No evidence that FLT3 status should be considered as an indicator for transplantation in acute myeloid leukemia (AML): an analysis of 1135 patients, excluding acute promyelocytic leukemia, from the UK MRC AML10 and 12 trials.
Fetal liver tyrosine kinase 3 (FLT3) internal tandem duplications (ITDs) are powerful adverse prognostic indicators for relapse in acute myeloid leukemia (AML) but the most efficacious therapy for FLT3/ITD(+) patients is currently unknown. We evaluated outcome according to FLT3/ITD status in 1135 adult patients treated according to United Kingdom Medical Research Council (UK MRC) AML protocols: 141 received an autograft, and 170 received a matched sibling allograft in first complete remission (CR). An FLT3/ITD was detected in 25% of patients and was an independent predictor for relapse (P < .001). It remained prognostic for increased relapse in patients who received a transplant (odds ratio [OR] = 1.91; 95% confidence intervals [CIs] = 1.13-3.21; P = .02), with no evidence of a difference in effect between patients who received an autograft (OR = 2.39; CIs = 1.24-4.62) and patients who received an allograft (OR = 1.31; CIs = 0.56-3.06) (test for interaction, P = .3) or between patients who did or did not receive a transplant (P = .4). These results were confirmed in an analysis of 186 patients randomized to receive or not receive an autograft in first CR and in a donor-versus-no donor analysis of 683 patients to assess the role of allograft (for latter, FLT3/ITD(-) OR = 0.70, CIs = 0.53-0.92; FLT3/ITD(+) OR = 0.59, CIs = 0.40-0.87; test for interaction, P = .5). These results suggest that at present there is no strong evidence that FLT3 status should influence the decision to proceed to transplantation.
Gale
Rosemary E
RE
Department of Haematology, Royal Free and University College Medical School, London, UK. rosemary.gale@ucl.ac.uk
Hills
Robert
R
Kottaridis
Panagiotis D
PD
Srirangan
Sivatharsini
S
Wheatley
Keith
K
Burnett
Alan K
AK
Linch
David C
DC
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D020440:Gene Duplication; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D033581:Stem Cell Transplantation / Q000379:methods; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D006113:United Kingdom; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3