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

Autor: Natalie S. Callander, Peiman Hematti, Kaitlin M. Woo, Vaishalee P. Kenkre, Mark B. Juckett, Walter L. Longo, Kyung Mann Kim, Aric C. Hall, Ryan J. Mattison, Christopher D'Angelo
Rok vydání: 2020
Předmět:
Adult
Male
Oncology
Cancer Research
medicine.medical_specialty
Transplantation Conditioning
Cyclophosphamide
medicine.medical_treatment
Population
Graft vs Host Disease
Decitabine
Hematopoietic stem cell transplantation
Infections
Article
03 medical and health sciences
0302 clinical medicine
Risk Factors
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Humans
Prospective Studies
education
Busulfan
Aged
education.field_of_study
business.industry
Hematopoietic Stem Cell Transplantation
Myeloid leukemia
Hematology
Middle Aged
Total body irradiation
Prognosis
Combined Modality Therapy
Fludarabine
Survival Rate
Leukemia
Myeloid
Acute
surgical procedures
operative
Myelodysplastic Syndromes
030220 oncology & carcinogenesis
Female
business
Vidarabine
Follow-Up Studies
030215 immunology
medicine.drug
Zdroj: Leuk Res
ISSN: 0145-2126
Popis: 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)).
Databáze: OpenAIRE
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