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Imatinib mesylate (for patients with Philadelphia chromosome [Ph1]-positive ALL).
Imatinib mesylate combined with combination chemotherapy (for patients with Ph1-positive ALL)
Central nervous system (CNS) prophylaxis therapy, including the following:
Cranial radiation therapy plus intrathecal (IT) methotrexate.
High-dose systemic methotrexate and IT methotrexate without cranial radiation therapy.
IT chemotherapy alone.
Remission induction therapy
Sixty percent to 80% of adults with ALL usually achieve a complete remission (CR) status following appropriate induction therapy. Appropriate initial treatment, usually consisting of a regimen that includes the combination of vincristine, prednisone, and an anthracycline, with or without asparaginase, results in a CR rate of up to 80%. In patients with Ph1-positive ALL, the remission rate is generally greater than 90% when standard induction regimens are combined with Bcr-abl tyrosine kinase inhibitors. In the largest study published to date of Ph1-positive ALL patients, overall survival (OS) for 1,913 adult ALL patients was 39% at 5 years.
Patients who experience a relapse after remission usually die within 1 year, even if a second CR is achieved. If there are appropriate available donors and if the patient is younger than 55 years, bone marrow transplantation may be a consideration in the management of this disease. Transplant centers performing five or fewer transplants annually usually have poorer results than larger centers. If allogeneic transplant is considered, transfusions with blood products from a potential donor should be avoided, if possible. [4,5,6,7,8,9,10]
Most current induction regimens for patients with adult ALL include combination chemotherapy with prednisone, vincristine, and an anthracycline. Some regimens, including those used in a Cancer and Leukemia Group B (CALGB) study (CLB-8811), also add other drugs, such as asparaginase or cyclophosphamide. Current multiagent induction regimens result in complete response rates that range from 60% to 90%.[1,4,5,11,12]
Imatinib mesylate is often incorporated into the therapeutic plan for patients with Ph1-positive ALL. Imatinib mesylate, an orally available inhibitor of the BCR-ABL tyrosine kinase, has been shown to have clinical activity as a single agent in Ph1-positive ALL.[13,14][Level of evidence: 3iiiDiv] More commonly, particularly in younger patients, imatinib is incorporated into combination chemotherapy regimens. There are several published single-arm studies in which CR rate and survival are compared with historical controls.