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

E. Estey, C. Koller, J. Cortes, P. Reed, E. Freireich, F. Giles, H. Kantarjian

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

It has been postulated that recurrence of disease in some patients with newly-diagnosed APL induced into CR, and subsequently maintained, with single agent oral ATRA results from the decline in ATRA levels that occurs with repeated dosing. Administration of liposomal ATRA (lipoATRA) circumvents, for perhaps several months, the decrease in ATRA levels and produces CRs in patients with relapsed APL. These findings led us to administer lipoATRA "monotherapy" 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 sensitivity level of 10 (-4) were positive at 3 or 6 months from CR date, in which case idarubicin was added to lipoATRA. If the PCR test was negative 9 months 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 months) with a median follow-up of 18 months (range up to 34 months). It is generally believed that this type of result would be unlikely with oral ATRA monotherapy. 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 patients remaining alive in CR. Comparison of this lipoATRA +/- idarubicin trial with oral ATRA + idarubicin induction and idarubicin + POMP maintenance, our previous trial, indicates similar survival, CR, and DFS in CR rates, with a suggestion that lipoATRA may produce lower CR rates and hence shorter survival in patients with high-risk disease (wbc count > 10,000/μl. Nonetheless, the rates and duration of PCR negativity produced by lipoATRA monotherapy suggest that lipoATRA is a superior anti-APL agent than oral ATRA.

Original languageEnglish (US)
Pages (from-to)309-316
Number of pages8
JournalLeukemia and Lymphoma
Volume42
Issue number3
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

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Keywords

  • Liposomal ATRA
  • Newly-diagnosed APL

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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