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. Ossenkoppele; F. Baron; G. Huls; J. J. Cornelissen

doi:https://doi.org/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, 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

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

56 Citations (Scopus)

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
Issue number	1
Early online date	2016
DOIs	https://doi.org/10.1038/leu.2016.183
Publication status	Published - 1 Jan 2017

Access to Document

https://doi.org/10.1038/leu.2016.183

Cite this

Versluis, J., In'T Hout, F. E. M., 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., Löwenberg, 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(1), 26-33. https://doi.org/10.1038/leu.2016.183

@article{9e845238819e427486f05b6599a6d3f5,

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.",

author = "J. Versluis and {In'T Hout}, {F. E.M.} and R. Devillier and {Van Putten}, {W. L.J.} and Manz, {M. G.} and Vekemans, {M. C.} and Legdeur, {M. C.} and Passweg, {J. R.} and J. Maertens and J. Kuball and Biemond, {B. J.} and Valk, {P. 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. L{\"o}wenberg and G. Ossenkoppele and F. Baron and G. Huls and Cornelissen, {J. J.}",

year = "2017",

month = jan,

day = "1",

doi = "https://doi.org/10.1038/leu.2016.183",

language = "English",

volume = "31",

pages = "26--33",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Nature Publishing Group",

number = "1",

}

Versluis, J, In'T Hout, FEM, Devillier, R, Van Putten, WLJ, Manz, MG, Vekemans, MC, Legdeur, MC, Passweg, JR, Maertens, J, Kuball, J, Biemond, BJ, Valk, PJM, Van Der Reijden, BA, Meloni, G, Schouten, HC, Vellenga, E, Pabst, T, Willemze, R, Löwenberg, 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, no. 1, 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 - In'T Hout, F. E.M.

AU - Devillier, R.

AU - Van Putten, W. L.J.

AU - Manz, M. G.

AU - Vekemans, M. C.

AU - Legdeur, M. C.

AU - Passweg, J. R.

AU - Maertens, J.

AU - Kuball, J.

AU - Biemond, B. J.

AU - Valk, P. 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 - Löwenberg, B.

AU - Ossenkoppele, G.

AU - Baron, F.

AU - Huls, G.

AU - Cornelissen, J. J.

PY - 2017/1/1

Y1 - 2017/1/1

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.

UR - http://www.scopus.com/inward/record.url?scp=84978472449&partnerID=8YFLogxK

U2 - https://doi.org/10.1038/leu.2016.183

DO - https://doi.org/10.1038/leu.2016.183

M3 - Article

C2 - 27416910

SN - 0887-6924

VL - 31

SP - 26

EP - 33

JO - Leukemia

JF - Leukemia

IS - 1

ER -

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

Abstract

Access to Document

Other files and links

Cite this