Influence of FLT3-internal tandem duplication allele burden and white blood cell count on the outcome in patients with intermediate-risk karyotype acute myeloid leukemia.
BACKGROUND
In patients with acute myeloid leukemia (AML), testing for fms-like tyrosine kinase-3 (FLT3)-internal tandem duplication (FLT3-ITD) and nucleophosmin-1 (NPM1) mutations can allow for further prognostic subclassification, but less is known about the effects of FLT3-ITD allele burden and presenting white blood cell count (WBC) within molecular subgroups.


METHODS
The authors retrospectively assessed 206 adult patients who had AML with an intermediate-risk karyotype and who received treatment on a uniform induction and consolidation chemotherapy regimen.


RESULTS
The presenting WBC was a prognostic factor for survival only in patients who had an FLT3-ITD mutation. On multivariate analysis, after correcting for age, WBC, secondary AML, and blast percentage, nucleophosmin-1 (NPM1)-mutated/FLT3-ITD-negative patients had superior overall survival compared with patients in the other molecular subgroups. Patients who had FLT3-ITD mutations had an inferior overall survival compared with patients who had NPM1 wild-type/FLT3-negative disease, and patients who had low or intermediate levels of the FLT-ITD of mutant allele had overall and disease-free survival similar to those in patients who had high-level mutations.


CONCLUSIONS
NPM1 and FLT3-ITD status, age, WBC, and secondary AML were identified as important prognostic variables that can help to risk stratify patients with AML who have intermediate-risk cytogenetics. FLT3 allele burden had no significant influence on outcomes after correcting for other variables.
Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Jonathan
J
How
Jenna
J
Sykes
Vikas
V
Gupta
Karen W L
KW
Yee
Aaron D
AD
Schimmer
Andre C
AC
Schuh
Mark D
MD
Minden
Suzanne
S
Kamel-Reid
Joseph M
JM
Brandwein
D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D005500:Follow-Up Studies; D020440:Gene Duplication; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D020080:Tandem Repeat Sequences / Q000235:genetics*; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3