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Clinical Trial
. 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

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Free PMC article
Clinical Trial

Evaluation of Induction Chemotherapies After Hypomethylating Agent Failure in Myelodysplastic Syndromes and Acute Myeloid Leukemia

Brian Ball et al. Blood Adv. .
Free PMC article

Abstract

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.

Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

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Figure 1.
Figure 1.
Kaplan-Meier estimates of the OS for different induction chemotherapy regimens. In MDS (A) and AML (B). Survival is expressed in months after induction. Each tick mark represents a censored patient. (A-B) No significant difference in survival among the induction regimens for patients with MDS or AML.
Figure 2.
Figure 2.
Landmark analysis of OS for patients undergoing allogeneic stem cell transplantation vs no transplantation. In MDS (A) and AML (B). Survival is expressed in months after induction. The landmark analysis was set 3 months after induction. Each tick mark represents a censored patient. (A-B) Significantly longer median survival for patients with MDS and AML treated with allogeneic transplantation when compared with those not undergoing transplantation. Allo, allogeneic transplantation.

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