Bone Marrow Transplantation for β Thalassemia Major: Long Term Experience from a Single Centre in India.
Authors: Chandy Mammen , Mathews Vikram , George Biju , Viswabandhya Auro , Kavitha M.L. , Srivastava Alok 
Published: October 2019

Abstract
From October 1991 to December 2006, 218 patients with β thalassemia major underwent allogeneic bone marrow transplant at this center. This represents 45% of all transplants performed here. The median age of this cohort of patients was 7 years (range: 2–24) with 144 males and 74 females. The pre-transplant characteristics were as follows: red cell transfusions: median: 92 units (range: 4–775), median serum ferritin: 2870ng/ml (range: 925 – 13600) with the majority having been on inadequate chelation. Patients were risk stratified by the criteria proposed by Lucarelli: Class I: 15 (6.9%), Class II: 89 (40.8%) Class III: 114 (52.3%). This distribution is a reflection of the poor pre-transplant care that many of these patients receive. Five (2.3%) patients were positive for hepatitis B surface antigen while 28 (13%) were positive for hepatitis C antibody. The donors were HLA AB and DR matched siblings in 202 cases and in 16 patients a HLA identical parent was the donor. One hundred and twenty five (57.3%) of the donors were heterozygous for thalassemia. There was major mismatch of ABO blood group in 25.2%. The bone marrow graft was red cell depleted by sedimentation with hydroxyethyl starch in these cases. There were no donor related complications. Busulfan (Bu) and cyclophosphamide (Cy) with or without ALG was used as the conditioning regime in all but 25 patients in whom Fludarabine was used along with Bu/Cy. Short methotrexate and cyclosporine was used for graft versus host disease prophylaxis. Cyclosporine was initiated on day - 4, continued for 6 months then tapered and stopped at one year in the absence of graft versus host disease (GVHD). Eighty (41%) of 195 assessable patients developed acute GVHD of which 64 (80%) were grade I and II and 16 (20%) were grade III and IV. Twelve (7.2%) of the 166 assessable patients developed chronic graft versus host disease, 10 were limited stage and two were extensive. Forty (18.3%) developed hemorrhagic cystitis which was grade I and II in 60% of the patients. Veno-occlusive disease as defined by the Seattle criteria occurred in 105 [48.2%] patients and this was the most common complication. The important causes of mortality within the first 100 days included: DAH (13), graft failure/ rejection (11), sepsis (10), VOD (9) and GVHD (7). With a mean follow up of 133 months (Range 6–183), 72 (80.8%) of 89 children in class II are alive and well, free off transfusion and off immunosuppression. However, among the 114 patients who were in Class III there was a 34.4% mortality and 19.4% rejection which means that these patients should receive better pre-transplant care and should be taken early for BMT. Allogeneic BMT at US$ 15–20,000 is equivalent to the cost of 3 years of transfusion and chelation and is a good alternative in the developing world.
Outcome of Allogeneic BMT for Thalassemia (5 year Kaplan-Meier estimate of OS and EFS) CLASS NUMBER SURVIVAL (%) EVENT FREE SURVIVAL (%) MORTALITY (%) All Patients 218 72.3±3.1 65.3±3.3 14.6 Class I 15 71.8±11.98 71.8±11.98 0 Class II 89 82.6±4.1 78.3±4.4 12.4 Class III 114 64.5±4.6 54.6±4.8 18.4