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
Tim Pfeiffer,
Michael Schleuning,
Jiri Mayer,
Karl-Heinz Haude,
Johanna Tischer,
Stefanie Buchholz,
Donald Bunjes,
Gesine Bug,
Ernst Holler,
Ralf G. Meyer,
Hildegard Greinix,
Christof Scheid,
Maximilian Christopeit,
Susanne Schnittger,
Jan Braess,
Günter Schlimok,
Karsten Spiekermann,
Arnold Ganser,
Hans-Jochem Kolb,
Christoph Schmid
Affiliations
Tim Pfeiffer
Department of Hematology and Oncology, Klinikum Augsburg, Germany
Michael Schleuning
Deutsche Klinik für Diagnostik, Wiesbaden, Germany
Jiri Mayer
Department of Hematology and Oncology, Masaryk University Hospital, Brno, Czech Republic
Karl-Heinz Haude
Department of Anesthesiology, Critical Care Medicine and Medical Statistics, Klinikum Augsburg, Germany
Johanna Tischer
Department of Hematology and Oncology, Ludwig-Maximilians-University Hospital, Munich, Germany
Stefanie Buchholz
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
Donald Bunjes
Department of Hematology and Oncology, University Hospital, Ulm, Germany
Gesine Bug
Department of Medicine II, Hematology/Oncology, Goethe University Hospital, Frankfurt a. M., Germany
Ernst Holler
Dept. of Hematology and Oncology, University Hospital, Regensburg, Germany
Ralf G. Meyer
University Medical Center, Department of Hematology, Oncology and Pneumology, Mainz, Germany
Hildegard Greinix
Department of Hematology and Oncology, BMT Unit, Medical University of Vienna, Austria
Christof Scheid
Department of Hematology and Oncology, University Hospital, Cologne, Germany
Maximilian Christopeit
State Center of Gene and Cell Therapy, Martin-Luther-University Halle/Wittenberg, Halle, Germany
Susanne Schnittger
MLL Munich Leukemia Laboratory, Munich, Germany
Jan Braess
Department of Hematology and Oncology, Krankenhaus der Barmherzigen Brüder, Regensburg, Germany
Günter Schlimok
Department of Hematology and Oncology, Klinikum Augsburg, Germany
Karsten Spiekermann
Department of Hematology and Oncology, Ludwig-Maximilians-University Hospital, Munich, Germany
Arnold Ganser
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
Hans-Jochem Kolb
Department of Medicine, Hematology/Oncology, Technische Universität München, Munich, Germany
Christoph Schmid
Department of Hematology and Oncology, Klinikum Augsburg, Germany
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.
