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  • Title: Single-agent liposomal all-trans retinoic acid can cure some patients with untreated acute promyelocytic leukemia: an update of The University of Texas M. D. Anderson Cancer Center Series.
    Author: Tsimberidou AM, Tirado-Gomez M, Andreeff M, O'Brien S, Kantarjian H, Keating M, Lopez-Berestein G, Estey E.
    Journal: Leuk Lymphoma; 2006 Jun; 47(6):1062-8. PubMed ID: 16840198.
    Abstract:
    The present study aimed to investigate single-agent liposomal all-trans retinoic acid (Lipo-ATRA) in untreated acute promyelocytic leukemia (APL). Induction therapy consisted of Lipo-ATRA 90 mg/m2 i.v. every other day. Patients in complete remission (CR) continued to receive Lipo-ATRA 90 mg/m2 i.v. three times a week for 9 months. Idarubicin was added only if a polymerase chain reaction test for promyelocytic leukemia-retinoic acid receptor alpha (sensitivity level, 10(-4)), performed every 3 months from CR, was positive. The results were compared with those of a historical control group treated with oral ATRA and idarubicin. Lipo-ATRA induced CR in 79% of patients; CR rates were 92% and 38% in patients with white blood cell (WBC) counts <10 x 10(9)/L and >10 x 10(9)/L, respectively. Ten of the 26 responders to Lipo-ATRA remain in first CR at a median of 6.4 years, despite never receiving idarubicin; all 10 had initial WBC counts <10 x 10(9)/L. The 5-year survival rate was 76% for patients treated with Lipo-ATRA. Comparisons with oral ATRA+idarubicin as given at M. D. Anderson are confounded because of their historical nature and the absence of ATRA from post-remission therapy in the former group. Nonetheless, a multivariate Cox model identified higher WBC counts and older age, but not treatment (historical vs. Lipo-ATRA), as being predictive of shorter relapse-free and overall survival. Lipo-ATRA can cure patients presenting with WBC counts <10 x 10(9)/L (low risk) without additional therapy, contrary to conventional ATRA, which, when given alone, probably cures no patients. The observation that patients can be cured of APL without the use of chemotherapy should encourage further study of 'targeted' therapy in APL and in other leukemias.
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