Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Spotlight
  • Published:

Treatment of acute promyelocytic leukemia: strategy toward further increase of cure rate

Leukemia volume 17, pages 1454–1463 (2003)Cite this article

Abstract

Acute promyelocytic leukemia (APL) has become a curable disease by all-trans retinoic acid (ATRA)-based induction therapy followed by two or three courses of consolidation chemotherapy. Currently around 90% of newly diagnosed patients with APL achieve complete remission (CR) and over 70% of patients are curable. To further increase the CR and cure rates, detection and diagnosis of this disease at its early stage is very important, hopefully before the appearance of APL-associated coagulopathy. In induction therapy, concomitant chemotherapy is indispensable, except for patients with low initial leukocyte counts. Prophylactic use of intrathecal methotrexate and cytarabine should be done, particularly for patients with hyperleukocytosis. If patients relapse hematologically or even molecularly, arsenic trioxide will be the treatment of choice under careful electrocardiogram monitoring. Am80, liposomal ATRA, gemtuzumab ozogamicin or ATRA in combination with cytotoxic drugs may be used at this stage or later. Allogeneic SCT will be the treatment of choice after patients of age <50 years have relapsed, provided that they have HLA-identical family donors or DNA-identical unrelated donors.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Huang M, Ye Y, Chen S, Chai J, Lu J, Zhoa L et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 1988; 72: 567–572.

    Article  CAS  PubMed  Google Scholar 

  2. Warrell Jr RP, Frankel SR, Miller Jr WH, Scheinberg DA, Itri LM, Hittelman WN et al. Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans -retinoic acid). N Engl J Med 1991; 324: 1385–1393.

    Article  PubMed  Google Scholar 

  3. Ohno R, Yoshida H, Fukutani H, Naoe T, Ohshima T, Kyo T et al. Multi-institutional study of all-trans-retinoic acid as a differentiation therapy of refractory acute promyelocytic leukemia. Leukemia 1993; 7: 722–727.

    Google Scholar 

  4. Fenaux P, Deley MC, Castaigne S, Archimbaud E, Chomienne C, Link H et al. Effect of all transretinoic acid in newly diagnosed acute promyelocytic leukemia. Results of a multicenter randomized trial. Blood 1993; 82: 3241–3249.

    Article  CAS  PubMed  Google Scholar 

  5. Avvisati G, Lo Coco F, Diverio D, Falda M, Ferrara F, Lazzarino M et al. AIDA (all-trans retinoic acid+idarubicin) in newly diagnosed acute promyelocytic leukemia: a Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) pilot study. Blood 1993; 82: 2175–2181.

    Article  Google Scholar 

  6. Kanamaru A, Takemoto N, Tanimoto M, Murakami H, Asou N, Kobayashi T et al. All-trans retinoic acid for the treatment of newly diagnosed acute promyelocytic leukemia. Blood 1995; 85: 1202–1206.

    Article  CAS  PubMed  Google Scholar 

  7. Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A et al. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med 1997; 337: 1021–1028.

    Article  CAS  PubMed  Google Scholar 

  8. Mandelli F, Diverio D, Avvisati G, Luciano A, Barbui T, Bernasconi C et al. Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Blood 1997; 90: 1014–1021.

    CAS  PubMed  Google Scholar 

  9. Asou N, Adachi K, Tamura J, Kanamaru A, Kageyama S, Hiraoka A et al. Analysis of prognostic factors in newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Japan Adult Leukemia Study Group. J Clin Oncol 1998; 16: 78–85.

    Article  CAS  PubMed  Google Scholar 

  10. Burnett AK, Grimwade D, Solomon E, Wheatley K, Goldstone AH . Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the Randomized MRC Trial. Blood 1999; 93: 4131–4143.

    Article  CAS  PubMed  Google Scholar 

  11. Fenaux P, Chastang C, Chevret S, Sanz M, Dombret H, Archimbaud E 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. Blood 1999; 94: 1192–1200.

    Article  CAS  PubMed  Google Scholar 

  12. Fenaux P, Chevret S, Guerci A, Fegueux N, Dombret H, Thomas X et al. Long-term follow-up confirms the benefit of all-trans retinoic acid in acute promyelocytic leukemia. Leukemia 2000; 14: 1371–1377.

    Article  CAS  PubMed  Google Scholar 

  13. Sanz MA, Martin G, Rayon C, Esteve J, Gonzalez M, Diaz-Mediavilla J et al. A modified AIDA protocol with anthracycline-based consolidation results in high antileukemic efficacy and reduced toxicity in newly diagnosed PML/RARalpha-positive acute promyelocytic leukemia. Blood 1999; 94: 3015–3021.

