Low Incidence of Relapse with a Moderate Conditioning Regimen of Fludarabine, Busulfan, and Melphalan for Patients with Myeloid Malignancies: A Single-Center Analysis of 100 Patients

• Published in: Transplantation and cellular therapy 2023-08, Vol.29 (8), p.512.e1-512.e8
• Main Authors: Jiang, Jie-ling, Gao, Wen-hui, Wang, Li-ning, Wan, Ming, Wang, Ling, Hu, Jiong
• Format: Article
• Language: English
• Subjects: Allogeneic hematopoietic stem cell transplantation; Busulfan; Conditioning regimen; Fludarabine; Melphalan; Myeloid malignancies
• ISSN: 2666-6367; 2666-6367
• DOI: 10.1016/j.jtct.2023.05.017

FBM conditioning (fludarabine, 2 days of busulfan, and melphalan 100 or 140 mg/m2) was associated with a low relapse rate and acceptable nonrelapse mortality (NRM) in patients with acute myeloid leukemia or myelodysplastic syndrome undergoing allogeneic hematopoietic stem cell transplantation.Melphalan at a moderate dose of 100 mg/m2 maintained the low relapse risk without excessive NRM in older adults.The FBM regimen should be used with caution in patients with high-risk Hematopoietic Cell Transplantation Comorbidity Index (≥3) owing to higher NRM. Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with standard myeloablative conditioning regimens such as fludarabine (Flu) and busulfan (Bu) remains a major concern in patients with myeloid malignancies. A low relapse rate has been reported when thiotepa or melphalan (Mel) is added to Flu-Bu, but at a possible increased risk of nonrelapse mortality (NRM). Here we evaluated the outcomes of 100 patients (70 with acute myeloid leukemia, 23 with myelodysplastic syndrome, 4 with chronic myelomonocytic leukemia, and 3 with granulocytic sarcoma) who underwent their first allo-HSCT after a moderate-dose FBM conditioning regimen consisting of Flu 150 mg/m2, Bu 6.4 mg/kg, and Mel 140 mg/m2 (n = 69), with Mel 100 mg/m2 for patients age >55 years and/or with a Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) ≥3 (n = 31). Donors were HLA-matched siblings (n = 19), matched unrelated donors (n = 4), and haploidentical donors (n = 77). The majority of patients (88%) had an intermediate or high Disease Risk Index. Out of 96 evaluable patients, 94 achieved neutrophil engraftment and had full donor chimerism on day +30 post-transplantation. After a median follow-up of 468 days (range, 55 to 1039 days), only 4 patients relapsed, with a 2-year cumulative incidence of relapse (CIR) of 5.3% ± 3.6%. The 100-day and 2-year NRM were 6.8% ± 4.4% and 12.3% ± 3.6%, respectively. At the last follow-up, the 2-year disease-free survival (DFS) and overall survival (OS) were 82.4% ± 4.2% and 80.3% ± 6.0%, respectively. Comparing the transplantation outcomes between patients receiving Mel 100 mg/m2 and those receiving Mel 140 mg/m2, showed no significant differences in NRM and CIR between the 2 groups and similar 2-year DFS and OS in the 2 groups, although the Mel 100 group had a higher median age (58 years versus 42 years; P < .001) and a higher percentage of patients with an HCT-CI ≥3 (P = .005). In t