Adult T Cell Leukemia-Lymphoma (ATL): State of the Art
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Purpose of Review
ATL is a rare and highly aggressive T cell malignancy caused by HTLV-1. We will review the state of the art of ATL epidemiology, pathogenesis, diagnosis, and treatment.
Because of population migration, cases of ATL in non-HTLV-1 endemic countries including North America and Europe are increasingly recognized. ATL has diverse clinical manifestations, limited treatment options not widely available globally, and poor prognosis despite therapy. A small subset of patients may achieve prolonged survival with antiviral therapy or allogeneic stem cell transplant. Mogamulizumab, an anti-CCR4 monoclonal antibody, and lenalidomide, an immunomodulatory drug, are approved for ATL in Japan. Molecular studies have identified key alterations in T cell signaling and DNA methylation that may further guide drug development. Patients should be encouraged to enroll in prospective clinical trials when possible.
Ongoing, collaborative, international research continues to elucidate disease pathogenesis and contribute to an evolving therapeutic landscape for ATL.
KeywordsHTLV-1 ATL Non-Hodgkin’s lymphoma
Compliance with Ethical Standards
Conflict of Interest
Adrienne Phillips is a principal investigator for a prospective, multicenter, randomized study of anti-CCR4 monoclonal antibody mogamulizumab (moga) vs investigator’s choice (IC) in the treatment of patients (pts) with relapsed/refractory (R/R) adult T cell leukemia-lymphoma (ATL) and received research funding. Janine Harewood declares that she has no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 4.Phillips AA, Shapira I, Willim RD. A critical analysis of prognostic factors in North American patients with human T-cell lymphotropic virus type-1-associated adult T-cell leukemia/lymphoma: a multicenter clinicopathologic experience and new prognostic score. Cancer. 2010;116(14):3438–46.CrossRefPubMedGoogle Scholar
- 5.Zell MI, Assal A, Konda B, Braunschweig I, Derman O, Kornblum N, et al. Analysis of large cohort shows that Caribbean adult T-cell leukemia/lymphoma is a chemotherapy refractory disease with very poor prognosis that behaves distinctly from Japanese subtypes. Blood. 2014;124:1685.Google Scholar
- 8.•• Watanabe T. Adult T-cell leukemia: molecular basis for clonal expansion and transformation of HTLV-1-infected T cells. Blood. 2017;129(9):1071–81. This is a comprehensive overview of recently uncovered information on the molecular basis of leukemogenesis in ATL. CrossRefPubMedPubMedCentralGoogle Scholar
- 9.•• Kataoka K, Nagata Y, Kitanaka A, Shiraishi Y, Shimamura T, Yasunaga J, et al. Integrated molecular analysis of adult T-cell leukemia/lymphoma. Nat Genet. 2015;47:1304–15. This is an integrated molecular study of 426 ATL cases which identifies alterations in T cell receptor-NFκB signaling, T cell trafficking, and other T cell related pathways which will guide the development of new diagnostics and therapeutics in ATL. CrossRefPubMedGoogle Scholar
- 14.Tanosaki R, Uike N, Utsunomiya A, Saburi Y, Masuda M, Tomonaga M, 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;14:702–8.CrossRefPubMedGoogle Scholar
- 31.Tsukasaki K, Hermine O, Bazarbachi A, Ratner L, Ramos JC, Harrington W Jr, 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(3):453–9.CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Suzumiya J, Ohshima K, Tamura K, Karube K, Uike N, Tobinai 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;20:715–21.CrossRefPubMedGoogle Scholar
- 44.•• Ishida T, Hishizawa M, Kato K, Tanosaki R, Fukuda T, Taniguchi S, 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(8):1734–41. This is the largest study of ATL patients receiving hematopoietic stem cell transplantation CrossRefPubMedGoogle Scholar
- 46.Kurata M, Yanagisawa A, Atsuta Y, Sakamaki H, Kato K, Ichinohe T, et al. Hematopoietic cell transplantation in Japan, Clinical blood. 2014;55(12):2381–2399, https://doi.org/10.11406/rinketsu.55.2381, https://www.jstage.jst.go.jp/article/rinketsu/55/12/55_2381/_article/-char/ja
- 54.Fuji S, Inoue Y, Utsunomiya A, Moriuchi Y, Uchimaru K, Choi I, et al. Pretransplantation anti-CCR4 antibody mogamulizumab against adult T-cell leukemia/lymphoma is associated with significantly increase risks of severe and corticosteroid-refractory graft-versus-host disease, nonrelapse mortality, and overall mortality. J Clin Oncol. 2016;34:3426–33.CrossRefPubMedGoogle Scholar
- 56.Ishida T, Jo T, Takemoto S, Suzushima H, Uozumi K, Yamamoto K, et al. Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study. Br J Haematol. 2015;169:672–82.CrossRefPubMedPubMedCentralGoogle Scholar
- 57.Phillips AA, Fields P, Hermine O, Ramos JC, Beltran BE, Pereira P, et al. A prospective, multicenter, randomized study of anti-CCR4 monoclonal antibody mogamulizumab (moga) vs investigator's choice (IC) in the treatment of patients (pts) with relapsed/refractory (R/R) adult T-cell leukemia-lymphoma (ATL). J Clin Oncol. 2016;34:abstr 7501.CrossRefGoogle Scholar
- 59.Mukhi N, Verma V, Ahmed A, et al. Romidepsin in relapsed/refratcory HTLV-1 associated adult T-cell lymphoma/leukemia: a case series. Blood. 2015;126:5113.Google Scholar
- 60.Lunning MA, Gonsky J, Ruan J, Phillips AA, Pulitzer M, Moskowitz A, et al. Pralatrexate in relapsed/refractory HTLV-1 associated adult T-cell lymphoma/leukemia: a New York City multi-institutional experience. Blood. 2012;120:2735.Google Scholar
- 64.• Hermine O, Ramos JC, Tobinai K. A review of new findings in adult T-cell leukemia-lymphoma: a focus on current and emerging treatment strategies. Adv Ther. 2018;35:135–52. A summary of recently completed and/or ongoing studies of novel therapies in ATL.Google Scholar
- 65.Suehiro Y, Hasegawa A, Iino T, Sasada A, Watanabe N, Matsuoka M, et al. Clinical outcomes of a novel therapeutic vaccine with Tax peptide-pulsed dendritic cells for adult T cell leukaemia/lymphoma in a pilot study. Br J Haematol. 2015;169(3):356–67. https://doi.org/10.1111/bjh.13302.CrossRefPubMedGoogle Scholar
- 66.Revaud D, Bejanariu A, Loussaief L, et al. Development of an anti-HTLV-1 vaccine for the treatment of adult T-cell leukemia/lymphoma. Presented at: 57th Annual Meeting and Exposition of the American Society of Hemtology, December 5–8, 2015, Orlando, FL.Google Scholar