Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma.

<h4>Background</h4>Human T-cell leukemia virus-associated adult T-cell leukemia-lymphoma (ATLL) has a very poor prognosis, despite trials of a variety of different treatment regimens. Virus expression has been reported to be limited or absent when ATLL is diagnosed, and this has suggeste...

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Autores principales:	Lee Ratner, William Harrington, Xuan Feng, Christian Grant, Steve Jacobson, Ariela Noy, Joseph Sparano, Jeannette Lee, Richard Ambinder, Nancy Campbell, Michael Lairmore, AIDS Malignancy Consortium
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c7fe39eca7bd417bbae03db9ff98ee58
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spelling	oai:doaj.org-article:c7fe39eca7bd417bbae03db9ff98ee582021-11-25T06:17:24ZHuman T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma.1932-620310.1371/journal.pone.0004420https://doaj.org/article/c7fe39eca7bd417bbae03db9ff98ee582009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19204798/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Human T-cell leukemia virus-associated adult T-cell leukemia-lymphoma (ATLL) has a very poor prognosis, despite trials of a variety of different treatment regimens. Virus expression has been reported to be limited or absent when ATLL is diagnosed, and this has suggested that secondary genetic or epigenetic changes are important in disease pathogenesis.<h4>Methods and findings</h4>We prospectively investigated combination chemotherapy followed by antiretroviral therapy for this disorder. Nineteen patients were prospectively enrolled between 2002 and 2006 at five medical centers in a phase II clinical trial of infusional chemotherapy with etoposide, doxorubicin, and vincristine, daily prednisone, and bolus cyclophosphamide (EPOCH) given for two to six cycles until maximal clinical response, and followed by antiviral therapy with daily zidovudine, lamivudine, and alpha interferon-2a for up to one year. Seven patients were on study for less than one month due to progressive disease or chemotherapy toxicity. Eleven patients achieved an objective response with median duration of response of thirteen months, and two complete remissions. During chemotherapy induction, viral RNA expression increased (median 190-fold), and virus replication occurred, coincident with development of disease progression.<h4>Conclusions</h4>EPOCH chemotherapy followed by antiretroviral therapy is an active therapeutic regimen for adult T-cell leukemia-lymphoma, but viral reactivation during induction chemotherapy may contribute to treatment failure. Alternative therapies are sorely needed in this disease that simultaneously prevent virus expression, and are cytocidal for malignant cells.Lee RatnerWilliam HarringtonXuan FengChristian GrantSteve JacobsonAriela NoyJoseph SparanoJeannette LeeRichard AmbinderNancy CampbellMichael LairmoreAIDS Malignancy ConsortiumPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 2, p e4420 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lee Ratner William Harrington Xuan Feng Christian Grant Steve Jacobson Ariela Noy Joseph Sparano Jeannette Lee Richard Ambinder Nancy Campbell Michael Lairmore AIDS Malignancy Consortium Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma.
description	<h4>Background</h4>Human T-cell leukemia virus-associated adult T-cell leukemia-lymphoma (ATLL) has a very poor prognosis, despite trials of a variety of different treatment regimens. Virus expression has been reported to be limited or absent when ATLL is diagnosed, and this has suggested that secondary genetic or epigenetic changes are important in disease pathogenesis.<h4>Methods and findings</h4>We prospectively investigated combination chemotherapy followed by antiretroviral therapy for this disorder. Nineteen patients were prospectively enrolled between 2002 and 2006 at five medical centers in a phase II clinical trial of infusional chemotherapy with etoposide, doxorubicin, and vincristine, daily prednisone, and bolus cyclophosphamide (EPOCH) given for two to six cycles until maximal clinical response, and followed by antiviral therapy with daily zidovudine, lamivudine, and alpha interferon-2a for up to one year. Seven patients were on study for less than one month due to progressive disease or chemotherapy toxicity. Eleven patients achieved an objective response with median duration of response of thirteen months, and two complete remissions. During chemotherapy induction, viral RNA expression increased (median 190-fold), and virus replication occurred, coincident with development of disease progression.<h4>Conclusions</h4>EPOCH chemotherapy followed by antiretroviral therapy is an active therapeutic regimen for adult T-cell leukemia-lymphoma, but viral reactivation during induction chemotherapy may contribute to treatment failure. Alternative therapies are sorely needed in this disease that simultaneously prevent virus expression, and are cytocidal for malignant cells.
format	article
author	Lee Ratner William Harrington Xuan Feng Christian Grant Steve Jacobson Ariela Noy Joseph Sparano Jeannette Lee Richard Ambinder Nancy Campbell Michael Lairmore AIDS Malignancy Consortium
author_facet	Lee Ratner William Harrington Xuan Feng Christian Grant Steve Jacobson Ariela Noy Joseph Sparano Jeannette Lee Richard Ambinder Nancy Campbell Michael Lairmore AIDS Malignancy Consortium
author_sort	Lee Ratner
title	Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma.
title_short	Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma.
title_full	Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma.
title_fullStr	Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma.
title_full_unstemmed	Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma.
title_sort	human t cell leukemia virus reactivation with progression of adult t-cell leukemia-lymphoma.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/c7fe39eca7bd417bbae03db9ff98ee58
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Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma.

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