High-dose cytarabine as salvage therapy for relapsed or refractory acute myeloid leukemia--is more better or more of the same?

Hematol Oncol. 2016 Mar;34(1):28-35. doi: 10.1002/hon.2191. Epub 2015 Feb 17.

Abstract

Cytarabine is the backbone of most chemotherapeutic regimens for acute myeloid leukemia (AML), yet the optimal dose for salvage therapy of refractory or relapsed AML (RR-AML) has not been established. Very high dose single-agent cytarabine at 36 g/m(2) (ARA-36) was previously shown to be effective and tolerable in RR-AML. In this retrospective analysis, we aim to describe the toxicity and efficacy of ARA-36 as salvage therapy for patients with AML who are primary refractory to intensive daunorubicin-containing induction or those relapsing after allogeneic stem cell transplant (alloSCT). Fifteen patients, median age 53 years, were included in the analysis. Six patients were treated for induction failure, one had resistant APL, and eight relapsed after alloSCT. Complete remission was achieved in 60% of patients. Surviving patients were followed for a median of 8.5 months. One-year overall survival was 54% (95% CI 30%-86%), and relapse rate from remission (n = 9) was 56%. Grade III/IV pulmonary, infectious, ocular and gastrointestinal toxicities occurred in 26%, 20%, 20% and 20% of patients respectively. Salvage therapy with ARA-36 regimen for RR-AML has considerable efficacy with manageable toxicity in patients with induction failure or post-transplant relapse. Overall survival in these high-risk patients still remains poor.

Keywords: high-dose cytarabine; refractory AML; relapsed AML.

Publication types

  • Evaluation Study

MeSH terms

  • Adolescent
  • Adult
  • Allografts
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Combined Modality Therapy
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Cytarabine / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm
  • Dyspnea / chemically induced
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Infections / etiology
  • Kaplan-Meier Estimate
  • Keratitis / chemically induced
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Recurrence
  • Remission Induction
  • Retrospective Studies
  • Salvage Therapy*
  • Treatment Outcome
  • Xerophthalmia / chemically induced
  • Young Adult

Substances

  • Antimetabolites, Antineoplastic
  • Cytarabine