Informace o publikaci

Allogeneic stem cell transplantation improves survival in patients with AML characterized by a high allelic ratio of mutant FLT3-ITD

Autoři	HO A. D. SCHETELIG J. BOCHTLER T. SCHAICH M. SCHÄFER-ECKART K. HÄNEL M. RÖSLER W. EINSELE H. KAUFMANN M. SERVE H. BERDEL W. E. STELLJES M. MAYER Jiří REICHLE A. BALDUS C. D. SCHMITZ N. KRAMER M. RÖLLIG C. BORNHÄUSER M. THIEDE C. EHNINGER G.
Rok publikování	2016
Druh	Článek v odborném periodiku
Časopis / Zdroj	Biology of Blood and Marrow Transplantation
Fakulta / Pracoviště MU	Lékařská fakulta
Citace
Doi	http://dx.doi.org/10.1016/j.bbmt.2015.10.023
Obor	Onkologie a hematologie
Klíčová slova	allogeneic transplantation; acute myeloid leukemia; FLT3-ITD; NPM1-mutation
Přiložené soubory	EL_1316948.pdf
Popis	Allogeneic transplantation (alloHCT) as post-remission therapy in patients with FLT3-ITD-positive intermediate-risk acute myeloid leukemia (AML) remains controversial. FLT3-ITD mutations are heterogeneous with respect to allelic ratio, location and length of the insertion, with a high mutant-to-wildtype ratio being consistently associated with inferior prognosis. We retrospectively analyzed the role of alloHCT in first remission in relationship to the allelic ratio and presence or absence of nucleophosmin 1 mutations (NPM1) in the SAL-AML2003 trial. FLT3-ITD mutations were detected in 209 patients and concomitant NPM1-mutations in 148 patients. Applying a pre-defined cutoff ratio of 0.8, AML was grouped into high- and low-ratio FLT3-ITD AML (HRFLT3-ITD and LRFLT3-ITD). Sixty-one patients (29%) were transplanted in first remission. Overall survival (OS) (HR 0.3, 95%CI 0.16 to 0.7, p=.004) and event-free survival (EFS) (HR 0.4, 95%CI 0.16 to 0.9, p=.02) were significantly increased in patients with HRFLT3-ITD AML who received alloHCT as consolidation treatment compared to patients who received consolidation chemotherapy. Patients with LRFLT3-ITD AML and wildtype NPM1 who received alloHCT in first remission had increased OS (HR 0.3; 95%CI 0.1 - 0.8, p=.02) and EFS (HR 0.2; 95%CI 0.1 - 0.8, p=.02) while alloHCT in first remission did not have a significant impact on OS and EFS in patients with LRFLT3-ITD AML and concomitant NPM1-mutation. In conclusion, our results provide additional evidence that alloHCT in first remission improves EFS and OS in patients with HRFLT3-ITD AML and in patients with LRFLT3-ITD AML and wildtype NPM.