Prognostic significance of FLT3 mutations in pediatric non-promyelocytic acute myeloid leukemia.
FLT3 is a receptor tyrosine kinase involved in the survival of hematopoietic stem cells, and mutations of FLT3 have been reported to be of prognostic significance. This is the first study of FLT3 mutations in pediatric non-promyelocytic AML patients that received the same treatment scheme in single institute. FLT3 internal tandem duplication of the juxtamembrane domain (FLT3/ITD) and a point mutation in the tyrosine kinase domain (FLT3/TKD) were analyzed in 61 patients by PCR of genomic DNA. The incidence of FLT/ITD and FLT/TKD were 6.6% (4/61) and 3.3% (2/61), respectively. Patients with FLT3/TKD remain alive after autologous stem cell transplantation. The disease-free survival (DFS) of patients with FLT3/ITD (0%) was significantly lower than that of the others (52%). FLT3/ITD was the sole adverse prognostic factor for DFS by multivariate analysis (RR=5.6). Patients with FLT3/ITD relapsed early after complete remission even after receiving bone marrow transplantation from a matched related donor with little BuCy conditioning. New therapeutic scheme such as stem cell transplantation with more intensive conditioning just after complete remission could be applied in pediatric non-promyelocytic AML patients with the FLT3/ITD mutation.
Kang
Hyoung Jin
HJ
Pediatric Oncology Branch, Division of Specific Organs Cancer, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
Hong
Seung-Hee
SH
Kim
In Hoo
IH
Park
Byung-Kiu
BK
Han
Kyou Sup
KS
Cho
Han Ik
HI
Shin
Hee Young
HY
Ahn
Hyo Seop
HS
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D016019:Survival Analysis; D051941:fms-Like Tyrosine Kinase 3
D011518:Proto-Oncogene Proteins; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3