Skip to main content

Advertisement

Log in

Role of Arsenic Trioxide in Acute Promyelocytic Leukemia

  • Leukemia (JP Dutcher, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia that is characterized by distinct clinical, morphological, cytogenetic, and molecular abnormalities. It is associated with a striking risk of early hemorrhagic death due to disseminated intravascular coagulation and hyperfibrinolysis. The prognosis of APL has improved dramatically following the introduction of all-trans retinoic acid (ATRA) and its combination with anthracycline-based chemotherapy during induction and consolidation. Patients with high-risk APL, defined by a white cell count >10 × 109/L at diagnosis, also appear to benefit from the addition of intermediate- or high-dose cytarabine during consolidation. Arsenic trioxide (ATO) has proved to be even more effective than ATRA as a single agent, and is now routinely used for the treatment of the 20%–30% of patients who manifest disease relapse after initial treatment with ATRA and chemotherapy. ATO has a toxicity profile that differs considerably from that of both ATRA and cytotoxic chemotherapy, and accordingly presents its own specific challenges during treatment. Optimizing a strategy for the incorporation of ATO into initial therapy is currently the focus of several cooperative group trials, with an emphasis on minimizing or even eradicating the use of chemotherapy. ATRA plus ATO without chemotherapy appears to be adequate during induction and consolidation for patients with standard-risk APL, but triple therapy that includes limited anthracycline or gemtuzumab ozogamicin (GO) during induction is required for high-risk APL. Uncertainty still exists regarding the minimum amount of chemotherapy and number of consolidation cycles necessary, the optimal scheduling of ATO, and the potential utility of oral ATO administration. Although prolonged oral maintenance therapy is usually included in most current APL treatment protocols, its value remains controversial, and the superior anti-leukemic efficacy of ATO-based therapy may facilitate its elimination in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Swerdlow S, Campo E, Harris N, et al. WHO classification of tumours of haematopoietic and lymphoid tissue: The International Agency for Research on Cancer; Lyon, 2008.

  2. Wang Z-Y, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood. 2008;111:2505–15.

    Article  PubMed  CAS  Google Scholar 

  3. Hillestad LK. Acute promyelocytic leukemia. Acta Med Scand. 1957;159:189–94.

    Article  PubMed  CAS  Google Scholar 

  4. Detourmignies L. Therapy-related acute promyelocytic leukemia: a report on 16 cases. J Clin Oncol. 1992;10:1430–5.

    PubMed  CAS  Google Scholar 

  5. Mistry AR, Felix CA, Whitmarsh RJ, et al. DNA topoisomerase II in therapy-related acute promyelocytic leukemia. N Engl J Med. 2005;352:1529–38.

    Article  PubMed  CAS  Google Scholar 

  6. Hasan SK, Mays AN, Ottone T, et al. Molecular analysis of t(15;17) genomic breakpoints in secondary acute promyelocytic leukemia arising after treatment of multiple sclerosis. Blood. 2008;112:3383–90.

    Article  PubMed  CAS  Google Scholar 

  7. Huang ME, Ye YC, Chen SR, et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988;72:567–72.

    PubMed  CAS  Google Scholar 

  8. de The H, Chomienne C, Lanotte M, et al. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus. Nature. 1990;347:558–61.

    Article  PubMed  Google Scholar 

  9. Kakizuka A, Miller Jr WH, Umesono K, et al. Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell. 1991;66:663–74.

    Article  PubMed  CAS  Google Scholar 

  10. Larson RA, Kondo K, Vardiman JW, et al. Evidence for a 15;17 translocation in every patient with acute promyelocytic leukemia. Am J Med. 1984;76:827–41.

    Article  PubMed  CAS  Google Scholar 

  11. Grimwade D, Biondi A, Mozziconacci MJ, et al. Characterization of acute promyelocytic leukemia cases lacking the classic t(15;17): results of the European Working Party. Groupe Francais de Cytogenetique Hematologique, Groupe de Francais d'Hematologie Cellulaire, UK Cancer Cytogenetics Group and BIOMED 1 European Community-Concerted Action “molecular cytogenetic diagnosis in haematological malignancies”. Blood. 2000;96:1297–308.

    PubMed  CAS  Google Scholar 

  12. Chen Z, Brand NJ, Chen A, et al. Fusion between a novel Kruppel-like zinc finger gene and the retinoic acid receptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia. EMBO J. 1993;12:1161–7.

