Abstract

Background: Core binding factor associated acute myelogenous leukemias (CBF AML) are characterized by unique fusion transcripts that are amenable to molecular monitoring. Multiple log reduction in the fusion transcript level has been reported to be associated with lower relapse rates in CBF AML (Liu-Yin JA et al. ASH 2007# 543). Addition of gemtuzumab ozogamicin (GO) to induction and consolidation has resulted in improved disease free survival (DFS) in patients with AML and “standardrisk” or “favorable cytogenetics” (Burnett,A. et al. ASH 2006#13). Historical data from M.D. Anderson Cancer Center indicates that induction/consolidation therapy with fludarabine, cytarabine and granulocyte colony stimulating factor (GCSF) (FLAG) results in improved event free survival (EFS) (median EFS not reached after median followup of 118 weeks) in patients with CBF AML (Borthakur et al. 2008, Cancer in press).

Method: In an attempt to improve upon these results we have initiated a study incorporating GO with FLAG (GO-FLAG) in induction/consolidation for treating patients with newly diagnosed CBF AML. We report on molecular responses in patients enrolled in this study. Extracted RNA is reverse transcribed and analyzed by real-time quantitative PCR for the fusion transcript associated with CBF leukemias. Values are expressed as a percentage of fusion transcript to normalizing ABL transcripts. The sensitivity of detection is approximately 1 in 100,000 for AML1-ETO and 1 in 10,000 for CBFb-MYH11.

Results: Seventeen (Inv 16=6/t 8;21=11) patients (male=15)[median age 49 years (range, 29–73)]have been treated to date with a median follow-up of 10 months (range,1–16). Patient characteristics at presentation include median WBC 10.4 (range, 1.5–41.5) x 106/ml, hemoglobin 9.3 (range, 7.8–11.9) gm/dL, platelet count 22 (range, 6–365) x 109/ml. Additional cytogenetic abnormalities were present in 10 patients; +8 and –Y being most frequent. Two patients had kit mutations. All patients achieved complete remission (CR) except one (partial remission). Two patients died in CR from infectious complications. There has been no relapse. Median pre-treatment value for fusion transcript to Abl ratio by Q-PCR is 100 (range, 100–857). After induction the median Q-OCR value dropped to 0.04 (range, 0–9.17) and after three cycles of therapy the median value is 0.01 (range, 0–0.12).

Conclusion: Induction/consolidation therapy with GO-FLAG regimen in CBF AML results in excellent molecular response. Further patient accrual and follow-up will generate information about impact on overall and disease/event free survival.

Disclosures: No relevant conflicts of interest to declare.

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