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Treatment and prognosis of adult T cell leukemia-lymphoma

INTRODUCTION

Adult T cell leukemia-lymphoma (ATL) is a peripheral T cell neoplasm associated with infection by the human T-lymphotropic virus, type I (HTLV-1). Although it is considered one of the highly aggressive T cell non-Hodgkin lymphoma (NHL) variants, the disease course is variable and sometimes quite indolent.

Four clinical variants of ATL have been described: acute, lymphoma-type (lymphomatous), chronic and smoldering; these appear to have differing genomic alterations and varying clinical courses, and may require different treatment.

The treatment of ATL is discussed here. The epidemiology, pathogenesis, clinical features, pathology, and diagnosis of ATL are discussed separately. (See "Clinical manifestations, pathologic features, and diagnosis of adult T cell leukemia-lymphoma".)

INDICATIONS FOR TREATMENT

As mentioned above, there are four clinical variants of adult T cell leukemia-lymphoma (ATL): acute, lymphoma-type, chronic, and smoldering [1,2]. These differ greatly in their presentation and prognosis. Therapy is usually offered to patients with acute, lymphoma-type, or unfavorable chronic type ATL while patients with typical chronic or smoldering ATL are observed initially. This is principally because conventional chemotherapy does not appear to improve the survival of patients with chronic or smoldering ATL [3,4]. The five-year survival rate of patients with chronic and smoldering ATL was 47 percent in one study [5].

As an example, a retrospective evaluation of 26 patients with smoldering ATL reported that 14 (54 percent) were alive without tumor progression at median follow-up of 6.5 years [4]. For those who died, the median time to transformation to a more aggressive variant was 38 months.

               