    PubMed  CAS  Google Scholar 

  13. Redner R, Rush E, Faas S, et al. The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion. Blood. 1996;87:882–6.

    PubMed  CAS  Google Scholar 

  14. Wells RA, Catzavelos C, Kamel-Reid S. Fusion of retinoic acid receptor alpha to NuMA, the nuclear mitotic apparatus protein, by a variant translocation in acute promyelocytic leukaemia. Nat Genet. 1997;17:109–13.

    Article  PubMed  CAS  Google Scholar 

  15. Arnould C, Philippe C, Bourdon V, et al. The signal transducer and activator of transcription STAT5b gene is a new partner of retinoic acid receptor alpha in acute promyelocytic-like leukaemia. Hum Mol Genet. 1999;8:1741–9.

    Article  PubMed  CAS  Google Scholar 

  16. Catalano A, Dawson MA, Somana K, et al. The PRKAR1A gene is fused to RARA in a new variant acute promyelocytic leukemia. Blood. 2007;110:4073–6.

    Article  PubMed  CAS  Google Scholar 

  17. Kondo T, Mori A, Darmanin S, et al. The seventh pathogenic fusion gene FIP1L1-RARA was isolated from a t(4;17)-positive acute promyelocytic leukemia. Haematologica. 2008;93:1414–6.

    Article  PubMed  CAS  Google Scholar 

  18. Yamamoto Y, Tsuzuki S, Tsuzuki M, et al. BCOR as a novel fusion partner of retinoic acid receptor alpha in a t(X;17)(p11;q12) variant of acute promyelocytic leukemia. Blood. 2010;116:4274–83.

    Article  PubMed  CAS  Google Scholar 

  19. Mistry AR, Pedersen EW, Solomon E, Grimwade D. The molecular pathogenesis of acute promyelocytic leukaemia: implications for the clinical management of the disease. Blood Rev. 2003;17:71–97.

    Article  PubMed  Google Scholar 

  20. Brown D, Kogan S, Lagasse E, et al. A PMLRARalpha transgene initiates murine acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 1997;94:2551–6.

    Article  PubMed  CAS  Google Scholar 

  21. Kelly LM, Kutok JL, Williams IR, et al. PML/RARalpha and FLT3-ITD induce an APL-like disease in a mouse model. Proc Natl Acad Sci U S A. 2002;99:8283–8.

    Article  PubMed  CAS  Google Scholar 

  22. Kottaridis PD, Gale RE, Frew ME, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001;98:1752–9.

    Article  PubMed  CAS  Google Scholar 

  23. Beitinjaneh A, Jang S, Roukoz H, Majhail NS. Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations in acute promyelocytic leukemia: a systematic review. Leuk Res. 2010;34:831–6.

    Article  PubMed  CAS  Google Scholar 

  24. Park JH, Qiao B, Panageas KS, et al. Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid. Blood. 2011;118:1248–54.

    Article  PubMed  CAS  Google Scholar 

  25. Douer D, Preston-Martin S, Chang E, et al. High frequency of acute promyelocytic leukemia among Latinos with acute myeloid leukemia. Blood. 1996;87:308–13.

    PubMed  CAS  Google Scholar 

  26. Estey E, Thall P, Kantarjian H, et al. Association between increased body mass index and a diagnosis of acute promyelocytic leukemia in patients with acute myeloid leukemia. Leukemia. 1997;11:1661–4.

    Article  PubMed  CAS  Google Scholar 

  27. Breen KA, Grimwade D, Hunt BJ. The pathogenesis and management of the coagulopathy of acute promyelocytic leukaemia. Br J Haematol. 2012;156:24–36. An excellent review of the coagulopathy that dominates the initial presentation and early treatment of APL.

    Article  PubMed  CAS  Google Scholar 

  28. Daniel MT, Koken M, Romagne O, et al. PML protein expression in hematopoietic and acute promyelocytic leukemia cells. Blood. 1993;82:1858–67.

    PubMed  CAS  Google Scholar 

  29. Falini B, Flenghi L, Fagioli M, et al. Immunocytochemical diagnosis of acute promyelocytic leukemia (M3) with the monoclonal antibody PG-M3 (anti-PML). Blood. 1997;90:4046–53.

