Matched Sibling Donor Transplantation

Human Leukocyte Antigen (HLA) system is pivotal to the outcome of Allo-BMT unlike solid organ transplantation. In an elegant set of experiments on dogs, which led to the successful inception of clinical Allogeneic BMT, Prof. E. D. Thomas and colleagues demonstrated the importance of match in the HLA system between the donor and the recipient to achieve engraftment as well as reduce the incidence of graft-versus-host disease (GVHD).

The HLA System

The HLA antigens are inherited as two sets, one from each parent. They are classified as Class 1 (HLA A, B, C) and Class 2 (HLA DR, DQ, DP). Mismatches in certain HLA antigens are more harmful than others. For example, a mismatch at HLA B is more acceptable than a mismatch at HLA A or HLA DR. HLA-matched family member was and still is considered the donor of choice for Allogeneic BMT for all indications; a paradigm which remains unchanged despite tremendous advancements in this field.

Graft Versus Host Disease

Matched sibling donor BMT is probably the safest form of Allogeneic BMT. However, it is not without risks or complications. Even though the major HLA antigens might be matched between the patient and the donor, the minor HLA antigens are often mismatched. This can cause complications in the form of GVHD and at the same time reduce the risk of disease recurrence by Graft Versus Tumour Effect.

Non-malignant Diseases

Certain diseases like Thalassemia, Sickle cell disease, Aplastic Anaemia and many other non-malignant diseases where, we do not need to eliminate the leukemia are best treated with matched sibling donor transplant. A patient with early stage of Thalassemia or Sickle Cell Anaemia has greater than 90% chance of being cured after a matched sibling donor transplantation. Hence, all patients with these diseases should undergo a BMT if a matched family donor is available.

Leukemia and Malignant Diseases

In-patients with leukemia, if the disease relapses after transplantation from a matched family donor, BMT from another matched family member or an alternate donor might be still an option.

Chances of Finding a HLA Matched Family Donor

Based on mendelian laws of inheritance, the chances of siblings being matched to each other at class I and II HLA locus are only 20-30%. Thus 70-80% of patients eligible for an Allo-BMT would be unlikely to find a donor within the family. Consanguinity between parents increase the chances of finding a HLA match within the family and even with parents. Thus, certain communities with a high incidence of consanguineous marriage are likely to have a higher frequency of certain common haplotypes and thus a greater likelihood of finding a match within the family. Nevertheless the large majority of patients do not find a matched family donor and are candidates for an alternative donor BMT.