Expression of CD4 is correlated with an unfavorable prognosis in wild-type NPM1, FLT3-ITD-negative cytogenetically normal adult acute myeloid leukemia.
BACKGROUND
In the cytogenetically normal population of AML (CN-AML), FLT3-ITD-positive and wild-type NPM1 is correlated with a worse outcome, and FLT3-ITD-negative with NPM1-mut is correlated with a better outcome. This leaves a large subpopulation of CN-AML patients without NPM1 or FLT3-ITD mutations with heterogeneous outcomes with overall survivals (OS) ranging from several weeks to years. Therefore, new prognostic markers are needed to better risk stratify this subset of patients.


METHODS
The retrospective study included 60 de novo adult AML patients diagnosed at our institution with normal karyotype, no FLT3-ITD or NPM1 mutations, and who did not receive allogeneic hematopoietic stem cell transplantations. We investigated the prognostic significance of immunophenotypic markers and clinical laboratory features in this double-negative population.


RESULTS
Older age (>60) and CD4 expression (14%) were significantly correlated with shorter event-free survival (EFS) (P < 0.001, P = 0.016, respectively). Expression of CD56 (12%), as well as lack of CD34 expression (19% of the cases), was also associated with a worse EFS (P = 0.048, P = 0.028, respectively). On multivariable analysis, CD4 expression and old age (>60) were identified as independent predictors for worse EFS (P = 0.016; P = 0.001, respectively) and OS (P = 0.048; P = 0.028, respectively).


CONCLUSIONS
Our results indicate that CD4 expression and older age are adverse prognostic factors in wild-type NPM1, FLT3-ITD-negative CN-AML.
Department of Laboratory Hematology, University Health Network, Toronto, ON, Canada.
R J
RJ
Guo
Department of Biostatistics, University Health Network, Toronto, ON, Canada.
E G
EG
Atenafu
Department of Hematology and Medical Oncology, University Health Network, Toronto, ON, Canada.
A D
AD
Schimmer
Department of Hematology and Medical Oncology, University Health Network, Toronto, ON, Canada.
M D
MD
Minden
Department of Laboratory Hematology, University Health Network, Toronto, ON, Canada.|Department of Hematology and Medical Oncology, University Health Network, Toronto, ON, Canada.
H
http://orcid.org/0000-0003-3106-2776
H
Chang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D015704:CD4 Antigens / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020440:Gene Duplication; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D009864:Ontario; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D020080:Tandem Repeat Sequences; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
D015415:Biomarkers; D015704:CD4 Antigens; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D051941:fms-Like Tyrosine Kinase 3
Acute myeloid Leukemia; CD4; FLT3-ITD; NPM1; immunophenotyping; normal karyotype; prognosis