Haploidentical Bone Marrow Transplants: Truths and myths

 

Bone Marrow is an ever-replenishing organ which can be viewed as a flowing river through various bones of the body at various stages of our life. It cannot be bound by any anatomical boundary like the liver, brain or the kidney, yet it remains the only organ in our body which produces a billion cells every minute to replace those dying ones.

This is unlike other organs which cannot replenish themselves once damaged. If the bone marrow ceases to function normally we cannot survive, and its function is finely balanced in the infinitesimal potential of the mother cells or the blood stem cells. Like the flowing river it can flood with excess of one type of cell and overwhelm the others (this happens in Blood Cancer or Leukaemia) or it might dry up like a desert (as in Aplastic Anaemia).

These conditions can arise due to genetic predispositions or unknown changes inside the stem cells. The changed or potentially malignant cells are kept under check by a group of blood cells of the immune system called Lymphocytes. Thus, a disease of the bone marrow arises due to failures at multiple fronts, but once they happen, survival is at stake.

Despite the most drastic and devastating nature of the diseases of the blood and bone marrow, they remain the most curable ones. This is because they are easily accessible to drugs, being in constant flow in the blood stream, unlike a solid organ cancer where the cancer cells might be protected due to lack of adequate blood supply. Most importantly, these diseases remain curable because the damaged blood cells and the incompetent immune system can be replaced by that from a healthy person.

Organ donation like in the case of heart, kidney or liver awaits the death of a healthy young person in an accident – an act of serendipity derived out of someone’s misfortune. But Bone Marrow is a nondescript organ which can be donated numerous times in one’s lifetime without incurring any harm. In solid organ transplantation, one survives at the cost of another life, but in Bone Marrow Transplantation one replenishes what one gives in no time.

Yet, despite the universal availability, not everyone can be a Bone Marrow donor. The donor has to be matched with the patient at all the 10 Human Leukocyte Antigens (HLA). These are signatures we inherit from our parents and pass on to our children. Our body is tutored from birth to react and reject any cells which do not carry the same signature or HLA, a bit like the way banks handle cheques.

By biological laws, a complete HLA match can be found within a family in only 1 in 4 cases. To get the same from a random person in the street would be less than a million. This probably explains why Bone Marrow cannot be bought or sold as an illegal trade like solid organs.

To circumvent the problem of finding a matching donor, the western world developed volunteer unrelated donor registries across America and Europe. The Caucasian gene being conserved within the population enabled patients of European decent to find a matching donor within such registries.

However, patients of African, Hispanic or Asian origins barely benefitted from such registries. The risk of doing BMT from donors mismatched at even 1 or 2 of the 10 HLA antigens was too high and the majority of the non-white patients thus struggled to get a BMT if needed when no HLA matched family donor was available.

On the other hand, what often surprised the researchers in the field of immunology and genetics was how a mother could bear a child for 9 months and deliver it healthy and alive even though it has inherited a set of HLA antigens from the father which is unknown to the mother and should be rejected as a rule. Yet, in most cases pregnancy is successful once conceived and this very rule by definition is violated. This was later recognized as ‘Tolerance’ which develops between the mother and the child. In terms of transplantation, the mother and child are natural donors for each other even though they do not share one half of the HLA antigens.

Through a better understanding of this phenomenon, Half-Matched or HLA Haploidentical family donor was recognized as a possible donor for BMT. Yet, the journey was not easy and many years of research culminated in successful conduct of Half-Matched or Haploidentical family donor BMT. For the reasons of natural tolerance which exists within a family this sort of transplantation is not possible from an unrelated donor with half-matched HLA antigens.

Haploidentical BMT was pioneered by Prof. Franco Aversa in Italy and researchers from Johns Hopkins, United States. In India, Dr. Suparno Chakrabarti initiated the first Haploidentical BMT program in India in 2011. This was later taken forward by Dr. Sarita Jaiswal. Nearly 100 Haploidentical transplants later, these doctors are acknowledged as world leaders in this field through their innovations and research.

Haploidentical BMT needs the right infrastructure and expertise for its success. BMT worldwide fails due to poor understanding of the intricate immune system of the human body. Conquering the final frontier is still a distant dream, but what is in offer right now puts us in a good space.

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