    CAS  PubMed  Google Scholar 

  14. Lengfelder E, Reichert A, Schoch C, Haase D, Haferlach T, Loffler H et al. Double induction strategy including high dose cytarabine in combination with all-trans retinoic acid: effects in patients with newly diagnosed acute promyelocytic leukemia. Leukemia 2000; 14: 1362–1370.

    Article  CAS  PubMed  Google Scholar 

  15. Asou N, Adachi K, Tamura J, Kanamaru A, Kageyama S, Hiraoka A et al. Analysis of prognostic factors in newly diagnosed acute promyelocytic leukemia: the APL92 study Japan Adult Leukemia Study Group (JALSG). Cancer Chemother Pharmacol 2001; 48 (Suppl 1) S65–S71.

    Article  PubMed  Google Scholar 

  16. Lo Coco F, Nervi C, Avvisati G, Mandelli F . Acute promyelocytic leukemia: a curable disease. Leukemia 1998; 12: 1866–1880.

    Article  CAS  PubMed  Google Scholar 

  17. Tallman MS, Nabhan C, Feusner JH, Rowe JM . Acute promyelocytic leukemia: evolving therapeutic strategies. Blood 2002; 99: 759–767.

    Article  CAS  PubMed  Google Scholar 

  18. Paietta E, Andersen J, Racevskis J, Gallagher R, Bennett J, Yunis J et al. Significantly lower P-glycoprotein expression in acute promyelocytic leukemia than in other types of acute myeloid leukemia: immunological, molecular and functional analyses. Leukemia 1994; 8: 968–973.

    CAS  PubMed  Google Scholar 

  19. Michieli M, Damiani D, Ermacora A, Geromin A, Michelutti A, Masolini P et al. P-glycoprotein (PGP), lung resistance-related protein (LRP) and multidrug resistance-associated protein (MRP) expression in acute promyelocytic leukaemia. Br J Haematol 2000; 108: 703–709.

    Article  CAS  PubMed  Google Scholar 

  20. Takeshita A, Shinjo K, Naito K, Ohnishi K, Sugimoto Y, Yamakawa Y et al. Role of P-glycoprotein in all-trans retinoic acid (ATRA) resistance in acute promyelocytic leukaemia cells: analysis of intracellular concentration of ATRA. Br J Haematol 2000; 108: 90–92.

    Article  CAS  PubMed  Google Scholar 

  21. Avvisati G, Petti MC, Lo-Coco F, Vegna ML, Amadori S, Baccarani M 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: 3141–3146.

    Article  CAS  PubMed  Google Scholar 

  22. Gallagher RE . Retinoic acid-resistance in acute promyelocytic leukemia. Leukemia 2002; 16: 1940–1958.

    Article  CAS  PubMed  Google Scholar 

  23. Jansen JH, de Ridder MC, Geertsma WM, Erpelinck CA, van Lom K, Smit EM et al. Complete remission of t(11; 17) positive acute promyelocytic leukemia induced by all-trans retinoic acid and granulocyte colony-stimulating factor. Blood 1999; 94: 39–45.

    Article  CAS  PubMed  Google Scholar 

  24. Culligan DJ, Stevenson D, Chee YL, Grimwade D . Acute promyelocytic leukaemia with t(11; 17)(q23; q12-21) and a good initial response to prolonged ATRA and combination chemotherapy. Br J Haematol 1998; 100: 328–330.

    Article  CAS  PubMed  Google Scholar 

  25. Petti MC, Fazi F, Gentile M, Diverio D, De Fabritiis P, De Propris MS et al. Complete remission through blast cell differentiation in PLZF/RARalpha-positive acute promyelocytic leukemia: in vitro and in vivo studies. Blood 2002; 100: 1065–1067.

    Article  CAS  PubMed  Google Scholar 

  26. Di Bona E, Avvisati G, Castaman G, Luce Vegna M, De Sanctis V, Rodeghiero F et al. Early haemorrhagic morbidity and mortality during remission induction with or without all-trans retinoic acid in acute promyelocytic leukaemia. Br J Haematol 2000; 108: 689–695.

    Article  CAS  PubMed  Google Scholar 

  27. Koyama T, Hirosawa S, Kawamata N, Tohda S, Aoki N . All-trans retinoic acid upregulates thrombomodulin and downregulates tissue-factor expression in acute promyelocytic leukemia cells: distinct expression of thrombomodulin and tissue factor in human leukemic cells. Blood 1994; 84: 3001–3009.

