Studies on treatment of acute promyelocytic leukemia with arsenic trioxide: remission induction, follow-up, and molecular monitoring in 11 newly diagnosed and 47 relapsed acute promyelocytic leukemia patients.
Fifty-eight acute promyelocytic leukemia (APL) patients (11 newly diagnosed and 47 relapsed) were studied for arsenic trioxide (As2O3) treatment. Clinical complete remission (CR) was obtained in 8 of 11 (72.7%) newly diagnosed cases. However, As2O3 treatment resulted in hepatic toxicity in 7 cases including 2 deaths, in contrast to the mild liver dysfunction in one third of the relapsed patients. Forty of forty-seven (85.1%) relapsed patients achieved CR. Two of three nonresponders showed clonal evolution at relapse, with disappearance of t(15;17) and PML-RARalpha fusion gene in 1 and shift to a dominant AML-1-ETO population in another, suggesting a correlation between PML-RARalpha expression and therapeutic response. In a follow-up of 33 relapsed cases over 7 to 48 months, the estimated disease-free survival (DFS) rates for 1 and 2 years were 63.6% and 41.6%, respectively, and the actual median DFS was 17 months. Patients with white blood cell (WBC) count below 10 x 10(9)/L at relapse had better survival than those with WBC count over 10 x 10(9)/L (P =.038). The duration of As2O3-induced CR was related to postremission therapy, because there was only 2 of 11 relapses in patients treated with As2O3 combined with chemotherapy, compared with 12 of 18 relapses with As2O3 alone (P =.01). Reverse transcription polymerase chain reaction (RT-PCR) analysis in both newly diagnosed and relapsed groups showed long-term use of As2O3 could lead to a molecular remission in some patients. We thus recommend that ATRA be used as first choice for remission induction in newly diagnosed APL cases, whereas As2O3 can be either used as a rescue for relapsed cases or included into multidrug consolidation/maintenance clinical trials.
Niu
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Shanghai Institute of Hematology, Department of Hematology/Oncology, Rui Jin Hospital/Samuel Waxman Cancer Research Foundation Joint Center for Cancer Differentiation Therapy Sponsored by Reliance Group Holdings Inc, China.
Yan
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Yu
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Sun
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Liu
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Li
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Wu
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Zhang
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Chen
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Zhou
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Li
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Zeng
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Yang
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Yuan
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Ren
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Cao
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Xiong
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Zhang
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Waxman
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Wang
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Chen
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Hu
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Shen
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Chen
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D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000009:adverse effects / Q000627:therapeutic use*; D002454:Cell Differentiation; D018572:Disease-Free Survival; D016903:Drug Monitoring; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D007964:Leukocytosis / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D012074:Remission Induction; D014178:Translocation, Genetic
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide