Fludarabine and Melphalan Results in Fewer Relapses Compared to Fludarabine and Targeted Busulfan in Patients Receiving Reduced Intensity Conditioning for AML and MDS

• Published in: Blood 2016-12, Vol.128 (22), p.3486-3486
• Main Authors: Caddell, Ryan James, Schaible, Braydon, Ma, Zhenjun, Dimaggio, Elizabeth, Tombleson, Rebecca, Anasetti, Claudio, Ayala, Ernesto, Betts, Brian C., Kharfan-Dabaja, Mohamed A., Locke, Frederick L., Nishihori, Taiga, Pidala, Joseph A., Fernandez, Hugo F., Mishra, Asmita
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.3486.3486

Introduction: Fludarabine (Flu)-based conditioning regimens, combined with either melphalan (Mel) or intravenous busulfan (Bu), are often utilized in patients undergoing allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). While recent data supports that a myeloablative conditioning (MAC) strategy improves survival in patients who are able to tolerate this approach, the optimal regimen for patients elderly or unfit for MAC remains unclear. A single-center retrospective analysis was performed to evaluate outcomes in patients with AML or MDS deemed eligible only for reduced intensity regimens. Methods: Patients with AML and MDS who underwent peripheral blood mobilized allogeneic HCT at a single institution between January 2008 and December 2014 were identified. Of those, patients who received conditioning with either once-daily Bu (75-95 mg/m2) targeted to an area under the curve of 3500 µM*L/min and Flu 160 mg/m2 (Flu/Bu 3500) or Mel 140 mg/m2 plus Flu 120-160 mg/m2 (Flu/Mel) were evaluated and compared. All disease statuses (complete remission (CR), second CR, or with active disease) at time of HCT were included. Regimen toxicities, cumulative incidences of acute and chronic graft-versus-host disease (GVHD), non-relapse mortality (NRM), cumulative incidence of relapse (CIR), progression free survival (PFS), and overall survival (OS) were evaluated. Results: We identified 150 consecutive patients who received Flu/Bu 3500 (n=81) or Flu/Mel (n=69). Regimens were selected at physicians’ discretion. The median ages for Flu/Bu 3500 and Flu/Mel were similar (66.9 (range, 48.2-75.9) and 65.8 (40.9-75.2) (p=0.14)). No differences were detected between the two groups with regard to recipient and donor gender, primary disease, donor type, recipient and donor cytomegalovirus (CMV) status, and Karnofsky performance status. Additionally, there were no differences between either groups in disease specific prognostic variables such as Disease Risk Index (Armand et al.), blast percentage at time of HCT, International Prognostic Scoring System (IPSS) and revised IPSS scoring in MDS patients, or AML cytogenetics at time of HCT. Patients receiving Flu/Mel had higher HCT-specific comorbidity index (HCT-CI, >3) when compared to Flu/Bu 3500 prior to transplantation (66.7% versus 46.9%, p=0.02). OS was similar between both arms (p=0.1) as was NRM (Hazard ratio (HR) 0.61 (CI, 0.34 - 1.1, p=0.1)) and PFS, HR 1.26 (