is a tough situation all around.  This was the reason for trying the WT1 modified T-cells and the decision to try Mylotarg (available only on a compassionate-use basis through Fred Hutch).  And while the Mylotarg was impressively effective against Allistaire’s cancer, one problem has been the incidence of cancer cells mutating in resistance to it and the risk of causing SOS (severe liver complication) in the context of transplant (which is why it was pulled by the FDA in 2010).

Once Allistaire’s heart began gaining strength as evidenced by ejection fractions (as determined by echocardiogram) in the high 30s and low 40s, the discussion began in earnest as to whether or not it might finally be time to give one more great thrust toward transplant.  Countless conversations between the Oncology, Bone Marrow Transplant and Cardiology doctors debated risks and benefits which were strongly tied to both keeping her disease under control long enough to get to transplant and what transplant regimen could give Allistaire the best chance at a cure and not kill her in the process.  When Dr. Bleakley first suggested the real possibility of a Haplo transplant, my gut response was to spit that idea right back out.  A Haplo-identical transplant is one in which the patient is half matched (5 out of 10) with a parent or sibling.

Because of this extreme mismatch, Haplo transplants have historically been associated with many poor outcomes including graft failure, high incidence of severe GVHD, high rates of infection and relapse.  Each awful complication results from attempts to respond and mitigate one of these other complications.  For example, because the HLA is only half matched between patient and donor, the patient’s immune system can attack and wipe out the graft/donor immune system.  Graft failure can be mitigated by increasing the intensity of conditioning to suppress the patient’s own immune system.  However, there is still the likelihood of severe and/or chronic GVHD where the donor immune system attacks the patient.  In order to combat this, the patient is given immune suppressants to tamp down the immune response in the donor cells.  This in turn results in severely lessened ability to fight infection and may reduce the Graft Versus Leukemia effect which is the advantageous and desirable element of the mismatch between “self” and “other.”  Remember that because cancer cells derive from healthy cells, they carry the HLA typing of the patient so when donor cells come into the patient’s body, they are more able to recognize the cancer cells as “other” and destroy them. Dr. Bleakley provided me with this paper, (Modern Approaches to HLA-haploidentical blood or marrow transplantation), which gives a historical overview of Haplo transplants.

Dr. Bleakley went on to describe a more recent approach to Haplo transplants which has yielded results on par with that of standard unrelated-matched donor transplants.  The most unique aspect of this transplant is that the extreme mismatch between patient and donor (half-matched parent or sibling) which would naturally produce immense GVHD, is greatly mitigated by giving a strong dose of the chemotherapy, cyclophosphamide (also known as Cytoxan), on days 3 and 4 after the infusion of the donor cells (the actual day of transplant).  This also occurs in the absence of any immune suppressants which are traditionally started at Day-1 (the day before transplant which is known as Day 0).  What this means is that when the donor cells go into the patient’s body, there is an uproar of immune systems in which the donor immune system begins to respond to the presence of “other” by rapidly dividing its Tcells and beginning the process of fight or GVHD.  There is nothing to lessen this response of the incoming donor cells because there are no immune suppressants present.  This is where the possibility of a cytokine storm comes in and where severe GVHD could take off if there was no intervening.  The possible cytokine storm must simply be managed as best as possible but the revving up of the donor Tcells is stopped in its tracks by these two large doses of cyclophosphamide on Day+3 and +4.  The cyclophosphamide targets rapidly dividing cells including the Tcells, which left unchecked, would produce immense GVHD.  The way that the whole graft/donor cells are not altogether wiped out by this chemo is that, according to a recent discovery, stem cells have proteins on their cell surfaces which make them immune to this particular chemo.  Also left, are a subset of Tcells which were not highly activated and can still go on to fight infection and provide GVL (Graft Versus Leukemia).  There are various versions of this “post-transplant Cy.”  Allistaire’s includes TBI (Total Body Irradiation) in the conditioning portion of the transplant which is essential given the aggressiveness of her AML and the ongoing presence of extramedullary disease.  Other “post-transplant Cy,” transplants may have reduced intensity conditioning.  Dr. Bleakley followed a transplant regimen based on the research described in this article (Total Body Irradiation-Based Myeloblative Haploidentical Stem Cell Transplantation in Patients Without Matched Sibling Donors), published in July 2015.

So at long last we come to this week of transplant.  And for those of you with eyes glazed over or simply head asleep on the keyboard, part of my motivation in going to such lengths to explain this transplant is not only for my own documentation, but also for folks out there in situations like ours who may need detailed information.  Given the condition of Allistaire’s heart and the aggressiveness of her disease, we therefore, chose a transplant with full-intensity conditioning and most importantly, full dose TBI which you can only have once in a lifetime.  The reason for choosing Sten as Allistaire’s donor is for three main reasons.  First off, Allistaire’s chance of both surviving transplant and having it actually cure her is extremely low and so ethically, the doctors do not feel right about asking an unrelated donor to undergo risk and burden to be her donor.  Secondly, given the highly fluctuating nature of Allistaire’s health and disease, the projected date of transplant could easily change which might mean we lose our donor who has constrained availability and requires more pre-planning because they would be donating on the other side of the earth (remember no U.S. donor matches).  Sten, as Allistaire’s father, is more than willing to take on risk and burden and is a highly committed and extremely flexible donor.  By the way, both he and I were options but it was concluded he was the better choice.  Lastly, the statistics for acute and chronic GVHD, NRM (non-relapse mortality), relapse, DFS (2 year Disease Free Survival) and OS (2 year Overall Survival), were on parr with the statistics for standard unrelated-matched donor transplants.  This means that we have the opportunity to give Allistaire as good of a chance at survival and a cure with her dad as a half HLA matched (haplo) donor as she would with a fully matched 10 out of 10 HLA matched unrelated donor with the added benefit that comes with having your awesome dad who is willing to literally lay down his life for you.

Thus far, Allistaire has received her infusion of Sten’s stem cells, essentially getting her transplant on Tuesday, January 12th.  She had no allergic reaction to the cells.  However, later in the evening she had a fever with higher heart rates.  Whenever an immune suppressed patient (in her case because of conditioning, not immune suppressing medications), gets a fever, blood cultures are drawn and antibiotics are started in case the fever is evidence of an infection.  Thankfully, Allistaire’s fever seems only related to her response to the mismatch of the incoming donor cells.  Dr. Bleakley was quite pleased as the fever was evidence of an immune response without the danger of a full on cytokine storm.

In the last few days, Allistaire has started to get some mouth sores, an expected result of conditioning which especially impacts rapidly dividing cells.  This means all the cells lining the digestive tract from the mouth all the way out the other side are hit hard.  This can result in mucoscitis.  She is more gaggy and nauseous, has thrown up a few time and has begun to eat far less.  At this point we are prioritizing her drinking the necessary fluids and continuing to take her oral meds, (rather than giving her IV fluids and IV meds which would be harder on her heart).  We are attempting to have her drink a pint of milk at each meal time to provide some calories in the form of protein and fat.  She may soon require her nutrition to be converted to TPN and lipids which are essentially IV forms of sustenance.

The next storm on the horizon begins tomorrow with the two days worth of cyclophosphamide infusions.  A side effect of cyclophosphamide can be bladder bleeding which they try to counteract with hyper-hydrating and a medication called Mesna.  Because of Allistaire’s weaker heart, they are reducing the hydration from the standard 1.5 times maintenance to 1.25 and are hopeful that this will both be enough to prevent the bladder bleeding and not overwhelm her heart.  Another serious and potentially fatal, but rare, possible side effect of cyclophosphamide is acute cardiomyopathy due to hemorrhagic myocarditis.  Depending on how things go, Allistiare could be transferred from the ICU back to the Cancer Unit early next week.

Honestly, it is an absolute wonder that she ever made it to this transplant.  Whether or not she will survive the transplant or it will be successful at curing her of her cancer are totally separate questions.  I am just simply in awe that we are here.  The Lord will continue to be faithful, morning by morning, come what may.

