FLT3 mutations in normal karyotype acute myeloid leukemia in first complete remission treated with autologous peripheral blood stem cell transplantation

Abstract

Summary:We retrospectively analysed the significance of FLT3 mutations in patients with acute myeloid leukemia (AML) having a normal karyotype, who were treated with highdose chemotherapy and autologous peripheral blood stem cell transplantation (auto-PBSCT). In all, 34 patients with normal karyotype AML in first complete remission receiving high-dose chemotherapy and auto-PBSCT were analysed based on the presence or absence of FLT3/ITDs and FLT3/D835. They were 16 males and 18 females and with a median age of 41.5 years. FLT3/ITDs were detected in eight of 34 patients (23.5 %), and FLT3 D835 mutations in two of 34 patients (5.9%). White blood cell count (P ¼ 0.0087), serum concentration of lactate dehydrogenase (P ¼ 0.005), and percentages of peripheral blood (P ¼ 0.0131) and bone marrow (BM) blasts (P ¼ 0.0312) were significantly higher in patients showing the FLT3 mutations. Overall survival (OS) and diseasefree survival (DFS) were similar between patients with or without FLT3 mutations (5 year DFS, 67.5 vs 68.55%, P ¼ 0.819; 5 year OS, 64.81 vs 78.88%, P ¼ 0.4457, by the log-rank test). FLT3 mutations demonstrate no further prognostic impact in patients with normal karyotype AML in first CR treated with high-dose chemotherapy and auto-PBSCT. Myeloablative chemotherapy supported by auto-PBSCT may overcome any poor prognostic implications of FLT3 mutations. Bone Marrow Transplantation (2005) 36, 977-983.

Clinical outcome of de novo acute myeloid leukaemia patients with normal cytogenetics is affected by molecular genetic alterations: a concise review

“…The authors concluded that there was no strong evidence to consider the presence of FLT3-ITD as a factor influencing the decision whether or not an SCT should be performed (Gale et al, 2005a). In contrast, in analyses restricted to CN-AML, the adverse prognostic effect of FLT3-ITD was overcome by allogeneic SCT , and autologous peripheral blood SCT in first CR (Yoshimoto et al, 2005;Palmieri et al, 2006). Whether allogeneic SCT may eventually improve outcome in FLT3-ITD positive AML patients remains to be determined in large prospective studies.…”

Southwestern Oncology Group pretreatment risk criteria as predictive or prognostic factors in acute myeloid leukemia

“…Data on molecular findings were not available for this study. NPM1 and FLT3 gene mutations are now relevant for prognosis assessment (28)(29)(30)(31)(32). However, when the patients of this cohort were diagnosed, this molecular analysis was not widely available.…”

Quantitation of hematogones at the time of engraftment is a useful prognostic indicator in allogeneic hematopoietic stem cell transplantation

“…To analyze clonality of IGH gene rearrangements status of hematogones, DNA was obtained from 10 000 double-sorted cells 22,23,29 from all recipients presenting Ͼ 0.1% MNCs of hematogones on FACS. Then PCR amplification of DJ H and VDJ H gene rearrangement was performed as described previously.…”