Central nervous system prophylaxis in adults with acute lymphoblastic leukemia: current and emerging therapies.
Central nervous system (CNS) recurrence continues to be a significant complication in the treatment of adult patients with acute lymphoblastic leukemia (ALL). Preventing CNS recurrence has been a therapeutic challenge and has not been addressed critically in many clinical trials. Adult studies modeled on childhood ALL studies have used multiple treatment modalities, including radiation therapy, systemic therapy, intrathecal therapy, and combinations thereof. Cranial irradiation is effective but is offset by substantial toxicity, including neurologic sequelae. Systemic chemotherapy, especially with cytarabine (AraC) and methotrexate, has demonstrated promise in decreasing CNS recurrence, but therapeutic levels of drugs in the cerebrospinal fluid (CSF) are not maintained. Intrathecal chemotherapy with or without high-dose systemic therapy is the most common approach to CNS prophylaxis. Liposomal AraC recently has become available and confers prolonged levels of free AraC in the CSF, a critical requirement for CNS prophylactic therapy. This review discusses the various modalities used for CNS prophylaxis in patients with ALL and the emerging trends, with specific emphasis on the outcome in terms of event-free survival and toxicity.
Jabbour
Elias
E
Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. ejabbour@mdanderson.com
Thomas
Deborah
D
Cortes
Jorge
J
Kantarjian
Hagop M
HM
O'Brien
Susan
S
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D002490:Central Nervous System / Q000473:pathology*; D016371:Cranial Irradiation; D006801:Humans; D007278:Injections, Spinal; D017254:Leukemic Infiltration / Q000517:prevention & control*; D055756:Meningeal Carcinomatosis / Q000517:prevention & control; D008577:Meningeal Neoplasms / Q000517:prevention & control; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D012008:Recurrence