Decitabine induction with myeloablative conditioning and allogeneic hematopoietic stem cell transplantation in high-risk patients with myeloid malignancies is associated with a high rate of infectious complications

Christopher R. D'Angelo, Aric Hall, Kaitlin M. Woo, Kyung Mann Kim, Walter Longo, Peiman Hematti, Natalie Callander, Vaishalee P. Kenkre, Ryan Mattison, Mark Juckett

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Patients with high-risk myelodysplastic syndrome or acute myeloid leukemia have an increased risk of death following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Decitabine has minimal non-hematologic toxicity and proven efficacy in myeloid diseases, and post-transplant cyclophosphamide (PTCy) has reduced rates of graft-versus-host-disease (GVHD). We hypothesized that decitabine induction with allo-HSCT and PTCy would improve outcomes in a high-risk myeloid disease population. We performed a phase-II trial of decitabine at 20 mg/m2 for 10 days followed by allo-HSCT using a myeloablative regimen of fludarabine, IV busulfan and 4 Gy total body irradiation with PTCy for GVHD prophylaxis. Twenty patients underwent decitabine induction and 17 patients proceeded to transplant per protocol. Median overall survival from decitabine induction was 210 days (95 % CI 122-not reached). All patients developed grade 4 neutropenia after decitabine, eleven patients (55 %) developed grade 3−4 infections, and 5 cases were fatal. There were 5/20 (25 %) long-term survivors with a median follow-up of 3.6 years. Decitabine induction followed by myeloablative allo-HSCT in a high-risk population was associated with a high risk of infection and mortality related to enhanced immunosuppression. Further exploration of decitabine conditioning on reduced intensity platforms and improved infectious prophylaxis and screening may better mitigate toxicity (ClinicalTrials.gov (NCT01707004)).

Original languageEnglish (US)
Article number106419
JournalLeukemia Research
Volume96
DOIs
StatePublished - Sep 2020
Externally publishedYes

Keywords

  • Allogeneic hematopoietic stem cell transplant
  • Clinical trial
  • Decitabine
  • High-risk myeloid disease
  • Immunosuppression
  • Infection

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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