Is Old (Fludrabine/Busulfan/Cyclophosphamide/rAntiThymocyteGlobulin) Conditioning Still Gold for Allogeneic Transplants in Transfusion Dependent Beta-Thalassemia of All Risk Categories in 21st Century?

• Published in: Indian journal of hematology & blood transfusion Vol. 39; no. 4; pp. 615 - 623
• Main Authors: Mehta, D. M. Pallavi, Khushoo, Vishvdeep
• Format: Journal Article
• Language: English
• Published: New Delhi Springer India 01.10.2023; Springer Nature B.V
• Subjects: Blood diseases; Blood Transfusion Medicine; Clinical outcomes; Hematology; Human Genetics; Immunosuppressive agents; Medicine; Medicine & Public Health; Oncology; Original; Original Article; Stem cell transplantation; Stem cells; Conditioning regimen; Hemoglobinopathies; Bone marrow graft; Allogeneic stem cell transplant
• ISSN: 0971-4502; 0974-0449; 0974-0449; 0971-4502
• DOI: 10.1007/s12288-023-01646-1

Allogeneic stem cell transplant (allo-SCT) is the only curative option for transfusion dependent thalassemia (TDT) until the gene therapy could bring paradigm shift. We analysed TDT allo-SCTs performed with Flu/Bu/Cy/rATG conditioning between October 2018 and April 2022 at our center. A retrospective analysis of 55 consecutive HLA matched alloSCT for TDT and was approved by hospital’s Institutional Review Board. Median age was 7(2–13) years. On presentation, number of patients with Class I, II, III were 18 (32.7%), 14(25.4%) and 23(41.8%) respectively {ClassIIIA = 14(25.4%),ClassIIIB = 9(16.3%)}. After downstaging, Class I, II, III were 22(40%), 15(27.2%) and 18(32.7%) patients respectively {ClassIIIA = 15(27.2%),ClassIIIB = 3(5.4%)}. Graft was bone marrow in 53(96.4%) and peripheral blood stem cell in 2(3.6%) patients. Mean CD34 stem cell dose was 3.28(1.2–6.5) × 10 6 /kg. Neutrophils and platelets engrafted at a median of 16(12–32) and 17(12–48) days. Median duration of follow-up was 20.7(1.8–43.9) months. There was no primary rejection. Although, mixed chimerism was common {17(30.9%)}, there was only one secondary rejection (1.8%). Venoocclusive disease was seen 12(21.8%) patients {mild = 9(75%), moderate = 2(16.6%) and severe = 1(8.3%)}. Acute and Chronic graft versus host disease was observed in 4(7.2%) and 4(7.2%) patients respectively. There was no treatment related mortality. Overall survival and Thalassemia Free Survival were 100% ± 0% and 98% ± 2% respectively. Flu/Bu/Cy/rATG conditioning with BM graft is a safe and effective regimen even in higher risk. It also highlights the importance of pretransplant downstaging of risk class in improving the outcomes.