Prospective Multicenter Study for Patients with Therapy - Related Acute Myeloid Leukemia (AML) Using Intensive Induction and Postremission Therapy.

Therapy - related acute myeloid leukemia (t-AML) is one of the most severe long - term complications of successful cancer treatment using chemo- and/or radiotherapy. Its frequency is increasing, also in patients with autoimmune disease after cytostatic therapy. Cytogenetic and molecular biological analysis have identified several subgroups, however large prospective trials on optimal treatment are lacking. In 1999 the German AMLCG started a prospective multicenter randomized trial including patients with t-AML. Patients received induction treatment, randomized to either TAD (standard dose thioguanine, araC, daunorubicin) followed by HAM (HAM, high-dose araC 1 or 3 g/m²x6/mitoxantrone 10mg/m²x3), or to induction by two courses of HAM. Above the age of 60 years, the second induction course was given only to patients with 5 % or more residual bone marrow blasts. Postremission therapy was randomized to either TAD followed by three year maintenance, or to autologous stem cell transplantation. Patients under the age of 60 years with a suitable donor received an allogeneic stem cell transplantation. 137 patients were included. The most frequent primary diagnoses were breast cancer (n = 43), Non Hodgkin’s lymphoma (n = 18), Hodgkin’s lymphoma (n = 9), autoimmune disease (n = 9), multiple myeloma (n = 5), germ cell tumor (n = 5) and ovarian cancer (n = 5). The median age was 57 years (23 – 77). 64 of 119 currently evaluable patients achieved CR (53,8 %), 34 (29 %) had persistent leukaemia, 20 (17,1 %) were classified as early death without evidence of disease. The CR rate was significantly lower than in 1532 patients with de novo AML (65,6 %), but higher than in patients with AML after MDS (46,8 %). Cytogenetic analysis was routinely performed in all patients with t-AML. 21 (17,7 %) had a favourable karyotype, 47 (39,5 %) an unfavourable karyotype, 51 (42,9 %) were classified as intermediate. Patients with favourable karyotype had a median survival of 25 months and an estimated survival rate at 5 yrs of 47,4 %. Median survival was 3 months for patients with unfavourable karyotype with an estimated survival rate of 12,5 %, while the intermediate group had a median survival of 19 months and an estimated survival rate of 24,2 %. This is one of the largest prospective studies on the therapy of patients with t-AML. The CR rate of all patients was inferior to patients with de novo AML. However, this difference was mainly due to the high number of patients with unfavourable karyotype. Within cytogenetically defined subgroups, the prognosis of t-AML patients does not differ significantly from patients with de novo AML.