To join the Bone Marrow Registry, go to Be The Match

Learn about how to donate your baby’s cord bloodFullSizeRender-25 FullSizeRender-23 FullSizeRender-38 IMG_2372 IMG_2365 IMG_2360 IMG_2356 FullSizeRender-40 FullSizeRender-39 IMG_7554 IMG_7543 IMG_2354 IMG_2352 FullSizeRender-41 IMG_2333 IMG_2325 IMG_2312 IMG_2303 IMG_2302 IMG_2300 IMG_2393 FullSizeRender-13 FullSizeRender-8 IMG_2391 FullSizeRender-7 FullSizeRender-12 FullSizeRender-14 FullSizeRender-13 FullSizeRender-21 FullSizeRender-22 FullSizeRender-19 FullSizeRender-27 FullSizeRender-29 FullSizeRender-28 IMG_2384

 

Juicy

Standard

IMG_2153Ours is a sanitized fight.  I have only ever seen two insects on the Unit.  One would never know there was weather outside were it not for the horizontal planes of glass affixed to the side of the new building to contrast the vertical slices of blue, orange and green glass.  The rain hits the horizontal slabs, reminding the inside dweller that life does indeed exist out of these confines.  How I treasure those horizontal planes. Ours is a tedious, slow fight of absurd wealth.  The amount of financial, material, technological and human resources brought to fight for Allistaire’s life is staggering.  The light is bright with cheery images on the walls and flashes of exuberant color.  Countless groups come to the hospital and to Ron Don to make the season joyous.  Gifts flow in and in and in.  Everywhere smiling faces, time given to compassionate conversations and cheering us on and rooting for Allistaire.  Everywhere love and support.  Ours is a fight with so many allies.

In anticipation of the movie, “Unbroken,” coming out, I am determined to read the book first.  Much to my chagrin, I have not read much of history and this account of World War II in the Pacific gives me a much enhanced admiration and appreciation for our veterans.  How they faced the horrors common to war is awe-inspiring.  Their fight was poorly financed, poorly equipped and fraught with terrors I cannot begin to grasp – exploding flesh from countless weapons, disease, lack of medical care, sharks, exposure, starvation, torture.  In the same way that we press forward, unwilling to loosen our grip on life, they endured, they strove to hold onto life.  When Allistaire was first diagnosed, I kept thinking, if I was a Haitian mother, I would simply have a dead child.  There would be no fight.  There would simply be a swift succumbing to wretched disease.  So it has been throughout history and so it is in countless stories across this earth at this very moment – fights for life – lives cherished and infinitely valuable.

I went to bed Thursday night with the thought that we have been given SO much.  It is privilege to even have the opportunity to fight alongside Allistaire for her life.  Few have been given so much with which to battle, to persevere.  Who are we to have been so blessed?  The thought of what people must endure on this earth is utterly heartbreaking.  This fight tears constantly at my heart and yet, it is gift.  It could be so very different.  I went to bed more at rest in my spirit.  I woke less and still woke with heightened anticipation, but not terror.  I know the Lord is good and He sees the whole expanse while my sight is limited to a ridiculous degree.  Who am I to say what is best and thus what tomorrow should bring?  I keep handing her over to Him, entrusting her to Him, entrusting my heart and my life to Him.  Do as you please Lord.  You are my whole heart and it swells with longing for you Lord.  I live a dual anticipation – what will come to pass with Allistaire and looking for what the Lord will do.  The question of “why,” has never dominated my thoughts.  The earth and all that is in it is broken and it longs with eager anticipation for the coming of Christ to fulfill all His promises and restore and redeem.  The question of why rests far more on, “Oh Lord, why have you brought this wild, wringing sorrow into my life?  You are not an arbitrary God.  You are a sovereign, beautiful God, so what is your good intention for this road you are having me walk?  Why us, why now, why here?  Who will you put in our path?  How can I walk these halls and these days with face radiant because I HAVE seen you?!”  I don’t believe in accident.  I ask, “why,” because I am on the lookout for the beauty of what the Lord will raise up out of these days.

I actually experienced rest Thursday night and woke Friday once again in prayer, once again asking the Lord to orient my heart to Him – that He would fill my vision.  He has provided so abundantly, will I curse Him now if things do not go as I desire?  He is not a fickle God.  Is He not still the same good God when blasts appear on the lab sheet, when Flow Cytometry reveals an ugly diseased marrow?  I rose from my surprisingly comfortable couch bed to go and find our nurse, Nate, to discover what the Lord gave this day.  Allistaire’s ANC was 230 and there were zero blasts.  This meant a green light for her bone marrow test and ecstatic joy.  My joy was compounded when the doctor who did Allistaire’s bone marrow brought out a bright red, juicy sample of bone marrow to show me and tell me how good things felt in there, how simply good the sample looked.  On Friday they did a bi-lateral biopsy and aspirate, meaning they took sample from both hips in order to ensure sufficient sample given how hard it was to achieve last time due to the fibrosis.  Friday’s sample showed a changed marrow.  So, no blasts, rising ANC, platelets and hematocrit, a juicy fabulous sample of her marrow, lots of energy and no pain – as Dr. Gardner said, we have “guarded optimism.”

After I put Allistaire down Friday for her nap, I went to Ron Don and laid down, intending to read, “Unbroken.”  With lights of the room blazing around me I allowed myself to succumb to sleep.  Three naps in one week – what in the world?  A year could go by and I would not have typically had a nap.  Naps don’t work for me.  But an incredible exhaustion settled me flat on the bed and I dozed.  Perhaps I should be packing clothes for the next few days, but who could know which way the next few days would twist and turn.  I met with Dr. Gardner on Thursday afternoon to discuss three things: what was necessary to move forward with transplant, Denver and discharge.

As Allistaire’s ANC rose over the past week, the team started talking about discharge.  One might think that I should be excited about getting booted from the hospital but in fact “out there,” is a terrifying world I’m not excited to take Allistaire into – especially not now.  The docs pointed out that she has an ANC now which means she has a few lymphocytes (white blood cells) to fight illness.  Yeah, but perfectly healthy people with astronomical ANCs are getting taken down left and right with the flu and various other horrid colds and such, not to mention the Hand, food and mouth disease and Whooping cough going around Montana that could carry itself in the backs of our family.  Now more than ever, it is utterly essential to protect Allistaire from getting sick.  If the chemo has miraculously succeeded in getting her disease knocked down enough to move forward with transplant, then a very precise timing begins where two very separate lives must intersect at exactly the right moment.  The “conditioning,” (chemo and radiation), for transplant is timed in alignment with the donor prepping for the removal of their stem cells.  Cells are living organisms and can only survive so long outside the body and as conditioning begins for Allistaire, the process of permanently destroying her bone marrow has begun.  So, it is imperative that nothing stands in Allistaire’s way of walking each carefully planned step forward to transplant if we are given that option.  Something like RSV (a respiratory virus) is actually fatal in transplant.  She won’t have time to “get over being sick.”  The thought of leaving the hospital means she and I will be trapped alone in our room at Ron Don.  She can’t be in the communal areas and in order to get food I would have to take her with me to the grocery store which is a hot-house of hacking, sick people and kids.  Our best option is to go very early in the morning or late at night when we have a chance at steering clear of the sickos.

Then there was the issue of Denver.  So the bummer news is that the initial findings of the study, in the adult patients anyways, is not too impressive.  Only about 25% had a good response.  As Dr. Tarlock later told me, these aren’t such poor statistics for a single agent and likely this drug will be combined with other therapies in the future to have a far greater effect.  The truth is too, that this trial is Phase One, meaning they are only testing for safety, not efficacy.  The point being, it doesn’t seem worth it to send Allistaire to another state, another hospital, another group of doctors for a drug that isn’t a likely hit for her – unless there are no other options of course.  Dr. Gardner was going to see if she could contact the principal investigator and get a sense of how the pediatric patients were responding, as it could be quite different from in the adults.

By the way, here is yet another plug for pediatric cancer research – did you know that the NCI (National Cancer Institute) only gives 3-4% of its annual budget to funding pediatric cancer research specifically?  Here’s the problem, far fewer children get cancer than adults so it is not in the pharmaceutical companies financial interest to fund research to treat pediatric cancer.  So really, kids only get what eventually might trickle down to them from cancer research in adults which means much more time passes before there are any breakthroughs for kids with cancer.  Additionally, there are a number of cancers that only children get, like neuroblastoma.  Even AML, which is the most common form of adult leukemia, most likely has different origins and characteristics for children than in adults.  When a child is treated for cancer, their body is rapidly growing and every organ from the heart to the liver and brain are being poisoned from the chemotherapy and radiation.  Chemo targets the fast growing cancer cells.  In kids, all the cells are growing far more rapidly than in adults which means their healthy cells are much more vulnerable to the onslaught of chemo and radiation.  When an adult is cured from cancer, their life has been extended by and average of 15 years.  When a child is cured from cancer, their life has been extended by an average of 71 years.  So if the NCI won’t fund pediatric cancer research and the pharmaceutical companies have no incentive to do so, it means the real hope for children with cancer rests with the private donor.  Allistaire has benefited directly and significantly from research at Fred Hutch which treats adults as well and I will continue to root for them and seek to raise money for what they are doing, but there is also a place for giving directly to childhood cancer research.

