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      Revised Adult T-Cell Leukemia-Lymphoma International Consensus Meeting Report

      research-article
      Author(s): , MD, PhD 1 , 2 , , MD, PhD 3 , , MD, PhD 4 , , MD, PhD 5 , , MD 6 , , MD, PhD 7 , , MD 8 , , MD, PhD 9 , , MD 10 , , MD, PhD 11 , , MD, PhD 12 , , MD 2 , , MD 13 , , MD, PhD 14 , , MD, PhD 4 , , MD, PhD 4 , , MD, PhD 4 , , MD 15 , , DO 16 , , MD, PhD 17 , , MD 18 , , MD 19 , , MD, PhD 20 , , MD, PhD 21 , , MD, PhD 22 , , MD, PhD 23 , , MD, PhD 24 , , MD, PhD 25 , , MD, PhD 26 , , MD, PhD 27 , , MD, PhD 28 , , MD, PhD 23
      Publication date (Electronic):
      Journal: Journal of Clinical Oncology
      Publisher: American Society of Clinical Oncology

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          Abstract

          Purpose

          Adult T-cell leukemia-lymphoma (ATL) is a distinct mature T-cell malignancy caused by chronic infection with human T-lymphotropic virus type 1 with diverse clinical features and prognosis. ATL remains a challenging disease as a result of its diverse clinical features, multidrug resistance of malignant cells, frequent large tumor burden, hypercalcemia, and/or frequent opportunistic infection. In 2009, we published a consensus report to define prognostic factors, clinical subclassifications, treatment strategies, and response criteria. The 2009 consensus report has become the standard reference for clinical trials in ATL and a guide for clinical management. Since the last consensus there has been progress in the understanding of the molecular pathophysiology of ATL and risk-adapted treatment approaches.

          Methods

          Reflecting these advances, ATL researchers and clinicians joined together at the 18th International Conference on Human Retrovirology—Human T-Lymphotropic Virus and Related Retroviruses—in Tokyo, Japan, March, 2017, to review evidence for current clinical practice and to update the consensus with a new focus on the subtype classification of cutaneous ATL, CNS lesions in aggressive ATL, management of elderly or transplantation-ineligible patients, and treatment strategies that incorporate up-front allogeneic hematopoietic stem-cell transplantation and novel agents.

          Results

          As a result of lower-quality clinical evidence, a best practice approach was adopted and consensus statements agreed on by coauthors (> 90% agreement).

          Conclusion

          This expert consensus highlights the need for additional clinical trials to develop novel standard therapies for the treatment of ATL

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          Most cited references81

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          Aberrant PD-L1 expression through 3'-UTR disruption in multiple cancers.

          Keisuke Kataoka, Yuichi Shiraishi, Yohei Takeda … (2016)
          Successful treatment of many patients with advanced cancer using antibodies against programmed cell death 1 (PD-1; also known as PDCD1) and its ligand (PD-L1; also known as CD274) has highlighted the critical importance of PD-1/PD-L1-mediated immune escape in cancer development. However, the genetic basis for the immune escape has not been fully elucidated, with the exception of elevated PD-L1 expression by gene amplification and utilization of an ectopic promoter by translocation, as reported in Hodgkin and other B-cell lymphomas, as well as stomach adenocarcinoma. Here we show a unique genetic mechanism of immune escape caused by structural variations (SVs) commonly disrupting the 3' region of the PD-L1 gene. Widely affecting multiple common human cancer types, including adult T-cell leukaemia/lymphoma (27%), diffuse large B-cell lymphoma (8%), and stomach adenocarcinoma (2%), these SVs invariably lead to a marked elevation of aberrant PD-L1 transcripts that are stabilized by truncation of the 3'-untranslated region (UTR). Disruption of the Pd-l1 3'-UTR in mice enables immune evasion of EG7-OVA tumour cells with elevated Pd-l1 expression in vivo, which is effectively inhibited by Pd-1/Pd-l1 blockade, supporting the role of relevant SVs in clonal selection through immune evasion. Our findings not only unmask a novel regulatory mechanism of PD-L1 expression, but also suggest that PD-L1 3'-UTR disruption could serve as a genetic marker to identify cancers that actively evade anti-tumour immunity through PD-L1 overexpression.
          Article 0 comments Cited 280 times – based on 0 reviews     Review now
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            Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma: a proposal from an international consensus meeting.

            Kunihiro Tsukasaki, Olivier Hermine, Ali Bazarbachi … (2009)
            Adult T-cell leukemia-lymphoma (ATL) is a distinct peripheral T-lymphocytic malignancy associated with a retrovirus designated human T-cell lymphotropic virus type I (HTLV-1). The diversity in clinical features and prognosis of patients with this disease has led to its subclassification into the following four categories: acute, lymphoma, chronic, and smoldering types. The chronic and smoldering subtypes are considered indolent and are usually managed with watchful waiting until disease progression, analogous to the management of some patients with chronic lymphoid leukemia (CLL) or other indolent histology lymphomas. Patients with aggressive ATL generally have a poor prognosis because of multidrug resistance of malignant cells, a large tumor burden with multiorgan failure, hypercalcemia, and/or frequent infectious complications as a result of a profound T-cell immunodeficiency. Under the sponsorship of the 13th International Conference on Human Retrovirology: HTLV, a group of ATL researchers joined to form a consensus statement based on established data to define prognostic factors, clinical subclassifications, and treatment strategies. A set of response criteria specific for ATL reflecting a combination of those for lymphoma and CLL was proposed. Clinical subclassification is useful but is limited because of the diverse prognosis among each subtype. Molecular abnormalities within the host genome, such as tumor suppressor genes, may account for these diversities. A treatment strategy based on the clinical subclassification and prognostic factors is suggested, including watchful waiting approach, chemotherapy, antiviral therapy, allogeneic hematopoietic stem-cell transplantation (alloHSCT), and targeted therapies.
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              Meta-analysis on the use of zidovudine and interferon-alfa in adult T-cell leukemia/lymphoma showing improved survival in the leukemic subtypes.

