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Leukemia Insights - Summer 2011

The standard therapy for AML is a combination of cytarabine and an anthracycline. With standard therapy the complete remission (CR) rates are 60% to 70% and the cure rates are 15% to 25%. Prognosis is related to 1) karyotype, 2) patient age, and 3) performance status and organ functions (Avivi I, Curren Opin Hematol, 2005, 12, 62-67). Patients with t(8;21), inversion 16 or t(15;17) have CR rates of 90% and cure rates of 50% to 80% (Byrd J, Blood, 2002, 100, 4325-4336) and (Slovak ML, Blood, 2000, 96, 4075-4083). Younger patients (age < 65 years) without these favorable chromosomal markers have CR rates of 70% to 80%, but the cure rates are only 30% to 35% (Bloomfield C, Cancer Res., 1998, 58, 4173-4179). 

Older patients and those with adverse karyotypes have CR rates of 35% to 50% and cure rates of 10% or less (Estey E, Lancet, 2006, 368,1894-1907) and (Godwin J, Crit Review Oncol Hematol, 2003, 48, S17-26). Although a “3+7” combination is very widely used, several studies have shown that higher doses of ara-C are associated with a better outcome, and this is best  represented in the meta-analysis published recently by Kern (Kern W, Cancer, 2006, 107, 116-124). Still, despite the use of higher doses of cytarabine or addition of other chemotherapy agents (e.g., etoposide, fludarabine) to the standard combination, the median progression-free survival is only approximately 7 months and most patients with AML will still relapse and require salvage therapy (Appelbaum F, Blood, 2006, 107, 3481-3485).

Salvage therapy options in AML are usually categorized based on cytogenetic and molecular markers at relapse. Foremost amongst these molecular markers are FLT3 (FMS-like tyrosine kinase) status. FLT3 is a Receptor tyrosine kinase (RTK) that activates intracellular pathways. Other well defined molecular markers that are used to stratify salvage therapeutic options are being identified. Further stratification is based on duration of initial remission and whether therapy is for first or subsequent relapses. Acute promyelocytic leukemia is treated as a separate entity due to its varied clinical course and
treatment regimens.

In this issue, Drs. Elias Jabbour and Naval Daver discuss salvage options currently available at MD Anderson Cancer Center. If you have any questions about these or any other study, do not hesitate to contact them or any Leukemia physician.

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