Busulfan and cyclophosphamide‐based conditioning regimen still holds the promise of being a safe and efficacious regimen for allogeneic transplantation in patients with transfusion‐dependent thalassemia, even in high risk. (26th July 2022)

• Record Type: Journal Article
• Authors: Mehta, Pallavi; Kapoor, Jyotsna; Singh, Aakanksha; Yadav, Neha; Singh, Reema; Halder, Rohan; Verma, Megha; Agrawal, Narendra; Ahmed, Rayaz; Bhurani, Dinesh
• Is Part Of: European journal of haematology. Volume 109:Number 5(2022)
• Page Start: 447
• Page End: 457
• Publication Date: 2022-07-26
• Subjects: BuCy conditioning regimen -- TDT -- Transplant; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; Blood -- Periodicals; 616.15005
• DOI: 10.1111/ejh.13825
• Languages: English
• ISSNs: 0902-4441

Abstract

Abstract: Busulfan and cyclophosphamide (BuCy)‐based regimen has been used as a standard myeloablative chemotherapy for haematopoietic stem cell transplantation in thalassemia. However, treosulfan‐based conditioning regimen has emerged due to concerns of toxicities. We retrospectively analysed the safety and efficacy of fludrabine/Bu/Cy/antithymocyte globulin (ATG) versus treosulfan/thiotepa/fludrabine regimens for Hematopoietic Stem Cell Transplant (HSCT) in transfusion‐dependent thalassemia (TDT) conducted at our institute (2013–2021). In 75 patients, 36 (48%) received Flu/Bu/Cy/ATG whereas 39 (52%) received Treo/Thio/Flu. Median age was 6 (1–12) and 9 (1–15) years, respectively. Number of patients with Classes I, II, and III were 14, 10, and 12 in Flu/Bu/Cy/ATG versus 2, 19, and 18 in Treo/Thio/Flu group, respectively. Graft was growth factor mobilized bone marrow in Flu/Bu/Cy/ATG versus peripheral blood stem cell in Treo/Thio/Flu group. Mean stem cell dose was 3.82 (2.2–9.1) versus 5 (1.65–8.01) 10 6 /kg in Flu/Bu/Cy/ATG versus Treo/Thio/Flu group, respectively. Neutrophils and platelets engrafted at a median of 16 (14–21) and 16 (9–47) days in Flu/Bu/Cy/ATG and 15 (10–20) and 13 (9–41) days in Treo/Thio/Flu group. Median duration of follow‐up was 28 (23–32.9) months. Five (6.6%) patients had rejection (all secondary). Venoocclusive disease was observed in 2 (5.7%) versus 4 (10.3%) patients ( p = .047), respectively. Flu/Bu/Cy/ATG had 4 (11.4%) patients with acute GVHD versus 15 (38.5%) patients which had significant impact on survival ( p = .038). We observed chronic GVHD in 4 (11.4%) and 11 (28.2%) patients, respectively, with significant impact on survival ( p = .031). Four (5.1%) patients had TRM in Treo/Thio/Flu group, in contrast to none in Flu/Bu/Cy/ATG group. Mixed chimerism was common in Flu/Bu/Cy/ATG {20 (57.1%)} versus Treo/Thio/Flu group {12 (30.1%)}. Five‐year Event Free Survival (EFS) and OS of entire cohort were 87% + 4% and 94% + 3%, respectively. Estimated TFS, EFS, OS of Flu/Bu/Cy/ATG versus Treo/Thio/Flu was 97.1% + 2.9% versus 89.2% + 5.1% ( p = .251), 97 + 3% versus 80.7 + 6% ( p = .041) and 100% versus 90.4 + 5% ( p = .067), respectively. In our experience, Flu/Bu/Cy/ATG regimen is safe and effective even in high‐risk TDT. However, one needs to be vigilant for mixed chimerism.