Bone Marrow Transplantation From HLA-Identical Sibling for Thalassemia.
Authors: Sabloff Mitchell , Chandy Mammen , Wang Zhiwei , Logan Brent , Li Chi-Kong , Irfan Syed M. , Eapen Mary , Walters Mark C. 
Published: October 2019

Abstract
Abstract 3361
Poster Board III-249
Allogeneic bone marrow transplantation (BMT) is curative treatment for β-Thalassemia major. The most extensive patient series have been reported by transplant teams in Italy. Outside these large groups, smaller, more limited series have reported variable results. Here we report the current experience of BMT for thalassemia outside Italy, and describe the characteristics and transplant outcomes in children after HLA-identical sibling BMT for thalassemia. Patients aged ≤20 years at BMT who received a myeloablative HLA-matched sibling BMT for thalassemia between 1995 and 2001 at 19 centers were eligible for the survey (n=179). Recipients of mobilized peripheral blood or umbilical cord blood stem cells, and reduced intensity transplant preparation were excluded as there were too few patients in each category for analysis. Also excluded were patients previously reported by the Italian centers. The median age at BMT was 7 years and the median follow-up of survivors was 6 years. Most recipients had high-risk features at BMT. The distribution of Lucarelli risk class I, II and III categories was 2%, 42%; and 36%, respectively. Data required to assign a risk category was not available for 20% of the study population. Before BMT, 85% had received ≥ 20 red blood cell transfusions. Of 87% who had a pre-BMT liver biopsy, 59% had portal fibrosis. There was hepatomegaly in 52% of patients and 94% had inadequate iron chelation therapy. All patients received busulfan and cyclophosphamide with or without anti-thymocyte globulin as the transplant conditioning regimen and almost all received cyclosporine-containing GVHD prophylaxis. The overall survival (OS) probabilities at 100 days and at 5 years were 85% and 80%, respectively. Seventeen patients (9.5%) had graft failure that was fatal in 11 cases. Six of 9 patients with graft failure survive after a successful second transplantation. Thirty-five patients (20%) died after BMT and the leading cause of death was interstitial pneumonitis in the current analysis. The probability of acute GVHD (grade II-IV) was 38% and the 5-year probability of chronic GVHD was 13%. Veno-occlusive disease (VOD) occurred frequently after BMT (n=58; 32% of patients) and 21 of the 35 (57%) patients who died after BMT had had a history VOD. A multivariate analysis showed that age at BMT ≥10 years (RR 2.16, 95% CI 1.1 – 4.23, p=0.025) and baseline hepatomegaly (RR 5.57, 95% CI 2.14 – 14.49, p<0.001) were associated with higher risk of mortality. The probabilities of disease-free survival (DFS) and OS are shown in the Table below. Younger patients without hepatomegaly fared the best and, older patients with hepatomegaly, the worst. This series confirms reports from large single center series that the results after HLA-matched sibling BMT for thalassemia major are optimized when performed in young children before the development of risk-factors for poor outcome. Pulmonary and hepatic complications were the leading cause of death in high-risk patients.
5-year OS 5-year DFS Age < 10 years without hepatomegaly 96% 93% Age < 10 years with hepatomegaly 73% 69% Age ≥ 10 years without hepatomegaly 86% 81% Age ≥ 10 years with hepatomegaly 53% 53%

Disclosures:
No relevant conflicts of interest to declare.