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Complete Remission after Treatment of Acute Promyelocytic Leukemia with Arsenic Trioxide

Complete Remission after Treatment of Acute Promyelocytic Leukemia with Arsenic Trioxide BackgroundTwo reports from China have suggested that arsenic trioxide can induce complete remissions in patients with acute promyelocytic leukemia (APL). We evaluated this drug in patients with APL in an attempt to elucidate its mechanism of action.MethodsTwelve patients with APL who had relapsed after extensive prior therapy were treated with arsenic trioxide at doses ranging from 0.06 to 0.2 mg per kilogram of body weight per day until visible leukemic cells were eliminated from the bone marrow. Bone marrow mononuclear cells were serially monitored by flow cytometry for immunophenotype, fluorescence in situ hybridization, reverse-transcription–polymerase-chain-reaction (RT-PCR) assay for PML–RAR-α fusion transcripts, and Western blot analysis for expression of the apoptosis-associated proteins caspases 1, 2, and 3.ResultsOf the 12 patients studied, 11 had a complete remission after treatment that lasted from 12 to 39 days (range of cumulative doses, 160 to 515 mg). Adverse effects were relatively mild and included rash, lightheadedness, fatigue, and musculoskeletal pain. Cells that expressed both CD11b and CD33 (antigens characteristic of mature and immature cells, respectively), and which were found by fluorescence in situ hybridization to carry the t(15;17) translocation, increased progressively in number during treatment and persisted in the early phase of complete remission. Eight of 11 patients who initially tested positive for the PML–RAR-α fusion transcript by the RT-PCR assay later tested negative; 3 other patients, who persistently tested positive, relapsed early. Arsenic trioxide induced the expression of the proenzymes of caspase 2 and caspase 3 and activation of both caspase 1 and caspase 3.ConclusionsLow doses of arsenic trioxide can induce complete remissions in patients with APL who have relapsed. The clinical response is associated with incomplete cytodifferentiation and the induction of apoptosis with caspase activation in leukemic cells. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The New England Journal of Medicine The New England Journal of Medicine

Complete Remission after Treatment of Acute Promyelocytic Leukemia with Arsenic Trioxide

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Publisher
The New England Journal of Medicine
Copyright
Copyright © 1998 Massachusetts Medical Society. All rights reserved.
ISSN
0028-4793
eISSN
1533-4406
DOI
10.1056/NEJM199811053391901
pmid
9801394
Publisher site
See Article on Publisher Site

Abstract

BackgroundTwo reports from China have suggested that arsenic trioxide can induce complete remissions in patients with acute promyelocytic leukemia (APL). We evaluated this drug in patients with APL in an attempt to elucidate its mechanism of action.MethodsTwelve patients with APL who had relapsed after extensive prior therapy were treated with arsenic trioxide at doses ranging from 0.06 to 0.2 mg per kilogram of body weight per day until visible leukemic cells were eliminated from the bone marrow. Bone marrow mononuclear cells were serially monitored by flow cytometry for immunophenotype, fluorescence in situ hybridization, reverse-transcription–polymerase-chain-reaction (RT-PCR) assay for PML–RAR-α fusion transcripts, and Western blot analysis for expression of the apoptosis-associated proteins caspases 1, 2, and 3.ResultsOf the 12 patients studied, 11 had a complete remission after treatment that lasted from 12 to 39 days (range of cumulative doses, 160 to 515 mg). Adverse effects were relatively mild and included rash, lightheadedness, fatigue, and musculoskeletal pain. Cells that expressed both CD11b and CD33 (antigens characteristic of mature and immature cells, respectively), and which were found by fluorescence in situ hybridization to carry the t(15;17) translocation, increased progressively in number during treatment and persisted in the early phase of complete remission. Eight of 11 patients who initially tested positive for the PML–RAR-α fusion transcript by the RT-PCR assay later tested negative; 3 other patients, who persistently tested positive, relapsed early. Arsenic trioxide induced the expression of the proenzymes of caspase 2 and caspase 3 and activation of both caspase 1 and caspase 3.ConclusionsLow doses of arsenic trioxide can induce complete remissions in patients with APL who have relapsed. The clinical response is associated with incomplete cytodifferentiation and the induction of apoptosis with caspase activation in leukemic cells.

Journal

The New England Journal of Medicine – The New England Journal of Medicine

Published: Nov 5, 1998

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