Bone marrow transplantation for thalassemia: a global perspective

Abstract

Even though severe thalassemia is a preventable disease, over 100,000 new cases are born yearly, particularly in the Middle East and South-East Asia. Most of these children may not reach adulthood because long-term appropriate supportive care is either inaccessible or unaffordable. Bone marrow transplantation (BMT) remains the only available definitive cure and success rates can be very high in appropriately selected patients, i.e. low-risk younger children with a matched family donor. In these circumstances BMT may be justified medically, ethically as well as financially, in fact, the cost of low-risk BMT is equivalent to that of a few years of non-curative supportive. This manuscript will briefly review the current status of bone marrow transplantation for thalassemia major with particular emphasis on a global prospective and present the experience of the Cure2Children Foundation supporting sustainable and scalable start up BMT programs in low-resource settings. The initial twelve consecutive patients managed in two start up BMT units in Pakistan (Children’s Hospital of the Pakistan Institute of Medical Sciences, Islamabad) and India (South East Asia Institute for Thalassemia, Jaipur) were included in this analysis. These initial six patients per each institution where purposely chosen as the focus of this report because they represent the steepest phase of the learning curve. The median age at transplant was 3.9 years, range 0.9 to 6.0, liver was no greater than 2 cm from costal margin, and all received matched related BMT. A structured on-site focused training program as well as ongoing intensive on-line cooperation was provided by the Cure2Children team of professionals. At a median follow-up of 7.5 months (range 3.5 to 33.5 months) both thalassemia-free and overall survival are 92%, one patient died of encephalitis-meningitis of unknown cause. No rejections where observed. Neutrophil recovery occurred at a median of 15.5 days (range 13-25) and platelet recovery at 18 days (range 12-27). Toxicities included, fever and neutropenia (10 patients), CMV reactivation (9 patients), acute GVHD grade 3 or less (4 patients), hypertension (4 patients), mild mucositis (3 patients), bacterial sepsis (1 patient). Median number of transfusions was 2 for red cells (range 0 to 7) and 5 for platelet transfusions (range 1 to 18). Median post-BMT hospital stay was 49 days (range 33 to 109). No patients developed significant chronic GVHD, one had a suspicion of malaria 8 months post-BMT and one of tuberculosis 11 months post-BMT, both where treated empirically and are doing well. The mean cost of a BMT and follow-up was around 10.164€ (8.952€ in Pakistan and 11.377€ in India), range 5.618€ to 14.604€.. In low resource settings matched-related low-risk BMT for thalassemia can be performed with outcomes comparable to richer countries and with a fraction of the costs even from the very beginning of newly developed BMT units and by relatively untrained personnel provided a structured and intensive cooperation program with BMT experts is provided. This observation may have important implications to increase access to cure thalassemia major worldwide and for the startup of new BMT services in low- to middle income countries.