All-trans retinoic acid for acute promyelocytic leukemia: Results of the New York study Journal Article

  

Authors:	Frankel, S. R.; Eardley, A.; Heller, G.; Berman, E.; Miller, W. H. Jr; Dmitrovsky, E.; Warrell, R. P. Jr
Article Title:	All-trans retinoic acid for acute promyelocytic leukemia: Results of the New York study
Abstract:	Objective: To evaluate the safety and efficacy of all-trans retinoic acid to induce complete remission and to examine its effects on duration of remission and survival in patients with acute promyelocytic leukemia. Design: Phase II evaluation and comparison with historical control patients. Setting: Tertiary care cancer referral center. Patients: Consecutive patients with morphologic diagnoses of acute promyelocytic leukemia were treated during a 2-year period with all-trans retinoic acid (daily oral dose, 45 mg/m2). Newly diagnosed patients discontinued the drug approximately 30 days after they achieved complete remission, at which time they received three courses of combination chemotherapy. Patients treated with previous cytotoxic chemotherapy who then relapsed were continued on all-trans retinoic acid as 'maintenance' therapy until they relapsed again. Results: 56 patients entered the study: 34 were newly diagnosed and 22 had relapsed from previous treatment. Fifty-one patients subsequently were found to have the PML/RAR-α gene rearrangement indicative of acute promyelocytic leukemia, and 44 of these patients achieved complete remission (86%; 95% Cl, 76% to 96%). A distinctive respiratory distress syndrome developed in 13 patients (23%) during treatment, and 5 patients (9%; Cl, 3% to 20%) died of this complication. The 5 patients who lacked PML/RAR-α rearrangements were withdrawn and given chemotherapy. The 13 patients given all-trans retinoic acid alone as maintenance therapy (10 of whom had relapsed from a chemotherapy-induced remission) had a median duration of remission of only 3.5 months (range, 1 to 23 months). Only 3 of 19 patients who relapsed from a remission induced by all-trans retinoic acid could be brought into remission again using this drug. The median survival time of all newly diagnosed patients has not been reached, but it now exceeds 31 months (range, 0.4 to 36+ months). No decrease in the early mortality rate was observed compared with a historical control group composed of 80 consecutive, newly diagnosed patients treated only with chemotherapy at this center; however, overall survival was superior. Conclusions: All-trans retinoic acid is an effective agent to induce remission in patients with a molecular diagnosis of acute promyelocytic leukemia, but remissions are short and resistance develops rapidly. Although the incidence of early death was not reduced, the use of all-trans retinoic acid to induce remission, followed by cytotoxic chemotherapy for 'consolidation,' was associated with longer survival times when compared with historical controls treated only with chemotherapy. Additional studies to prevent or mitigate consequences of the 'retinoic acid syndrome' and to identify specific patients who might benefit from earlier intervention with chemotherapy are needed to maximize the advantages of this approach.
Keywords:	adolescent; adult; cancer survival; controlled study; aged; major clinical study; clinical trial; cancer combination chemotherapy; drug efficacy; drug safety; cytarabine; controlled clinical trial; phase 2 clinical trial; dexamethasone; monoclonal antibody; survival time; cancer regression; daunorubicin; acute myeloblastic leukemia; heparin; idarubicin; blood clotting disorder; leukocytosis; retinoic acid; intravenous drug administration; oral drug administration; respiratory distress syndrome; leukapheresis; antileukemic agent; human; male; female; priority journal; article
Journal Title:	Annals of Internal Medicine
Volume:	120
Issue:	4
ISSN:	0003-4819
Publisher:	American College of Physicians
Date Published:	1994-02-15
Start Page:	278
End Page:	286
Language:	English
DOI:	10.7326/0003-4819-120-4-199402150-00004
PROVIDER:	scopus
PUBMED:	8291820
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0028008950&doi=10.7326%2f0003-4819-120-4-199402150-00004&partnerID=40&md5=9facb12f9e7b8bb8810254158a0048be
Notes:	Export Date: 14 January 2019 -- Article -- Source: Scopus

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