Fractionated gemtuzumab ozogamicin combined with intermediate-dose cytarabine and daunorubicin as salvage therapy in very high-risk AML patients: a bridge to reduced intensity conditioning transplant?

Ann Hematol. 2017 Mar;96(3):363-371. doi: 10.1007/s00277-016-2899-0. Epub 2016 Dec 23.

Abstract

Outcome of patients with primary refractory/relapsed (R/R) acute myeloid leukemia (AML) remains dismal. Herein, we present a retrospective monocentric study of 24 very high-risk AML patients who received a combination of fractionated gemtuzumab ozogamicin (GO) with intermediate-dose cytarabine and daunorubicin as salvage therapy. Median age was 55.3 years. Diagnostic was secondary AML for 33% of them. Seven patients had favorable risk, 8 had intermediate-1 or intermediate-2, and 6 had unfavorable risk of AML according to the European LeukemiaNet prognostic index. Complete remission was achieved in 50% of cases (46% in refractory and 55% in relapsed AML) without excessive toxicity. Thirteen patients could be referred for transplant. Only allogeneic hematopoietic stem cell transplantation provided a benefit in this patient cohort with a 1-year overall survival of 50.7 versus 18.1% in the absence of transplantation. Patients treated with reduced intensity conditioning (RIC) showed a longer survival as compared to those undergoing myeloablative conditioning regimen mainly because of decreased toxicity.Our data suggest that salvage therapy with fractionated GO combined with intermediate-dose cytarabine and daunorubicin in very high-risk patients may serve as a potential bridge therapy to RIC transplant.

Keywords: Acute myeloid leukemia; Bridge to allogeneic stem cell transplantation; Gemtuzumab ozogamicin; Refractory; Relapse; Salvage.

MeSH terms

  • Adult
  • Aged
  • Aminoglycosides / administration & dosage*
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Cohort Studies
  • Cytarabine / administration & dosage*
  • Daunorubicin / administration & dosage*
  • Female
  • Gemtuzumab
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Salvage Therapy / methods*
  • Transplantation Conditioning / methods*
  • Treatment Outcome
  • Young Adult

Substances

  • Aminoglycosides
  • Antibodies, Monoclonal, Humanized
  • Cytarabine
  • Gemtuzumab
  • Daunorubicin