    PubMed  CAS  Google Scholar 

  30. Sanz MA, Coco FL, Martín G, et al. Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood. 2000;96:1247–53.

    PubMed  CAS  Google Scholar 

  31. Frankel SR, Eardley A, Lauwers G, et al. The "retinoic acid syndrome" in acute promyelocytic leukemia. Ann Intern Med. 1992;117:292–6.

    Article  PubMed  CAS  Google Scholar 

  32. Fenaux P, Le Deley M, Castaigne S, et al. Effect of all transretinoic acid in newly diagnosed acute promyelocytic leukemia. Results of a multicenter randomized trial. European APL 91 Group. Blood. 1993;82:3241–9.

    PubMed  CAS  Google Scholar 

  33. Fenaux P, Chastang C, Chevret S, et al. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood. 1999;94:1192–200.

    PubMed  CAS  Google Scholar 

  34. Head D, Kopecky K, Weick J, et al. Effect of aggressive daunomycin therapy on survival in acute promyelocytic leukemia. Blood. 1995;86:1717–28.

    PubMed  CAS  Google Scholar 

  35. Avvisati G, Petti MC, Lo-Coco F, et al. Induction therapy with idarubicin alone significantly influences event-free survival duration in patients with newly diagnosed hypergranular acute promyelocytic leukemia: final results of the GIMEMA randomized study LAP 0389 with 7 years of minimal follow-up. Blood. 2002;100:3141–6.

    Article  PubMed  CAS  Google Scholar 

  36. Mandelli F, Diverio D, Avvisati G, et al. Molecular remission in PML/RARα-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Blood. 1997;90:1014–21.

    PubMed  CAS  Google Scholar 

  37. Sanz MA, Martín G, Rayón C, et al. A modified AIDA protocol with anthracycline-based consolidation results in high antileukemic efficacy and reduced toxicity in newly diagnosed PML/RARα-positive acute promyelocytic leukemia. Blood. 1999;94:3015–21.

    PubMed  CAS  Google Scholar 

  38. Ades L, Chevret S, Raffoux E, et al. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2006;24:5703–10.

    Article  PubMed  CAS  Google Scholar 

  39. Lo-Coco F, Avvisati G, Vignetti M, et al. Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation for adults younger than 61 years: results of the AIDA-2000 trial of the GIMEMA Group. Blood. 2010;116:3171–9. An example of what can be achieved when APL is treated with (a) ATRA and anthracycline-based chemotherapy, and (b) intensified consolidation that includes intermediate-dose cytarabine.

    Article  PubMed  CAS  Google Scholar 

  40. Sanz MA, Montesinos P, Rayon C, et al. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood. 2010;115:5137–46.

    Article  PubMed  CAS  Google Scholar 

  41. Shen Z-X, Shi Z-Z, Fang J, et al. All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 2004;101:5328–35.

    Article  PubMed  CAS  Google Scholar 

  42. Ravandi F, Estey E, Jones D, et al. Effective treatment of acute promyelocytic leukemia with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin. J Clin Oncol. 2009;27:504–10. This study demonstrates that ATRA/ATO in induction and consolidation is adequate for low-risk patients, but high-risk patients had inferior outcomes despite gemtuzumab ozogamicin.

    Article  PubMed  CAS  Google Scholar 

  43. Powell BL, Moser B, Stock W, et al. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010;116:3751–7. A randomized phase III study that clearly demonstrated the benefit of including ATO in post-remission therapy.

    Article  PubMed  CAS  Google Scholar 

  44. Iland HJ, Bradstock K, Supple SG, et al. All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4). Blood. 2012;120:1570–80. This study reports excellent interim analysis results with a regimen that incorporates the 3 most active agents currently available for the treatment of APL (ATRA, ATO, and idarubicin). Exposure to idarubicin was limited to one cycle, and the white cell count at diagnosis was not associated with a significant increase in early deaths or relapses.

    Article  PubMed  CAS  Google Scholar 

  45. Lo-Coco F, Avvisati G, Orlando SM, et al. ATRA and asenic trioxide (ATO) vs ATRA and idarubicin (AIDA) for newly diagnosed, non high-risk acute promyelocytic leukemia (APL): results of the phase III, prospective, randomized, Intergroup APL0406 Study by the Italian-German Cooperative Groups GIMEMA-SAL-AMLSG. In: 54th American Society of Hematology Annual Meeting. Atlanta, GA. 2012. This is an important report, currently available only in abstract form. It demonstrates in a randomized, phase III study that ATRA/ATO is non-inferior, and probably superior, to an ATRA/chemotherapy strategy for patients with low- or intermediate-risk disease.

