Re-Evaluation of Risk Factors for Relapse in APL Patients Treated with All-Trans Retinoic Acid (ATRA) and Arsenic Trioxide (ATO) Frontline Chemotherapy
Yi Zhou, Rajyalakshmi Luthra, Farhad Ravandi, Hagop Kantarjian, Jeffrey L Jorgensen, Carlos Bueso-Ramos, L Jeffrey Medeiros, Sergej Konoplev. The University of Texas, MD Anderson Cancer Center, Houston, TX
Background: FLT3 internal tandem duplication (ITD) is the most common genetic abnormality in acute promyelocytic leukemia (APL) besides t(15;17)(q22;q21)/PML-RARA. It is present in approximately 35% of APL cases, and is often associated with leukocytosis and the microgranular variant, two risk factors for adverse outcome. Nevertheless, the clinical impact of FLT3-ITD in APL is controversial. The differences in opinion may, in part, be related to heterogeneous treatment protocols. Use of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO)- based chemotherapy is now considered state-of-the-art frontline therapy for APL, resulting in over 90% complete remission (CR) and 85% 3-year overall survival. In this study, we aim to assess the prognostic significance of FLT3-ITD and other known risk factors in APL patients uniformly treated with ATRA and ATO.
Design: We retrospectively studied 92 consecutive, newly diagnosed APL patients who were uniformly treated with ATRA and ATO-based chemotherapy and underwent FLT3 mutation analysis at the time of initial diagnosis. Clinical, morphologic, immunophenotypic, cytogenetic and molecular results were reviewed. Associations with relapse were analyzed using Kaplan-Meier survival analysis.
Results: The patient cohort had a median age 52 years (range, 18-88 yr) and included 39 males and 53 females. The median follow-up period is 30 months (range, 2 to 95 mo). Of 92 cases, 25 (27%) presented with leukocytosis (WBC >10K), 13 (14%) showed microgranular morphology, 6 (7%) were positive for CD56, and 31 (34%) had FLT3 ITD. During the follow-up, 4 (4%) patients relapsed, and no patients died of APL. All 4 relapsed patients presented with leukocytosis (WBC>50K) at initial diagnosis, 2 of them had FLT3-ITD and 2 had microgranular morphology. The 2 cases with wild type FLT3 had additional cytogenetic alterations involving chromosomes 7 or 17. Outcome analysis showed that leukocytosis and microgranular variant are significant risk factors for relapse (p<0.05), whereas FLT3-ITD mutation and CD56 expression are not.
Conclusions: ATRA and ATO based frontline chemotherapy has achieved remarkable outcomes in APL patients. Nevertheless, leukocytosis, especially WBC> 50K, and microgranular variant remain as significant risk factors for relapse. FLT3-ITD, despite its presence in 76% of APL cases with leukocytosis, is not a significant predictor of relapse in patients treated with the state-of-the-art therapeutic regimen.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 226, Tuesday Morning