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

It has been postulated that recurrence of disease in some patients with new ly-diagnosed APL induced into CR, and subsequently maintained, with single agent oral ATRA results from the decline in ATRA levels that occurs with re peated dosing. Administration of liposomal ATRA (lipoATRA) circumvents, for perhaps several months, the decrease in ATRA levels and produces CRs in pa tients with relapsed APL. These findings led us to administer lipoATRA "mon otherapy" to patients with newly-diagnosed APL. Patients received lipoATRA (90 mg/m2) for induction and continued to receive the drug, by itself, for 9 months unless 2 PCR tests done within 2-4 weeks of each other at a sensit ivity level of 10 (-4) were positive at 3 or 6 months from CR date, in whic h case idarubicin was added to lipoATRA. If the PCR test was negative 9 mon ths from CR date, treatment stopped. 34 patients were enrolled, of whom 79% entered CR. The PCR test at time of CR was positive in 23/24 patients, but was negative in 24/26 (92%) 3 months later. Of most interest 11 of the 26 evaluable, responding patients have remained PCR negative (tested Q 3 month s) with a median follow-up of IS months (range up to 34 months). It is gene rally believed that this type of result would be unlikely with oral ATRA mo notherapy. Recurrence of morphologic APL has occurred in 4 patients, at 5, 6, 12, and 12 months, with a median follow-up time of 18 months in the pati ents remaining alive in CR. Comparison of this lipoATRA +/- idarubicin tria l with oral ATRA + idarubicin induction and idarubicin + POMP maintenance, our previous trial, indicates similar survival, CR, and DFS in CR rates, wi th a suggestion that lipoATRA may produce lower CR rates and hence shorter survival in patients with high-risk disease (wbc count > 10,000/mul. Noneth eless, the rates and duration of PCR negativity produced by lipoATRA monoth erapy suggest that lipoATRA is a superior anti-APL agent than oral ATRA.