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Büchner (Abstract)

Cellular Therapy and Transplantation (CTT), Vol. 2, No. 5, 2009
doi: 10.3205/ctt-2009-en-000048.03
© The Authors. This abstract is provided under the following license:
Creative Commons Attribution 3.0 Unported


Memorial lecture at the "Joint EBMT Pediatric Working Party – 3rd Raisa Gorbacheva Memorial Meeting on Hematopoietic Stem Cell Transplantation", Saint Petersburg, Russia, September 17–20, 2009


Raisa Gorbacheva Memorial Lecture

Treatment of acute myeloid leukemia: Present status and new directions III

Thomas Büchner

Professor of Medicine and Hematology, University of Münster, Germany

Correspondence: Thomas Büchner MD PhD, Professor of Medicine and Hematology, University of Münster, Germany, E-mail: buechnr@spam is baduni-muenster.de

Abstract

Numerous international multicenter trials on AML treatment have been published since 1981. The extract from these trials shows an increase of the mean complete remission rates between the 1980s and thereafter both in younger and older patients. Patients receiving post-remission consolidation and who were randomized to receive prolonged maintenance chemotherapy showed a significantly longer relapse-free survival than those randomized to no further treatment. A similar randomization between prolonged maintenance and high-dose AraC consolidation groups resulted again in a significantly superior relapse-free survival in the maintenance arm. In the current AMLCG trial, patients were randomized upfront between double induction with standard dose and high-dose (TAD–HAM) chemotherapy versus double high-dose chemotherapy (HAM–HAM). No difference was observed in the overall survival or in the relapse rate of either younger or older patients. G-CSF priming before and together with all chemotherapy, as well as autologous stem cell transplantation versus prolonged maintenance chemotherapy did not improve clinical outcomes.
     
In summary of the multiple international trials, the anti-leukemic potential of existing chemotherapy may not be further improved by intensification. The way forward might be connected genetic classification of the individual AML. Many different mutations and their combinations have been described with marked influences on the outcome, such as the CEBPαgene mutation. The mutations and combinations other than NPM1/FLT3 contribute prognostic factors for only small groups of patients. The vast majority of AML patients can be prognostically classified on the basis of 3 factors: (1) age – younger versus older than 60 years, (2) abnormal karyotypes – favorable versus intermediate versus unfavorable, and (3) normal karyotypes with isolated NPM1 mutation versus FLT3-ITD. As a useful compromise our group prefers to compare allo-SCT patients with chemotherapy cases comparable in major risk factors such as cytogenetics, age, de-novo/secondary AML, type of induction treatment, and follow-up time. Transplant-related mortality may be overcome through the use of reduced intensity conditioning.

In summary, we can conclude that there is good justification for allo-SCT if family donor is available, or even an unrelated donor in the instance of adult high-risk AML. A strictly prospective multicenter trial is necessary to define  the role of allo-SCT in AML. Apart from allo-SCT, novel targeted treatments—like tyrosine kinase inhibitors and Mylotarg—may now be used against AML. The most popular ones are all-trans retinoic acid (ATRA) and arsenic trioxide—which have been successfully applied in APL—while some FLT3 inhibitors like sorafenib and midostaurin are currently being investigated in randomized trials, and agents like decitabine and 5-azacytidine are being used to target the hypermethylation of histones in AML. The novel targeted agents are particularly indicated in older age.

Keywords: acute myeloblastic leukemia, treatment options, efficiency, multicenter trials

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