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. Lowenberg, G. OssenkoppeleF. Baron, G. Huls, J. J. Cornelissen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

46 Citations (Web of Science)

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 - Jan 2017

Keywords

  • ACUTE MYELOID-LEUKEMIA
  • STEM-CELL TRANSPLANTATION
  • MINIMAL RESIDUAL DISEASE
  • 1ST COMPLETE REMISSION
  • INTERNAL TANDEM DUPLICATION
  • ACUTE MYELOGENOUS LEUKEMIA
  • NO-DONOR ANALYSIS
  • UK MRC AML-10
  • REDUCED-INTENSITY
  • ALLOGENEIC TRANSPLANTATION

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