Bone marrow transplantation in patients with thalassemia

Abstract

In this study we report the long-term results of bone marrow transplantation (BMT) in 113 patients (M 56, F 57) with thalassemia major (TM) who were given 117 transplants from HLA identical sibling donor between May 1983 and September 2005. The median age was 9.09 years (0.11-28.11). The median number of transfusions given before BMT was 136 (2-900). The pretransplant liver biopsy performed in 78 patients showed: chronic persistent hepatitis in 35, mild chronic active hepatitis (CAH) in 10, moderate CAH in 23, severe CAH in 10. All patients received the same preparative therapy consisting of busulphan (BU) (13-14 mg/kg) and cyclophosphamide (200 mg/kg), preceded by an hypertransfusion regimen for 2-3 weeks. For graft-versus-host disease (GvHD) prophylaxis, 38 patients were given cyclosporine (CSA) alone and 75 received CSA and short course methotrexate. The median number of transplanted nucleated cells was 4.8 × 108/kg (2.3-10.1). Marrow engraftment was evident in 111 patients. The median time to achieve 0.5 × 109/L neutrophils and 50 × 109/L platelets was 19 (11-37) and 24 (10-55) days respectively. Four patients had an autologous reconstitution and are currently alive under transfusion therapy. The probability of graft rejection was 6.6%. The actuarial probability of developing acute GvHD grade II-IV and cumulative chronic GvHD was 21% and 17% (7% limited, 10% extensive) respectively. Transplant related mortality was 8.8%. Ten patients died for BMT related causes: pneumonia in 4, heart failure in 3, encephalopathy in 2, aGvHD in 1. Two late deaths occurred, one for septic shock 54 months post-BMT and one for parotitis carcinoma 138 months after BMT. As of October 2005, 101 patients are alive and 97 of them are cured after a median follow-up of 158 months (1-269). The 10-year actuarial probability of survival and disease-free survival (DFS) was 91% and 87% respectively. In multivariate analysis, no adverse risk factor affecting survival and DFS was identified among recipient-donor age and sex, number of pre-BMT transfusions, level of ferritin, type of CAH, grade of liver fibrosis, serum GPT level, HBV and HCV serology, dose of BU, type of GvHD prophylaxis, marrow cell dose. This study confirms the feasibility of curing the majority of patients with TM by BMT. In this study we report the long-term results of bone marrow transplantation (BMT) in 113 patients (M 56, F 57) with thalassemia major (TM) who were given 117 transplants from HLA identical sibling donor between May 1983 and September 2005. The median age was 9.09 years (0.11-28.11). The median number of transfusions given before BMT was 136 (2-900). The pretransplant liver biopsy performed in 78 patients showed: chronic persistent hepatitis in 35, mild chronic active hepatitis (CAH) in 10, moderate CAH in 23, severe CAH in 10. All patients received the same preparative therapy consisting of busulphan (BU) (13-14 mg/kg) and cyclophosphamide (200 mg/kg), preceded by an hypertransfusion regimen for 2-3 weeks. For graft-versus-host disease (GvHD) prophylaxis, 38 patients were given cyclosporine (CSA) alone and 75 received CSA and short course methotrexate. The median number of transplanted nucleated cells was 4.8 × 108/kg (2.3-10.1). Marrow engraftment was evident in 111 patients. The median time to achieve 0.5 × 109/L neutrophils and 50 × 109/L platelets was 19 (11-37) and 24 (10-55) days respectively. Four patients had an autologous reconstitution and are currently alive under transfusion therapy. The probability of graft rejection was 6.6%. The actuarial probability of developing acute GvHD grade II-IV and cumulative chronic GvHD was 21% and 17% (7% limited, 10% extensive) respectively. Transplant related mortality was 8.8%. Ten patients died for BMT related causes: pneumonia in 4, heart failure in 3, encephalopathy in 2, aGvHD in 1. Two late deaths occurred, one for septic shock 54 months post-BMT and one for parotitis carcinoma 138 months after BMT. As of October 2005, 101 patients are alive and 97 of them are cured after a median follow-up of 158 months (1-269). The 10-year actuarial probability of survival and disease-free survival (DFS) was 91% and 87% respectively. In multivariate analysis, no adverse risk factor affecting survival and DFS was identified among recipient-donor age and sex, number of pre-BMT transfusions, level of ferritin, type of CAH, grade of liver fibrosis, serum GPT level, HBV and HCV serology, dose of BU, type of GvHD prophylaxis, marrow cell dose. This study confirms the feasibility of curing the majority of patients with TM by BMT.