Risk-Adapted Therapy of Acute Myeloid Leukemia of Adults (18-60 Years) According to the Cytogenetic Result

Summary

The concept of the investigators risk-adapted multicenter treatment trial for younger adults, AML HD98A, is based on the results of the AML HD93 trial and on published data. Definition of risk groups is different compared to the AML HD93 trial; high-risk: refractory disease after first induction therapy and/or high risk karyotype \[abn(3q), -5/5q-, -7/7q-, abn(12p), abn(17p), complex\]; intermediate-risk: complete remission after induction therapy and intermediate risk karyotype \[normal, abn(11q23), abn(16q22), other rare aberrations\]; low-risk: complete remission after induction therapy and low risk karyotype \[t(8;21)\]. Patients exhibiting a t(15;17) were treated in a separated trial (APL HD95). Treatment consists of a first induction therapy with ICE followed by a second cycle ICE in case of response to first induction therapy. Patients with refractory disease after first induction therapy are assigned to a salvage therapy with A-HAM (all-trans retinoic acid, high-dose cytarabine and mitoxantrone) and the search for potential hematopoietic stem cell donors is extended from the family to unrelated persons. All patients achieving a CR after induction therapy with ICE are assigned to a first consolidation therapy with HAM. For intermediate-risk patients a peripheral stem cell or a bone marrow harvest are intended during the hematological recovery after the first consolidation. Second consolidation therapy was stratified according to the risk definition. For high risk patients a allogeneic transplantation is assigned from a related or unrelated donor preferentially after a dose-intensified conditioning therapy. All patients with intermediate risk and an HLA-matched family donor are assigned to allogeneic transplantation. Intermediate-risk patients without a family donor and normal karyotype at diagnosis are randomized between an autologous stem cell transplantation and a second course of HAM. The other intermediate-risk patients are assigned to autologous transplantation. For low-risk patients a second course of HAM is assigned.

Timeline

Start

1998-05

Primary completion

2005-05

Completion

2005-05

Publications

• Prochazka KT, Pregartner G, Rucker FG, Heitzer E, Pabst G, Wolfler A, Zebisch A, Berghold A, Dohner K, Sill H. Clinical implications of subclonal TP53 mutations in acute myeloid leukemia. Haematologica. 2019 Mar;104(3):516-523. doi: 10.3324/haematol.2018.205013. Epub 2018 Oct 11.
• Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, Potter NE, Heuser M, Thol F, Bolli N, Gundem G, Van Loo P, Martincorena I, Ganly P, Mudie L, McLaren S, O'Meara S, Raine K, Jones DR, Teague JW, Butler AP, Greaves MF, Ganser A, Dohner K, Schlenk RF, Dohner H, Campbell PJ. Genomic Classification and Prognosis in Acute Myeloid Leukemia. N Engl J Med. 2016 Jun 9;374(23):2209-2221. doi: 10.1056/NEJMoa1516192.
• Buchner T, Schlenk RF, Schaich M, Dohner K, Krahl R, Krauter J, Heil G, Krug U, Sauerland MC, Heinecke A, Spath D, Kramer M, Scholl S, Berdel WE, Hiddemann W, Hoelzer D, Hehlmann R, Hasford J, Hoffmann VS, Dohner H, Ehninger G, Ganser A, Niederwieser DW, Pfirrmann M. Acute Myeloid Leukemia (AML): different treatment strategies versus a common standard arm--combined prospective analysis by the German AML Intergroup. J Clin Oncol. 2012 Oct 10;30(29):3604-10. doi: 10.1200/JCO.2012.42.2907. Epub 2012 Sep 10.
• Gaidzik VI, Bullinger L, Schlenk RF, Zimmermann AS, Rock J, Paschka P, Corbacioglu A, Krauter J, Schlegelberger B, Ganser A, Spath D, Kundgen A, Schmidt-Wolf IG, Gotze K, Nachbaur D, Pfreundschuh M, Horst HA, Dohner H, Dohner K. RUNX1 mutations in acute myeloid leukemia: results from a comprehensive genetic and clinical analysis from the AML study group. J Clin Oncol. 2011 Apr 1;29(10):1364-72. doi: 10.1200/JCO.2010.30.7926. Epub 2011 Feb 22.
• Schlenk RF, Dohner K, Mack S, Stoppel M, Kiraly F, Gotze K, Hartmann F, Horst HA, Koller E, Petzer A, Grimminger W, Kobbe G, Glasmacher A, Salwender H, Kirchen H, Haase D, Kremers S, Matzdorff A, Benner A, Dohner H. Prospective evaluation of allogeneic hematopoietic stem-cell transplantation from matched related and matched unrelated donors in younger adults with high-risk acute myeloid leukemia: German-Austrian trial AMLHD98A. J Clin Oncol. 2010 Oct 20;28(30):4642-8. doi: 10.1200/JCO.2010.28.6856. Epub 2010 Aug 30.
• Kayser S, Schlenk RF, Londono MC, Breitenbuecher F, Wittke K, Du J, Groner S, Spath D, Krauter J, Ganser A, Dohner H, Fischer T, Dohner K; German-Austrian AML Study Group (AMLSG). Insertion of FLT3 internal tandem duplication in the tyrosine kinase domain-1 is associated with resistance to chemotherapy and inferior outcome. Blood. 2009 Sep 17;114(12):2386-92. doi: 10.1182/blood-2009-03-209999. Epub 2009 Jul 14.

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Indications