Patients with relapsed acute lymphoblastic leukemia (ALL) have an extremely poor prognosis. Patients with acute lymphoblastic leukemia (ALL) who experience a relapse following chemotherapy and maintenance therapy are unlikely to be cured by further chemotherapy alone. These patients should be considered for reinduction chemotherapy followed by allogeneic bone marrow transplantation. Reinduction regimens include the hyper-CVAD protocol and high-dose Ara-C–based regimens. There is no preferred protocol at this time as investigtion has not yet identified a superior regimen.
Relatively few studies have compared transplantation with chemotherapy in adults with acute lymphoblastic leukemia (ALL) and results are contradictory. It is generally accepted now that with the decrease in transplant mortality stem cell transplantation, especially allogeneic transpalntation is indicated in relapsed ALL.
Patients with Ph1-positive ALL, meaning those preceded by CML, will often be taking imatinib at the time of relapse and thus will have imatinib-resistant disease. Dasatinib, a novel tyrosine kinase inhibitor with efficacy against several different imatinib-resistant BCR/ABL mutants, has been approved for use in Ph1-positive ALL patients who are resistant to or intolerant of imatinib. The approval was based on a series of trials involving patients with chronic myelogenous leuekmia, one of which included small numbers of patients with lymphoid blast crisis or Ph1-positive ALL. In one study, 10 such patients were treated with dasatinib in a dose escalation study. Seven of these patients had a complete hematologic response (<5% marrow blasts with normal peripheral blood counts), three of whom had a complete cytogenetic response. The common toxicities were reversible myelosuppression (89%) and pleural effusions (21%). Virtually all of these patients relapsed within 6 months of the start of treatment with dasatinib. It si thus evident that transpalntation remains appropriate even for these patients.
Pui CH, Evans WE.Treatment of acute lymphoblastic leukemia. Engl J Med. 2006 Jan 12;354(2):166-78.
Samuel ED, Sakamoto KM.. Topics in pediatric leukemia–acute lymphoblastic leukemia.MedGenMed. 2005 Mar 7;7(1):23
Pui, Ching-Hon, Evans, William E.
Treatment of Acute Lymphoblastic Leukemia
N Engl J Med 2006 354: 166-178