Subject(s)
Chromosome Breakpoints , Chromosomes, Human, Pair 15/genetics , Chromosomes, Human, Pair 17/genetics , Leukemia, Promyelocytic, Acute/genetics , Neoplasms, Second Primary/genetics , Oncogene Proteins, Fusion/genetics , Translocation, Genetic/genetics , Adult , Aged , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Chromosomes, Human, Pair 15/ultrastructure , Chromosomes, Human, Pair 17/ultrastructure , Female , Humans , Leukemia, Promyelocytic, Acute/etiology , Male , Middle Aged , Mitoxantrone/adverse effects , Mitoxantrone/therapeutic use , Multiple Sclerosis/drug therapy , Neoplasms/drug therapy , Protein Isoforms/genetics , Topoisomerase II Inhibitors/adverse effects , Topoisomerase II Inhibitors/therapeutic useABSTRACT
We report the clinical features and treatment outcome of 33 patients with multiple sclerosis who developed acute promyelocytic leukemia. Thirty patients were previously exposed to mitoxantrone. The median latency period between treatment initiation and acute promyelocytic leukemia diagnosis was 32 months. The PML-RARA bcr1 iso-form was identified in 87% of cases. Twenty-nine (90%) patients achieved hematologic remission after all-trans retinoic acid and chemotherapy (n = 31) or arsenic trioxide and all-trans retinoic acid. Consolidation included modified chemotherapy or arsenic trioxide. At a median follow up of 26 months, 23 patients are in complete remission, 4 relapsed and one developed secondary leukemia. The 5-year cumulative incidence of relapse and overall survival were 23% and 68%, respectively. Although treatment heterogeneity and suboptimal post-remission therapy must be taken into account, overall results and development of secondary leukemia in one patient suggest that effective and less toxic agents like arsenic trioxide warrants further investigation in this context.
