Prognostic impact of melphalan dose and total body irradiation use in patients with acute myeloid leukemia undergoing allogeneic stem cell transplantation with reduced-intensity conditioning

Leuk Lymphoma. 2019 Jun;60(6):1493-1502. doi: 10.1080/10428194.2018.1535115. Epub 2018 Nov 20.

Abstract

To evaluate the prognostic impact of melphalan dose and total body irradiation (TBI) use in acute myeloid leukemia patients undergoing reduced-intensity allogeneic transplantation, we retrospectively compared outcomes of patients receiving a higher-dose (120-140 mg/m2, n = 379) or lower-dose melphalan (80-110 mg/m2, n = 128) with or without TBI of ≤4 Gy. At 3 years, overall survival was 48.9% in the higher-dose group versus 40.3% in the lower-dose group (p = .013). This survival benefit was attributed to lower tumor-related mortality (23.9% vs. 31.7%; p = .049). Non-relapse mortality did not differ (24.8% vs. 23.5%, p = .59). The beneficial effect of a higher-dose melphalan was more evident when combined with TBI in younger patients, those not in complete remission, and those with good performance status. Our findings support the use of a higher-dose melphalan in combination with TBI for reduced-intensity conditioning in physically fit patients.

Keywords: Melphalan; acute myeloid leukemia; hematopoietic stem cell transplantation; reduced-intensity conditioning; total body irradiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Chemoradiotherapy / adverse effects
  • Chemoradiotherapy / methods*
  • Chemoradiotherapy / statistics & numerical data
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Japan / epidemiology
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Melphalan / administration & dosage*
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / prevention & control
  • Prognosis
  • Registries / statistics & numerical data
  • Retrospective Studies
  • Transplantation Conditioning / adverse effects
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous / adverse effects
  • Transplantation, Homologous / methods
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives
  • Whole-Body Irradiation / adverse effects
  • Whole-Body Irradiation / methods*
  • Young Adult

Substances

  • Vidarabine
  • fludarabine
  • Melphalan