[Thalassemia Reports 2013; 3(s1):e42] [page 103] Bone marrow transplantation for thalassemia: a global perspective Mohamed Hamed Hussein, 1 Mohamed El Missiry, 1 Sadaf Khalid, 1 Naila Yaqub, 2 Sarah Khan Gilani, 2 Itrat Fatima, 2 Tatheer Zara, 2 Priya Marwah, 3 Rajpreet Soni, 3 Frederic Bernard, 1 Annunziata Manna, 1 Cornelio Uderzo, 1 Lawrence Faulkner 1 1 Cure2Children Foundation, Florence-Italy; 2 Children’s Hospital Pakistan Institute of Medical Sciences, Islamabad-Pakistan; 3 South East Asia Institute for Thalassemia, Jaipur, India 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 appropri- ately 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 equiv- alent 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 set- tings. 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 relat- ed BMT. A structured on-site focused training program as well as ongo- ing 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 chron- ic 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 tha- lassemia can be performed with outcomes comparable to richer coun- tries and with a fraction of the costs even from the very beginning of newly developed BMT units and by relatively untrained personnel pro- vided 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 start- up of new BMT services in low- to middle income countries. Introduction Severe thalassemia accounts for a substantial proportion of child- hood mortality, morbidity, health care expenses and donated blood con- sumption in the Middle East and South-East Asia, were carrier rate ranges of 5 to 30%.(1) In spite of significant progress in supportive care which, in the best circumstances, may extend life expectancy well into adulthood,(2) most patients in low- to middle-income areas, where thalassemia is most prevalent, do not survive beyond 20 years of age and the risk of blood-borne infections, primarily hepatitis C, remains significant.(3) Even the definition of thalassemia major in low-resource settings is not very clear cut, in fact, the standard criteri- on of ≥8 red cell transfusions/year may not apply to a setting where pre-transfusion hemoglobin are often as low as 3-4 g/dL and where tha- lassemia intermedia phenotypes frequently occur; in these circum- stance the term severe thalassemia, meaning inability to keep a spon- taneous hemoglobin greater than 7 g/dL, i.e. the threshold below which most centers would recommend a regular transfusion regimen2, might better apply. Bone marrow transplantation (BMT) has been shown to cure tha- lassemia over 30 years ago(4) and remains the only definitive cure with thalassemia-free survival rates consistently reported over 80% in selected young low-risk patients with a histocompatible family donor.(5) BMT has also been shown to improve quality of life.(6,7) In areas where thalassemia is endemic, there is a severe shortage of cen- ters for the cure of this diseases;(8,9) this is not only due to lack of financial resources, in fact BMT is less expensive compared to long- Correspondence: Lawrence B. Faulkner ©Copyright M.H. Hussein et al., 2013 Licensee PAGEPress, Italy Thalassemia Reports 2013; 3(s1):e42 doi:10.4081/thal.2013.s1.e42 This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 3.0) which permits any noncom- mercial use, distribution, and reproduction in any medium, provided the orig- inal author(s) and source are credited. Parts of this work were presented at the “3 rd Pan-European Conference on Haemoglobinopathies and Rare Anaemias”, Limassol (Cyprus), 24-26 October 2012. Thalassemia Reports 2013; volume 3(s1):e42 Non-commercial use only