Skip to main content
Top
Published in: International Journal of Hematology 3/2018

01-03-2018 | Case Report

Long-term clinical remission maintained after cessation of zidovudine and interferon-α therapy in chronic adult T-cell leukemia/lymphoma

Authors: Lucy B. Cook, Aileen G. Rowan, Maria A. Demontis, Sophie Sagawe, Nicolas A. Gillet, Anat Melamed, Claire Greiller, Aviva Witkover, Charles R. M. Bangham, Graham P. Taylor

Published in: International Journal of Hematology | Issue 3/2018

Login to get access

Abstract

Globally, > 5–10 million people are estimated to be infected with Human T-lymphotropic virus type 1 (HTLV-1), of whom ~ 5% develop adult T-cell leukemia/lymphoma (ATL). Despite advances in chemotherapy, overall survival (OS) has not improved in the 35 years since HTLV-1 was first described. In Europe/USA, combination treatment with zidovudine and interferon-α (ZDV/IFN-α) has substantially changed the management of patients with the leukemic subtypes of ATL (acute or unfavorable chronic ATL) and is under clinical trial evaluation in Japan. However, there is only a single published report of long-term clinical remission on discontinuing ZDV/IFN-α therapy and the optimal duration of treatment is unknown. Anecdotal cases where therapy is discontinued due to side effects or compliance have been associated with rapid disease relapse, and it has been widely accepted that the majority of patients will require life-long therapy. The development of molecular methods to quantify minimal residual disease is essential to potentially guide therapy for individual patients. Here, for the first time, we report molecular evidence that supports long-term clinical remission in a patient who was previously treated with ZDV/IFN-α for 5 years, and who has now been off all therapy for over 6 years.
Literature
1.
go back to reference Gessain A, Cassar O. Epidemiological aspects and world distribution of HTLV-1 infection. Front Microbiol. 2012;3:388 (PubMed PMID: 23162541, PMCID: 3498738).CrossRefPubMedPubMedCentral Gessain A, Cassar O. Epidemiological aspects and world distribution of HTLV-1 infection. Front Microbiol. 2012;3:388 (PubMed PMID: 23162541, PMCID: 3498738).CrossRefPubMedPubMedCentral
2.
go back to reference Yamaguchi K, Watanabe T. Human T lymphotropic virus type-I and adult T-cell leukemia in Japan. Int J Hematol. 2002;76(Suppl 2):240–5 (PubMed PMID: 12430931).CrossRefPubMed Yamaguchi K, Watanabe T. Human T lymphotropic virus type-I and adult T-cell leukemia in Japan. Int J Hematol. 2002;76(Suppl 2):240–5 (PubMed PMID: 12430931).CrossRefPubMed
3.
go back to reference Katsuya H, Ishitsuka K, Utsunomiya A, Hanada S, Eto T, Moriuchi Y, et al. Treatment and survival among 1594 patients with ATL. Blood. 2015;126(24):2570–7 (PubMed PMID: 26361794).CrossRefPubMed Katsuya H, Ishitsuka K, Utsunomiya A, Hanada S, Eto T, Moriuchi Y, et al. Treatment and survival among 1594 patients with ATL. Blood. 2015;126(24):2570–7 (PubMed PMID: 26361794).CrossRefPubMed
4.
go back to reference 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(3):428–37 (PubMed PMID: 1751370).CrossRefPubMed 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(3):428–37 (PubMed PMID: 1751370).CrossRefPubMed
5.
go back to reference 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(5):672–82 (PubMed PMID: 25733162).CrossRefPubMedPubMedCentral 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(5):672–82 (PubMed PMID: 25733162).CrossRefPubMedPubMedCentral
6.
go back to reference Tsukasaki K, Utsunomiya A, Fukuda H, Shibata T, Fukushima T, Takatsuka Y, 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(34):5458–64 (PubMed PMID: 17968021. Epub 31 Oct 2007. eng).CrossRefPubMed Tsukasaki K, Utsunomiya A, Fukuda H, Shibata T, Fukushima T, Takatsuka Y, 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(34):5458–64 (PubMed PMID: 17968021. Epub 31 Oct 2007. eng).CrossRefPubMed
