Haematologica
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Published online 27 November 2008
Haematologica, Vol 94, Issue 1, 46-53 doi:10.3324/haematol.13110
Copyright © 2009 by Ferrata Storti Foundation
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Acute Myeloid Leukemia

Correlation of minimal residual disease cell frequency with molecular genotype in patients with acute myeloid leukemia

Corine J. Hess1, Nicole Feller1, Fedor Denkers1, Angèle Kelder1, Pauline A. Merle1, Michael C. Heinrich2, Amy Harlow2, Johannes Berkhof3, Gert J. Ossenkoppele1, Quinten Waisfisz1, Gerrit J. Schuurhuis1

1 Department of Hematology, VU University Medical Center, Amsterdam, the Netherlands
2 Department of Pathology and Medicine, Oregon Health and Science University Cancer Institute and Portland Veterans Affairs Medical Center, Portland, OR, USA
3 Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands

Correspondence: Gerrit J. Schuurhuis, PhD, Department of Hematology, BR248, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. E-mail:gj.schuurhuis{at}vumc.nl

Background: About 70–80 percent of patients with acute myeloid leukemia enter complete remission, but at least half of these patients who achieve remission go on to relapse. Improved treatment is likely to come from increasing the time to relapse, especially for younger patients. With the vastly increasing number of targeted therapies there is a strong need for short-term end-points to efficiently test such therapies for further pursuance. Minimal residual disease assessment may offer such an end-point since it is a strong independent prognostic factor. As proof of principle we examined this concept for FLT3-ITD status at diagnosis.

Design and Methods: We determined FLT3-ITD status in bone marrow samples from 196 patients with newly diagnosed acute myeloid leukemia. The frequencies of residual leukemic cells of these 196 patients were assessed in 267 follow-up bone marrow samples using immunophenotypic assessment of minimal residual disease.

Results: The median frequency of residual leukemic cells after the first cycle of chemotherapy was 8.5-fold higher in patients with FLT3-ITD than in those with wild type FLT3. Such a difference translates into differences in survival, even if other potentially outcome-modulating mutations, such as NPM1, KIT, NRAS, KRAS, FLT3-exon 20 and PTPN11 are included in the analysis.

Conclusions: This study shows that it could be possible to study the efficacy of FLT3 inhibitors using the level of minimal residual disease as a short-term end-point.

Key words: acute myeloid leukemia, minimal residual disease, FLT3.






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