Treatment of newly diagnosed and relapsed acute promyelocytic leukemia with intravenous liposomal all-trans retinoic acid

A novel intravenous liposomal formulation of all-trans retinoic acid (ATRA) was evaluated in 69 patients with acute promyelocytic leukemia (APL): 32 n ew diagnoses, 35 relapses, and 2 oral ATRA failures, Liposomal ATRA (90 mg/ m(2)) was administered every other day until complete remission (CR) or a m aximum of 56 days. Treatment following OR was liposomal ATRA with or withou t chemotherapy, In an intent-to-treat (ITT) analysis of all patients, OR ra tes were 62%, 70%, and 20% in newly diagnosed, group 1 first relapses (ATRA naive or off oral ATRA more than or equal to 1 year), or group 2 relapses (second or subsequent relapse or first relapses off oral ATRA less than 1 y ear), respectively, In 56 evaluable patients (receiving 4 or more doses), O R rates for the same groups were 87% (20 of 23), 78% (14 of 18), and 23% (3 of 13), Remission failure in newly diagnosed patients was not from resista nt disease, Several patients in CR became polymerase chain reaction (PCR) n egative for promyelocytic leukemia/retinoic acid receptor-alpha (PML/RAR al pha) after liposomal ATRA alone. Toxicity was generally mild, most commonly headaches (67.5%), Eighteen patients (26%) had ATRA syndrome develop durin g induction. One-year survival of ITT patients was 62%, 56%, and 20% for ne wly diagnosed, group 1, and group 2, respectively. The medium duration of O R has not yet been reached and was 18 and 5.5 months in the same groups. Th ese results demonstrate that liposomal ATRA is effective in inducing CR in newly diagnosed or group 1 APL patients. It provides a reliable dosage of A TRA for patients with APL unable to swallow or absorb medications and can i nduce molecular remissions without chemotherapy. (C) 2001 by The American S ociety of Hematology.