Lay Summary: CLAG and purine analogs for AML are reviewed.
The purine nucleoside analogues (PNA), fludarabine (FA), cladribine (2-chlorodeoxyadenosine, 2-CdA) and 2′-deoxycoformycin (DCF), represent a novel group of cytotoxic agents with high activity in low-grade lymphoid malignancies. However, several investigations have revealed that these agents are active also in acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML). Synergistic interaction between FA or 2-CdA with cytarabine (Ara-C) have been demonstrated in both preclinical and clinical studies. The addition of anthracyclines to induction therapy does not appear to result in a substantial advantage in terms of CR achievement and duration. Clinical studies have confirmed the efficacy of PNA alone or in combination protocols in the treatment of AML. These regimens seem to produce superior results with acceptable toxicities in previously treated and relapsed, poor risk AML. However, early relapses remain a significant problem in a majority of refractory or relapsed patients in CR after treatment with PNA based regimens. To prolong remission duration or even cure AML, auto–or allo stem cell transplantation should be considered. However, FAMP or 2-CdA containing regimens may impair mobilization and collection of stem cells from peripheral blood for autotransplantation. On the other hand, cladribine is sometimes used in non-myeloablative allogeneic transplants.
In the final analysis, I consider the CLAG regimen to be within the standard of care for relapsed AML, or in preparation for a stem cell transplant in poor risk patients.In the final analysis, I consider this drag and the CLAG regimen to be within the standard of care for relapsed AML, unless there is specific plan language that excludes it on specific grounds.
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