  46. Au WY. A biography of arsenic and medicine in Hong Kong and China. Hong Kong Med. 2011;17:507–13.

    CAS  Google Scholar 

  47. Zhang T, Sun H, Hu H. Treatment of acute promyelocytic leukemia with Ailing number one combination therapy: a study of 73 cases [in Chinese]. Heilongjiang J Tradit Chin Med. 1981;4:40–4.

    Google Scholar 

  48. Sun H, Ma L, Hu X, Zhang T. Ai-Lin I treated 32 cases of acute promyelocytic leukemia. Chin J Integrat Chin West Med. 1992;12:170–1.

    Google Scholar 

  49. Chen GQ, Shi XG, Tang W, et al. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): I. As2O3 exerts dose-dependent dual effects on APL cells. Blood. 1997;89:3345–53.

    PubMed  CAS  Google Scholar 

  50. Zheng X, Seshire A, Ruster B, et al. Arsenic but not all-trans retinoic acid overcomes the aberrant stem cell capacity of PML/RARalpha-positive leukemic stem cells. Haematologica. 2007;92:323–31.

    Article  PubMed  CAS  Google Scholar 

  51. Nasr R, Guillemin M-C, Ferhi O, et al. Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation. Nat Med. 2008;14:1333–42.

    Article  PubMed  CAS  Google Scholar 

  52. Forkner C, Scott T. Arsenic as a therapeutic agent in chronic myelogenous leukemia: preliminary report. JAMA. 1931;97:3–5.

    Article  Google Scholar 

  53. Shen ZX, Chen GQ, Ni JH, et al. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood. 1997;89:3354–60.

    PubMed  CAS  Google Scholar 

  54. Soignet SL, Maslak P, Wang ZG, et al. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N Engl J Med. 1998;339:1341–8.

    Article  PubMed  CAS  Google Scholar 

  55. Soignet SL, Frankel SR, Douer D, et al. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol. 2001;19:3852–60.

    PubMed  CAS  Google Scholar 

  56. Niu C, Yan H, Yu T, et al. 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. Blood. 1999;94:3315–24.

    PubMed  CAS  Google Scholar 

  57. Spencer A, Firkin F. Arsenic trioxide treatment of relapsed acute promyelocytic leukaemia: initial Australian experience. Aust N Z J Med. 1999;29:385–6.

    Article  PubMed  CAS  Google Scholar 

  58. Kwong YL, Au WY, Chim CS, et al. Arsenic trioxide- and idarubicin-induced remissions in relapsed acute promyelocytic leukaemia: clinicopathological and molecular features of a pilot study. Am J Hematol. 2001;66:274–9.

    Article  PubMed  CAS  Google Scholar 

  59. Au WY, Lie AKW, Chim CS, et al. Arsenic trioxide in comparison with chemotherapy and bone marrow transplantation for the treatment of relapsed acute promyelocytic leukaemia. Ann Oncol. 2003;14:752–7.

    Article  PubMed  CAS  Google Scholar 

  60. Leoni F, Gianfaldoni G, Annunziata M, et al. Arsenic trioxide therapy for relapsed acute promyelocytic leukemia: a bridge to transplantation. Haematologica. 2002;87:485–9.

    PubMed  CAS  Google Scholar 

  61. Raffoux E, Rousselot P, Poupon J, et al. Combined treatment with arsenic trioxide and all-trans-retinoic acid in patients with relapsed acute promyelocytic leukemia. J Clin Oncol. 2003;21:2326–34.

    Article  PubMed  CAS  Google Scholar 

  62. Shigeno K, Naito K, Sahara N, et al. Arsenic trioxide therapy in relapsed or refractory Japanese patients with acute promyelocytic leukemia: updated outcomes of the phase II study and postremission therapies. Int J Hematol. 2005;82:224–9.

    Article  PubMed  CAS  Google Scholar 

  63. Lazo G, Kantarjian H, Estey E, et al. Use of arsenic trioxide (As2O3) in the treatment of patients with acute promyelocytic leukemia: the M. D. Anderson experience. Cancer. 2003;97:2218–24.