Okay, back to the most significant issue at hand – what reality will enable Allistaire to move forward with transplant?  What must be true from the results of the bone marrow aspirate and PET/CT?  Dr. Gardner said the most important piece is that the disease in her marrow must be quite low.  The less there is in her marrow, the more likely the transplant is to succeed.  So while the transplant allows the patient to not be in remission, it is still far better that they are.  She said that if the pathologist looks at Allistaire’s sample under the microscope and she is morphological remission which is defined as 5% or less disease (this is the lowest detectable amount with the microscope), then she will be in good shape to move forward with transplant.  Of course there is also the issue of her chloromas (locations of solid leukemia).  One would presume that if the chemo worked in her marrow, it would do the same in the chloromas but apparently tumors have their own micro environments that can allow and promote cancer cell growth that doesn’t take place outside of them.  Only the PET/CT will tell the truth about what’s going on inside, but so far she has not had any pain which is a good sign.  Neither Dr. Gardner nor Dr. Bleakley are super concerned with the chloromas simply because they can be treated with focal radiation if necessary.  Of course this is not optimal as every part of the body that is exposed to radiation is more prone to develop cancer in the future and can be damaged or deformed.  I am sure that an increase in the number or size of the chloromas would require quite a discussion, even if her marrow was in good shape.

I left my time with Dr. Gardner with the plan that she would see what she could find out from Denver, and that if her marrow looked good, we would be discharged from the hospital and if not, we would stay in.  So what’s the point of packing I thought.  I lay in a flattened, utterly still state.  The phone rang with that attention grabbing number ever emblazoned into my brain: (206) 987-2000.  My heart jumps every single time that number shows up on my phone.  Even when all has been well that number gets my heart thumping and dampness of the palm.  It was Dr. Shoeback, the attending doctor at Children’s.  “The pathologist can see no cancer cells in Allistaire’s sample.”  WHAT?  Utter ELATION!!!!!!!!  I could not believe my ears!  Allistaire is in morphological remission and only the possibility of a horrible PET/CT stands in her way of moving forward with transplant.  After the exhausting torture of her last relapse, I could not have imaged this being possible.  But it worked!!!!!!  On Monday we should have results back from Flow Cytometry, but that will only give us a number below 5% and while it would be awesome if it was zero, it doesn’t need to be any less than 5% to be given the open door to transplant.

On Monday at 1:15pm, Allistaire will have her PET/CT scan and by the end of the day, I should hear from Dr. Gardner with the results.  Of course a plan can’t really be formulated until all the data is in, but the AML docs and Dr. Gardner are discussing with Dr. Bleakley what would be the best plan for “bridge chemo.”  It is necessary to have some form of treatment between the end of this round of chemo and conditioning chemo because you ethically can’t get the donor moving forward with their steps until you know you really can have a transplant.  By the way, while Allistaire has no U.S. donor, Dr. Bleakley is trying her best to exhaust all possible options for Allistaire.  She is in contact with the German version of the FDA to get approval on their end to get a consent process with the overseas donor to manipulate the T-cells.  I think the idea is that this is an additional step taken with the donor’s cells and because the donor’s cells are technically part of the donor or owned by the donor, they have to give consent.  If you want a super interesting read on this topic, check out, “The Immortal Life of Henrietta Lacks.”  If approval is given through the German system, Dr. Bleakley can then seek out approval from the FDA.  Even if all this approval goes through, there is still the issue of the timing and age of the cells given the additional time that would be required to process the cells in Seattle.  If the donor is from a “major center,” in the German system, this increases the likelihood that the quality and timing of the cells could work.  Dr. Bleakley says that ultimately it will be up for Sten and I to decide what we want to do.  It’s a gamble really.  The conditioning chemo for the trial transplant and the standard transplant are different.  The donor cells could arrive from overseas and it be determined that they are not in good enough condition to be processed and take out the naive T-cells.  In this case only the minimal processing that always occurs with donor cells would take place and Allistaire would get the transfusion of donor cells as is.  There is a lot to consider, if even we end up having that choice to make.  In the mean time, Allistaire will need some chemo to keep the bad guys down.  This could either be another round of the DMEC (Decitabine, Mitoxantrone, Etoposide, Cytarabine) which she just had – in the clinical trial it has been given in one to three courses.  Because her heart remains in good shape, this would be an option.  Additionally, Decitabine can become even more effective over multiple courses in the same way that Azacitadine does, which she had post-transplant last time.  Another option would be Decitabine alone.  Lots of brainstorming amongst the docs is necessary.

I can hardly believe it.  I can hardly take it in.  I cannot stop smiling!!!!!  My girl has been given one more open door.  Every day of this journey feels like walking around a blind corner.  There is absolutely no way to predict what the next day will bring.  Often the entire trajectory of your world can shift from morning to night.  The wind blows, the seas rage and toss and yet the north star is unmoving.  I keep my eyes fixed on Christ, my one sure hold.  Tomorrow morning we rise to a new day.  I have no idea what will be known when I lay down to sleep Monday night.  What if this whole thing, this crazy journey is just so that I would meet Debbie today in the rug aisle in Target?  What if all these years of highs and dark lows are so that I could tell her, Debbie, my hope is in God!  My hope is in God!  Not that He will save Allistaire, though I have joyous confidence that He can overcome the most hideous of cancer cells, but that this whole crazy life and world are His and He will accomplish the beauty of His will which is more magnificent and glorious than we could ever, ever imagine.  His promises are sure footings.  Debbie, your hope can be in God, in Christ the Savior who was born to bring peace and goodwill to all men!  Oh let the whole earth, the whole wondrous earth sing His praises, may every cell of my flesh rise up and strain to declare His love, His beauty, His overcoming power to redeem and raise the dead, the dead heart, the dead flesh.  He is coming, He is coming and I am on the lookout!

(The top picture is of the vial of her bone marrow aspirate and the the tiny bit of bone is the biopsy.  I’ve included at the end a number of pics from three years ago – always wild to see some perspective on our journey)IMG_2149 IMG_2154 IMG_2155 IMG_2159 IMG_2160 IMG_2161 IMG_2164 IMG_2173 IMG_2181Allistaire with Papa sisters and cousins 1 Christmas Family Cancer Fears Me DSCN4804 DSCN4805 DSCN4806

Black Waves

Standard

IMG_2005“To swim in the ocean, you dive through the waves as they come at you,” my friend Matt tells me as he points to the horizon and the relentless pounding of ancient force.

I do my best to dive through the first wave, but I don’t quite make it and the curling power forces me down.  My body is tumbling in the cold water.  I try to get my footing on the sand that gives way.  Breath.  Breath.  I see the next one coming and before I can recover, it slams me down again.  The waves kept coming, utterly oblivious to my plight.  This must be what it feels like to be drowning, but that won’t happen.  It can’t happen, right?  After three or four waves I finally scrambled out of the pull of the waves, tired and shaken on the sand.

Matt is dead.  The incomprehensible happened.  And it’s happened so many times since.

My friend and her daughter are back on the Unit.  She tells me how little there is left to try, how she must hang on for a clinical trial she hopes to get on, but it may not be until January.  She walks slow in the hall, bearing up under the pain that seems to be everywhere.  It has not mattered that her disease gave her an over 80% chance at survival.  Her she is.

I saw a dad I know the other day.  He and his daughter had driven hours to come visit one of her friends whose cancer keeps returning in the lungs, a bone cancer.  This is how it goes and when it does, it almost always spells the end, eventually.  He tells me of some of her other friends, this one at home on hospice to the north and the other to the south.

Hospice.  “They went home on hospice.”  Has a word ever cut so brutally.  It is like a dirty, ragged knife, cutting slow but deep.  It is tearing through your gut and it is so horridly slow but you can do nothing to stop its course.

I look at my friend and her daughter and think, here we are, we have at last become, “those people.”  Those, that even within this small harsh world, have become “other.”  We are the lepers.  We are the stories to steer clear of.  We are the living, breathing, shuffling statistics we have all sought to disregard.

I debated when my alarm went off this morning whether or not to give into the desire for sleep, but rather determined to get up and climb up and down the overly warm stairwell as some attempt at excercise.  The nurse came in as expected for 6 am vitals and I asked her to see Allistaire’s labs.

“They’re all normal,” she said, “but the ANC isn’t back yet.”

The sickle came swift and sliced through my legs and left me collapsed.

“That means there are blasts,” I stammer and my eyes scan as she gets to the right page on her computer and there it is, everything is back now.

Absolute Blast Count: 10; Absolute Neutrophil Count: 0

Her ANC had been at zero for sixteen days and then on Friday it peeked up at 8.  I was so relieved to see no blasts.  Yesterday it was 20 with no blasts.  Every day in rounds the resident repeats the same refrain, “awaiting count recovery.”  That is what we’re here for.  Get the chemo and then wait and wait and wait to see if it worked.

