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

Lee Ratner, William Harrington, Xuan Feng, Christian Grant, Steve Jacobson, Ariela Noy, Joseph A. Sparano, Jeanette Lee, Richard Ambinder, Nancy Campbell, Michael Lairmore

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background: 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. Methods and Findings: 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. Conclusions: 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.

Original languageEnglish (US)
Article numbere4420
JournalPLoS One
Volume4
Issue number2
DOIs
StatePublished - Feb 10 2009

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Deltaretrovirus
Adult T Cell Leukemia Lymphoma
Chemotherapy
T-cells
lymphoma
leukemia
Viruses
drug therapy
T-lymphocytes
Induction Chemotherapy
therapeutics
Drug Therapy
Therapeutics
Phase II Clinical Trials
Lamivudine
Zidovudine
Viral RNA
vincristine
prednisone
Vincristine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ratner, L., Harrington, W., Feng, X., Grant, C., Jacobson, S., Noy, A., ... Lairmore, M. (2009). Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma. PLoS One, 4(2), [e4420]. https://doi.org/10.1371/journal.pone.0004420

Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma. / Ratner, Lee; Harrington, William; Feng, Xuan; Grant, Christian; Jacobson, Steve; Noy, Ariela; Sparano, Joseph A.; Lee, Jeanette; Ambinder, Richard; Campbell, Nancy; Lairmore, Michael.

In: PLoS One, Vol. 4, No. 2, e4420, 10.02.2009.

Research output: Contribution to journalArticle

Ratner, L, Harrington, W, Feng, X, Grant, C, Jacobson, S, Noy, A, Sparano, JA, Lee, J, Ambinder, R, Campbell, N & Lairmore, M 2009, 'Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma', PLoS One, vol. 4, no. 2, e4420. https://doi.org/10.1371/journal.pone.0004420
Ratner, Lee ; Harrington, William ; Feng, Xuan ; Grant, Christian ; Jacobson, Steve ; Noy, Ariela ; Sparano, Joseph A. ; Lee, Jeanette ; Ambinder, Richard ; Campbell, Nancy ; Lairmore, Michael. / Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma. In: PLoS One. 2009 ; Vol. 4, No. 2.
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