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Cited by 105Retinoids in leukemia and cellular processesAcute Myeloid Leukemia ResearchAcne and Rosacea Treatments and Effects

Molecular Remissions Induced by Liposomal-Encapsulated All-Trans Retinoic Acid in Newly Diagnosed Acute Promyelocytic Leukemia

Estey, Elihu H., Giles, Francis J., Kantarjian, Hagop, O’Brien, Susan, Cortes, Jorge, Freireich, Emil J, Lopez-Berestein, Gabriel, Keating, Michael·1999·Blood
DOI 10.1182/blood.v94.7.2230.419k05_2230_2235
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Abstract

All-trans retinoic acid administered orally (oral ATRA) may not regularly lead to either molecular complete remissions (CRs) or prolonged hematologic CRs (HCR) unless combined with chemotherapy. Because serum tretinoin concentrations are higher, and maintained longer, after use of liposomal-encapsulated ATRA (lipoATRA) rather than oral ATRA, we investigated lipoATRA monotherapy in newly diagnosed acute promyelocytic leukemia (APL). Patients received lipoATRA 90 mg/m2 every other day for remission induction. The same dose was given 3 times a week until 9 months had elapsed from HCR date. Treatment then stopped. Chemotherapy (idarubicin 12 mg/m2daily 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 (median age, 54 years; median white blood cell [WBC] count 4,500/μL). The HCR rate was 12/18 (67%, 95% confidence interval [CI], 41% to 87%). This rate was similar to that we observed in a previous study using oral ATRA + idarubicin. Nine of 10 patients studied at HCR date were PCR-positive. Subsequently, 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 months. 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 had not received idarubicin when the PCR was evaluated, 0 of 12 were PCR-positive 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 follow-up time of 13 months in the 11 patients remaining in first CR. The median follow-up time is 9½ months (range, 3 to 17) in the 9 patients who have received only lipoATRA and who remain PCR-negative and in first CR. Our data suggest that lipoATRA is an effective means of producing molecular CR in newly diagnosed APL.

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Crossref · 10.1182/blood.v94.7.2230.419k05_2230_2235

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Authors
Estey, E. H., Giles, F. J., Kantarjian, H., O’Brien, S., Cortes, J., Freireich, E. J., Lopez-Berestein, G., & Keating, M.
Affiliations
  • The University of Texas MD Anderson Cancer Center (US)
  • From the Departments of Leukemia and Biologic/Immunologic Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
1999-10-01
Volume
94
Issue
7
Pages
2230-2235
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood.v94.7.2230.419k05_2230_2235
OpenAlex
W2396977323
Cited by
105
References
18
Citations by year
2024: 2 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 3 · 2015: 5 · 2014: 3 · 2013: 1 · 2012: 1
FWCI
3.79
Type
journal article
Language
en
Open access
closed
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Health Sciences › Medicine › Dermatology › Acne and Rosacea Treatments and Effects
Keywords
acute promyelocytic leukemia, all-trans retinoic acid, molecular remission, idarubicin, PML-RARA fusion, PCR monitoring, remission induction, monotherapy, relapse detection, minimal residual disease, prognostic factors
MeSH terms
Administration, Oral, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Drug Administration Schedule, Drug Carriers, Humans, Liposomes, Neoplasm Proteins, Remission Induction, Tretinoin, Idarubicin, Gene Rearrangement, Leukemia, Promyelocytic, Acute, Oncogene Proteins, Fusion, Confidence Intervals, Polymerase Chain Reaction

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