Send to

Choose Destination
Blood Adv. 2018 Aug 28;2(16):2063-2071. doi: 10.1182/bloodadvances.2018015529.

Evaluation of induction chemotherapies after hypomethylating agent failure in myelodysplastic syndromes and acute myeloid leukemia.

Author information

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Malignant Hematology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
Clinical Hematology, Centre Hospitalier Universitaire Saint-Louis and Paris 7 University, Paris, France.
Leukemia Program, Cleveland Clinic, Cleveland, OH.
Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD.
Department of Hematology and Medical Oncology, Paracelsus Medical University Hospital Salzburg, Salzburg, Austria.
Institut Paoli-Calmettes, Marseille, France.
Serviço de Hematologia, Instituto Português de Oncologia de Lisboa, Lisbon, Portugal.
Department of Hematology, Oncology, and Clinical Immunology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Centre Hospitalier Universitaire Nice, Nice, France.
Universitätsklinikum Carl Gustav Carus, Dresden, Germany; and.
Hematology Department, Yale New Haven Hospital, New Haven, CT.


Hypomethylating agent (HMA) failure in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) carries a poor prognosis with limited treatment options. Although intensive, remission induction chemotherapy is often used subsequently, in particular to bridge to allogeneic transplantation, it is not clear whether an advantage exists for any particular regimen. Based on an international collaboration, we retrospectively analyzed induction response rate and survival in 366 patients after HMA failure. Patients received 7+3, intermediate- to high-dose cytarabine (IDAC), or purine nucleoside analog-based regimens. For the MDS cohort (n = 307), the overall response rate (ORR) was 41%; median overall survival (OS) was 10.8 months, and 40% of responding patients bridged to allogeneic stem cell transplant (allo-SCT). For the AML cohort (n = 59), the ORR was 32%, OS 6 months, and 42% of responding patients bridged to allo-SCT. Prognostic factors for response in MDS included adverse cytogenetics (odds ratio [OR], 0.46, P = .01), age ≥65 years (OR, 0.47; P < .01), and use of IDAC (OR, 2.91, P = .01). Shorter survival was associated with adverse cytogenetics (hazard ratio [HR], 1.43; P = .06). In the AML cohort, OS was decreased by disease progression at time of HMA failure (HR, 2.66; P = .02) and prolonged with use of an anthracycline-containing regimen (HR, 0.37; P = .01). In conclusion, intensive chemotherapy after HMA failure may be a reasonable treatment option for selected patients as a bridge to allogeneic transplantation and should be considered a potential platform for future investigations.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center