It hasn’t worked.  The chemo has failed to control her disease, much less to suppress it to get into a position for transplant.  It only takes the sighting of those few horrific blasts to know there will be no transplant next and what’s next requires a move to Denver.  I imagine we will still have to wait until her ANC gets up to 200 to do the bone marrow test.  You have to have enough recovery of the marrow to get a clearer idea of the amount of disease.  What is clear is that her cancer is recovering along with some healthy cells.

I should also update the news that there is no match for a donor in the United States.  Not one.  She needed a U.S. donor to be able to get the Naive T-Cell depleted transplant that Dr. Bleakley is overseeing.  It is just baffling and hard to imagine that in the whole of the United States there is not one person who can offer Allistaire the cells she would need for another chance at life.  Please, if you are not on the registry, ask yourself why not?  How often are you given a chance to save someone’s life?  This is not abstract.  This is as tangible as it gets!  You haven’t had the time yet to go online to check it out?  You’re afraid of the pain?  Please, are these reasons to deprive someone the chance at life?  So many have said they love Allistaire, they are praying for Allistaire.  Is any child less worthy of life?  I asked Dr. Bleakley if they could do another search for a U.S. donor if we ended up having more time before transplant and she said it was a matter of very diminishing returns.  But you know what?  It only takes one person to be a match, ONE.  You could be that one person.  Click HERE to sign up to be on the bone marrow registry.  And please pass on this appeal to as many as you can.

The last two days have been pretty wonderful with Allistaire.  I wish you could see her bright face and mischievous twinkle in her eyes.  “You distract him,” she hoarsely whispers.  “Connor, I think there may be dragons outside Allistaire’s room.  Can you go keep a look out?”  Connor, the CNA, joyfully plays along, and Allistaire speeds with IV pole in hand from bathroom to bed and throws the pale blue covers over her head.  I cry out, “Oh Connor, where is Allistaire?  I fear she has been eaten by the dragons.”  The blankets wiggle and giggle with her uncontrolled delight.  She wants to play this game over and over.  Her appetite has been better and eating has become much less of a struggle.  It still takes about two hours per meal but at least now she is getting in a reasonable amount at most meals.  Her weight only dropped point two kilograms over the week that she didn’t eat much.  She has loved having Betsy, the music therapist come by and sing songs together and play instruments.  Two sweet young ladies from the ministry of University Presbyterian Church, Side-By-Side, came and played with her Friday afternoon.  She absolutely loved having them and was desperate to have them stay longer.  They promised to be back in seven days.

We’ve gotten into a little routine she loves.  When I leave either in the morning or at her nap time, she whispers with glee, “you go over there by the curtain and I will tell you things.”  So I obey and go stand at attention by the curtain.  “I love you and I hope you have a good time exercising (insert whatever activity I’m off to do), and I’ll see you after my nap.”  Then she blows me kisses and I respond in turn, “Allistaire, I love you, I hope you sleep well, and I’ll see you when you wake up.”  I obnoxiously blow millions of kisses.  Her eyes, so bright with happiness and her sweet, little voice tilting up and down with her words.

No matter how my times I have bent my knee before the Lord, submitting to whatever His will might be in her life, in my life, in our lives, I don’t know any better how to let her go.  I have made no progress in my ability to know how to let her go.  My whole being soars and stretches with love for her.  This little girl becomes only more and more precious to me.  And I just can’t comprehend someone so wondrously alive being dead.  She is no different from millions of other children who have been lost.  She is no more valuable than any other human, any other mom, sister, dad, grandparent that has died.  But these millions upon millions of deaths do nothing to diminish the loss of her.  If she dies, it will take all of her.  She will be gone from this life.  I see all that we’ve been given, these years with her, even these three whole years since she first became sick.  I see how fortunate we’ve been to live in this time and in this place, we have been given so, so much.  I see the overwhelming kindness of so many people, both that I know and those we’ve never met.  I look at the Lord and I know I will see her again.  I believe in the good that will come.  But here and now, her loss would be loss. Her gone would leave a gaping hole.  This life will no longer contain that voice, those bright eyes, that laugh.

I know I must go on, putting one foot in front of the other, going through each step that must be taken.  I am asking God to hold me up.  I am asking God to give me moments of joy in this midst of these crashing black waves.  I will keep my face to Him, but it is a face streaming with tears, agony of heart, gasping of breath.  Lead me by your hand down this road Oh Lord.  I cling to you.  I may even need you to carry me, I don’t know that I can will my feet to move forward into that darkness.

I cling to your promise.  “I am in that dark place, Jai.  You will be found my me.  I am the God that turns darkness into light.  I am the redeemer God.”IMG_1992

A Thousand Barricades

Standard

IMG_1926Written yesterday:

Your body rebels and declares no one should need rise before 4 am, and yet out there in the dark crisp cold of night, yet early morn, you relish the clarity of stars and moon and blue light on snow as though you have snuck in and been witness to that which is the earth’s own private beauty, beauty sown in the hours that only animals inhabit.  My lungs stretched and with wide-spread arms, pulled in freshest air and with glee, took in the tiny twinkle of stars, each one called out by name, by my God, by my Father.  And with deep breath, I asked again that the Lord would hear my cry, that He would hold me up in the day and days to come.  I thought back to the unexpected conversation with Nate about sorrow, about loss, about fainting hearts and my words that yearned to encourage that it is good to be broken, to be at loss, to know neediness because it is the way into knowing God and mysteriously we find ourselves stronger than expected because our need and our brokenness has led us to God, to be bound to an almighty, all-knowing good God.  And under that purest clear of night sky, I asked myself again, if I actually believe it all.  My answer came, not with the request for this outcome or that, but simply, show me your face God and help me to yield myself and my life once more, again and again to you.

I left Bozeman this morning and arrived in Seattle in clouds and gray, unseasonably warm with no need for a coat.  As I crept through traffic along I-5, I thought back to that December day exactly three years ago.  Dr. Tarlock called on that Friday afternoon to say simply that they had found tumor cells in Allistaire’s bone marrow and we needed to come to the hospital.  Results weren’t supposed to come until the following Tuesday, but there was the word “cancer” and “tumor” scrawled on a pink sticky note and then the warm pink glow of winter afternoon light on the faces of two little girls in car seats as I drove north on I-5.  An overly peppy song played in the car with words that defied the upbeat tone:  “Blessed be your name in the land that is plentiful, where your streams of abundance flow.  Blessed be your name.  Blessed be your name when I’m found in the desert place, though I walk through the wilderness, blessed be your name.  Every blessing you pour out, I turn back to praise.  When the darkness closes in, Lord, still I will say, blessed be the name of the Lord…blessed be your glorious name.  Blessed be your name, when the sun’s shining down on me, when the world’s all as it should be, blessed be your name.  Blessed be your name on the road marked with suffering, though there’s pain in the offering, blessed be your name.  Every blessing you pour out, I turn back to praise.  When the darkness closes in Lord, still I will say, blessed be the name of the Lord, blessed be your name.”  Allistaire, never able to pass up a good beat, rocked out in the back seat and bright smiles lit up their faces.

Lulled by traffic and familiarity with the song, I startled at the words, “You give and take away. You give and take away. My heart will choose to say, Lord blessed be your name.”  I looked in the rearview mirror at those two happy faces of my daughters, oblivious to what ill fortune had befallen us, and wondered whether or not there was a future that would still hold those two sets of laughing eyes, laughter playing off laughter.  And so, from the very beginning I have looked this threat, this terror, this sorrow in the eye.  I refuse to turn away or diminish, but I look it dead on and I call out to the Lord.  Help me, oh God above, you who call out each of the stars by name, give me eyes to see what good you will bring out of this brokenness and more than anything, help me to fix my eyes on you and call you blessed because you have upheld my heart and strengthened my faith that I might endure for the joy set before me, if even the joy does not come until I “cross over the river and rest in the shade of the trees.”

I wanted to go home.  Last time Allistaire relapsed, a span of five whole months passed before I returned home.  That was far too long to be away, but in those days, and even in these, home feels like another world, a world which might only exist in my imagination and it has seemed easier not to taunt myself, but to stay fixed on the reality at hand, to keep my hand and heart on the endeavor to fight for Allistaire’s life.  But my sweet mother-in-law took me at my word that I wanted to be home more often, and gleefully declared, “let’s be radical.  Let’s just make it happen.”  So while only 41 days had transpired, I got on a plane late Thursday night.  The Bridger’s were still there, glowing with snow covered ridge in light of fullest moon.  I walked through the door and the same strange smell of our home, greeted me.  I stood, unmoving, staring at the kitchen counters and could hardly believe that not long ago, I lugged in bags of groceries and stood with cutting board and knife preparing dinners, trying to push myself to try new recipes on occasion.  How often had I stood on one side of the island, preparing breakfast, cleaning up breakfast, emptying and filling the dishwasher while Allistaire sat on the opposite side, breakfast and lunch day after day after day.  Had that really ever happened or has she always been sick, always been bald and in bed, always been vulnerable with no white blood cells, always, always fighting her “sickness.”  Had there ever really been ordinary days, most beautiful, most cherished, ordinary days of incalculable value and beautiful ordinary delight?