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Literature review current through: Jun 2014. | This topic last updated: Mar 3, 2014.
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References
Top
  1. Ravandi F, O'Brien S. Chronic lymphoid leukemias other than chronic lymphocytic leukemia: diagnosis and treatment. Mayo Clin Proc 2005; 80:1660.
  2. Shimoyama M. Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87). Br J Haematol 1991; 79:428.
  3. Ishitsuka K, Tamura K. Treatment of adult T-cell leukemia/lymphoma: past, present, and future. Eur J Haematol 2008; 80:185.
  4. Ishitsuka K, Ikeda S, Utsunomiya A, et al. Smouldering adult T-cell leukaemia/lymphoma: a follow-up study in Kyushu. Br J Haematol 2008; 143:442.
  5. Takasaki Y, Iwanaga M, Imaizumi Y, et al. Long-term study of indolent adult T-cell leukemia-lymphoma. Blood 2010; 115:4337.
  6. Tsukasaki K, Hermine O, Bazarbachi A, et al. Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma: a proposal from an international consensus meeting. J Clin Oncol 2009; 27:453.
  7. Vose J, Armitage J, Weisenburger D, International T-Cell Lymphoma Project. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol 2008; 26:4124.
  8. Suzumiya J, Ohshima K, Tamura K, et al. The International Prognostic Index predicts outcome in aggressive adult T-cell leukemia/lymphoma: analysis of 126 patients from the International Peripheral T-Cell Lymphoma Project. Ann Oncol 2009; 20:715.
  9. Kwee TC, Kwee RM, Nievelstein RA. Imaging in staging of malignant lymphoma: a systematic review. Blood 2008; 111:504.
  10. Utsunomiya A, Hanada S, Terada A, et al. Adult T-cell leukemia with leukemia cell infiltration into the gastrointestinal tract. Cancer 1988; 61:824.
  11. Tobinai K. Current management of adult T-cell leukemia/lymphoma. Oncology (Williston Park) 2009; 23:1250.
  12. Shimoyama M, Ota K, Kikuchi M, et al. Chemotherapeutic results and prognostic factors of patients with advanced non-Hodgkin's lymphoma treated with VEPA or VEPA-M. J Clin Oncol 1988; 6:128.
  13. Shimoyama M, Ota K, Kikuchi M, et al. Major prognostic factors of adult patients with advanced T-cell lymphoma/leukemia. J Clin Oncol 1988; 6:1088.
  14. Tobinai K, Shimoyama M, Minato K, et al. Japan Clinical Oncology Group trial of second-generation "LSG4 protocol" in aggressive lymphoma including ATL: prognostic factors and a predictive model (abstract). Proc Am Soc Clin Oncol 1994; 13:378a.
  15. Tsukasaki K, Tobinai K, Shimoyama M, et al. Deoxycoformycin-containing combination chemotherapy for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study (JCOG9109). Int J Hematol 2003; 77:164.
  16. Yamada Y, Tomonaga M, Fukuda H, et al. A new G-CSF-supported combination chemotherapy, LSG15, for adult T-cell leukaemia-lymphoma: Japan Clinical Oncology Group Study 9303. Br J Haematol 2001; 113:375.
  17. Tsukasaki K, Utsunomiya A, Fukuda H, et al. VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study JCOG9801. J Clin Oncol 2007; 25:5458.
  18. Yamada Y, Kamihira S, Amagasaki T, et al. Adult T cell leukemia with atypical surface phenotypes: clinical correlation. J Clin Oncol 1985; 3:782.
  19. Jo T, Ishida T, Takemoto S, et al. Randomized phase II study of mogamulizumab (KW-0761) plus VCAP-AMP-VECP (mLSG15) versus mLSG15 alone for newly diagnosed aggressive adult T-cell leukemia-lymphoma (ATL) (Abstract 8506). J Clin Oncol 2013; 31:519s.
  20. Teshima T, Akashi K, Shibuya T, et al. Central nervous system involvement in adult T-cell leukemia/lymphoma. Cancer 1990; 65:327.
  21. Dungerwalla M, Osuji N, Waldman AD, et al. Isolated central nervous system involvement in adult T-cell lymphoma/leukaemia. Br J Haematol 2005; 130:511.
  22. Di Venuti G, Nawgiri R, Foss F. Denileukin diftitox and hyper-CVAD in the treatment of human T-cell lymphotropic virus 1-associated acute T-cell leukemia/lymphoma. Clin Lymphoma 2003; 4:176.
  23. Matsushita K, Matsumoto T, Ohtsubo H, et al. Long-term maintenance combination chemotherapy with OPEC/MPEC (vincristine or methotrexate, prednisolone, etoposide and cyclophosphamide) or with daily oral etoposide and prednisolone can improve survival and quality of life in adult T-cell leukemia/lymphoma. Leuk Lymphoma 1999; 36:67.
  24. Kojima H, Hori M, Shibuya A, et al. Successful treatment of a patient with adult T-cell leukemia by daily oral administration of low-dose etoposide. Decrease in the amount of HTLV-I proviral DNA revealed by the polymerase chain reaction method. Cancer 1993; 72:3614.
  25. Hande KR, Garrow GC. Acute tumor lysis syndrome in patients with high-grade non-Hodgkin's lymphoma. Am J Med 1993; 94:133.
  26. Taylor GP, Matsuoka M. Natural history of adult T-cell leukemia/lymphoma and approaches to therapy. Oncogene 2005; 24:6047.
  27. Matutes E, Taylor GP, Cavenagh J, et al. Interferon alpha and zidovudine therapy in adult T-cell leukaemia lymphoma: response and outcome in 15 patients. Br J Haematol 2001; 113:779.
  28. Gill PS, Harrington W Jr, Kaplan MH, et al. Treatment of adult T-cell leukemia-lymphoma with a combination of interferon alfa and zidovudine. N Engl J Med 1995; 332:1744.
  29. White JD, Wharfe G, Stewart DM, et al. The combination of zidovudine and interferon alpha-2B in the treatment of adult T-cell leukemia/lymphoma. Leuk Lymphoma 2001; 40:287.
  30. Hermine O, Allard I, Lévy V, et al. A prospective phase II clinical trial with the use of zidovudine and interferon-alpha in the acute and lymphoma forms of adult T-cell leukemia/lymphoma. Hematol J 2002; 3:276.
  31. Ratner L, Harrington W, Feng X, et al. Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma. PLoS One 2009; 4:e4420.
