Prolonged Monthly Myelosuppressive Maintenance Chemotherapy in Acute Myeloid Leukemia: The AMLCG Experience.

Abstract

We have previously shown that a monthly myelosuppressive chemotherapy proved superior to high-dose cytarabine consolidation therapy (J Clin Oncol 2003, 21:4496) after induction therapy and induction-type consolidation therapy. In the multicenter AMLCG 1999 trial, we reported that this maintenance therapy resulted in equal results with lower therapy-related morbidity and death-rate compared to autologous stem cell transplantation in patients <60 years of age. However, data about the feasibility and compliance of this prolonged maintenance therapy are still lacking. In the AMLCG 1999 trial, patients <60 years of age were randomized upfront to receive either an autologous stem cell transplantation or a maintenance therapy for three years from achievement of complete remission after consolidation therapy TAD. Patients ≥60 years of age were assigned to maintenance therapy following consolidation therapy. Maintenance courses were araC 100mg/m2 q 12 hr sc × 10 and either daunorubicin 45mg/m2 × 2 (AD), or thioguanine 100mg/m2 q 12hr × 10 (AT), or cyclophosphamide 1g/m2 iv (AC), and again AT-AD-AT-AC-. In patients with a leukopenia <1.000/μl or thrombocytopenia <20.000/μl after two following cycles, dosage was permanently reduced by 50%. Of all patients who achieved a CR before July 1st 2004, 269 patients <60 years were randomized to receive maintenance, and all 423 patients ≥60 years were assigned to maintenance. Out of the 692 patients, 211 patients (30.5%) did not receive maintenance therapy due to: allogeneic (49, 7.1%) or autologous (6, 0.9%) stem cell transplantation, early relapse (52, 7.5%), withdrawal of consent (17, 2.5%), medical reasons other than relapse (53, 7.7%), other reasons not classified (7, 1.0%) or death in CR (27, 3.9%). In 78 patients (11.3%) the application of maintenance therapy cannot be followed due to loss of follow-up or incomplete documentation. For the remaining 403 (58.2%) patients with a documented start of the maintenance therapy, the median number of maintenance courses applied was 6 (1st to 3rd quartile: 2–16) over a median duration from achievement of CR of 10 months (1st to 3rd quartile: 5–24). Due to fixed dose adjustment rules, the median dosage of the applied chemotherapy declined from 90.5% (range 8.2–183.3%) in the first course to 47.1% (range 6.6–128.6%) in the third course. From the fifth course on, the median dosage was between 22.2 and 26.3%. Out of the 403 patients who started maintenance, therapy was terminated early in 346 patients (85.9%) due to: an allogeneic stem cell transplantation in 1st CR (3 patients, 0.7%); relapse (175, 43.4%); withdrawal of consent (17, 4.2%); medical reasons other than relapse (72, 17.9%); other reasons not classified (13, 3.2%), loss of follow-up or incomplete documentation (56, 13.9%); and death in CR (10, 2.5%). Of the latter, 5 patients (1.2%) succumbed to therapy-related death. Of the 129 patients experiencing a relapse free survival of ≥ three years, the median number of applied courses was 20 (1st to 3rd quartile: 4–29) over a median duration of 31 months after achieving CR (1st to 3rd quartile: 11–36). Taken together, this results show that a prolonged monthly myelosuppressive maintenance therapy as part of a postremission therapy in AML is feasible and shows a high compliance and acceptance among patients.