Recommending Allogeneic Hematopoietic Stem Cell Transplantation is a Gut-Wrenching Decision in Medicine

How I struggle with it

Today’s guest post is from Aaron Goodman, MD, a transplanter at UC San Diego. In this essay, he agonizes about a decision many hematologist-oncologists face: should I transplant this person? I too have been there, and experienced all these emotions.

A few years ago, I got annoyed by the state of the evidence, and asked Sunny Kim to investigate. Our results were published in JAMA IM. She found that 93-96% of these decisions lack randomized evidence. This is simply not good enough. Randomization is possible and needed, and you will soon see why.

Vinay Prasad MD

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By Aaron Goodman, MD

A 22 year old anxiously sits in front of me in the Blood and Marrow Transplantation (BMT) clinic.  Surrounded by his parents and fiancé, they keenly await my recommendations with trepidation. 

Only two months before, he had just graduated college, started a new job, and got engaged to the love his life.  One unfortunate morning he awoke with gingival bleeding and bruises over his body.   Soon he developed fevers and confusion and was rushed to the emergency room and was found to have a white blood cell count over 150,000, hemoglobin of 5, and platelet count of 15.  After numerous blood tests and bone marrow biopsy he was diagnosed with acute myeloid leukemia (AML), a life changing and threatening diagnosis. 

He was treated with intensive chemotherapy resulting in destruction of both his leukemia and his own immune system.  He spent the next month in the hospital in a positive pressure room being pumped continuously full of blood, platelet transfusions, and antibiotics to keep him alive. Fortunately, he achieved a complete remission (clearance of the leukemia from the bone marrow with recovery of normal hematopoiesis) and was referred to my BMT clinic for consideration of an allogeneic hematopoietic stem cell transplantation.

A basic primer on allogenic hematopoietic stem cell transplantation (allo-HSCT): 

Allo-HSCT is a procedure where hematopoietic stem cells are collected from a donor (either a related family member or unrelated donor) and are infused into the recipient (patient).  Prior to the stem cell infusion, patients receive a combination of chemotherapy +/- radiation along with potent concoction immunosuppressive therapies with the goal to eradicate any residual cancer while simultaneously allowing acceptance of the donor’s immune system.  The infused stem cells find their way to the recipient’s bone marrow where, over time, restore normal hematopoiesis and immunity. 

The procedure is magical for some, but deadly for others.   Allo-HSCT comes at the cost of severe toxicities including organ damage from chemotherapy, infections, and graft vs. host disease (GVHD).  In fact, even in well selected patients up to 10-20% can die as a result of complications from the transplant and not from their cancer (transplant related mortality).  Furthermore, many of those who survive the procedure will suffer lifelong complications including infections, chronic GVHD, secondary malignancies, and need for chronic immunosuppressive medications.  Some survivors live hard, damaged lives.

For these reasons: recommending allo-HSCT is the toughest medical decision I have to make.  To put it bluntly, by recommending an allo-HSCT, I may kill my patient.  For patients with no other curative treatment options (like poor risk leukemias) the decision to recommend transplant is easier as without allo-HSCT they will die from their disease.   

However, some patients, such as those with intermediate risk disease in remission, the necessity for allo-HSCT is not so clear cut.  Patients with intermediate risk AML in remission have a chance (20-40%) of being cured without receiving an allo-SCT.   

So why on earth would I recommend a procedure with a 10-20% of killing my patient when perhaps they are already cured?  Here in lies the crux to the deepest and vexing problem we transplanters face.  Unfortunately, we have yet to develop precise tools to adequately predict which patients are cured vs. destined to relapse and die from their disease. 

We are desperately trying to figure this out to do using technology such minimal residual disease (MRD) detection, but we are still far from perfect in predicting.  Based off observational data and some prospective clinical trials we know in general patients with intermediate risk AML have better survival with allo-HSCT.  However, many (as high as 20-40%) will achieve long term survival without allo-HSCT.  Let’s take a step back. 

This means if I recommend allo-HSCT to 15 patients with intermediate risk AML as many as 5 of them do not need the procedure!  If roughly 20% of patients die as a result of allo-HSCT, 1 of 15 patients will die from a procedure they did not need!  1 in 15 is not trivial!

Somehow in a 1 hour clinic visit I am supposed to adequately convey my recommendations of to proceed or not to allo-HSCT.   These decisions are supposed to be mutually made with the physician incorporating the patient’s preferences.

 However, in the end, it is my decision to recommend or not.  It is my decision that may either cure a patient destined to die of his leukemia or end the life of a patient who is already cured. 

As many of my clinic discussions have ended, he  asked me the existential question “doc what would you do for yourself in this situation”.   Honestly, I do not know.