Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio

J. Versluis, F. E.M. In'T Hout, R. Devillier, W. L.J. Van Putten, M. G. Manz, M. C. Vekemans, M. C. Legdeur, J. R. Passweg, J. Maertens, J. Kuball, B. J. Biemond, P. J.M. Valk, B. A. Van Der Reijden, G. Meloni, H. C. Schouten, E. Vellenga, T. Pabst, R. Willemze, B. Löwenberg, G. OssenkoppeleF. Baron, G. Huls, J. J. Cornelissen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Post-remission treatment (PRT) in patients with cytogenetically normal (CN) acute myeloid leukemia (AML) in first complete remission (CR1) is debated. We studied 521 patients with CN-AML in CR1, for whom mutational status of NPM1 and FLT3-ITD was available, including the FLT3-ITD allelic ratio. PRT consisted of reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (alloHSCT) (n=68), myeloablative conditioning (MAC) alloHSCT (n=137), autologous hematopoietic stem cell transplantation (autoHSCT) (n=168) or chemotherapy (n=148). Favorable overall survival (OS) was found for patients with mutated NPM1 without FLT3-ITD (71±4%). Outcome in patients with a high FLT3-ITD allelic ratio appeared to be very poor with OS and relapse-free survival (RFS) of 23±8% and 12±6%, respectively. Patients with wild-type NPM1 without FLT3-ITD or with a low allelic burden of FLT3-ITD were considered as intermediate-risk group because of similar OS and RFS at 5 years, in which PRT by RIC alloHSCT resulted in better OS and RFS as compared with chemotherapy (hazard ratio (HR) 0.56, P=0.022 and HR 0.50, P=0.004, respectively) or autoHSCT (HR 0.60, P=0.046 and HR 0.60, P=0.043, respectively). The lowest cumulative incidence of relapse (23±4%) was observed following MAC alloHSCT. These results suggest that alloHSCT may be preferred in patients with molecularly intermediate-risk CN-AML, while the choice of conditioning type may be personalized according to risk for non-relapse mortality.

Original languageEnglish
Pages (from-to)26-33
Number of pages8
JournalLeukemia
Volume31
Issue number1
DOIs
Publication statusPublished - 1 Jan 2017

Cite this

Versluis, J., In'T Hout, F. E. M., Devillier, R., Van Putten, W. L. J., Manz, M. G., Vekemans, M. C., ... Cornelissen, J. J. (2017). Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio. Leukemia, 31(1), 26-33. https://doi.org/10.1038/leu.2016.183