Long-Term Results of Bone Marrow Transplantation for Thalassemia Major in Pescara.
Authors: Di Bartolomeo Paolo , Santarone Stella , Di Bartolomeo Erminia , Nicolucci Antonio , Olioso Paola , Bavaro Pasqua , Papalinetti Gabriele , Di Carlo Paolo , Torlontano Glauco 
Published: October 2019

Abstract
In this study we report the long-term results of bone marrow transplantation (BMT) in 111 patients (M 56, F 55) with thalassemia major (TM) who were given 115 transplants in Pescara between May 1983 and February 2004. The median age was 10.06 years (0.11–28.11). The median number of transfusions given before BMT was 139 (2–900). The median level of ferritin at time of BMT was 1328 (258–6640). Twenty-three patients showed evidence of HBV infection and 59 of HCV infection. A pretransplant liver biopsy was performed in 78 patients. On the basis of Knodell classification, results of liver biopsy were: mild siderosis with normal histology in 1 patient, chronic persistent hepatitis in 34, mild chronic active hepatitis (CAH) in 10, moderate CAH in 23, severe CAH in 10. Results of liver fibrosis were: no fibrosis in 4 patients, mild fibrosis in 39, moderate in 25 and severe in 10. All patients showed normal ejection fraction evaluated by echocardiogram (median 62%, range 56% to 70%). One hundred and seven patients received their marrow from HLA identical siblings, 3 from HLA identical parent and 1 from HLA identical uncle. All patients received the same preparative therapy consisting of Busulphan (BU) (13–14 mg/Kg) and Cyclophosphamide (CY) (200 mg/Kg), preceded by an hypertransfusion regimen for 2–3 weeks. For graft-versus-host disease (GvHD) prophylaxis, 37 patients were given Cyclosporine (CSA) alone and 74 received CSA in association with short course Methotrexate. The median number of transplanted nucleated cells was 4.7 x 108/Kg (2.3–10.1). Marrow engraftment was evident in 109 patients. The median time to achieve 0.5x109/L neutrophils and 50x109/L platelets was 19 (11–37) and 24 (10–55) days respectively. Four patients showed graft rejection and were given a second BMT from the same donor. 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 9%. Ten patients died for BMT related causes: pneumonia in 4, heart failure in 3 patients, encephalopathy in 2, aGvHD in 1. The median day of death was day 41 (12–212). Two late deaths occurred. One patient died of septic shock 54 months post-BMT. One patient died for parotitis carcinoma 138 months after BMT. As of July 2004, 99 patients are alive. Ninety five are cured after a median follow-up of 160 months (5–254). Four patients had an autologous reconstitution and are currently alive under transfusion therapy. To-date, 4 patients are receiving immunosuppressive therapy for active chronic GvHD. The 10-year actuarial probability of survival and disease-free survival (DFS) was 90% and 86% 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. Three studies were activated in the post-transplant course in order to normalize the serum ferritin with phlebotomy (28 patients), to treat HCV related CAH (9 patients) and to ameliorate the growth velocity with recombinant human growth hormone (7 patients).