In the morning I opened my eyes to that same beautiful wood paneled ceiling, to the blue of sky up the hill and stateliness of evergreens framed by my bedroom windows.  With trepidation, I entered her room.  There hung her school uniforms, white and pale blue shirts with peter pan collars and navy and plaid jumpers, worn sometimes with white knee socks and sometimes with navy tights.  I found a bag with her school pictures, gym shoes and the cloud, puffy with cotton balls and raining bright silver streamers of rain.  And my breath caught in my throat as I realized how close this all was to walking into the abandoned room of a dead child.  I looked up the wall at her artwork, and the number one outlined in pinto beans and bins of toys on the floor.  And the question stabbed through me over and over, what if she never returns?

Wednesday had been a particularly hard day.  Sten left the day before, great welling of tears in his eyes as he held her goodbye, not knowing if he would ever again see her with hair.  Who would she be when he came back?  Her hair had started to fall out and began to coat everything, including Doggie.  Hair all over her clothes, in her mouth and food.  I told her I would cut it before I left, but I wasn’t prepared for her request Wednesday morning that I cut it because it was bothering her.  In my unconscious mind, I still had one full day left with her before more of her would be stolen away.  But I knew she was right, and I forced my hand to function and grasp the scissors and not gasp at every cut through the blonde hair that has never had the chance to grow more than five inches long.  And there she sat, part of her gone and in her place a prison inmate, a child being sent to the gas chambers.  We walked a slow drudge to the bathtub room to wash away the debris of life, of a hoped for life, a life that had appeared to be thriving.  I asked the CNA to change the bed while we were gone, to take away the scant pile of blonde clippings.

Two hours of eating lunch only yielded five bites and not even a cup of milk completed.  I had to entrust the nurse to put her down for her nap so that I could drive downtown for the transplant consult meeting with Dr. Marie Bleakley.  I sat across from her just as I had a year and a half ago, to go over the transplant for Allistaire, to hear the heavy realities and hopefully be shown the ray of light in all the pressing darkness.  The one year survival rate for patients getting a second transplant is 25%.  Of those, only half live more than five years.  So 12.5%, that’s the odds, if she can even get to transplant.  In her favor is that fact that she is a child with a healthy body, besides cancer, that because she has not had TBI (total body irradiation) they can give her the most powerful transplant in existence.  Lastly, she was in remission for nearly a year which says something about the aggressiveness of her disease.  However, in order to get to transplant, the doctors will make a subjective decision about whether or not she has “responsive disease.”  They must see a significant improvement in her chloromas (the six places of solid leukemia).  If her disease can march ahead undaunted in the face of these four powerful chemotherapies she has just received, a second transplant is highly unlikely to stop it.  So while, thankfully, there is a transplant that does not require remission, nevertheless, they need to see a disease that gives evidence that it can be shut down.  If this round of chemo does not work, must likely we will go to Denver to do the DOT1L inhibitor trial.

The most optimal transplant for her is the clinical trial, for which Dr. Bleakley is the principal investigator.  What is unique about this transplant, is not the conditioning regimen (chemo and radiation) but what is done to the donor cells.  Dr. Bleakley’s team, in her words, “attaches little magnets to the naive T-cells and removes them, returning the remaining cells to the patient.”  The goal of doing this is to reduce the incidence and severity of GVHD (graft versus host disease) in which the donor cells see the host/patient as foreign and attack the body of the host.  GVHD can be debilitating and even cause death.  So while it is really desirable to reduce GVHD, there is the concern that in doing so, there may be a reduced GVL (graft versus leukemia) effect.  The great hope of transplant goes beyond the decimation of the conditioning regimen, and is more firmly rooted in the science of the donor cells seeing the host’s cancer cells as foreign and killing them.  Forty-six patients have undergone this manipulated T-cell transplant and there are quite promising results in terms of reduced GVHD.  I was also delighted to learn that there has been a reduced incidence of relapse amongst the AML patients on the study.  Dr. Bleakley says that perhaps they are removing some GVL effect when they remove the naive T-cells, but it seems they are also enhancing/enabling the GVL effect more greatly specifically with the AML patients.  An otherwise very soft-spoken woman, Dr. Bleakley becomes much more animated when she discusses the power and hope of immune therapy.  She explains that she and a number of her colleagues were trained under Dr. Stan Riddell at Fred Hutch who was in turn trained by Dr. Phil Greenberg.  The primary purpose of developing this transplant is to provide a platform for the immune therapy that doctors like Dr. Greenberg and Dr. Jensen are developing.  The idea is this – you can’t have raging GVHD which requires immunsuppressants and make use of the wonders of modified T-cells – the fighters of the immune system.  There is no point in being given amazing, super powered T-cells if you just to have suppress them.

Needless to say, listening to her describe this new transplant that would provide the best shot at being able to receive the modified T-cells that Dr. Greenburg is developing, was the ray of light I was desperate to cling to.  Of course, simply getting Allistaire in a position with her disease to be able to even have a transplant feels nearly impossible given how many treatments failed the first time she relapsed.  Then Dr. Bleakley revealed another major barrier to Allistaire being able to have this transplant.  She must have a U.S. donor.  The donor search team has identified a 10 out of 10 donor for her in the German system, but this transplant necessitates a donor from the States.  The reason for this is that as soon as the cells are harvested, they begin to die and degrade.  The manipulation of the T-cells for the trial requires an entire day of work once the cells arrive.  By adding on the time it would take the cells to get from Europe to the U.S., the cells would probably not be in good enough condition for the transplant.  Because the cells are being manipulated, consent from the donor is required.  This process and approval has been set up for the trial in the U.S. with the FDA.  Not only would the cells be too old if they came from overseas, there is no regulatory process in place to allow a foreign donor.  It is possible that there is someone on the registry in the U.S. that could be a match for Allistaire, but that is currently unknown.  The protocol for the donor search process halts the search for a donor once an acceptable donor is located.  The probable reason why it has been easier to find Allistaire a donor in the German system is because the folks on that registry actually pay to be on the registry and renew their commitment annually.  Additionally, I think these potential donors start out with giving a blood sample unlike U.S. donors who only give a swab of cheek cells.  This means that the German system can offer much higher level testing/matching than the U.S. system straight out the gate.  The German registry also pays for the remainder of the testing necessary to determine a match.  In the U.S., it costs three to five thousand dollars to test each potential donor.  This is why the search protocol is to stop the search once a donor is located.  There is no reason to continue spending money to test additional potential donors, if you’ve found one that will work. Dr. Bleakley has instructed the search team to pursue U.S. donors, so we will have to wait and see.  Kind of a wake up to realize that though there may be 22.5 million people on the U.S. registry, there still may not be a person that will match Allistaire and allow her to have the opportunity for this amazing transplant option.  Are you on the bone marrow registry? Click HERE to join.

If Allistaire were unable to get a matched 10 out of 10 U.S. donor, and she was in a position to receive a transplant, she could have a the standard transplant and use the donor from the German system.  Like the naive T-cell depleted transplant, a standard transplant does not require remission but requires the collaborative agreement amongst the doctors that Allistaire’s disease has responded enough to therapy to give the transplant a higher likelihood of success.  The third option is to have a cord blood transplant.  There is debate about whether or not cord blood transplants result in greater GVHD.  The two clear down sides to a cord blood transplant for Allistaire is that it absolutely requires strict remission and it would prevent her from being eligible for the modified T-cells developed in Dr. Greenburg’s lab, as that study requires a matched 10 out of 10 donor.

Yesterday I spent some time on the phone with Kira, the transplant insurance coordinator at SCCA (Seattle Cancer Care Alliance).  At the end of my meeting with Dr. Bleakley, she asked, “So your insurance is going to pay for this?”  Oh dear, I had not even thought of that.  I just assumed we were in the clear because of that awesome bill that was signed into law in 2013 prohibiting insurance companies in Montana from denying clinical trials to cancer patients.  Dr. Bleakley said that sometimes insurance companies with deny all clinical trials and sometimes they will allow Phase 2 trials but not Phase 1.  So a conversation with Kira was in order.  I was baffled and enraged when she told me that the insurance companies have found away to get around that law and can still deny any clinical trial they like.  “They would rather her be dead!”  I cried out.  Healthy is better than sick, but dead is all the better still.  Dead people don’t cost anything.  I asked her if they just deny clinical trials  outright and she said that they used to but that it’s not quite that bad anymore.  She encouraged me that she and her team are here to fight on Allistaire’s behalf and that like the insurance companies, they too have ways to get around the barricades the insurance companies throw up.  She described several different tacts they can take, one of which involved a 30 day appeal process.  “We don’t have 30 days!”  I yelled.  Fortunately, Kira said a number of the appeal processes can take just a matter of a few days.  So there is hope that we can get approval through insurance but the process cannot even begin until the doctors can say that Allistaire is actually in a position to have a transplant.

