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.

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/m, Bu 6.4 mg/kg, and Mel 140 mg/m (n = 69), with Mel 100 mg/m 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/m and those receiving Mel 140 mg/m, 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 the total cohort, the sole independent factor associated with transplantation outcomes was HCT-CI ≥3, which correlated with higher NRM and inferior DFS and OS. Our study suggests that moderate-intensity FBM conditioning is feasible for patients with myeloid malignancies, with a low relapse rate without increased NRM. A lower Mel dose of 100 mg/m maintained the low risk of relapse without excess NRM in older adults. However, the FBM regimen should be used with caution in patients with high-risk HCT-CI (≥3).