Single cycle of arsenic trioxide-based consolidation chemotherapy spares anthracycline exposure in the primary management of acute promyelocytic leukemia

Steven D. Gore, Ivana Gojo, Mikkael A. Sekeres, Lawrence Morris, Marcel Devetten, Katarzyna Jamieson, Robert L. Redner, Robert Arceci, Ibitayo Owoeye, Tianna Dauses, Esther Schachter-Tokarz, Robert E. Gallagher

Research output: Contribution to journalArticle

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Abstract

Purpose: Event-free survival following all-trans-retinoic acid (ATRA) -based therapy for acute promyelocytic leukemia (APL) averages 70% at 5 years. While arsenic trioxide (ATO) can induce remissions in 95% of relapsed patients, few studies have addressed the integration of ATO into the primary management of APL. This study examines the efficacy of a single cycle of ATO-based consolidation therapy in a treatment regimen designed to decrease exposure to other cytotoxic agents. Patients and Methods: After induction with ATRA and daunorubicin (DRN), untreated patients with APL received 3 days of cytarabine and DRN followed by 30 doses of ATO beginning on day 8. Molecular remitters received 2 years of risk-based maintenance therapy. Results: Forty-one of 45 patients receiving induction therapy achieved remission; four patients died (one before treatment was initiated). Thirty-seven patients received consolidation and maintenance; of these one patient relapsed (CNS) and one died in remission during maintenance therapy (hepatic sickle cell crisis). With a median follow-up of 2.7 years, estimated disease-free survival was 90%; overall survival for all patients was 88%. Despite a total anthracycline dose of only 360 mg/m2, cardiac ejection fraction decreased by ≥ 20% in 20% of patients. Conclusion: These data, combined with other recent studies using ATO in the primary management of APL, demonstrate the important role that ATO can play in the primary management of this curable disease. Future studies should continue to focus on reducing the toxicity of treatment without increasing the relapse rate.

Original languageEnglish (US)
Pages (from-to)1047-1053
Number of pages7
JournalJournal of Clinical Oncology
Volume28
Issue number6
DOIs
StatePublished - Feb 20 2010

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Consolidation Chemotherapy
Acute Promyelocytic Leukemia
Anthracyclines
Daunorubicin
Therapeutics
Tretinoin
Disease-Free Survival
arsenic trioxide
Cytarabine
Cytotoxins
Disease Management
Hepatocytes
Maintenance

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Single cycle of arsenic trioxide-based consolidation chemotherapy spares anthracycline exposure in the primary management of acute promyelocytic leukemia. / Gore, Steven D.; Gojo, Ivana; Sekeres, Mikkael A.; Morris, Lawrence; Devetten, Marcel; Jamieson, Katarzyna; Redner, Robert L.; Arceci, Robert; Owoeye, Ibitayo; Dauses, Tianna; Schachter-Tokarz, Esther; Gallagher, Robert E.

In: Journal of Clinical Oncology, Vol. 28, No. 6, 20.02.2010, p. 1047-1053.

Research output: Contribution to journalArticle

Gore, SD, Gojo, I, Sekeres, MA, Morris, L, Devetten, M, Jamieson, K, Redner, RL, Arceci, R, Owoeye, I, Dauses, T, Schachter-Tokarz, E & Gallagher, RE 2010, 'Single cycle of arsenic trioxide-based consolidation chemotherapy spares anthracycline exposure in the primary management of acute promyelocytic leukemia', Journal of Clinical Oncology, vol. 28, no. 6, pp. 1047-1053. https://doi.org/10.1200/JCO.2009.25.5158
Gore, Steven D. ; Gojo, Ivana ; Sekeres, Mikkael A. ; Morris, Lawrence ; Devetten, Marcel ; Jamieson, Katarzyna ; Redner, Robert L. ; Arceci, Robert ; Owoeye, Ibitayo ; Dauses, Tianna ; Schachter-Tokarz, Esther ; Gallagher, Robert E. / Single cycle of arsenic trioxide-based consolidation chemotherapy spares anthracycline exposure in the primary management of acute promyelocytic leukemia. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 6. pp. 1047-1053.
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abstract = "Purpose: Event-free survival following all-trans-retinoic acid (ATRA) -based therapy for acute promyelocytic leukemia (APL) averages 70{\%} at 5 years. While arsenic trioxide (ATO) can induce remissions in 95{\%} of relapsed patients, few studies have addressed the integration of ATO into the primary management of APL. This study examines the efficacy of a single cycle of ATO-based consolidation therapy in a treatment regimen designed to decrease exposure to other cytotoxic agents. Patients and Methods: After induction with ATRA and daunorubicin (DRN), untreated patients with APL received 3 days of cytarabine and DRN followed by 30 doses of ATO beginning on day 8. Molecular remitters received 2 years of risk-based maintenance therapy. Results: Forty-one of 45 patients receiving induction therapy achieved remission; four patients died (one before treatment was initiated). Thirty-seven patients received consolidation and maintenance; of these one patient relapsed (CNS) and one died in remission during maintenance therapy (hepatic sickle cell crisis). With a median follow-up of 2.7 years, estimated disease-free survival was 90{\%}; overall survival for all patients was 88{\%}. Despite a total anthracycline dose of only 360 mg/m2, cardiac ejection fraction decreased by ≥ 20{\%} in 20{\%} of patients. Conclusion: These data, combined with other recent studies using ATO in the primary management of APL, demonstrate the important role that ATO can play in the primary management of this curable disease. Future studies should continue to focus on reducing the toxicity of treatment without increasing the relapse rate.",
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T1 - Single cycle of arsenic trioxide-based consolidation chemotherapy spares anthracycline exposure in the primary management of acute promyelocytic leukemia

AU - Gore, Steven D.

AU - Gojo, Ivana

AU - Sekeres, Mikkael A.

AU - Morris, Lawrence

AU - Devetten, Marcel

AU - Jamieson, Katarzyna

AU - Redner, Robert L.

AU - Arceci, Robert

AU - Owoeye, Ibitayo

AU - Dauses, Tianna

AU - Schachter-Tokarz, Esther

AU - Gallagher, Robert E.

PY - 2010/2/20

Y1 - 2010/2/20

N2 - Purpose: Event-free survival following all-trans-retinoic acid (ATRA) -based therapy for acute promyelocytic leukemia (APL) averages 70% at 5 years. While arsenic trioxide (ATO) can induce remissions in 95% of relapsed patients, few studies have addressed the integration of ATO into the primary management of APL. This study examines the efficacy of a single cycle of ATO-based consolidation therapy in a treatment regimen designed to decrease exposure to other cytotoxic agents. Patients and Methods: After induction with ATRA and daunorubicin (DRN), untreated patients with APL received 3 days of cytarabine and DRN followed by 30 doses of ATO beginning on day 8. Molecular remitters received 2 years of risk-based maintenance therapy. Results: Forty-one of 45 patients receiving induction therapy achieved remission; four patients died (one before treatment was initiated). Thirty-seven patients received consolidation and maintenance; of these one patient relapsed (CNS) and one died in remission during maintenance therapy (hepatic sickle cell crisis). With a median follow-up of 2.7 years, estimated disease-free survival was 90%; overall survival for all patients was 88%. Despite a total anthracycline dose of only 360 mg/m2, cardiac ejection fraction decreased by ≥ 20% in 20% of patients. Conclusion: These data, combined with other recent studies using ATO in the primary management of APL, demonstrate the important role that ATO can play in the primary management of this curable disease. Future studies should continue to focus on reducing the toxicity of treatment without increasing the relapse rate.

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