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

Cancer. 2024 Oct 15;130(20):3452-3462. doi: 10.1002/cncr.35433. Epub 2024 Jun 19.

Abstract

Introduction: NPM1-mutated (NPM1mut) myeloid neoplasms (MNs) with <20% bone marrow (BM) blasts (NPM1mut MNs<20) are uncommon, and their classification remains inconsistent.

Methods: The clinicopathologic features of 54 patients with NPM1mut MNs <20 were evaluated and compared with wild-type NPM1 MNs <20 and NPM1mut MNs≥20, respectively.

Results: NPM1mut 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 NPM1mut 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 NPM1mut MNs <20 had marrow blast progression to ≥20%.

Conclusions: Overall, NPM1mut MNs define a unique entity independent of BM blast percentage.

Keywords: NPM1 mutation; intensive chemotherapy; myelodysplastic syndromes; myeloid neoplasms; stem cell transplant.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Marrow / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Myeloproliferative Disorders / drug therapy
  • Myeloproliferative Disorders / genetics
  • Myeloproliferative Disorders / pathology
  • Nuclear Proteins* / genetics
  • Nucleophosmin*
  • Prognosis
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • Nucleophosmin
  • NPM1 protein, human
  • Nuclear Proteins
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3