Transplant outcomes of the triple-negative NPM1/FLT3-ITD/CEBPA mutation subgroup are equivalent to those of the favourable ELN risk group, but significantly better than the intermediate-I risk group after allogeneic transplant in normal-karyotype AML

The prognostic significance of molecular mutations (FLT3-ITD, NPM1, and CEBPA mutations) was examined in patients with normal-karyotype acute myeloid leukaemia (NK-AML) after allogeneic haematopoietic cell transplantation (HCT). In total, 115 patients received allogeneic HCT for NK-AML and were evaluated for FLT3-ITD, NPM1, and CEBPA mutations in diagnostic samples and for long-term outcomes following HCT, retrospectively. The prevalences of FLT3-ITD^pos, NPM1 ^mut, and CEBPA ^dm (double mutations) were 32.2, 43.5, and 24.6 %, respectively. The triple-negative group (NPM1 ^wild/FLT3-ITD^neg/non-CEBPA ^dm) showed a similar transplant outcome to those in the favourable European LeukemiaNet (ELN) risk group for overall survival (OS) (60.9 vs. 63.7 %; p = 0.810), but a more favourable OS than others in the intermediate-I risk group (40.0 %; p = 0.034). Also, the triple-negative group showed a similar relapse rate at 5 years compared with those in the favourable risk group (9.7 vs. 15.5 %; p = 0.499), but a lower rate of relapse than the others in the intermediate-I risk group (15.5 vs. 48.6 %; p = 0.004). The 5-year relapse incidences were 4.0 % (NPM1 ^mut/FLT3-ITD^neg), 14.7 % (CEBPA ^dm), 15.5 % (NPM1 ^wild/FLT3-ITD^neg/non-CEBPA ^dm), 39.1 % (NPM1 ^mut/FLT3-ITD^pos/non-CEBPA ^dm), and 66.7 % (NPM1 ^wild/FLT3-ITD^pos/non-CEBPA ^dm). Thus, the triple-negative (NPM1 ^wild/FLT3-ITD^neg/non-CEBPA ^dm) group showed favourable long-term outcomes after allogeneic HCT in NK-AML, similar to those of the favourable risk group by the ELN risk classification.