While bone marrow and peripheral blood stem cell transplants have a proven track record of success, the search process can take several months. Despite almost 13 million registered volunteer donors are presently accessible worldwide, many patients do not get HLA matched grafts. Hence, the applicability of HSC transplantation has markedly expanded with the introduction of UCB, especially for ethnic and racial minorities. Therefore, UCB has gained popularity and acceptability as an alternative transplant source for patients lacking appropriate adult donors. In a report of 623 consecutive patients undergoing myeloablative transplant at the University of Minnesota, Tomblyn and colleagues14
have shown that ALL (acute lymphoblastic leukemia) patient lacking a sibling donor can seek UCB or a well-matched unrelated donor and have equivalent long-term survival. After a median of 8.3 years of follow up, five year overall survival, leukemia free survival (LFS) and relapse were 29, 26 and 43 per cent respectively. Five year LFS was 40, 42 and 49 per cent with related donors (RD), well matched unrelated donors (URD) and UCB sources, respectively, while relapse was 31, 17 and 27 per cent in the same group. Several additional studies support satisfactory results of UCB transplant as compared to other sources of haematopoietic stem cells15,16
In addition to paediatric and adult haematological malignancies, UCB has potential applications in non-malignant and metabolic disorders17
. Due to the decreased risk of graft versus host diseases (GVHD) the use of UCB transplant over related BMT in thalassaemia18,19
. In cases of Fanconi anemia, Gluckman et al20
have demonstrated significantly improved engraftment (89 vs 69%) and survival (52 vs. 13%) in those received fludarabine versus no fludarabine.
In metabolic storage disorders the only therapeutic option is enzyme replacement therapy which is expensive with a long-term requirement. Hence, UCB transplant is desirable and a promising alternative therapeutic option with long term benefits. Prasad et al21
have reported results of 159 paediatic patients with inherited metabolic disorders who received UCB transplant. Engraftment occurred in 87.1 per cent and one year overall survival was 71.8 per cent. Notably those children with high performance status had better overall survival of nearly 85 per cent which emphasizes the importance of UCB transplant early in the course of the disease.
Most UCB banks in India have been opened in the last few years, and UCB transplantation is in its infancy, very few reports are available for application to acquired and constitutional haematological disorders and none for metabolic disorders. Till date approximately 32 patients have been transplanted using related or unrelated UCB. Of these 2 patients of relapsed leukemia were transplanted using mismatched sibling cord [UCB processed at Life cell and Cryo Bank] and one died of disease relapse and other of sepsis. One child was transplanted using fresh fully matched cord and the child is well 12 years on and did not go through any cord bank. In 15 patients mainly for relapsed leukemia and aplastic anemia unrelated cord blood was used with TRM of 55 per cent at Apollo, Chennai. While one patient of leukemia transplanted at Gujarat Cancer & Research Institute (GCRI), Ahmedabad expired due to disease related mortality after transplantation. The high mortality rate appears to be due to selection of high risk cases under this group (personal communication with Dr Revathi Raj, Chennai and Dr Sandip Shah, Ahmedabad).
To date, around 13 cases of thalassaemia have been treated using UCB transplantation. Of these, six cases were transplanted using fully matched sibling UCB at Apollo hospitals, Chennai. UCB units were obtained from Life Cell and Cord bank. Thalassemia free survival was 83 per cent and all patients had additional bone marrow from siblings as there was inadequate cell dose in cord blood (personal communication with Dr Revathi Raj, Chennai). Similarly, seven unrelated UCB units were utilized to treat thalassaemia cases at GCRI, Ahmedabad. The unrelated UCB units were procured from Relicord and Stemcyte UCB banks. TRM was 0 per cent at both the centers. At GCRI, Ahmedabad, two thalassaemia patients had disease free survival after 2 years and 1 year of transplantation, and one remained hospitalized post-transplantation. Failure of engraftment was observed in four cases which is likely to be due to low number of total nucleated cell (TNC) (2-3×107
) used in transplantation (personal communication from Dr Sandip Shah, Ahmedabad). Considering large number of thalassaemia patients born in the country; these transplantations are comparatively very less mainly because of cost prohibition, lack of sufficient UCB depository and because public UCB banks are in early stage of development. In the coming years with an increased transplantation using UCB as a source of haematopoietic stem cells, more experience will undoubtedly be gained22