    Article  PubMed  CAS  Google Scholar 

  64. Aribi A, Kantarjian HM, Estey EH, et al. Combination therapy with arsenic trioxide, all-trans retinoic acid, and gemtuzumab ozogamicin in recurrent acute promyelocytic leukemia. Cancer. 2007;109:1355–9.

    Article  PubMed  CAS  Google Scholar 

  65. Carmosino I, Latagliata R, Avvisati G, et al. Arsenic trioxide in the treatment of advanced acute promyelocytic leukemia. Haematologica. 2004;89:615–7.

    PubMed  CAS  Google Scholar 

  66. Thomas X, Pigneux A, Raffoux E, et al. Superiority of an arsenic trioxide-based regimen over a historic control combining all-trans retinoic acid plus intensive chemotherapy in the treatment of relapsed acute promyelocytic leukemia. Haematologica. 2006;91:996–7.

    PubMed  CAS  Google Scholar 

  67. Shen Y, Shen ZX, Yan H, et al. Studies on the clinical efficacy and pharmacokinetics of low-dose arsenic trioxide in the treatment of relapsed acute promyelocytic leukemia: a comparison with conventional dosage. Leukemia. 2001;15:735–41.

    Article  PubMed  CAS  Google Scholar 

  68. Thirugnanam R, George B, Chendamarai E, et al. Comparison of clinical outcomes of patients with relapsed acute promyelocytic leukemia induced with arsenic trioxide and consolidated with either an autologous stem cell transplant or an arsenic trioxide-based regimen. Biol Blood Marrow Transplant. 2009;15:1479–84. This paper addresses the issue of how to consolidate patients following achievement of a second CR after ATO-based therapy. Patients treated with further ATO/ATRA had a better EFS than patients who subsequently underwent autologous stem cell transplantation.

    Article  PubMed  CAS  Google Scholar 

  69. Sanz MA, Grimwade D, Tallman MS, et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European Leukemia Net. Blood. 2009;113:1875–91.

    Article  PubMed  CAS  Google Scholar 

  70. Hu J, Liu Y-F, Wu C-F, et al. Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 2009;106:3342–7.

    Article  PubMed  CAS  Google Scholar 

  71. Dai C-W, Zhang G-S, Shen J-K, et al. Use of all-trans retinoic acid in combination with arsenic trioxide for remission induction in patients with newly diagnosed acute promyelocytic leukemia and for consolidation/maintenance in CR patients. Acta Haematol. 2009;121:1–8.

    Article  PubMed  CAS  Google Scholar 

  72. Estey E, Garcia-Manero G, Ferrajoli A, et al. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood. 2006;107:3469–73.

    Article  PubMed  CAS  Google Scholar 

  73. Mathews V, George B, Lakshmi KM, et al. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity. Blood. 2006;107:2627–32.

    Article  PubMed  CAS  Google Scholar 

  74. Ghavamzadeh A, Alimoghaddam K, Ghaffari SH, et al. Treatment of acute promyelocytic leukemia with arsenic trioxide without ATRA and/or chemotherapy. Ann Oncol. 2006;17:131–4.

    Article  PubMed  CAS  Google Scholar 

  75. Ghavamzadeh A, Alimoghaddam K, Rostami S, et al. Phase II study of single-agent arsenic trioxide for the front-line therapy of acute promyelocytic leukemia. J Clin Oncol. 2011;29:2753–7. Together with [76•], these data show the results of treatment with single agent ATO during induction and consolidation.

    Article  PubMed  CAS  Google Scholar 

  76. Mathews V, George B, Chendamarai E, et al. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: long-term follow-up data. J Clin Oncol. 2010;28:3866–71. Together with [75•], these data show the results of treatment with single agent ATO during induction and consolidation.

    Article  PubMed  CAS  Google Scholar 

  77. Gore SD, Gojo I, Sekeres MA, et al. Single cycle of arsenic trioxide-based consolidation chemotherapy spares anthracycline exposure in the primary management of acute promyelocytic leukemia. J Clin Oncol. 2010;28:1047–53.

    Article  PubMed  CAS  Google Scholar 

  78. Iland HJ, Bradstock K, Seymour J, et al. Results of the APML3 trial incorporating all-trans-retinoic acid and idarubicin in both induction and consolidation as initial therapy for patients with acute promyelocytic leukemia. Haematologica. 2012;97:227–34.

