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

Brian Ball, Rami S. Komrokji, Lionel Adès, Mikkael A. Sekeres, Amy E. DeZern, Lisa Pleyer, Norbert Vey, António Almeida, Ulrich Germing, Thomas Cluzeau, Uwe Platzbecker, Steven D. Gore, Pierre Fenaux, Thomas Prebet*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


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 afterHMAfailure. Patients received 713, intermediate-to high-dose cytarabine (IDAC), or purine nucleoside analog-based regimens. For the MDS cohort (n 5 307), 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 5 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 5 .01), age $65 years (OR, 0.47; P, .01), and use of IDAC (OR, 2.91, P 5 .01). Shorter survival was associated with adverse cytogenetics (hazard ratio [HR], 1.43; P 5 .06). In the AML cohort, OS was decreased by disease progression at time of HMA failure (HR, 2.66; P 5 .02) and prolonged with use of an anthracycline-containing regimen (HR, 0.37; P 5 .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.

Original languageEnglish
Pages (from-to)2063-2071
Number of pages9
JournalBlood advances
Issue number16
Publication statusPublished - 28 Aug 2018
Externally publishedYes


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