    Article  CAS  PubMed  Google Scholar 

  28. Menell JS, Cesarman GM, Jacovina AT, McLaughlin MA, Lev EA, Hajjar KA . Annexin II and bleeding in acute promyelocytic leukemia. N Engl J Med 1999; 340: 994–1004.

    Article  CAS  PubMed  Google Scholar 

  29. Barbui T, Finazzi G, Falanga A . The impact of all-trans-retinoic acid on the coagulopathy of acute promyelocytic leukemia. Blood 1998; 91: 3093–3102.

    Article  CAS  PubMed  Google Scholar 

  30. Frankel SR, Eardley A, Lauwers G, Weiss M, Warrell Jr RP . The retinoic acid syndrome in acute promyelocytic leukemia. Ann Intern Med 1992; 117: 292.

    Article  CAS  PubMed  Google Scholar 

  31. De Botton S, Dombret H, Sanz M, Miguel JS, Caillot D, Zittoun R et al. Incidence, clinical features, and outcome of all trans-retinoic acid syndrome in 413 cases of newly diagnosed acute promyelocytic leukemia. Blood 1998; 92: 2712–2718.

    Article  CAS  PubMed  Google Scholar 

  32. Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A et al. Clinical description of 44 patients with acute promyelocytic leukemia who developed the retinoic acid syndrome. Blood 2000; 95: 90–95.

    CAS  PubMed  Google Scholar 

  33. Camacho LH, Soignet SL, Chanel S, Ho R, Heller G, Scheinberg DA et al. Leukocytosis and the retinoic acid syndrome in patients with acute promyelocytic leukemia treated with arsenic trioxide. J Clin Oncol 2000; 18: 2620–2625.

    Article  CAS  PubMed  Google Scholar 

  34. Tallman MS . Retinoic acid syndrome: a problem of the past? Leukemia 2002; 16: 160–161.

    Article  CAS  PubMed  Google Scholar 

  35. Wiley JS, Firkin FC . Reduction of pulmonary toxicity by prednisolone prophylaxis during all-trans retinoic acid treatment of acute promyelocytic leukemia. Leukemia 1995; 9: 774–778.

    CAS  PubMed  Google Scholar 

  36. Mandelli F, Diverio D, Avvisati G, Luciano A, Barbui T, Bernasconi C et al. Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Blood 1997; 90: 1014–1021.

    CAS  PubMed  Google Scholar 

  37. Diverio D, Rossi V, Avvisati G, De Santis S, Pistilli A, Pane F et al. Early detection of relapse by prospective reverse transcriptase-polymerase chain reaction analysis of the PML/RARalpha fusion gene in patients with acute promyelocytic leukemia enrolled in the GIMEMA-AIEOP multicenter ‘AIDA’ trial. Blood 1998; 92: 784–789.

    Article  CAS  PubMed  Google Scholar 

  38. Warrell Jr RP . Retinoid resistance in acute promyelocytic leukemia: new mechanisms, strategies, and implications. Blood 1993; 82: 1949–1953.

    Article  CAS  PubMed  Google Scholar 

  39. Ding W, Li YP, Nobile LM, Grills G, Carrera I, Paietta E et al. Leukemic cellular retinoic acid resistance and missense mutations in the PML-RARalpha fusion gene after relapse of acute promyelocytic leukemia from treatment with all-trans retinoic acid and intensive chemotherapy. Blood 1998; 92: 1172–1183.

    Article  CAS  PubMed  Google Scholar 

  40. Kagechika H, Kawachi E, Hashimoto Y, Himi T, Shudo K . Retinobenzoic acids. 1. Structure–activity relationships of aromatic amides with retinoidal activity. J Med Chem 1988; 31: 2182–2192.

    Article  CAS  PubMed  Google Scholar 

  41. Hashimoto Y, Kagechika H, Kawachi E, Fukazawa H, Saito G, Shudo K . Correlation of differentiation-inducing activity of retinoids on human leukemia cell lines HL-60 and NB-4. J Cancer Res Clin Oncol 1995; 121: 696–698.

    Article  CAS  PubMed  Google Scholar 

  42. Tobita T, Takeshita A, Kitamura K, Ohnishi K, Yanagi M, Hiraoka A et al. Treatment with a new synthetic retinoid, Am80, of acute promyelocytic leukemia relapsed from complete remission induced by all-trans retinoic acid. Blood 1997; 90: 967–973.

