Combination of FLT3-ITD Allelic Ratio, NPM1 Mutation, and Immunophenotypic Markers to Modulate Outcome Prediction in Patients with Normal Karyotype Acute Myelogenous Leukemia Undergoing Hematopoietic Stem Cell Transplantation

Gina Jiang; Jose-Mario Capo-Chichi; Aijun Liu; Eshetu G Atenafu; Rajat Kumar; Mark D Minden; Hong Chang

doi:10.1016/j.bbmt.2020.07.017

Combination of FLT3-ITD Allelic Ratio, NPM1 Mutation, and Immunophenotypic Markers to Modulate Outcome Prediction in Patients with Normal Karyotype Acute Myelogenous Leukemia Undergoing Hematopoietic Stem Cell Transplantation

Biol Blood Marrow Transplant. 2020 Nov;26(11):1995-2000. doi: 10.1016/j.bbmt.2020.07.017. Epub 2020 Jul 23.

Authors

Gina Jiang¹, Jose-Mario Capo-Chichi², Aijun Liu³, Eshetu G Atenafu⁴, Rajat Kumar⁵, Mark D Minden⁵, Hong Chang⁶

Affiliations

¹ Department of Laboratory Hematology, University Health Network, University of Toronto, Toronto, Ontario, Canada.
² Department of Clinical Laboratory Genetics, Genome Diagnostics, University Health Network, University of Toronto, Toronto, Ontario, Canada.
³ Department of Hematology, Beijing Chaoyang Hospital, Capital University Beijing, Beijing, China.
⁴ Department of Biostatistics, University Health Network, Toronto, Ontario, Canada.
⁵ Department of Hematology and Medical Oncology, University Health Network, University of Toronto, Toronto, Ontario, Canada.
⁶ Department of Laboratory Hematology, University Health Network, University of Toronto, Toronto, Ontario, Canada. Electronic address: hong.chang@uhn.on.ca.

PMID: 32712325
DOI: 10.1016/j.bbmt.2020.07.017

Abstract

NPM1 mutation status and the allelic ratio (AR) of FLT3-internal tandem duplication (FLT3-ITD) are routinely tested for disease risk stratification in patients with normal karyotype (NK) acute myelogenous leukemia (AML); however, the predictive impact of immunophenotypic markers on different NPM1/FLT3 genotypes remains unclear. We performed a retrospective analysis of 423 patients with NK-AML subclassified into groups based on NPM1/FLT3 genotype. Allogeneic hematopoietic stem cell transplantation (HSCT) was performed in 124 of 423 patients (29%) and was significantly associated with longer event-free survival (EFS) and overall survival (OS), except for patients with the favorable genotype, defined as mutated NPM1 (NPM1^mut) combined with normal FLT3 status (FLT3-ITD^neg) or FLT3-ITD AR <.5 (FLT3-ITD^low). A subset of AML patients bearing the favorable NPM1^mut/FLT3-ITD^neg/low genotype share similar outcomes with AML patients who have the intermediate FLT3/NPM1 genotype defined by normal NPM1 (NPM1^wt) and FLT3-ITD^neg/low. In these individuals, the lack of CD13 expression (CD13^neg) was associated with shorter EFS (P = .041) and OS (P = .017). CD13^neg was an independent predictor for shorter OS (hazard ratio, 1.985; P = .028).

Keywords: AML; FLT3-ITD; Immunophenotyping; NPM1; Prognosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Hematopoietic Stem Cell Transplantation*
Humans
Karyotype
Leukemia, Myeloid, Acute* / genetics
Leukemia, Myeloid, Acute* / therapy
Mutation
Nuclear Proteins / genetics
Nucleophosmin
Retrospective Studies
fms-Like Tyrosine Kinase 3 / genetics

Substances

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