Benefits, challenges of bone marrow transplant as cure for thalassemia

Thalassemia is a group of inherited blood disorders characterized by reduced or absent production of haemoglobin, which leads to anaemia and other complications. Thalassemia major is the most severe form of thalassemia, and it usually requires lifelong blood transfusions and chelation therapy to manage its complications. However, bone marrow transplant (BMT) is a curative option for thalassemia major patients, and it can replace the defective bone marrow with healthy bone marrow stem cells from a compatible donor. Among the different types of BMT, matched sibling BMT is the most successful in terms of survival and cure rates, especially in the paediatric age group. In this article, we will discuss the rationale, procedure, outcomes, and challenges of matched sibling BMT for thalassemia major patients in the paediatric age group.

Rationale for matched sibling BMT in thalassemia major

The main rationale for BMT in thalassemia major is to replace the defective bone marrow with healthy bone marrow stem cells that can produce normal haemoglobin and reduce or eliminate the need for lifelong transfusions and chelation therapy. However, BMT is not a simple procedure, and it carries risks and complications that need to be weighed against its potential benefits.

One of the main factors that determine the success of BMT in thalassemia major is the compatibility between the donor and the recipient. In general, the closer the match, the better the outcomes, and the lower the risk of complications such as graft rejection, graft-versus-host disease (GVHD), and infections. Matched sibling BMT is the preferred option for thalassemia major patients, as it offers the highest chance of finding a compatible donor and achieving a successful outcome.

Matched sibling BMT is based on the principle of human leukocyte antigen (HLA) matching, which involves testing the HLA markers of the donor and the recipient to find a compatible match. HLA markers are proteins on the surface of cells that help the immune system distinguish between self and non-self cells. In general, a donor who shares identical HLA markers with the recipient is more likely to provide a successful transplant and avoid complications.

The probability of finding a matched sibling donor depends on the genetic makeup of the family members. Siblings have a 25% chance of being an HLA match, a 50% chance of being a partial match, and a 25% chance of being incompatible. Therefore, thalassemia major patients who have a matched sibling donor have a higher chance of finding a compatible donor and achieving a successful BMT.

Matched sibling BMT is considered the gold standard treatment for thalassemia major, as it offers the highest chance of cure and long-term survival. Several studies have reported high success rates of matched sibling BMT in thalassemia major patients, with cure rates ranging from 70% to 90% and overall survival rates ranging from 80% to 95%.

The success of matched sibling BMT in thalassemia major depends on several factors, including the age of the patient, the severity of the disease, the stage of the disease, the presence of complications, and the quality of the donor's stem cells. In general, younger patients who undergo BMT before the age of 7 have better outcomes than older patients who undergo BMT later in life.

Matched sibling BMT is also associated with a lower risk of complications such as graft rejection, GVHD, and infections compared to other types of BMT, such as unrelated donor BMT or haploidentical BMT. This is because matched sibling BMT offers a higher degree of HLA matching, which reduces the risk of immune system conflicts between the donor and the recipient.

However, matched sibling BMT is not without risks and complications. The conditioning regimen can cause side effects such as nausea, vomiting, hair loss, and increased risk of infections. The engraftment of the donor's cells can cause complications such as GVHD, a condition in which the donor's immune cells attack the recipient's organs and tissues, causing inflammation and damage.

Challenges of matched sibling BMT in thalassemia major

Despite the high success rates of matched sibling BMT in thalassemia major, several challenges remain in the implementation and access to this treatment option. One of the main challenges is the availability of matched sibling donors, as not all patients have a matched sibling donor in their family.

Another challenge is the cost and accessibility of BMT, as it requires specialized medical facilities, equipment, and expertise. The cost of BMT can also be prohibitive for many patients and their families, especially in low- and middle-income countries where healthcare resources are limited. Moreover, the availability of health insurance coverage for BMT varies widely across countries and regions, which further limits the access to this treatment option.

The procedure also requires a long hospital stay, which can be stressful and isolating for the patient and their family. Moreover, the conditioning regimen and the post-transplant monitoring require close medical supervision and management, which can be challenging for patients who live far from the transplant centre.

Matched sibling BMT is a curative option for thalassemia major patients, especially in the paediatric age group.

(Dr Ragesh R Nair is Director, Centre for Blood Diseases, BMT & Cancer Immunotherapy, Oncology, Meitra Hospital, Kozhikode.)