Low-Dose Azacitidine with DNMT1 Level Monitoring to Treat Post-Transplantation Acute Myelogenous Leukemia or Myelodysplastic Syndrome Relapse

Masumi Ueda, Najla El-Jurdi, Brenda Cooper, Paolo Caimi, Linda Baer, Merle Kolk, Lauren Brister, David N. Wald, Folashade Otegbeye, Hillard M. Lazarus, Brenda M. Sandmaier, Basem William, Yogen Saunthararajah, Philip Woost, James W. Jacobberger, Marcos de Lima

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Patients with early relapse of acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) after hematopoietic cell transplantation (HCT) have a poor prognosis, and no standard treatment. Twenty-nine patients with early disease recurrence post-transplantation were treated with azacitidine (AZA; median dose, 40 mg/m2/day for 5 to 7 days). At a median follow-up of 6.3 months (range, 1.3 to 41.1 months), 7 patients (27%) had a response to AZA, defined as complete remission, hematologic improvement, or improved donor chimerism. Response occurred after a median of 3 cycles, and the median duration of response was 70 days (range, 26 to 464 days). Median survival was 6.8 months (95% confidence interval, 3.8 to 11.1 months). Survival was similar in the patients receiving an AZA dose ≤40 mg/m2 and those receiving an AZA dose >40 mg/m2. Six patients receiving donor lymphocyte infusion with AZA had a response or stable disease without worsening graft-versus-host-disease. We retrospectively used a flow cytometry assay to explore DNA-methyltransferase-1 in blood mononuclear cells as a potential pharmacodynamic marker to assess intracellular drug targeting in 8 patients. No correlation with AZA dose or response was observed. Low-dose AZA appears to have comparable efficacy to higher-dose AZA post-HCT. A significant proportion of this poor-risk population responded to low-dose AZA, suggesting a dose-independent, noncytotoxic mechanism for antileukemic activity.

Original languageEnglish (US)
Pages (from-to)1122-1127
Number of pages6
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number6
DOIs
StatePublished - Jun 2019
Externally publishedYes

Bibliographical note

Funding Information:
Financial disclosure: This work was funded in part by a Conquer Cancer Foundation of the American Society of Clinical Oncology Young Investigator Award YIA 9939 (to M.U.) and American Cancer Society Grant IRG-91-022-18 (to B.M.W.). Any opinions, findings, and conclusions expressed in this manuscript are those of the authors and do not necessarily reflect those of the American Society of Clinical Oncology or the Conquer Cancer Foundation.

Keywords

  • AML
  • Allogeneic transplantation
  • Azacitidine
  • MDS
  • Relapse

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