Risk-stratified Therapy for Primary and Secondary AML and MDS. A Randomized Study by AMLCG in Relation to Cytogenetically Defined Prognostic Factors (1) on the Role of High-dose AraC as Part of Double Induction, (2) on G-CSF Priming, and (3) on High-dose Chemotherapy With Stem Cell Transplantation

The present study by the German AML Cooperative Group has been designed in order to investigate the effects of AML typical therapeutic strategies for AML and related diseases. Thus, the entry criteria are age starting from 16 years with no upper age limit, de novo AML or AML secondary to chemotherapy or radiotherapy of another disease or myelodysplasia subtype RAEB with bone marrow blasts greater than 10 %. All randomization is stratified according to karyotype favorable / intermediate / unfavorable. Additional stratification is according to LDH </>= 700 U and age </>= 60 Y. Standard treatment is (A) double induction with TAD and HAM, consolidation with TAD and maintenance treatment with monthly AD-AT-AC-AT -, rotatingly. Experimental modifications to be compared with stan-dard treatment are (B) double induction with HAM-HAM, (C) multiple course G-CSF before and during chemotherapy courses and (D) instead of maintenance treatment myeloablative consolidation with Bu/Cy and autologous blood stem cell transplantation. Intent to treat conditions are guaranteed by randomization before induction treatment starts. In order to evaluate the effect of every single modification randomization to (C) is equally distributed to the patients in treatment arms (A) and (B) which is also true for the randomization to (D) (balanced randomization). Similarly balanced between treatment arms are the patients according to diagnosis, age and risk factors like serum LDH and karyotype. In order to adapt treatment intensity to age patients of 60 years and older receive the second induction course only in case of 5 % or more residual bone marrow blasts. In addition, the AraC dose in HAM is reduced to 1 instead of 3 g/sqm in this age group. Furthermore, there is no treatment arm including stem cell transplantation in patients of 60+ years. Pri-mary endpoint to compare the therapeutic strategies is event-free survival from treatment start (A, B, C) and from achievement of remission (D), respectively.

By this design the AMLCG 2000 trial can contribute relevant experiences on optimum therapeutic strategies for the biological subgroups of de novo AML, secondary AML and MDS. Furthermore, new biological subgroups and their significance related to treatment strategies can be defined.