NPM1-mutated myeloid neoplasms are a unique entity not defined by bone marrow blast percentage

NPM1-mutated (NPM1^mut) myeloid neoplasms (MNs) with <20% bone marrow (BM) blasts (NPM1^mut MNs<20) are uncommon, and their classification remains inconsistent.

The clinicopathologic features of 54 patients with NPM1^mut MNs <20 were evaluated and compared with wild-type NPM1 MNs <20 and NPM1^mut MNs≥20, respectively.

NPM1^mut MNs had similar features regardless of blast percentage, except for higher IDH2 (29% vs 7%, p = .023) and FLT3 (70% vs 11%, p < .001) frequency in patients with ≥20% BM blasts. Thirty-three (61%) patients with NPM1^mut MNs <20 received low-intensity chemotherapy (LIC) and 12 (22%) received intensive chemotherapy (IC). Higher complete remission rates (75% vs 27%, p = .006) and median overall survival (mOS) (not reached vs 30.4 months, p = .06) were observed with IC compared to LIC. Young patients (age <60 years) did not reach mOS either when treated with LIC or IC. Stem cell transplant was associated with increased survival only in patients treated with LIC (HR, 0.24; p = .025). No differences in mOS were observed by BM blast strata (32.2 months, not reached and 46.9 months for <10%, 10%-19%, and ≥20% blasts, p = .700) regardless of treatment modality (LIC: p = .900; IC: p = .360). Twenty-three patients (43%) with NPM1^mut MNs <20 had marrow blast progression to ≥20%.

Overall, NPM1^mut MNs define a unique entity independent of BM blast percentage.