Radiation-free reduced-intensity hematopoietic stem cell transplantation with in vivo T-cell depletion from matched related and unrelated donors for Fanconi anemia: prognostic factor analysis

• Published in: Experimental hematology 2022-05, Vol.109, p.27-34
• Main Authors: Rostami, Tahereh, Mousavi, Seyed Ali, Kiumarsi, Azadeh, Kasaeian, Amir, Rad, Soroush, Yaghmaie, Marjan, Ghavamzadeh, Ardeshir, Mousavi, Seied Asadollah
• Format: Article
• Language: English
• Subjects: Busulfan - therapeutic use; Fanconi Anemia - drug therapy; Graft vs Host Disease - drug therapy; Graft vs Host Disease - etiology; Graft vs Host Disease - prevention & control; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - methods; Humans; Prognosis; Retrospective Studies; T-Lymphocytes; Transplantation Conditioning - methods; Unrelated Donors
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2022.02.003

•The survival rate of Fanconi patients at 1 year was 84.14%, and at 5 years, 82.16%.•Myeloid recovery occurred in all patients (100%) at a median of 11 days (range: 5–16 days).•Stem cell source and type of donor did not statistically associate with the occurrence of chronic GvHD.•Fanconi patient characteristics before transplant, including only the presence of cardiopulmonary, genitourinary tract, central nervous system, and limb malformations, significantly affected patient survival rates. Fanconi anemia (FA) is a rare and complex genetic disorder, clinically characterized by bone marrow failure, congenital defects, and cancer predisposition. Hematopoietic stem cell transplantation (HSCT) represents the only therapeutic option to restore normal hematopoiesis after the occurrence of marrow failure or clonal hematopoietic abnormality. However, radiation exposure during transplant may increase the risk of later malignancies. In this retrospective study, we analyzed the results of HSCT with a radiation-free, busulfan-based conditioning regimen in FA patients. A total of 122 patients (median age: 8 years, range: 2–18 years) with FA who underwent HSCT between January 2008 and January 2020 were enrolled in this study and followed up to the end of 2020. The preparative regimen included busulfan (0.2 mg/kg/day, days –9 to –6), cyclophosphamide (15 mg/kg/day, days –5 to –2), and in vivo T-cell depletion with rabbit anti-thymocyte globulin. All patients received graft-versus-host disease prophylaxis with cyclosporine combined with methotrexate. We used the Kaplan–Meier method, log-rank test, and Cox proportional hazards models to analyze patient survival. Peripheral blood, bone marrow and cord blood hematopoietic stem cells were used in 84 (68.9%), 31 (25.4%) and 7 (5.7%) patients, respectively. Donors were matched siblings in 48 (39.3%), matched other relatives in 56 (45.9%), and matched unrelated persons in 18 (14.8%) patients. With a median follow-up time of 24.25 months, graft rejection occurred in only one patient. The 1- and 5-year overall survival rates were 84.14% (95% confidence interval: 76.02–89.70) and 82.16% (95% confidence interval: 73.01–88.45), respectively. Of the patient characteristics documented before transplant, the presence of cardiopulmonary, genitourinary tract, central nervous system, and limb malformations significantly affected survival rates. Our results indicate excellent outcomes in patients with FA undergoing HSCT with a radiation-fre