    Article  CAS  PubMed  Google Scholar 

  43. Shinjo K, Takeshita A, Ohnishi K, Sakura T, Miyawaki S, Hiraoka A et al. Good prognosis of patients with acute promyelocytic leukemia who achieved second complete remission (CR) with a new retinoid, Am80, after relapse from CR induced by all-trans-retinoic acid. Int J Hematol 2000; 72: 470–473.

    CAS  PubMed  Google Scholar 

  44. Estey EH, Giles FJ, Kantarjian H, O'Brien S, Cortes J, Freireich EJ et al. Molecular remissions induced by liposomal-encapsulated all-trans retinoic acid in newly diagnosed acute promyelocytic leukemia. Blood 1999; 94: 2230–2235.

    Article  CAS  PubMed  Google Scholar 

  45. Douer D, Estey E, Santillana S, Bennett JM, Lopez-Bernstein G, Boehm K et al. Treatment of newly diagnosed and relapsed acute promyelocytic leukemia with intravenous liposomal all-trans retinoic acid. Blood 2001; 97: 73–80.

    Article  CAS  PubMed  Google Scholar 

  46. Soignet SL, Benedetti F, Fleischauer A, Parker BA, Truglia JA, Ra Crisp M et al. Clinical study of 9-cis retinoic acid (LGD1057) in acute promyelocytic leukemia. Leukemia 1998; 12: 1518–1521.

    Article  CAS  PubMed  Google Scholar 

  47. Sun HD, Ma L, Hu XC, Zhang TD, Rong FX, Wang XH et al. Sixteen cases of long-term survivors with acute promyelocytic leukemia treated with traditional Chinese medicine, Ailin No. 1. Informat Tradition Chin Med 1991 (Chinese); 6: 39.

    Google Scholar 

  48. Sun HD, Ma L, Hu XC, Zhang TD . Treatment of 32 cases of acute promyelocytic leukemia with traditional Chinese medicine, Ailin No.1. Chin J Integrat Chin West Med 1992 (Chinese); 12: 170–171.

    Google Scholar 

  49. Zhang P, Wang SY, Hu LH, Shi FD, Qiu FQ, Hong GJ et al. Treatment of 72 cases of acute promyelocytic leukemia with intravenous arsenic trioxide. Chin J Hematol 1996 (Chinese with English abstract); 2: 58–59.

    Google Scholar 

  50. Shen ZX, Chen GQ, Ni JH, Li XS, Xiong SM, Qiu QY 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: 3354–3360.

    Article  CAS  PubMed  Google Scholar 

  51. Soignet SL, Maslak P, Wang ZG, Jhanwar S, Calleja E, Dardashti LJ et al. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N Engl J Med 1998; 339: 1341–1348.

    Article  CAS  PubMed  Google Scholar 

  52. Ohnishi K, Yoshida H, Shigeno K, Nakamura S, Fujisawa S, Naito K et al. Prolongation of the QT interval and ventricular tachycardia in patients treated with arsenic trioxide for acute promyelocytic leukemia. Ann Intern Med 2000; 133: 881–885.

    Article  CAS  PubMed  Google Scholar 

  53. Unnikrishnan D, Dutcher JP, Varshneya N, Lucariello R, Api M, Garl S et al. Torsades de pointes in 3 patients with leukemia treated with arsenic trioxide. Blood 2001; 97: 1514–1516.

    Article  CAS  PubMed  Google Scholar 

  54. Westervelt P, Brown RA, Adkins DR, Khoury H, Curtin P, Hurd D et al. Sudden death among patients with acute promyelocytic leukemia treated with arsenic trioxide. Blood 2001; 98: 266–271.

    Article  CAS  PubMed  Google Scholar 

  55. Huang SY, Chang CS, Tang JL, Tien HF, Kuo TL, Huang SF et al. Acute and chronic arsenic poisoning associated with treatment of acute promyelocytic leukaemia. Br J Haematol 1998; 103: 1092–1095.

    Article  CAS  PubMed  Google Scholar 

  56. Ohnishi K, Yoshida H, Shigeno K, Nakamura S, Fujisawa S, Naito K et al. Arsenic trioxide therapy for relapsed or refractory Japanese patients with acute promyelocytic leukemia: need for careful electrocardiogram monitoring. Leukemia 2002; 16: 617–622.