Bone marrow tests occur between day 28 and day 35 of a round of chemo and necessitates an ANC of 200 or higher.  There need to be enough cells present, indicating sufficient rebound of the marrow, to really determine how effective the chemo was.  Day 28 will be December 17th.  Bone marrow test results take about 48 hours but because she also needs PET/CT scan, we will likely get some telling results on the day of testing.

Every where I turn there are barricades to the road ahead.  At so many points, the door could be slammed shut on Allistaire’s life.  I know that no matter the number of road blocks or the seeming difficulty, nothing is hard with the Lord.  With His word He spoke the world into existence.  These seemingly insurmountable walls are like wee blades of grass to God.  I know He is able.  I don’t know however, what His plan is.  It is hard not to lose hope.  I spoke with a staff person at the hospital a while ago and I know I sounded like the downer because I continued to point out that her death is entirely possible.  The person responded that she and her coworkers could not do their jobs if they did not hope for life for her and so many like her.  Yes I hope for her life, but I cannot have the endpoint of my hope be in whether or not she lives.  My hope must, it must go beyond the grave.  The trajectory of my hope ends in God, it ends in the fulfillment of all He claims is true.  My hope rests in His promises that proclaim that all life is eternal, and life for those that love Him, are with Him for eternity and that He will redeem all things.  He promises that these sufferings will one day be shown to be “light and momentary,” and that they are “achieving for us an eternal glory that far outweighs them all.”  My hope enfolds the hope for her temporal life, and my temporal life, but it far exceeds these and strives on, yearning forward to eternal life, pure, abundant, eternal life with God where sickness and death are forever done away with and life incompressible rises up.

Sunday night, after we finished decorating the Christmas tree and put Solveig to bed, Sten and I sat in the light of the beautiful tree.  How many Christmases have we sat before the tree, the light reflected in purples, blue, pink and yellow?  Last year when I packed up the Christmas decorations, I wondered what this Christmas would hold.  I wonder now what next Christmas will be.  Sten and I sat and cried, heaves and silent sobs.  Every joy I have known with Allistaire, now sits tied and counter-balanced with cutting pain and sorrow.  We ate pancakes Saturday morning and Allistaire was not there.  She was not in the snow seeking just the right tree.  Solveig hung the ornaments that were Allistaire’s, carefully selected each year with the intent that one day she would have her own home, her own Christmas tree.  When the three deer crossed the snowy meadow, I could not call to Allistaire, to quick, get the binoculars.  She was not there.  Will the brightness of her eyes ever again cheer eagerly at the sight of animals in the field?

Being home was hard.  My imagination so honed.  But being with Solveig was wonderful.  When Solveig came out over Thanksgiving, the priority was for she and Sten to spend time with Allistaire.  At home, we had the joy of spending time together in ordinary ways.  It really was a full, wonderful four days.  On Friday, I took Solveig out of school early to get her flu shot and head over to The Coffee Pot, Solveig’s favorite lunch spot.  Then on to my favorite antique store and a few errands before we met up with Sten to go see Big Hero 6 all together.  The night finished up with burgers at Ale Works, another favorite of ours.  Yes, we settled down into the booth in the train car where we four have often sat.  There was an empty place at the table that threatened to steal the joy of the present, and clamp down sorrow.  But on we went.  Saturday we slept in and then had chocolate chip and apple pancakes.  We drove up past Bridger Bowl and used our $5 Forrest Service pass to get a happy little bright green pine tree.  I put away the Halloween decorations that have just sat unattended.  Later in the afternoon we went into to town where Main Street is closed off for the Christmas stroll.  This year it was nearly 60 degrees warmer than last year.  We enjoyed the artisans at SLAM fest and then a great dinner and show at our favorite venue, Peach Street Studios. It was a splendid day all around. On Sunday I had the joy of hiking the M with my friend Hope and talking over breakfast.  Lunch was with dear April and the unexpected conversation with Nate.  Sunday night we finished up the Christmas decorating.  The garland and trees, the light-up snowman for Allistaire’s room sit still in the dark boxes, hoping for use another year.  On my last day, I spent hours at breakfast with Pam, my dear, dear friend who knows best this hard road.  I could never have imagined the gift of her friendship.  We have committed to be there for one another.  We dream of our children being adults together, but come what may, we look forward to the hope of being gray haired old ladies together.  Jess and I, spent time and rejoiced at already having nearly 15 years of friendship.  Jess blessed me with tear filled green eyes and tales of missing me.  The afternoon wrapped up with an appointment with the social worker at the Bozeman Deaconness Cancer Center to explore options for counseling and then an all family get together at our house over pizza, salad and cherry crisp.

Solveig could be heard crying in her room after I put her to sleep.  Another leaving.  Unknown days.  A black wall of unknown past December 17th.  With trepidation I walked the hall to Allistaire’s room at the hospital, fearful of blood counts and possible blasts.  Rather, I was greeted with the sound of Allistaire’s laughter with Papa in the room while I talked with Kathy the nutritionist who says she has one and a half kilograms wiggle room with her weight before a feeding tube would need to be seriously considered.  Then Dr. Leary appeared for rounds with news that both her ANC and ABC (Absolute Blast Count) remain at zero.  Oh how I love, love, love that little girl.  I laughed out loud when I saw her very silly head, now far more bald with the exception of the fringe of wispy blonde hairs framing her face and neck.  What is hilarious is the spiky brown hairs in the back that stand with resolute determination to stake their claim to her cranium.  They look like the have no intention of going anywhere but maker her look so very silly.  She was full of joy and glee, drawing and coloring at her table.  On Wednesday night she had spiked a fever, which necessitated blood cultures and broad-spectrum antibiotics until they could determine the source of the infection.  When I left on Thursday, she was a feeble little child who wouldn’t eat and only wanted to lay in bed with warm packs on her tummy.  She has had constant diarrhea for the past few weeks and seems to have pain from cramping.  It was hard to leave her when all I wanted was to curl around her and bring comfort.  So it was exceptionally lovely to find her in much better spirits.

We are twenty-two days into this round and 14 days of zero ANC.  We wait.  I try to get as many calories in her as possible.  Oreo shakes have seemed to help that task a bit.  I don’t take it a day at a time.  There are windows of hours and moments that require the aid of the Lord.  I told Nate about manna.  Such a crazy tale, but really so beautiful.  The Lord provided manna for the Israelites in the desert for food.  But only for a day.  They could not save or horde the manna.  They had to trust the Lord that He would again provide for them the next day.  They had to put their hope in His faithfulness, His sincere love for them and His actual capacity to provide.  I eat the manna.  His mercies are new every morning.  Great is His faithfulness.

IMG_1918 IMG_1921 IMG_1923 IMG_1925 IMG_1928 IMG_1931 IMG_1933 IMG_1939 IMG_1941 IMG_1944 IMG_1946 IMG_1949 IMG_1953 IMG_1956 IMG_1959 IMG_1961
IMG_1966 IMG_1975 IMG_1979 IMG_1982 IMG_1985 IMG_19863 Years ago, December 9, 2011:

DSCN4615 DSCN4616 DSCN4621 DSCN4626

Dread, Hope, Dread

Standard

IMG_1612I know I should go to bed but I know that when I do, tomorrow will hasten its coming.  So fast it will fly and then we will have arrived on the threshold of that day we must enter the hospital.  I strain to slow my steps as though I can with force of will prevent the series of events which will come, which must come to bring us to Wednesday morning.  The halls are bright with light and the colors, blue, orange, green are meant to be cheery, modern.  But to a prison cell it feels we are being sent.  And the dread is not because of the annoyance of people perpetually coming and going or the fact that we are closed into a tiny space where no normal advances of life can take place, where we are stunted in 4 hour cycles of vitals.  No, that is endurable, that is bearable.  The dread, though weighty, sinks slow and silent, settling firmly in my heart, in my gut.  Will she ever leave again?  Will the sweet small child who walks through those doors ever, ever return?  I KNOW what happens in that place.  I know what terrors lurk.  I feel as though I’m walking my child to the gallows.  I’m doing this, in her innocence, I lead her into that place.  But I have no other choice.  I must hand her over.  It’s breaking my heart to know what will soon be done to her, again.  How can she endure?  She is so small.  And she must do it all over again for a second time.  My heart tears with screams – how can I be forced to choose between these poisons and destroyers of chemotherapy and radiation, and her death?  Neither are good!  I despise being crammed in this wretched crack of murderous choices.

