Faculty Collaboration Database

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. Leuk Res 2020 Sep;96:106419

Date

07/20/2020

Pubmed ID

32683127

Pubmed Central ID

PMC7484445

DOI

10.1016/j.leukres.2020.106419

Scopus ID

2-s2.0-85087860176 (requires institutional sign-in at Scopus site)   10 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)).

Author List

D'Angelo CR, Hall A, Woo KM, Kim K, Longo W, Hematti P, Callander N, Kenkre VP, Mattison R, Juckett M

Authors

Peiman Hematti MD Professor in the Medicine department at Medical College of Wisconsin
Walter L. Longo MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
Busulfan
Combined Modality Therapy
Female
Follow-Up Studies
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Leukemia, Myeloid, Acute
Male
Middle Aged
Myelodysplastic Syndromes
Prognosis
Prospective Studies
Risk Factors
Survival Rate
Transplantation Conditioning
Vidarabine