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 AML 10 and 12 trials
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Gale, RE
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机构:UCL Royal Free & Univ Coll Med Sch, Dept Haematol, London WC1E 6HX, England
Gale, RE
Hills, R
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机构:UCL Royal Free & Univ Coll Med Sch, Dept Haematol, London WC1E 6HX, England
Hills, R
Kottaridis, PD
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机构:UCL Royal Free & Univ Coll Med Sch, Dept Haematol, London WC1E 6HX, England
Kottaridis, PD
Srirangan, S
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机构:UCL Royal Free & Univ Coll Med Sch, Dept Haematol, London WC1E 6HX, England
Srirangan, S
Wheatley, K
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机构:UCL Royal Free & Univ Coll Med Sch, Dept Haematol, London WC1E 6HX, England
Wheatley, K
Burnett, AK
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机构:UCL Royal Free & Univ Coll Med Sch, Dept Haematol, London WC1E 6HX, England
Burnett, AK
Linch, DC
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机构:UCL Royal Free & Univ Coll Med Sch, Dept Haematol, London WC1E 6HX, England
Linch, DC
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[1] UCL Royal Free & Univ Coll Med Sch, Dept Haematol, London WC1E 6HX, England
[2] Univ Birmingham, Clin Trials Unit, Birmingham, W Midlands, England
Fetal liver tyrosine kinase 3 (FLT3) internal tandem duplications (ITDs) are powerful adverse prognostic indicators for relapse in acute myelold 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.