    Article  CAS  PubMed  Google Scholar 

  57. Niu C, Yan H, Yu T, Sun HP, Liu JX, Li XS 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: 3315–3324.

    Article  CAS  PubMed  Google Scholar 

  58. Soignet SL, Frankel SR, Douer D, Tallman MS, Kantarjian H, Calleja E et al. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol 2001; 19: 3852–3860.

    Article  CAS  PubMed  Google Scholar 

  59. Lu DP, Qiu JY, Jiang B, Wang Q, Liu KY, Liu YR et al. Tetra-arsenic tetra-sulfide for the treatment of acute promyelocytic leukemia: a pilot report. Blood 2002; 99: 3136–3143.

    Article  CAS  PubMed  Google Scholar 

  60. Sievers EL, Larson RA, Stadtmauer EA, Estey E, Lowenberg B, Dombret H et al. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol 2001; 19: 3244–3254.

    Article  CAS  PubMed  Google Scholar 

  61. Petti MC, Pinazzi MB, Diverio D, Romano A, Petrucci MT, De Santis S et al. Prolonged molecular remission in advanced acute promyelocytic leukaemia after treatment with gemtuzumab ozogamicin (Mylotarg CMA-676). Br J Haematol 2001; 115: 63–65.

    Article  CAS  PubMed  Google Scholar 

  62. Estey EH, Giles FJ, Beran M, O'Brien S, Pierce SA, Faderl SH et al. Experience with gemtuzumab ozogamycin (‘mylotarg’) and all-trans retinoic acid in untreated acute promyelocytic leukemia. Blood 2002; 99: 4222–4224.

    Article  CAS  PubMed  Google Scholar 

  63. Jurcic JG, DeBlasio T, Dumont L, Yao TJ, Scheinberg DA .Molecular remission induction with retinoic acid and anti-CD33 monoclonal antibody HuM195 in acute promyelocytic leukemia. Clin Cancer Res 2000; 6: 372–380.

    CAS  PubMed  Google Scholar 

  64. Warrell Jr RP, He LZ, Richon V, Calleja E, Pandolfi PP . Therapeutic targeting of transcription in acute promyelocytic leukemia by use of an inhibitor of histone deacetylase. J Natl Cancer Inst 1998; 90: 1621–1625.

    Article  CAS  PubMed  Google Scholar 

  65. Lin RJ, Nagy L, Inoue S, Shao W, Miller Jr WH, Evans RM . Role of the histone deacetylase complex in acute promyelocytic leukaemia. Nature 1998; 391: 811–814.

    Article  CAS  PubMed  Google Scholar 

  66. Kiyoi H, Naoe T, Yokota S, Nakao M, Minami S, Kuriyama K et al. Internal tandem duplication of FLT3 associated with leukocytosis in acute promyelocytic leukemia. Leukemia Study Group of the Ministry of Health and Welfare (Kohseisho). Leukemia 1997; 11: 1447–1452.

    Article  CAS  PubMed  Google Scholar 

  67. Noguera NI, Breccia M, Divona M, Diverio D, Costa V, De Santis S et al. Alterations of the FLT3 gene in acute promyelocytic leukemia: association with diagnostic characteristics and analysis of clinical outcome in patients treated with the Italian AIDA protocol. Leukemia 2002; 16: 2185–2189.

    Article  CAS  PubMed  Google Scholar 

  68. Yee KW, O'Farrell AM, Smolich BD, Cherrington JM, McMahon G, Wait CL et al. SU5416 and SU5614 inhibit kinase activity of wild-type and mutant FLT3 receptor tyrosine kinase. Blood 2002; 100: 2941–2949.

    Article  CAS  PubMed  Google Scholar 

  69. Propper DJ, McDonald AC, Man A, Thavasu P, Balkwill F, Braybrooke JP et al. Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C. J Clin Oncol 2001; 19: 1485–1492.

    Article  CAS  PubMed  Google Scholar 

  70. Byrd JC, Edenfield WJ, Shields DJ, Dawson NA . Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: a clinical review. J Clin Oncol 1995; 13: 1800–1816.

    Article  CAS  PubMed  Google Scholar 

  71. Giralt S, O'Brien S, Weeks E, Luna M, Kantarjian H . Leukemia cutis in acute promyelocytic leukemia: report of three cases after treatment with all-trans retinoic acid. Leuk Lymphoma 1994; 14: 453–456.

    Article  CAS  PubMed  Google Scholar 

  72. Weiss MA, Warrell Jr RP . Two cases of extramedullary acute promyelocytic leukemia. Cytogenetics, molecular biology, and phenotypic and clinical studies. Cancer 1994; 74: 1882–1886.