But I yield.  I take her by her small, warm hand and I will lead her in.  It does not take long in the fight against cancer to know so clearly how each step forward is gift, pure, free, underserved, gift.  For you see those falling away around you and you know how very fortunate you are.  The sun has shone upon you, you are the blessed and you have absolutely no room to grumble or complain – for you still stand.  I don’t know what the days ahead may hold.  I don’t know how long we will be locked in that place or if ever, ever my beloved Allistaire will come out, marred, but alive and radiant.

This morning we went to clinic and Allistaire had labs drawn, then we saw the nurse practitioner.  At the end of the appointment we had the joy of having Dr. Gardner come by as well.  She was able to relay the discussion regarding Allistaire that the Hem/Onc and transplant doctors had this past Thursday.  They agreed to prioritize a clinical trial transplant whose aim is to reduce Graft Versus Host Disease (GVHD).  Based on Allistaire’s HLA (Human Leukocyte Antigen) typing, they are optimistic that they will be able to find a 10 out of 10 matched, unrelated donor that will fulfill the protocol’s requirements.  The trial is testing the efficacy of removing “naive T cells” from the donor cells and returning the remaining cells to the patient, leaving the memory T cells.  For those new to bone marrow transplants, the idea is not only that you myeloblate (utterly destroy) the patient’s marrow in the hope that you also destroy the cancerous cells, but that the real beauty of transplant is mythical GVL (Graft Versus Leukemia).  When you receive the infusion of the new donor cells, these cells enter the patient’s body and sees their body as foreign.  The immune system is created to search out and destroy what is foreign and unwelcome.  This means that both healthy and cancerous cells may be attacked.  The attach of healthy cells is known as GVHD and the attack against cancerous cells in the case of leukemia is known as GVL.  So this transplant is designed to remove the T cells that indiscriminately destroy and leave the rest.  While I love the thought of less GVHD, I asked Dr. Gardner with concern, whether or not such a transplant would produce diminished GVL.  With a smile, she said, no, they don’t think so, they have had very promising results.

Another upside of this transplant, is that with diminished risk of GVHD, there is a greater likelihood that Allistaire would be in a better position to receive the infusion of the modified TCRs (T cell Receptor).  When you have GVHD, one may need to go on immune suppressants, often steroids, to reduce the immune response of the T cells.  The most common places under attack are the skin, liver and gut.  It would make no sense for Allistaire to receive fancy, modified T cells only to suppress them with steroids, rendering them ineffective.

Perhaps the greatest ray of hope, came with the words, “transplant without remission.”  It sounds like the transplant doctors are still willing to go ahead with this transplant, even if Allistaire is not in remission.  To qualify for the trial, Allistaire would have to have 10,000 or less circulating peripheral blasts, a 10 out of 10 matched, unrelated donor, and generally be in good condition (organs functioning well, no out of control infection, etc.).  Dr. Bleakley, the principal investigator for the trial at Fred Hutch, does not view Allistaire’s chloromas (solid leukemia outside of marrow), as disqualifiers.  Of course it would still be optimal for these spots to be gone or substantially so, but their presence would not close the door for her.  It may mean, however, that she would need focalized radiation to these locations in addition to TBI (Total Body Irradiation).

Suddenly, the yellow walls of the room felt fitting for the hope swelling in my chest.  There may be a way through.  There is a ray of hope.  That is what I needed to face an indefinite inpatient stay.  Knowing there is hope, spurs one onto fight.  Before this conversation with Dr. Gardner, it just seemed like this was all doomed to fail which made it all the harder to willingly walk into that lock-down prison.  Good fortune continued with Allistaire drawing her first person and getting bumped up in the schedule for her “back poke,” where they test her spinal fluid for leukemia and inject a chemo, cytarabine.

Allistaire had just been wheeled into the recovery room where they practically kick you out 5 minutes after a procedure, when our nurse practitioner walked in with the lab results.  In the appointment we’d had everything back with the exception of the ANC (Absolute Neutrophil Count) which always takes longer.  All her labs had looked great, despite her falling blood counts which are naturally to be expected because of the advance of her leukemia and the chemotherapy.  The ANC was fine, 1022.

The absolute smack in the face was the presence of an Absolute Blast Count – 68.  Blasts are immature cells and they can be completely normal depending on their location and number.  Blasts in the peripheral blood, and of more than just a few, are most likely leukemic.  There was that wretched number declaring the very real increase of her cancer, such that it has pushed out cancer cells into the bloodstream, and this, even in the face of seven days of chemo.  Now, Decitabine is not a hard-core chemo, is known to take a while to be effective and is not what we are relying on to get her cancer into remission.  Yet, it makes you want to throw up on the spot.  Blasts are the harbinger of things grossly out of control in the marrow.  Their presence stings and burns the mind.  Blasts were the evidence that every round of chemo prior to her first transplant had failed.  It is not an overstatement to say that they strike terror.

All the hope I had known in that yellow room thirty minutes before, seemed to have been violently suctioned away.  I felt panic and desperate need to talk to Dr. Gardner about this most wretched development.  She appeared shortly and said in short, “I don’t want to blow it off, but it does not add to my level of concern.  It does not surprise me and it doesn’t change our plan.”  She affirmed all of my assertions regarding Decitabine that I had quickly thrown together in my mind.  Well, I would have felt a lot more free-spirited joy had those blasts never shown their ugly faces, but all hope is not lost.

For now it is late, but I have one last morning to sleep in and snuggle with my girl, just the two of us.  No lights, no pumps or beeping sounds, no interruptions for vitals.  One more morning and day of seeming normalcy.

For more information on the transplant trial, click the link below.  The trial for the modified TCRs is below that.

Selective Depletion of CD45RA+T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD

Laboratory-Treated T Cells in Treating Patients With High-Risk Relapsed Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia Previously Treated With Donor Stem Cell Transplant

Explanation of TCRs from the Juno Therapeutics Website

IMG_1561 IMG_1562 IMG_1570 IMG_1572 IMG_1577 IMG_1580 IMG_1590 IMG_1597 IMG_1604 IMG_1608 IMG_1611
IMG_1613 IMG_1620 IMG_1622 IMG_1623

Press On

Standard

IMG_1435This is my 200th post on this blog.  The 200th time I’ve sat down before these black keys, trying to look back over the days and hours, to look into myself and ask what I feel, what have been the colors of this day, what was the angle of light and shadow.  What were the moments that seemed to sum up the experience, this strange realm in which I dwell.  I look up and out, expecting like a Montana sky to see far, to feel the refreshing of expanse, to relish in the way it dwarfs me.  Somehow to feel so small seems to satisfy, perhaps because down deep I am so keenly aware of my smallness, my finiteness.  But the sky, oh sky, whether by day with extravagant drape of blue or stormy steel of cloud underbellies, or that singing silence of stars – sky at dark – the sky gives my tiny self context.  I am swept up within and so it is when I lift my eyes to The Lord.

Allistaire was still asleep in the recovery room after anesthesia for her PET/CT scan and so I slipped out to use the bathroom.  Through the window of another room, I caught a glimpse of a woman, head turned far to the side and eyes closed with an expression of pain.  Then came the cry, that distinctive cry of a newborn, clutched in her arms as the two nurses surrounded, attempting a blood draw or an IV.  I remember holding Solveig when that first needle came and then another and another, to vaccinate her against diseases that cripple and kill if not protected against.  My tears ran hot as I pressed her body against my chest, as she flexed in pain.  Brokenness, we are born broken, vulnerable.

We were to meet Dr. Gardner along with Ashlei our social worker and a member of the PAC  team (Pediatric Advanced Care Team) up on Forrest 7.  Forrest 7 is the Cancer and Blood Disorder Unit for children under 13.  The older kids are one floor up.  As I walked down that long white corridor to the Unit, memory upon memory threatened to swamp me, like dark waves pressing up the sides of a little dingy.  I looked out the window as we passed, the leaves turning, but the same scene regardless of the season.  The smell hit me next and I dreaded walking through that door.  When my eyes first opened this morning as weak light entered the room at Ron Don, I wished to somehow prevent the coming of this day, as though eyelids open would welcome in a torrent of sorrow.  To walk through that door was to submit to what was coming, to acknowledge the reality of all this.  For I have already walked this road, I know it intimately, all its contours and paths.  Today felt like a sentencing, knowing we would sit across the table from Allistaire’s doctor and be handed the options set up against the realities of her disease.  It must be the exaggerated difference of what I see with my eyes when I look at her and what all these tests declare, that makes swallowing what’s to come so very difficult.  It is like putting one foot in front of the other, willing yourself to hand yourself over to be thrown in the lion’s den.  You have been there before and only narrowly escaped, but with your flesh tattered and raw.  The wounds have really only begun to heal and you are thrust back into that place.