    Article  PubMed  CAS  Google Scholar 

  79. Au W-Y, Kwong Y-L. Arsenic trioxide: safety issues and their management. Chung Kuo Yao Li Hsueh Pao. 2008;29:296–304.

    PubMed  CAS  Google Scholar 

  80. Firkin F. Oral administration of arsenic trioxide in the treatment of acute promyelocytic leukaemia and accelerated phase chronic myeloid leukaemia: an Australian single-center study. Intern Med J. 2012;42:948–52.

    Article  PubMed  CAS  Google Scholar 

  81. Kumana CR, Au WY, Lee NSL, et al. Systemic availability of arsenic from oral arsenic-trioxide used to treat patients with hematological malignancies. Eur J Clin Pharmacol. 2002;58:521–6.

    Article  PubMed  CAS  Google Scholar 

  82. Siu C-W, Au W-Y, Yung C, et al. Effects of oral arsenic trioxide therapy on QT intervals in patients with acute promyelocytic leukemia: implications for long-term cardiac safety. Blood. 2006;108:103–6.

    Article  PubMed  CAS  Google Scholar 

  83. Au W-Y, Kumana CR, Lee HKK, et al. Oral arsenic trioxide-based maintenance regimens for first complete remission of acute promyelocytic leukemia: a 10-year follow-up study. Blood. 2011;118:6535–43. Shows oral ATO used primarily for prolonged maintenance of first CR is safe and beneficial.

    Article  PubMed  CAS  Google Scholar 

  84. Au WY, Li C-K, Lee V, et al. Oral arsenic trioxide for relapsed acute promyelocytic leukemia in pediatric patients. Pediatr Blood Cancer. 2012;58:630–2.

    Article  PubMed  Google Scholar 

  85. Lu D-P, Qiu J-Y, Jiang B, et al. Tetra-arsenic tetra-sulfide for the treatment of acute promyelocytic leukemia: a pilot report. Blood. 2002;99:3136–43.

    Article  PubMed  CAS  Google Scholar 

  86. Zhu Z-H, Wu D-P, Jin J, et al. Oral realgar-indigo naturalis formula achieved comparably high rate of remission and survival to intravenous arsenic trioxide as a front-line treatment in newly diagnosed acute promyelocytic leukemia: a multi-center randomized trial APL07. In: 54th American Society of Hematology Annual Meeting. Atlanta, GA. 2012. This report, currently available only in abstract form, provides data that an oral arsenic formulation (realgar-indigo naturalis) is as effective as IV ATO when combined with ATRA during induction and maintenance.

  87. Chen H, MacDonald RC, Li S, et al. Lipid encapsulation of arsenic trioxide attenuates cytotoxicity and allows for controlled anticancer drug release. J Am Chem Soc. 2006;128:13348–9.

    Article  PubMed  CAS  Google Scholar 

  88. Diaz Z, Mann KK, Marcoux S, et al. A novel arsenical has antitumor activity toward As2O3-resistant and MRP1/ABCC1-overexpressing cell lines. Leukemia. 2008;22:1853–63.

    Article  PubMed  CAS  Google Scholar 

  89. Konig A, Wrazel L, Warrell Jr RP, et al. Comparative activity of melarsoprol and arsenic trioxide in chronic B-cell leukemia lines. Blood. 1997;90:562–70.

    PubMed  CAS  Google Scholar 

  90. Au W-Y, Tam S, Fong BM, Kwong Y-L. Determinants of cerebrospinal fluid arsenic concentration in patients with acute promyelocytic leukemia on oral arsenic trioxide therapy. Blood. 2008;112:3587–90.

    Article  PubMed  CAS  Google Scholar 

  91. Au W-Y, Hon C, Yau K, et al. Two cases of monocular visual loss during oral arsenic trioxide therapy of acute promyelocytic leukemia. Am J Hematol. 2009;84:699.

    Article  PubMed  Google Scholar 

Download references

Disclosure

H.J. Iland: Provided expert testimony to Phebra, received payment for development of educational presentations from Novartis and Elsevier, and had conference accommodation expenses covered by Roche; J.F Seymour: Consultancy for Phebra.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Iland, H.J., Seymour, J.F. Role of Arsenic Trioxide in Acute Promyelocytic Leukemia. Curr. Treat. Options in Oncol. 14, 170–184 (2013). https://doi.org/10.1007/s11864-012-0223-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11864-012-0223-3

Keywords

Navigation