7.
go back to reference Takasaki Y, Iwanaga M, Imaizumi Y, Tawara M, Joh T, Kohno T, et al. Long-term study of indolent adult T-cell leukemia-lymphoma. Blood. 2010;115(22):4337–43 (PubMed PMID: 20348391. Epub 30 March 2010. eng).CrossRefPubMed Takasaki Y, Iwanaga M, Imaizumi Y, Tawara M, Joh T, Kohno T, et al. Long-term study of indolent adult T-cell leukemia-lymphoma. Blood. 2010;115(22):4337–43 (PubMed PMID: 20348391. Epub 30 March 2010. eng).CrossRefPubMed
8.
go back to reference Hishizawa M, Kanda J, Utsunomiya A, Taniguchi S, Eto T, Moriuchi Y, et al. Transplantation of allogeneic hematopoietic stem cells for adult T-cell leukemia: a nationwide retrospective study. Blood. 2010;116(8):1369–76 (PubMed PMID: 20479287).CrossRefPubMed Hishizawa M, Kanda J, Utsunomiya A, Taniguchi S, Eto T, Moriuchi Y, et al. Transplantation of allogeneic hematopoietic stem cells for adult T-cell leukemia: a nationwide retrospective study. Blood. 2010;116(8):1369–76 (PubMed PMID: 20479287).CrossRefPubMed
9.
go back to reference Gill PS, Harrington W Jr, Kaplan MH, Ribeiro RC, Bennett JM, Liebman HA, et al. Treatment of adult T-cell leukemia-lymphoma with a combination of interferon alfa and zidovudine. N Engl J Med. 1995;332(26):1744–8 (PubMed PMID: 7760890).CrossRefPubMed Gill PS, Harrington W Jr, Kaplan MH, Ribeiro RC, Bennett JM, Liebman HA, et al. Treatment of adult T-cell leukemia-lymphoma with a combination of interferon alfa and zidovudine. N Engl J Med. 1995;332(26):1744–8 (PubMed PMID: 7760890).CrossRefPubMed
10.
go back to reference Hermine O, Bouscary D, Gessain A, Turlure P, Leblond V, Franck N, et al. Brief report: treatment of adult T-cell leukemia-lymphoma with zidovudine and interferon alfa. N Engl J Med. 1995;332(26):1749–51 (PubMed PMID: 7760891).CrossRefPubMed Hermine O, Bouscary D, Gessain A, Turlure P, Leblond V, Franck N, et al. Brief report: treatment of adult T-cell leukemia-lymphoma with zidovudine and interferon alfa. N Engl J Med. 1995;332(26):1749–51 (PubMed PMID: 7760891).CrossRefPubMed
11.
go back to reference Bazarbachi A, Plumelle Y, Carlos Ramos J, Tortevoye P, Otrock Z, Taylor G, 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(27):4177–83 (PubMed PMID: 20585095).CrossRefPubMed Bazarbachi A, Plumelle Y, Carlos Ramos J, Tortevoye P, Otrock Z, Taylor G, 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(27):4177–83 (PubMed PMID: 20585095).CrossRefPubMed
12.
go back to reference Tamiya S, Matsuoka M, Etoh K, Watanabe T, Kamihira S, Yamaguchi K, et al. Two types of defective human T-lymphotropic virus type I provirus in adult T-cell leukemia. Blood. 1996;88(8):3065–73 (PubMed PMID: 8874205).PubMed Tamiya S, Matsuoka M, Etoh K, Watanabe T, Kamihira S, Yamaguchi K, et al. Two types of defective human T-lymphotropic virus type I provirus in adult T-cell leukemia. Blood. 1996;88(8):3065–73 (PubMed PMID: 8874205).PubMed
13.
go back to reference Demontis MA, Hilburn S, Taylor GP. Human T cell lymphotropic virus type 1 viral load variability and long-term trends in asymptomatic carriers and in patients with human T cell lymphotropic virus type 1-related diseases. AIDS Res Hum Retrovir. 2013;29(2):359–64 (PubMed PMID: 22894552).PubMed Demontis MA, Hilburn S, Taylor GP. Human T cell lymphotropic virus type 1 viral load variability and long-term trends in asymptomatic carriers and in patients with human T cell lymphotropic virus type 1-related diseases. AIDS Res Hum Retrovir. 2013;29(2):359–64 (PubMed PMID: 22894552).PubMed
14.