I know the trees will soon lose all of their leaves and we have months ahead of us of dark grey and cold wet, this Washington winter. Immediately sun on snow and the crisp, invigorating freshness of winter in Montana rushes into my view and I grieve knowing this little girl who talked about skiing all summer will most assuredly not ski this season, if ever again.  There are a thousand wounds of what will not be that slash and slash.  I circle and circle these sorrows, perhaps because they are easier to bear than that center of deep black, that greatest loss.  My world has constricted once again.  So narrow is the focus, yet so looming.  Again the mission of getting her into remission in order to do another transplant.  While her bone marrow only shows 0.9% leukemia, the biopsy of her lymph node and bone both confirmed leukemic involvement outside of her marrow.  They were unable to do Flow Cytometry on the bone marrow aspirate of her arm because the marrow was too fibrotic, but the old school method of using stains confirmed the presence of leukemia cells.  The PET/CT scan also revealed a broiling terror no eye could have guessed.  Outside of her marrow, the PET scan revealed leukemia in her right proximal humerus, right axillary lymph node, left distal femur, anterior compartment of bilateral thighs and in her left hand.  There is also a lymph node in her left groin that may be leukemic, it is not clear.

It’s her little sweet left hand that hurts the worst.  Somehow looking at that small hand, knowing what is eating away at it inside, oh, it feels like it’s stealing away my child, this girl who is so full of life.  And when the sobs come it seems my cranium cannot contain the agony of losing her, the pressure unrelenting behind my eyes.  And there are the words I know would come, must come.  “We will give her chemotherapy and while there is a trial for transplant without remission she may be eligible for, we will have to discuss the worth of that.”  All the doctors agree that if she “progresses,” if her leukemia becomes worse with chemo than it will progress with transplant.  So we forge ahead with chemo, praying this time it works.  Those three rounds of failed attempts last time she relapsed are seared into my mind.  I fear nothing will be able to stop this thing.  I fear watching the life vanish from her eyes.

We decided with the directing of the doctors to proceed with a chemo regimen called DMEC which is a wild combination of Decitabine, Mitoxantrone (also known as Blue Thunder), Etoposide and Cytarabine.  She has actually had all of these chemos before but at different times and in different combinations.  On Thursday or Friday she will have her third Hickman catheter installed and then she will be given 7 days of Decitabine, which can be done at the outpatient Hem/Onc clinic.  She will be then admitted to the inpatient unit and be given infusions of the other three chemos.  These are power house chemos which also are known to have the high potential to weaken the heart.  Allistaire has had weakening and dilation of her heart before resulting from chemo and has been on Enalapril for about a year and half to help it recover.  Thankfully, it is currently in really good condition, but this is the organ we most pray will be spared. A weak or damaged heart or other organs may close the door to transplant.  This combination of chemos is currently under study but has shown such promising results that the doctors here are willing to try it on Allistaire despite it not being a standard protocol.  Somehow the Decitabine changes the leukemia cells in a way that “primes” them to be more vulnerable to the destructive powers of the other chemos.  Once she is admitted for the remaining three chemos, it will be a standard 28 day cycle where her blood counts drop, with her ANC (Absolute Neutrophil Count) falling to zero, and then waiting for them to recover.  Once her ANC reaches 200 again, another Bone Marrow Aspirate and probably PET/CT will be conducted to determine the effectiveness of treatment.

Because Allistaire has extramedullary disease (leukemia outside of the marrow), it is necessary to give her systemic chemo prior to a transplant, even though the percentage within her marrow is currently so low.  If the DMEC round fails, there are still a few other options.  The trial in Denver for the DOT1L would still be an option, assuming her marrow is over 10%.  They are also conducting a study with the drug Panobinastat her at Children’s that they could try.  The other advantage of giving Allistaire chemo before transplant is that it takes a bit of time to find a matched bone marrow donor and arrange the actual donation.  This is not a quick turn around like using cord blood would be.  However, they will also be looking for a cord blood match and reserving that if it became needed.  I don’t have a lot of details on the actual transplant options because we are simply not there yet, though it sounds like we will be meeting with the transplant docs at SCCA relatively soon to review what may be available to her.  One of the greatest advantages Allistaire has is that in her clinical trial transplant last June 2013, she did not have TBI (Total Body Irradiation).  This is radiation of the entire body and can only be given once in a lifetime given its very detrimental cognitive and growth side effects.  Because she hasn’t had it before actually gives her more options.  It is possible that if she were able to move forward with a transplant that she could participate in a trial using modified T-cells in a way that differs from the T-cell therapy that children with ALL (Acute Lymphoblastic Leukemia) receive.  She is eligible based on her HLA typing but she is under the weight requirement of 30kg.  She is only 17.3kg but they are willing to consider whether or not they can modify the trial for her.  The weight requirement is due to the amount of blood they need to take for all of the tests.  If you want to be inspired by the wonders of current cancer research, check out the Juno Therapeutics website that explains the TCR therapy that may benefit Allistaire.  Be sure to check out the mad scientist, Dr. Phil Greenburg, who is leading this research and watch the video that shows the modified T-cells obliterating cancer cells.  It’ll make you want to stand up and cheer and maybe weep for the beauty of creation and science, being the study of what our Lord made.

The chimerism test on Allistaire’s marrow, which looks at what percentage of her marrow is her donor (stem cells from transplant) and what percentage is herself (the cancer cells), showed that she is approximately 96% donor and 4% host/her own cancer cells.  It’s hard to see this first glimpse of her donor cells losing their ground.  But to you, most honored and cherished of women, to you, her donor out there across the globe somewhere in Europe, know this, though your cells may not prevail in my daughter’s flesh, it is because of your incredibly generosity in giving of your own flesh that my child has had life for the past sixteen months.  And you have given all who know and love Allistaire precious time with her that would certainly not have been.  You have allowed countless memories and joys to pile up.  You have given my sweet girl, Solveig, memories of her sister that her younger mind might never have held on to.  Thank you.  We are forever and ever indebted to you and I pray God may bless you for your sacrificial giving.  And if there are any of you out there who have yet to join the Bone Marrow Registry, I implore you to consider offering up yourself to be the source of life for another person desperate for a way through, hopeful for life.  It is so easy to register.  Just go to Be The Match.org and answer a few questions and they will send a little kit in the mail for you to swab your cheek and get a few cells that will give them preliminary information about your HLA type.  While Be The Match is the primary registry in the United States, all of the registries around the world are linked, which means your cells could be a gift to someone on the far reaches of the globe, someone you cannot even imagine but is ever so real.

My life has dwindled down to this constricted place, this place of fight, this place where all energy is funneled into the battle to save a body, because it is the dwelling place of a spirit so dearly loved.  As has been true before, there are dark walls looming, surrounding, overwhelming and threatening.  The view on our lives as we knew it has been slammed shut.  In only a few days Allistaire and I will go back into that physical prison of the hospital where she cannot even leave her room and I must leave the Unit altogether if I do leave her room.  Every time I need to have food heated up, I will have to ask the nurse for help.  Countless strangers will come and go in our small space.  A message on the phone in our Ron Don room asks us to fill out paperwork for Adopt-A-Family if we are going to be here over Christmas.  I know we will be and it is like so many pains that you cannot stop before they have torn into your heart, severing.  The wounds come but I know I will not be destroyed.  I recall to mind the treasures the Lord a long time ago buried in my heart.  In the days of those first surrounding walls, I beat my fists in fury against them and cried out to God to help me find a way through or over or under them.  I used all of my finite might to war against them.  And then my sweet, patient God told me to turn around and fix my eyes on Him, on Christ, the author and perfecter of my faith.  He helped me to have eyes to see that He is my dwelling place, He is my Sabbath rest, He is my very way, my very life.  He enabled me to see that my boundary lines had indeed fallen in pleasant places and then with slightest of breath He caused those walls to simply tumble down.  He blew and the waters of the Red Sea parted and He brought the insurmountable walls in my life crashing down.  The Lord has been good to me.

So I choose to stand with those incredible three men of faith.  I stand with Shadrach, Meshach and Abednego who knew the Lord could save them from the fire but stood with resolute declaration, that even if He did not, they would not bow down to any other God, because they knew that regardless of the outcome, their God was the one true God.  I walk into the fire knowing God can preserve the life of my child, and even if He does not, He is my God and I will never stop worshipping Him.  I love you Father.  I love you and I am afraid.  My heart threatens to fail within me.  Hold me up.  Take my life.  I lay it down before you.  I know I will see the goodness of the Lord in the land of the living.IMG_1379 IMG_1385 IMG_1401 IMG_1406 IMG_1408 IMG_1410 IMG_1415 IMG_1428 IMG_1429 IMG_1430 IMG_1431IMG_1399