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; Markus G. Manz; Marie-Christiane Vekemans; M-C. Legdeur; J. R. Passweg; J. Maertens; J. Kuball; B. J. Biemond; Peter J. M. Valk; B. A. van der Reijden; G. Meloni; H. C. Schouten; E. Vellenga; T. Pabst; R. Willemze; B. Lowenberg; G. Ossenkoppele; Frederic Baron; G. Huls; J. J. Cornelissen

doi:10.1038/leu.2016.183

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, Markus G. Manz, Marie-Christiane Vekemans, M-C. Legdeur, J. R. Passweg, J. Maertens, J. Kuball, B. J. Biemond, Peter J. M. Valk, B. A. van der Reijden, G. Meloni, H. C. Schouten, E. Vellenga, T. Pabst, R. Willemze, B. Lowenberg, G. OssenkoppeleFrederic Baron, G. Huls, J. J. Cornelissen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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 language	English
Pages (from-to)	26-33
Number of pages	8
Journal	Leukemia
Volume	31
Early online date	15-Jul-2016
DOIs	https://doi.org/10.1038/leu.2016.183
Publication status	Published - 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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Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio
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Versluis, J., 't Hout, F. E. M. I., Devillier, R., van Putten, W. L. J., Manz, M. G., Vekemans, M.-C., Legdeur, M.-C., Passweg, J. R., Maertens, J., Kuball, J., Biemond, B. J., Valk, P. J. M., van der Reijden, B. A., Meloni, G., Schouten, H. C., Vellenga, E., Pabst, T., Willemze, R., Lowenberg, B., ... Cornelissen, J. J. (2017). Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio. Leukemia, 31, 26-33. https://doi.org/10.1038/leu.2016.183

@article{5f8f0ad9bbac4048913e2ffef1be749a,

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

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.",

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",

author = "J. Versluis and \{'t Hout\}, \{F. E. M. In\} and R Devillier and \{van Putten\}, \{W. L. J.\} and Manz, \{Markus G.\} and Marie-Christiane Vekemans and M-C. Legdeur and Passweg, \{J. R.\} and J. Maertens and J. Kuball and Biemond, \{B. J.\} and Valk, \{Peter J. M.\} and \{van der Reijden\}, \{B. A.\} and G. Meloni and Schouten, \{H. C.\} and E. Vellenga and T. Pabst and R. Willemze and B. Lowenberg and G. Ossenkoppele and Frederic Baron and G. Huls and Cornelissen, \{J. J.\}",

year = "2017",

doi = "10.1038/leu.2016.183",

language = "English",

volume = "31",

pages = "26--33",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Nature Publishing Group",

}

Versluis, J, 't Hout, FEMI, Devillier, R, van Putten, WLJ, Manz, MG, Vekemans, M-C, Legdeur, M-C, Passweg, JR, Maertens, J, Kuball, J, Biemond, BJ, Valk, PJM, van der Reijden, BA, Meloni, G, Schouten, HC, Vellenga, E, Pabst, T, Willemze, R, Lowenberg, B, Ossenkoppele, G, Baron, F, Huls, G & Cornelissen, JJ 2017, 'Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio', Leukemia, vol. 31, pp. 26-33. https://doi.org/10.1038/leu.2016.183

TY - JOUR

T1 - Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio

AU - Versluis, J.

AU - 't Hout, F. E. M. In

AU - Devillier, R

AU - van Putten, W. L. J.

AU - Manz, Markus G.

AU - Vekemans, Marie-Christiane

AU - Legdeur, M-C.

AU - Passweg, J. R.

AU - Maertens, J.

AU - Kuball, J.

AU - Biemond, B. J.

AU - Valk, Peter J. M.

AU - van der Reijden, B. A.

AU - Meloni, G.

AU - Schouten, H. C.

AU - Vellenga, E.

AU - Pabst, T.

AU - Willemze, R.

AU - Lowenberg, B.

AU - Ossenkoppele, G.

AU - Baron, Frederic

AU - Huls, G.

AU - Cornelissen, J. J.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - ACUTE MYELOID-LEUKEMIA

KW - STEM-CELL TRANSPLANTATION

KW - MINIMAL RESIDUAL DISEASE

KW - 1ST COMPLETE REMISSION

KW - INTERNAL TANDEM DUPLICATION

KW - ACUTE MYELOGENOUS LEUKEMIA

KW - NO-DONOR ANALYSIS

KW - UK MRC AML-10

KW - REDUCED-INTENSITY

KW - ALLOGENEIC TRANSPLANTATION

U2 - 10.1038/leu.2016.183

DO - 10.1038/leu.2016.183

M3 - Article

C2 - 27416910

SN - 0887-6924

VL - 31

SP - 26

EP - 33

JO - Leukemia

JF - Leukemia

ER -

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

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Keywords

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