We started a prospective randomized multicenter trial to examine the importance of the infusion schedule of Ara-C as part of the Mito-FLAG regimen in patients (pts) with relapsed or primary refractory acute myeloid leukemia (AML). The treatment consisted of mitoxantrone (7 mg/m2, days 1/3/5), fludarabine (15 mg/m2, q-12h, days 1–5), Ara-C as bolus (B) (1000 mg/m2 over 1 h, q-12h, days 1–5) or continuous infusion (CI) (125 mg/m2 over 24 h, days 1–5) and G-CSF (5 μg/kg/day, day 0 until a neutrophile count of 0.5 × 109/μl). Since 11/1999, 253 pts from 36 centers in Germany entered the study (131 men, 122 women, aged 19–75 years, median 59 years). 131 pts (52%) showed a primary refractory AML or had relapsed within 6 months after 1st complete remission (CR), whereas 120 pts had suffered their 1st relapse after 6–18 months (79 pts/31%) or later (41 pts/16%). Only 2 pts with a 2nd relapse were enrolled. The diagnoses according to FAB criteria were as follows: M0 - 17 pts, M1 - 55 pts, M2 - 71 pts, M3 - 2 pts, M4 - 44 pts, M5 - 27 pts, M6 - 9 pts, M7 - 2 pts, 26 pts were not classified. 62 pts (25%) had a poor risk karyotype (defined as aberrations on the chromosomes 5, 7, 8 or multiple). In 50 pts (20%) an elevated leukocyte count (> 20 × 109/μl) was observed. 22 pts (9%) had relapsed after prior hematopoietic stem cell transplantation (HSCT). Currently 249 pts are evaluable for response and 231 pts for toxicity and survival. Following Mito-FLAG, 120 pts (48%) achieved CR and 43 pts (17%) partial remission (PR), for an overall response rate of 65%. 206 pts experienced at least one episode of febrile neutropenia with a median duration of 8 (1–53) days. 19 pts (8%) suffered an early death because of toxicity (n=11) or progressive AML (n=8). Out of 163 responders, 8 pts were consolidated by high-dose therapy with autologous HSCT and 48 pts underwent allogeneic HSCT after dose-reduced conditioning. With a median follow-up of 40.2 months (0–93), the probabilities of event-free survival (EFS) and overall survival (OS) after 3 years were 13% and 19%, respectively. In responding pts the median duration of EFS and OS were 8.4 and 10 months, the 3-year-rates of EFS and OS were 28% and 33%, respectively. In conclusion, Mito-FLAG is an effective and well tolerated regimen in the salvage therapy of pts with AML.

Disclosures: Off Label Use: The use of fludarabine is off-label for the treatment of AML..

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