Early September 2016, on a late evening I received a call from the E.R (Emergency Room) that a young 18 year old boy’s family was seeking an emergency opinion from a hematologist for their son. He was found to have severe pancytopenia [severe reduction of all three cell lines –Hemoglobin (Hb), white blood cells (WBCs) and platelets] noted on a blood count (CBC) done for progressive fatigue over a month, and new onset rashes all over his body since a day.
His evaluation revealed a related rare disorder of the bone marrow, called severe aplastic anemia (SAA), that occurs due to near complete dysfunction of the entire hematopoietic functioning(involving Hb, WBC and platelets). If left untreated, such patients rapidly detioriate and die either due to the severe thrombocytopenia (low platelets) related massive bleeding, or severe opportunistic infections (fungal, bacterial or viral) due to their extreme low blood counts.
In addition, these patients remain transfusion dependent (requiring blood and platelet transfusions almost every 2 weeks) till any definitive therapy. Fortunately, none of that happened and he lives today, healthy and upbeat as any young teenager would, though still under a close supervision. He underwent a procedure called as a bone marrow transplant (BMT), with his younger sibling brother being the stem cell donor.
The patient experienced two episodes of near fatal infections, along with several bleeding episodes due to his low platelets, before undergoing a transplant. His pre-transplant journey from severe and complete transfusion dependence and repeated vulnerability to infections, to a state of complete transfusion independence, post-transplant with now normal blood counts remains a miraculous ordeal lasting close to 4 months. The family was indeed fortunate enough to have their son back from the brink of death!
Bone marrow transplants (BMT) are complicated procedures that involve replacing the entire hematopoietic(blood) system in an affected person through guided chemotherapy and subsequently, substituting it with a healthy donor hematopoietic stem cells (HSC). It is these donor HSCs, which eventually replenishes the patients hematopoietic system over time, and gives rise to all living blood cells like white blood cells (WBC), red blood cells(RBC) and platelets, giving a new lease of life to the patient and his/her family.
Several disorders benefit from such procedures. In addition to the described case above of a classical patient with aplastic anemia, BMTs are indicated in several other congenital bone marrow failure syndromes, hereditary diseases caused by faulty hemoglobin synthesis like thalassemia’s, sickle cell anemias, immunodeficiency disorders with an impaired ability of their immune system to fight infections, life threatening blood cancers like multiple myelomas, leukemia and several other types of advanced tumors like lymphomas, neuroblastomas, etc.
Approximately 1500 BMTs were recorded from 11 centers in a major publication from CMC Vellore, in Aug 2008. Since then many more centers have been developed and an estimated 8,000 more patients have undergone hematopoietic stem cell transplants (HSCT) in India. These are average numbers, as many centers do not participate in reporting and registering their transplant data.
The reported success rate of transplants from India have been from 20% in uncontrolled blood cancers to 80% in young, fit patients with aplastic anemia, who can be transplanted quickly before they develop serious infections or bleeding. These success rates have been comparable to the west, but in general, the success rate of the HSCT depends a lot on the indication of the transplant, and a lot on the fitness of the patient.
A factor that also plays a role is the optimum timing of the transplant. Long waiting queues at large centers in combination with lack of awareness about other centers offering such facilities, often changes the dynamics of a disease. In the last decade, several other institutions (including Mumbai) have come up offering such BMT services, with a high focus on quality and outcomes, but at a high cost to the family, more so due to the complexity of the process and its complications, and lack of adequate insurance cover.
Hematopoietic stem cell transplant (HSCT) is called BMT, when the HSC are obtained from the bone marrow, peripheral blood stem cell transplant (PBSCT) when they are procured from the peripheral blood and cord blood transplant (CBT) when the umbilical cord blood is the source of the HSC.
Autologous HSCT is done by collecting the patient’s own HSC, before giving them high dose chemotherapy, and then re-infusing these preserved HSC back to the patients after chemotherapy. In certain diseases, only stem cells from a normal healthy donor can be given to the patient to replace the damaged or the diseased bone marrow. This is called an allogeneic (donor other than the patient himself, i.e. either a sibling donor or an unrelated donor searched through stem cell registries)hematopoietic stem cell transplant (HSCT).
The high costs of the transplants are often related to the high costs of the care and in general, a self-paying Indian with poor insurance cover. The process of allo-transplants begins with identifying and appropriately staging the disease. The patient’s close relatives or even unrelated donors are tested for their compatibility of their human leukocyte antigens (HLAs).These are proteins seen on many cells in our body and can be used to characterize an individual. Since each patient has only 25% chance of finding an identical match within the family, many patients do not find a suitable identically matched donor within the family.
In absence of an appropriate match, there is a need to find an unrelated donor or a matched cord blood unit and these can be found from certain stem cell registries. India has two prominent independent stem cell registries, namely DATRI and MDRI (Marrow donor registry of India), together having approximately 2,00,000 registered stem cell donors, a sad fact considering the strength of the Indian population. Any potential stem cell donors can register and voluntarily donate their stem cells at one of their registered locations, through an informed process. These stem cells can then be used for any potential patients in the near future. Once considered as fit enough, patients are shifted to a specially designed high-efficiency particulate air (HEPA) rooms. These HEPA air purified rooms are specifically designed to ensure the air within is filtered, to reduce the chances of fungal infections, a high possibility in any patients with a compromised immunity status. The transplant (auto + allo) then begins with a carefully guided chemotherapeutic regimen and sometimes even radiation, given over five to seven days, destroying the patient’s original marrow and thereby creating enough space in his bone for the new stem cells to arrive in and expand. The donor stem cells (HSC) are then harvested either from the donor and then infused in the patient’s veins, just like any blood transfusion.
There is no surgery involved, contrary to other organ transplants like liver, renal, heart etc. It then takes about 2-3 weeks for the new hematopoietic system to form, during which patients are kept isolated and monitored for complications. The patient is then discharged, if he recovers his blood counts, and is stable. He/She is then followed up in the outpatient clinic for 2-4 months to watch for any further complications like infections, considering the new acquired immunity will take its due time to become more robust. In allogeneic HSCT, the donor cells can sometimes attack the recipient’s body and present with a condition called Graft versus host disease (GVHD), which can be devastating, if not adequately controlled.
The other complications include an occasional rejection of the donor stem cells, thus a complete failure to produce a new marrow. This entire process requires the patient to be admitted in the transplant unit for atleast a 4 weeks, isolated from the environment and the family, with only occasional visits allowed, under all aseptic precautions.
BMT is a specialized procedure and requires a specialized team of trained BMT physicians (Hematologists or Medical oncologists), physicians trained to handle opportunistic infections, specially trained nurses, well equipped and a standardized laboratory offering rapid diagnostic tests for BMT care, and moreover a hospital and management well suited to the needs of the transplant care, in addition to a robust socio economic support system.