Central nervous system relapse in acute promyelocytic leukemia: Two cases and a systematic review

Abstract Central nervous system (CNS) relapse in patients with acute promyelocytic leukemia (APL) is an uncommon event but increasingly reported in the all- trans -retinoic acid (ATRA) era. No standard of care for treating these patients currently exists. We describe 2 cases and review previous reports. Review of the medical literature revealed 61 additional patients, ranging in age from 3.5 to 73 years (median, 39 years). Leukocyte count at initial diagnosis ranged from 1.3 to 307 × 10 9 /L (median, 25.6 × 10 9 /L). Nearly all received ATRA first-line. Only 36% of the relapses were isolated to the CNS, and 86% of patients suffered from neurologic symptoms. Patients were treated with intrathecal chemotherapy alone, radiation alone, or both. In total, 75% of patients treated achieved CNS remission. The success rate of achieving CNS remission by combining radiation and intrathecal chemotherapy was 100%, superior to either modality alone (50% and 75%, respectively). All patients treated with craniospinal radiation were alive and free of disease at 1 year. Patients with APL should be fully evaluated at onset of new neurologic symptoms. Patients with APL with CNS relapse warrant systemic workup because most will not have isolated disease.