    Article  CAS  PubMed  Google Scholar 

  73. Tobita T, Shinjyo K, Yanagi M, Takeshita A, Ohnishi K, Ohno R . Relapse in the external auditory canal of acute promyelocytic leukemia after treatment with all-trans retinoic acid. Intern Med 1997; 36: 484–486.

    Article  CAS  PubMed  Google Scholar 

  74. Specchia G, Lo Coco F, Vignetti M, Avvisati G, Fazi P, Albano F et al. Extramedullary involvement at relapse in acute promyelocytic leukemia patients treated or not with all-trans retinoic acid: a report by the Gruppo Italiano Malattie Ematologiche dell'Adulto. J Clin Oncol 2001; 19: 4023–4028.

    Article  CAS  PubMed  Google Scholar 

  75. Breccia M, Petti MC, Testi AM, Specchia G, Ferrara F, Diverio D et al. Ear involvement in acute promyelocytic leukemia at relapse: a disease-associated ‘sanctuary’? Leukemia 2002; 16: 1127–1130.

    Article  CAS  PubMed  Google Scholar 

  76. Hickstein DD, Hickey MJ, Collins SJ . Transcriptional regulation of the leukocyte adherence protein beta subunit during human myeloid cell differentiation. J Biol Chem 1988; 263: 13863–13867.

    Article  CAS  PubMed  Google Scholar 

  77. Latagliata R, Petti MC, Fenu S, Mancini M, Spiriti MA, Breccia M et al. Therapy-related myelodysplastic syndrome – acute myelogenous leukemia in patients treated for acute promyelocytic leukemia: an emerging problem. Blood 2002; 99: 822–824.

    Article  CAS  PubMed  Google Scholar 

  78. Sanz MA, Arcese W, de la Rubia J, Lo Coco F, Labopin M, Bacigalupo A et al. Stem cell transplantation (SCT) for acute promyelocytic leukemia (APL) in the ATRA era: a survey of the European Blood and Marrow Transplantation Group (EBMT) [abstract]. Blood 2000; 96: 2246.

    Article  Google Scholar 

  79. Collins SJ . Acute promyelocytic leukemia: relieving repression induces remission. Blood 1998; 91: 2631–2633.

    Article  CAS  PubMed  Google Scholar 

  80. Strudwick S, Borden KLB . Finding a role for PML in APL pathogenesis: a critical assessment of potential PML activities. Leukemia 2002; 16: 1906–1917.

    Article  CAS  PubMed  Google Scholar 

  81. Ferbeyre G . PML a target of translocations in APL is a regulator of cellular senescence. Leukemia 2002; 16: 1918–1926.

    Article  CAS  PubMed  Google Scholar 

  82. Lutz PG, Moog-Lutz C, Cayre YE . Signaling revisited in acute promyelocytic leukemia. Leukemia 2002; 16: 1933–1939.

    Article  CAS  PubMed  Google Scholar 

  83. Grimwade David, Lo Coco F . Acute promyelocytic leukemia: a model for the role of molecular diagnosis and residual disease monitoring in directing treatment approach in acute myeloid leukemia. Leukemia 2002; 16: 1959–1973.

    Article  CAS  PubMed  Google Scholar 

  84. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001; 344: 1031–1037.

    Article  CAS  PubMed  Google Scholar 

  85. Takeshita A, Sakamaki H, Miyawaki S, Kobayashi T, Kuriyama K, Yamada O et al. Significant reduction of medical costs by differentiation therapy with all-trans retinoic acid during remission induction of newly diagnosed patients with acute promyelocytic leukemia. The Japan Adult Leukemia Study Group. Cancer 1995; 76: 602–608.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all members of JALSG for their cooperation in the JALSG studies, and Ms Rena Okano for her excellent assistance in the preparation of manuscript.

Author information

Authors and Affiliations

  1. Aichi Cancer Center, Nagoya, 464-8681, Japan

    R Ohno, N Asou & K Ohnishi

  2. Kumamoto University School of Medicine, Kumamoto, 860-0811, Japan

    R Ohno, N Asou & K Ohnishi

  3. Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Japan

    R Ohno, N Asou & K Ohnishi

Authors
  1. R Ohno
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N Asou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K Ohnishi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ohno, R., Asou, N. & Ohnishi, K. Treatment of acute promyelocytic leukemia: strategy toward further increase of cure rate. Leukemia 17, 1454–1463 (2003). https://doi.org/10.1038/sj.leu.2403031

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2403031

Keywords

This article is cited by

Search

Advanced search

Quick links