Myeloablative chemotherapy followed by autologous stem cell infusion may overcome the adverse prognostic impact of FLT3 (foetal liver tyrosine kinase 3) mutations in patients with acute myeloid leukaemia and normal karyotype.
In this study, we analysed the prognostic relevance of foetal liver tyrosine kinase 3 (FLT3) mutations in 73 patients with acute myeloid leukaemia (AML) with normal karyotype, who survived induction and consolidation and received autologous stem cell transplantation (ASCT) after successful mobilization of peripheral blood stem cell (PBSC). There were 44 males and 29 females with a median age of 54 years (range 20-77). Overall, 16 out of 73 autografted patients (22%) had FLT3 mutations. More in detail, FLT3/ITDs were detected in 10 out of 73 patients (14%), while FLT3 D835 mutations were detected in five cases (7%). One patient (1%) was found as having both abnormalities. White blood cell count (p=0.009), serum concentration of lactate dehydrogenase (p=0.01), and percentages of peripheral blood (p=0.002) and bone marrow blasts (p=0.03) were significantly higher in patients showing the FLT3 mutations. On the contrary, overall survival and disease-free survival were similar between patients with or without FLT3 mutations (p=0.73 and 0.78, respectively). In conclusion, our data suggest that myeloablative chemotherapy supported by auto-PBSCT may overcome the adverse prognostic implications of FLT3 mutations in AML. However, it is to consider that autografted patients are highly selected for best response to induction, consolidation and mobilization, as well as for minor non-haematologic toxicity.
Palmieri
Salvatore
S
Division of Haematology and Stem cell Transplantation Unit, Cardarelli Hospital, Naples, Italy. salpalmieri@libero.it
Ferrara
Felicetto
F
Leoni
Franco
F
Ciolli
Stefania
S
Pollio
Filiberto
F
D'Amico
Maria Rosaria
MR
Celentano
Maria
M
Viola
Assunta
A
Vicari
Laura
L
Izzo
Barbara
B
Pane
Fabrizio
F
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D011379:Prognosis; D012074:Remission Induction; D016019:Survival Analysis; D020080:Tandem Repeat Sequences; D014182:Transplantation, Autologous; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
D000970:Antineoplastic Agents; D019653:Myeloablative Agonists; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3