              Ali Bazarbachi, Yves Plumelle, Juan Carlos Ramos … (2010)
              Human T-cell lymphotropic virus type-I-associated adult T-cell leukemia/lymphoma (ATL) is an aggressive, chemotherapy-resistant malignancy. Multiple small studies using zidovudine (AZT) and interferon-alfa (IFN-α) have shown response in patients with ATL. However, the impact of this innovative antiviral treatment strategy on long-term survival remains undetermined. We report a meta-analysis of antiviral therapy of ATL. Medical records of 254 patients with ATL who were treated in the United States, the United Kingdom, Martinique, and continental France were individually reviewed. According to Shimoyama classification, there were 116 patients with acute ATL, 18 patients with chronic ATL, 11 patients with smoldering ATL, and 100 patients with ATL lymphoma. In 231 patients with available survival data, first-line therapy was recorded in 207 patients. Five-year overall survival rates were 46% for 75 patients who received first-line antiviral therapy (P = .004), 20% for 77 patients who received first-line chemotherapy, and 12% for 55 patients who received first-line chemotherapy followed by antiviral therapy. Patients with acute, chronic, and smoldering ATL significantly benefited from first-line antiviral therapy, whereas patients with ATL lymphoma experienced a better outcome with chemotherapy. In acute ATL, achievement of complete remission with antiviral therapy resulted in 82% 5-year survival. Antiviral therapy in chronic and smoldering ATL resulted in 100% 5-year survival. Multivariate analysis confirmed that first-line antiviral therapy significantly improves overall survival of patients with ATL (hazard ratio, 0.47; 95% CI, 0.27 to 0.83; P = .021). These results confirm the high efficacy of AZT and IFN, which should now be considered the gold standard first-line therapy in leukemic subtypes of ATL.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Clin Oncol
                Journal ID (iso-abbrev): J. Clin. Oncol
                Journal ID (hwp): jco
                Journal ID (pmc): jco
                Journal ID (publisher-id): JCO
                Title: Journal of Clinical Oncology
                Publisher: American Society of Clinical Oncology
                ISSN (Print): 0732-183X
                ISSN (Electronic): 1527-7755
                Publication date (Print): 10 March 2019
                Publication date (Electronic): 18 January 2019
                Publication date PMC-release: 10 March 2020
                Volume: 37
                Issue: 8
                Pages: 677-687
                Affiliations
                [ 1 ]Imperial College Healthcare National Health Service (NHS) Trust, London, United Kingdom
                [ 2 ]Imperial College London, London, United Kingdom
                [ 3 ]Osaka International Cancer Institute, Osaka, Japan
                [ 4 ]Necker University Hospital, Paris, France
                [ 5 ]American University of Beirut, Beirut, Lebanon
                [ 6 ]University of Miami, Miami, FL
                [ 7 ]Washington University School of Medicine, St Louis, MO
                [ 8 ]Memorial Sloan Kettering Cancer Center, New York, NY
                [ 9 ]Guys and St Thomas Hospital, Kings Health Partners, London, United Kingdom
                [ 10 ]Fundeni Clinical Institute, Bucharest, Romania
                [ 11 ]Emergency University Hospital, Bucharest, Romania
                [ 12 ]University College London Hospitals NHS Trust, London, United Kingdom
                [ 13 ]National Cancer Institute, Bethesda, MD
                [ 14 ]Universidade Federal da Bahia, Salvador, Brazil
                [ 15 ]Weill Cornell Medical College, New York, NY
                [ 16 ]University of Nebraska, Omaha, NE
                [ 17 ]Mashhad University of Medical Sciences, Mashhad, Iran
                [ 18 ]Nagasaki University, Nagasaki, Japan
                [ 19 ]National Kyushu Cancer Center, Fukuoka, Japan
                [ 20 ]Iwate Medical University, Morioka, Japan
                [ 21 ]Kagoshima University Hospital, Kagoshima, Japan
                [ 22 ]University of the Ryukyus, Okinawa, Japan
                [ 23 ]The University of Tokyo, Tokyo, Japan
                [ 24 ]Kyoto University, Kyoto, Japan
                [ 25 ]Hamamatsu University School of Medicine, Hamamatsu, Japan
                [ 26 ]Imamura General Hospital, Kagoshima, Japan
                [ 27 ]Kumamoto University, Kumamoto, Japan
                [ 28 ]Saitama Medical University, Saitama, Japan
                Author notes

                L.B.C. and S.F. contributed equally to this work.

                Kunihiro Tsukasaki, MD, Department of Hematology, International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1298, Japan; Twitter: @htlvnet; e-mail: tsukasak@ 123456saitama-med.ac.jp .
                Article
                Publisher ID: 1800501
                DOI: 10.1200/JCO.18.00501
                PMC ID: 6494249
                PubMed ID: 30657736
                SO-VID: 7ec0fd43-ccfb-49f3-9056-24e64123e9e6
                Copyright © © 2019 by American Society of Clinical Oncology
                License:

                Licensed under the Creative Commons Attribution 4.0 License: https://creativecommons.org/licenses/by/4.0/

                History
                Date accepted : 18 October 2018
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 83, Pages: 12
                Categories
                Subject: Special Article
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