Molecular remissions induced by liposomal-encapsulated all-trans retinoic acid in newly diagnosed acute promyelocytic leukemia

All-trans retinoic acid administered orally (oral ATRA) may not regularly l ead to either molecular complete remissions (CRs) or prolonged hematologic CRs (HCR) unless combined with chemotherapy. Because serum tretinoin concen trations are higher, and maintained longer, after use of liposomal-encapsul ated ATRA (lipoATRA) rather than oral ATRA, we investigated lipoATRA monoth erapy in newly diagnosed acute promyelocytic leukemia (APL). Patients recei ved lipoATRA 90 mg/m(2) every other day for remission induction. The same d ose was given 3 times a week until 9 months had elapsed from HCR date. Trea tment then stopped, Chemotherapy (idarubicin 12 mg/m(2) daily days 1-2 for 2 courses) was to be added only if 2 polymerase chain reaction (PCR) tests, performed 2 weeks apart, were positive at 3, 6, or 9 months from HCR date. The sensitivity level of the PCR was 10(-4). We treated 18 patients (media n age, 54 years; median white blood cell [WBC] count 4,500/mu L). The HCR r ate was 12/18 (67%, 95% confidence interval [CI], 41% to 87%). This rate wa s similar to that we observed in a previous study using oral ATRA + idarubi cin. Nine of 10 patients studied at HCR date were PCR-positive. Subsequentl y, however overall (+/- idarubicin) rates of PCR positivity were 0/12 at 3 months, 1/10 at 6 months, 1/7 at 9 and 12 months, and 0/4 at 15 to 17 month s. Idarubicin has been added in 3 patients, with this addition occurring at 6 months in 2 patients and at 9 months in 1 patient. Among patients who ha d not received idarubicin when the PCR was evaluated, 0 of 12 were PCR-posi tive at 3 months, 1 of 10 was positive at 6 months, 1 of 6 was positive at 9 months, 0 of 4 were positive at 12 months, and 0 of 3 were positive at 15 to 17 months. Morphologic APL has recurred in 1 patient, with a median fol low-up time of 13 months in the 11 patients remaining in first CR. The medi an follow-up time is 91/2 months (range, 3 to 17) in the 9 patients who hav e received only lipoATRA and who remain PCR-negative and in first CR. Our d ata suggest that lipoATRA is an effective means of producing molecular CR i n newly diagnosed APL. (C) 1999 by The American Society of Hematology.