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

Abstract

Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with standard myeloablative conditioning regimens such as Flu-Bu (fludarabine and busulfan) remains a major concern in patients with myeloid malignancies. A low relapse rate was reported when thiotepa or melphalan (Mel) were added to Flu-Bu, but this might increase the non-relapse mortality (NRM). Here, we evaluated the outcomes of 100 patients (70 acute myeloid leukemia, 23 myelodysplastic syndrome, 4 chronic myelomonocytic leukemia, and 3 granulocytic sarcoma) who received their first allo-HSCT after moderate-dose FBM conditioning regimen (fludarabine 150 mg/m2, busulfan 6.4 mg/kg, and melphalan 140 mg/m2, n=69; or lower-dose melphalan at 100 mg/m2 for patients over 55 years old and/or those with HCT-CI ≥3, n=31). The donors were HLA-matched siblings (n=19), unrelated donors (n=4), and haplo-identical donors (n=77). A total of 88% patients had an intermediate or high disease risk index (DRI). Out of 96 evaluable patients, 94 achieved neutrophil engraftment and had full donor chimerism on day 30. After a median follow-up of 468 days (range, 55-1039 days), only four patients relapsed with 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 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. Moreover, when comparing the transplantation outcomes between patients with melphalan 100 mg/m2 and 140 mg/m2, the NRM and CIR were not significantly different and the 2-year DFS and OS were similar in both groups, although the Mel 100 group was associated with a higher median age (58 vs 42 years, p<0.001) and a higher percentage of patients with HCT-CI ≥3 (p=0.005). For the whole group, the only independent factor associated with transplantation outcomes was HCT-CI ≥3, which led to higher NRM and inferior DFS and OS. Our study suggested that moderate-intensity FBM conditioning was feasible for patients with myeloid malignancies with a low relapse rate without increased NRM. A lower dose of melphalan at 100 mg/m2 maintained the low relapse risk without excess NRM for older adults. However, the FBM regimen should be used with caution in patients with high-risk HCT-CI (≥3).