Fludarabine, cytarabine, and mitoxantrone (FLAM) for the treatment of relapsed and refractory acute lymphoblastic leukemia in adults. A phase II study by the Polish Adult Leukemia Group (PALG)

Abstract

6723 Background: Outcome of adult ALL patients who fail to achieve CR or who relapse soon after initial response is poor. The goal of this phase II study by the Polish Adult Leukemia Group (PALG) was to evaluate safety and efficacy of a new FLAM regimen in this group of patients. Methods: The treatment consisted of fludarabine 2x30 mg/m2 iv on d. 1, 2, 8, 9 + AraC 8x100 mg/m2 iv on d. 1, 2, 8, 9 + mitoxantrone 10 mg/m2 on d. 3, 10. Thirty-five pts were included with primary (n=10) or secondary (n=2) refractoriness, early (before 6 months) 1st relapse (n=11), 1st relapse after HSCT regardless CR duration (n=8), 2nd or subsequent relapse (n=3), and 2nd lymphoblast crisis in course of CML (n=1). Median age was 32 (19–60) y, gender: m/f –49%/51%. 43% of pts were bcr/abl –positive. Results: 51% of patients responded to FLAM, including CR –17/34 (primary resistance 6/10, resistant relapse 1/2, untreated relapse 10/21) and return to chronic phase after CML blast crisis –1/1. Among those who failed to respond, 6 pts died in aplasia (bacterial sepsis –4, cerebral bleeding –1, cardiotoxicity –1) and 11 pts had leukemia regrowth after the transient cytopenia. Five out of 6 patients who died of severe adverse events were over >45 years old. All patients but one experienced grade IV neutropenia and thrombocytopenia. Median time to ANC >0.5 G/L and PLT >50 G/L recovery was 26 (0–36) d. and 29 (13–43) d., respectively. Non-hematological grade III-IV toxicity was as follows: infections –62%, vomiting –18%, bleeding –6%, cardiotoxicity –6%, hepatotoxicity –3%, and constipation –3%. Patients required 5 (0–12) RBC and 5 (0–16) PLT transfusions. 69% of pts received G-CSF for 11 (3–25) d. Median duration of iv. antibiotics was 27 (8–41) d. Patients stayed in hospital for a median of 32 (12–46) d. Conclusions: Our results indicate that FLAM regimen has a potent anti-leukemic activity and let achieve CR in approximately half of poor-prognosis resistant and relapsed adult ALL. Because of prolonged cytopenia, this therapy should be considered with caution for patients aged >45 years. No significant financial relationships to disclose.