Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide Journal Article
| Authors: | Soignet, S. L.; Maslak, P.; Wang, Z. G.; Jhanwar, S.; Calleja, E.; Dardashti, L. J.; Corso, D.; DeBlasio, A.; Gabrilove, J.; Scheinberg, D. A.; Pandolfi, P. P.; Warrell Jr, R. P. |
| Article Title: | Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide |
| Abstract: | Background: Two 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. Methods: Twelve 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. Results: Of 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. Conclusions: Low 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. |
| Keywords: | adolescent; adult; child; treatment outcome; aged; middle aged; fatigue; dose response; drug efficacy; antineoplastic agents; flow cytometry; bone marrow cells; apoptosis; neoplasm proteins; recurrence; cell differentiation; caspases; rash; arsenic trioxide; arsenicals; leukemia, promyelocytic, acute; oxides; leukocytes, mononuclear; drug mechanism; cd11b antigen; acute myeloblastic leukemia; oncogene proteins, fusion; remission; remission induction; immunophenotyping; antigens, cd; musculoskeletal disease; cd33 antigen; vertigo; humans; human; priority journal; article |
| Journal Title: | New England Journal of Medicine |
| Volume: | 339 |
| Issue: | 19 |
| ISSN: | 0028-4793 |
| Publisher: | Massachusetts Medical Society |
| Date Published: | 1998-11-05 |
| Start Page: | 1341 |
| End Page: | 1348 |
| Language: | English |
| DOI: | 10.1056/nejm199811053391901 |
| PUBMED: | 9801394 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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