Haploidentical transplant for paediatric patients with severe thalassaemia using post‐transplant cyclophosphamide and methotrexate: A prospectively registered multicentre trial from the Bone Marrow Failure Working Group of Hunan Province, China

• Published in: British journal of haematology 2023-02, Vol.200 (3), p.329-337
• Main Authors: Hu, Jian, Gong, Susu, Chen, Keke, Yang, Rui, Wang, Leyuan, Yang, Kaitai, Nie, Lin, Zou, Lang, Su, Tao, Chen, Cong, Xu, Yajing, He, Xianglin, Yang, Liangchun, Xiao, Hong, Fu, Bin
• Format: Article
• Language: English
• Subjects: Blood diseases; Bone Marrow Failure Disorders - drug therapy; Bone marrow transplantation; Bronchiolitis Obliterans Syndrome; Child; China; Collagen; Cyclophosphamide; Cyclophosphamide - therapeutic use; Graft vs Host Disease - drug therapy; Graft vs Host Disease - etiology; Graft vs Host Disease - prevention & control; Graft-versus-host reaction; haploidentical transplant; Hematology; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Leukocytes (neutrophilic); Methotrexate; Methotrexate - therapeutic use; Pancytopenia - etiology; Pediatrics; post‐transplant cyclophosphamide; thalassaemia; Thalassemia; Thalassemia - complications; Transplantation Conditioning - adverse effects; Transplantation, Haploidentical - adverse effects; Transplants & implants
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.18520

Summary Haploidentical transplantation strategies for patients with transfusion‐dependent thalassaemia (TD‐TM) remain to be investigated. In this study, 54 paediatric patients with TD‐TM were treated with a novel approach using post‐transplant cyclophosphamide (PTCy) and low‐dose methotrexate (LD‐MTX), following a myeloablative regimen. The incidence of neutrophil and platelet engraftment was 96.3% ± 2.6% and 94.4% ± 3.1% respectively. The cumulative incidence of grades II–III acute graft‐versus‐host disease (GVHD) was 13.8% ± 4.8% at 100 days. At three years, the cumulative incidence of chronic GVHD was 28.5% ± 8.5%. With a median follow‐up of 520 days (132–1325 days), the overall survival (OS) and event‐free survival (EFS) were 98.1% ± 1.8% and 90.7% ± 3.9% respectively. Compared with the low‐dose cyclophosphamide (CTX) conditioning regimen (120 mg/kg), the high‐CTX regimen (200 mg/kg) achieved a higher incidence of stable engraftment (100% vs 66.7% ± 15.7%, p = 0.003), a comparable incidence of grades II–III acute GVHD, a lower incidence of chronic GVHD (20.2% ± 8.3% vs 66.6% ± 19.2%, p = 0.011), and better overall survival (100% vs 88.9% ± 10.5%, p = 0.025) as well as EFS (95.6% ± 3.1% vs 66.7% ± 15.7%, p = 0.008). Our results using unmanipulated haploidentical grafts and PTCy with LD‐MTX in TD‐TM are encouraging. (chictr.org.cn ChiCTR1800017969)