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Influence of molecular subgroups on outcome of acute myeloid leukemia with normal karyotype in 141 patients undergoing salvage allogeneic stem cell transplantation in primary induction failure or beyond first relapse

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PFEIFFER Tim SCHLEUNING Michael J. MAYER Jiří HAUDE Karl Heinz TISCHER Johanna BUCHHOLZ Stefanie BUNJES Donald W. BUG Gesine HOLLER Ernst MEYER Ralf Georg GREINIX Hildegard T. SCHEID Christof CHRISTOPEIT Maximilian SCHNITTGER Susanne BRAESS Jan SCHLIMOK Günter SPIEKERMANN Karsten GANSER Arnold KOLB Hans Jochem SCHMID Çhristof C.

Rok publikování 2013
Druh Článek v odborném periodiku
Časopis / Zdroj Haematologica/the hematology journal
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
Doi http://dx.doi.org/10.3324/haematol.2012.070235
Obor Onkologie a hematologie
Klíčová slova acute granulocytic leukemia; adult; aged; allogeneic stem cell transplantation;
Popis Based on molecular aberrations, in particular the NPM1 mutation (NPM1mut) and the FLT3 internal tandem duplication (Flt3-ITD), prognostic subgroups have been defined among patients with acute myeloid leukemia with normal karyotype. Whereas these subgroups are known to play an important role in outcome in first complete remission, and also in the indication for allogeneic stem cell transplantation, data are limited on their role after transplantation in advanced disease. To evaluate the role of molecular subgroups of acute myeloid leukemia with normal karyotype after allogeneic stem cell transplantation beyond first complete remission, we analyzed the data from 141 consecutive adults (median age: 51.0 years, range 18.4-69.3 years) who had received an allogeneic transplant either in primary induction failure or beyond first complete remission. A sequential regimen of cytoreductive chemotherapy (fludarabine, high-dose AraC, amsacrine) followed by reduced intensity conditioning (FLAMSA-RIC), was uniformly used for conditioning. After a median follow up of three years, overall survival from transplantation was 64+/-4%, 53+/-4% and 44+/-5% at one, two and four years, respectively. Forty patients transplanted in primary induction failure achieved an encouraging 2-year survival of 69%. Among 101 patients transplanted beyond first complete remission, 2-year survival was 81% among patients with the NPM1mut/FLT3wt genotype in contrast to 43% in other genotypes. Higher numbers of transfused CD34+ cells (hazard ratio 2.155, 95% confidence interval 0.263-0.964, P=0.039) and favorable genotype (hazard ratio 0.142, 95% confidence interval: 0.19-0.898, P=0.048) were associated with superior overall survival in multivariate analysis. In conclusion, patients with acute myeloid leukemia with normal karyotype can frequently be rescued after primary induction failure by allogeneic transplantation following FLAMSA-RIC. The prognostic role of NPM1mut/FLT3-ITD based subgroups was carried through after allogeneic stem cell transplantation beyond first complete remission.

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