Abstract
Background: Central nervous system (CNS) relapse can complicate the course of patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) and chemotherapy, especially of those with high WBC at diagnosis (≥10 × 109/L). While ATRA and anthracyclines do not crosses the cerebrospinal fluid barrier, some trials for APL includes the use of intratechal prophylaxis or high-dose cytarabine, at least in high-risk patients, to avoid the CNS relapses. However, the convenience of CNS prophylaxis in APL patients is a matter of controversy.Objectives: Analyze the incidence and characteristics of CNS involvement at first relapse, in patients with newly diagnosed APL treated with ATRA and reinforced anthracycline monochemotherapy, without CNS prophylaxis.Methods: From 1999 to 2005, 564 patients (median age 40 years, range 2-83) were included in the PETHEMA LPA99 trial. Induction therapy consisted of ATRA and idarubicin. Patients in CR received 3 monthly courses of risk-adapted consolidation therapy as follows:i.“low-risk” patients (WBC <10×109/l and platelets >40×109/l), idarubicin 5 mg/m2/d × 4 (course #1), mitoxantrone 10 mg/m2/d × 5 (course #2), and idarubicin 12 mg/m2/d × 1 (course #3);ii.“intermediate-risk “ (WBC <10×109/l and platelet <40×109/l) and “high-risk” (WBC >10×109/l) patients received ATRA (45 mg/m2/d × 15) in combination with reinforced chemotherapy (Idarubicin 7 mg/m2/d in the course #1 and two days instead of one in the course #3).Maintenance therapy consisted of low-dose oral chemotherapy (mercaptopurine and methotrexate with ATRA). We measured the cumulative incidence (CI) of CNS involvement at first relapse during the course of APL patients who achieved the CR.Results: CR was achieved in 511 patients (91%). The median follow-up of the cohort was 57 months (range 20–94 months). Overall, 52 patients relapsed, of whom 5 presented a first relapse in CNS. In all cases, CNS relapses occurred without bone marrow or other extramedullary involvement. CNS relapses occurred after a median of 14 months (range 10–41 months) from the achievement of CR. At the initial diagnosis, APL were classified, according to the Sanz score, as low-, intermediate- and high-risk, in 0, 2, and 3 patients, respectively. The median WBC at diagnosis was 34.5 × 109/L (range 1.9–68.8 × 109/L), and 4 patients showed a Bcr3 PML-RARalpha isoform. Using a competitive-risk method, the overall 5 year CI of CNS relapse was 1.03%. The 5 year CI of CNS relapse in low-, intermediate- and high-risk patients was 0%, 0.77% and 2.71%, respectively (low- vs high-risk and intermediate vs high-risk; p=0.12 and p=0.11, respectively). The 5 year CI of CNS relapse in patients with Bcr3 and Bcr1 PML-RARalpha isoform was 0.45% and 2.44%, respectively (p=0.12).Conclusion: Despite the lack of intratechal prophylaxis or high-dose cytarabine in the therapeutic schedule of the LPA99 trial, the overall 5 year CI of CNS relapse was very low (1%). Our results does not hold up the systematic use of CNS prophylaxis in APL patients treated with ATRA and reinforced anthracycline monochemotherapy.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have