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, 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 - Lowenberg, B.
AU - Ossenkoppele, G.
AU - Baron, F.
AU - Huls, G.
AU - Cornelissen, J. J.
PY - 2017/1
Y1 - 2017/1
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.
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
SN - 0887-6924
VL - 31
SP - 26
EP - 33
JO - Leukemia
JF - Leukemia
IS - 1
ER -