  32. Kchour G, Tarhini M, Kooshyar MM, et al. Phase 2 study of the efficacy and safety of the combination of arsenic trioxide, interferon alpha, and zidovudine in newly diagnosed chronic adult T-cell leukemia/lymphoma (ATL). Blood 2009; 113:6528.
  33. Hodson A, Crichton S, Montoto S, et al. Use of zidovudine and interferon alfa with chemotherapy improves survival in both acute and lymphoma subtypes of adult T-cell leukemia/lymphoma. J Clin Oncol 2011; 29:4696.
  34. Bazarbachi A, Plumelle Y, Carlos Ramos J, et al. Meta-analysis on the use of zidovudine and interferon-alfa in adult T-cell leukemia/lymphoma showing improved survival in the leukemic subtypes. J Clin Oncol 2010; 28:4177.
  35. Bazarbachi A, Suarez F, Fields P, Hermine O. How I treat adult T-cell leukemia/lymphoma. Blood 2011; 118:1736.
  36. Tsukasaki K, Maeda T, Arimura K, et al. Poor outcome of autologous stem cell transplantation for adult T cell leukemia/lymphoma: a case report and review of the literature. Bone Marrow Transplant 1999; 23:87.
  37. Fukushima T, Miyazaki Y, Honda S, et al. Allogeneic hematopoietic stem cell transplantation provides sustained long-term survival for patients with adult T-cell leukemia/lymphoma. Leukemia 2005; 19:829.
  38. Itonaga H, Tsushima H, Taguchi J, et al. Treatment of relapsed adult T-cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation: the Nagasaki Transplant Group experience. Blood 2013; 121:219.
  39. Utsunomiya A, Miyazaki Y, Takatsuka Y, et al. Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2001; 27:15.
  40. Kami M, Hamaki T, Miyakoshi S, et al. Allogeneic haematopoietic stem cell transplantation for the treatment of adult T-cell leukaemia/lymphoma. Br J Haematol 2003; 120:304.
  41. Okamura J, Utsunomiya A, Tanosaki R, et al. Allogeneic stem-cell transplantation with reduced conditioning intensity as a novel immunotherapy and antiviral therapy for adult T-cell leukemia/lymphoma. Blood 2005; 105:4143.
  42. Feyler S, Prince HM, Pearce R, et al. The role of high-dose therapy and stem cell rescue in the management of T-cell malignant lymphomas: a BSBMT and ABMTRR study. Bone Marrow Transplant 2007; 40:443.
  43. Yonekura K, Utsunomiya A, Takatsuka Y, et al. Graft-versus-adult T-cell leukemia/lymphoma effect following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2008; 41:1029.
  44. Harashima N, Kurihara K, Utsunomiya A, et al. Graft-versus-Tax response in adult T-cell leukemia patients after hematopoietic stem cell transplantation. Cancer Res 2004; 64:391.
  45. Choi I, Tanosaki R, Uike N, et al. Long-term outcomes after hematopoietic SCT for adult T-cell leukemia/lymphoma: results of prospective trials. Bone Marrow Transplant 2011; 46:116.
  46. Tanosaki R, Uike N, Utsunomiya A, et al. Allogeneic hematopoietic stem cell transplantation using reduced-intensity conditioning for adult T cell leukemia/lymphoma: impact of antithymocyte globulin on clinical outcome. Biol Blood Marrow Transplant 2008; 14:702.
  47. Tobinai K. Clinical trials for human T-cell lymphotropic virus type I-associated peripheral T-cell lymphoma in Japan. Semin Hematol 2010; 47 Suppl 1:S5.
  48. Hishizawa M, Kanda J, Utsunomiya A, et al. Transplantation of allogeneic hematopoietic stem cells for adult T-cell leukemia: a nationwide retrospective study. Blood 2010; 116:1369.
  49. Kanda J, Hishizawa M, Utsunomiya A, et al. Impact of graft-versus-host disease on outcomes after allogeneic hematopoietic cell transplantation for adult T-cell leukemia: a retrospective cohort study. Blood 2012; 119:2141.
  50. Ishida T, Hishizawa M, Kato K, et al. Allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia-lymphoma with special emphasis on preconditioning regimen: a nationwide retrospective study. Blood 2012; 120:1734.
  51. Yasuda N, Lai PK, Ip SH, et al. Soluble interleukin 2 receptors in sera of Japanese patients with adult T cell leukemia mark activity of disease. Blood 1988; 71:1021.
  52. Yoshie O, Fujisawa R, Nakayama T, et al. Frequent expression of CCR4 in adult T-cell leukemia and human T-cell leukemia virus type 1-transformed T cells. Blood 2002; 99:1505.
  53. Yamamoto K, Utsunomiya A, Tobinai K, et al. Phase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody, in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma. J Clin Oncol 2010; 28:1591.
  54. Ishida T, Joh T, Uike N, et al. Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study. J Clin Oncol 2012; 30:837.
  55. Mone A, Puhalla S, Whitman S, et al. Durable hematologic complete response and suppression of HTLV-1 viral load following alemtuzumab in zidovudine/IFN-{alpha}-refractory adult T-cell leukemia. Blood 2005; 106:3380.
  56. Ravandi F, Faderl S. Complete response in a patient with adult T-cell leukemia (ATL) treated with combination of alemtuzumab and pentostatin. Leuk Res 2006; 30:103.
  57. Ishitsuka K, Suzumiya J, Aoki M, et al. Therapeutic potential of arsenic trioxide with or without interferon-alpha for relapsed/refractory adult T-cell leukemia/lymphoma. Haematologica 2007; 92:719.
  58. Hermine O, Dombret H, Poupon J, et al. Phase II trial of arsenic trioxide and alpha interferon in patients with relapsed/refractory adult T-cell leukemia/lymphoma. Hematol J 2004; 5:130.
  59. Maeda Y, Yamaguchi T, Hijikata Y, et al. Clinical efficacy of all-trans retinoic acid for treating adult T cell leukemia. J Cancer Res Clin Oncol 2008; 134:673.
  60. Simone CB 2nd, Morris JC, Stewart DM, et al. Radiation therapy for the management of patients with HTLV-1-associated adult T-cell leukemia/lymphoma. Blood 2012; 120:1816.
  61. Katsuya H, Yamanaka T, Ishitsuka K, et al. Prognostic index for acute- and lymphoma-type adult T-cell leukemia/lymphoma. J Clin Oncol 2012; 30:1635.