go back to reference Gillet NA, Malani N, Melamed A, Gormley N, Carter R, Bentley D, et al. The host genomic environment of the provirus determines the abundance of HTLV-1-infected T-cell clones. Blood. 2011;117(11):3113–22 (PubMed PMID: 21228324. PMCID: 3062313).CrossRefPubMedPubMedCentral Gillet NA, Malani N, Melamed A, Gormley N, Carter R, Bentley D, et al. The host genomic environment of the provirus determines the abundance of HTLV-1-infected T-cell clones. Blood. 2011;117(11):3113–22 (PubMed PMID: 21228324. PMCID: 3062313).CrossRefPubMedPubMedCentral
15.
go back to reference Manivannan K, Rowan AG, Tanaka Y, Taylor GP, Bangham CR. CADM1/TSLC1 identifies HTLV-1-infected cells and determines their susceptibility to CTL-mediated lysis. PLoS Pathog. 2016;12(4):e1005560 (PubMed PMID: 27105228. PMCID: 4841533).CrossRefPubMedPubMedCentral Manivannan K, Rowan AG, Tanaka Y, Taylor GP, Bangham CR. CADM1/TSLC1 identifies HTLV-1-infected cells and determines their susceptibility to CTL-mediated lysis. PLoS Pathog. 2016;12(4):e1005560 (PubMed PMID: 27105228. PMCID: 4841533).CrossRefPubMedPubMedCentral
16.
go back to reference Cook LB, Rowan AG, Melamed A, Taylor GP, Bangham CR. HTLV-1-infected T cells contain a single integrated provirus in natural infection. Blood. 2012;120(17):3488–90 (PubMed PMID: 22955925. PMCID: 3482858).CrossRefPubMedPubMedCentral Cook LB, Rowan AG, Melamed A, Taylor GP, Bangham CR. HTLV-1-infected T cells contain a single integrated provirus in natural infection. Blood. 2012;120(17):3488–90 (PubMed PMID: 22955925. PMCID: 3482858).CrossRefPubMedPubMedCentral
17.
go back to reference Hodson A, Laydon DJ, Bain BJ, Fields PA, Taylor GP. Pre-morbid human T-lymphotropic virus type I proviral load, rather than percentage of abnormal lymphocytes, is associated with an increased risk of aggressive adult T-cell leukemia/lymphoma. Haematologica. 2013;98(3):385–8 (PubMed PMID: 22875625. PMCID: 3659941).CrossRefPubMedPubMedCentral Hodson A, Laydon DJ, Bain BJ, Fields PA, Taylor GP. Pre-morbid human T-lymphotropic virus type I proviral load, rather than percentage of abnormal lymphocytes, is associated with an increased risk of aggressive adult T-cell leukemia/lymphoma. Haematologica. 2013;98(3):385–8 (PubMed PMID: 22875625. PMCID: 3659941).CrossRefPubMedPubMedCentral
18.
go back to reference Iwanaga M, Watanabe T, Utsunomiya A, Okayama A, Uchimaru K, Koh KR, et al. Human T-cell leukemia virus type I (HTLV-1) proviral load and disease progression in asymptomatic HTLV-1 carriers: a nationwide prospective study in Japan. Blood. 2010;116(8):1211–9 (PubMed PMID: 20448111).CrossRefPubMed Iwanaga M, Watanabe T, Utsunomiya A, Okayama A, Uchimaru K, Koh KR, et al. Human T-cell leukemia virus type I (HTLV-1) proviral load and disease progression in asymptomatic HTLV-1 carriers: a nationwide prospective study in Japan. Blood. 2010;116(8):1211–9 (PubMed PMID: 20448111).CrossRefPubMed
19.
go back to reference Tsukasaki K, Tsushima H, Yamamura M, Hata T, Murata K, Maeda T, et al. Integration patterns of HTLV-I provirus in relation to the clinical course of ATL: frequent clonal change at crisis from indolent disease. Blood. 1997;89(3):948–56 (PubMed PMID: 9028326).PubMed Tsukasaki K, Tsushima H, Yamamura M, Hata T, Murata K, Maeda T, et al. Integration patterns of HTLV-I provirus in relation to the clinical course of ATL: frequent clonal change at crisis from indolent disease. Blood. 1997;89(3):948–56 (PubMed PMID: 9028326).PubMed
Metadata
Title
Long-term clinical remission maintained after cessation of zidovudine and interferon-α therapy in chronic adult T-cell leukemia/lymphoma
Authors
Lucy B. Cook
Aileen G. Rowan
Maria A. Demontis
Sophie Sagawe
Nicolas A. Gillet
Anat Melamed
Claire Greiller
Aviva Witkover
Charles R. M. Bangham
Graham P. Taylor
Publication date
01-03-2018
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 3/2018
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-017-2361-7

Other articles of this Issue 3/2018

International Journal of Hematology 3/2018 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine