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

2017 ◽  
Vol 107 (3) ◽  
pp. 378-382 ◽  
Author(s):  
Lucy B. Cook ◽  
Aileen G. Rowan ◽  
Maria A. Demontis ◽  
Sophie Sagawe ◽  
Nicolas A. Gillet ◽  
...  
Keyword(s):  
T Cell ◽  
Clinical Remission ◽  
Interferon Α ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia

Long-term study of indolent adult T-cell leukemia-lymphoma

Blood ◽  
2010 ◽  
Vol 115 (22) ◽  
pp. 4337-4343 ◽  
Author(s):  
Yumi Takasaki ◽  
Masako Iwanaga ◽  
Yoshitaka Imaizumi ◽  
Masayuki Tawara ◽  
Tatsuro Joh ◽  
...  
Keyword(s):  
T Cell ◽  
Survival Curve ◽  
Performance Status ◽  
Survival Rates ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
High Concentration ◽  
Adult T Cell Leukemia ◽  
Long Term Study

Abstract The long-term prognosis of indolent adult T-cell leukemia-lymphoma (ATL) is not clearly elucidated. From 1974 to 2003, newly diagnosed indolent ATL in 90 patients (65 chronic type and 25 smoldering type) was analyzed. The median survival time was 4.1 years; 12 patients remained alive for more than 10 years, 44 progressed to acute ATL, and 63 patients died. The estimated 5-, 10-, and 15-year survival rates were 47.2%, 25.4%, and 14.1%, respectively, with no plateau in the survival curve. Although most patients were treated with watchful waiting, 12 patients were treated with chemotherapy. Kaplan-Meier analyses showed that advanced performance status (PS), neutrophilia, high concentration of lactate dehydrogenase, more than 3 extranodal lesions, more than 4 total involved lesions, and receiving chemotherapy were unfavorable prognostic factors for survival. Multivariate Cox analysis showed that advanced PS was a borderline significant independent factor in poor survival (hazard ratio, 2.1, 95% confidence interval, 1.0-4.6; P = .06), but it was not a factor when analysis was limited to patients who had not received chemotherapy. The prognosis of indolent ATL in this study was poorer than expected. These findings suggest that even patients with indolent ATL should be carefully observed in clinical practice. Further studies are required to develop treatments for indolent ATL.

scholarly journals Therapy-induced selective loss of leukemia-initiating activity in murine adult T cell leukemia

2010 ◽  
Vol 207 (13) ◽  
pp. 2785-2792 ◽  
Author(s):  
Hiba El Hajj ◽  
Marwan El-Sabban ◽  
Hideki Hasegawa ◽  
Ghazi Zaatari ◽  
Julien Ablain ◽  
...  
Keyword(s):  
T Cell ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Short Term ◽  
Adult T Cell Leukemia ◽  
Human T Cell ◽  
Long Term Prognosis ◽  
Cell Immortality

Chronic HTLV-I (human T cell lymphotropic virus type I) infection may cause adult T cell leukemia/lymphoma (ATL), a disease with dismal long-term prognosis. The HTLV-I transactivator, Tax, initiates ATL in transgenic mice. In this study, we demonstrate that an As2O3 and IFN-α combination, known to trigger Tax proteolysis, cures Tax-driven ATL in mice. Unexpectedly, this combination therapy abrogated initial leukemia engraftment into secondary recipients, whereas the primary tumor bulk still grew in the primary hosts, only to ultimately abate later on. This loss of initial transplantability required proteasome function. A similar regimen recently yielded unprecedented disease control in human ATL. Our demonstration that this drug combination targeting Tax stability abrogates tumor cell immortality but not short-term growth may foretell a favorable long-term efficiency of this regimen in patients.

Characteristics of chemotherapy-induced clinical remission in long survivors with aggressive adult T-cell leukemia/lymphoma

1993 ◽  
Vol 17 (2) ◽  
pp. 157-166 ◽  
Author(s):  
Kunihiro Tsukasaki ◽  
Shuichi Ikeda ◽  
Ken Murata ◽  
Takahiro Maeda ◽  
Sunao Atogami ◽  
...  
Keyword(s):  
T Cell ◽  
Clinical Remission ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia

IRF-4 and Interferon Resistance in Adult T-Cell Leukemia/Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2531-2531
Author(s):  
Juan Carlos Ramos ◽  
Plillip Ruiz ◽  
Lee Ratner ◽  
Edward W. Harjaj ◽  
Izidore Lossos ◽  
...  
Keyword(s):  
Transcription Factor ◽  
T Cell ◽  
Antiviral Therapy ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Molecular Features ◽  
Interferon Resistance

Abstract Adult T-cell leukemia-lymphoma (ATLL) is a generally fatal CD4 helper T-cell malignancy caused by the human T-cell Leukemia virus type I (HTLV-I). Most ATLL patients fare very poorly with conventional chemotherapy; however interferon-alpha (IFN-α) based antiviral therapy has produced long-term clinical remissions in a subset of patients. Despite this, most patients succumb to their disease regardless of treatment. Little is known about the mechanisms of interferon resistance in ATLL and other tumors. Specific defects in proteins involved or affecting the IFN signaling pathway have been described in other malignancies that are often resistant to interferon, such as cutaneous T-cell lymphoma and melanoma. Many of the elegant molecular pathogenesis studies of ATLL have focused on the viral transactivator Tax, in tax expressing cell lines, although this oncoprotein is not detected in primary unmanipulated tumors. We studied primary ATLL tumors and identified molecular features linked to sensitivity and resistance to antiviral (IFN) therapy. Serial ex-vivo analysis of unmanipulated primary leukemic cells obtained from ATLL patients prior to and during induction treatment with parenteral AZT and IFN-α revealed significantly higher induction of IFN regulated genes (Affymetrix gene chip) in patients who had an excellent response to this therapy. Interferon Regulatory Factor 4 (IRF-4) has oncogenic activity in vitro and is expressed in poor prognosis aggressive lymphomas. This transcription factor has also been shown to oppose the antiproliferative effects of interferon perhaps through activity on Toll-like receptor mediated pathways. Analysis of primary unmanipulated ATLL tumors from patients who had received antiviral therapy demonstrated the expression of IRF-4 protein in 7 tumors, 6 of which were from patients who failed this therapy. In contrast, 9 tumors lacked IRF-4 protein, including those from 5 complete and 2 partial responders. Detection of IRF-4 protein by Western blot correlated with high mRNA expression by quantitative RT-PCR studies. Expression of IRF-4 in primary ATLL was independent of the HTLV-I oncoprotein Tax, (which reportedly transactivates this transcription factor). IRF-4 is also a putative target gene of the oncogenic NF-κB subunit c-Rel. We found enhanced nuclear expression of c-Rel in 6 of 7 IRF-4+ ATLL tumors indicating a link between these two anti-apoptotic molecules in ATLL. Finally, PCR based gene rearrangement studies demonstrated the persistence of circulating T-cell clones in our long-term survivors, who have been maintained on AZT and IFN-α for years. In summary, the expression of nuclear c-Rel and IRF-4 occurs in the absence of Tax in primary ATLL and is associated with resistance to IFN-α based therapy. These molecular features may help guide treatment. AZT and IFN-a therapy is a suppressive rather than curative regimen in ATLL, and patients who achieve clinical remission with these drugs should remain on maintenance therapy indefinitely. Studies of the role of IRF-4, c-Rel, and their signaling properties in ATLL are in progress.

The Combination of Arsenic Trioxide and Interferon-Alpha Eradicates Leukemia Initiating Cells in TAX-Driven Murine Adult T Cell Leukemia/Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2714-2714
Author(s):  
Ali Bazarbachi ◽  
Hiba El Hajj ◽  
Marwan El-Sabban ◽  
Hideki Hasegawa ◽  
Ghazi Zaatari ◽  
...  
Keyword(s):  
T Cell ◽  
Conflicts Of Interest ◽  
Critical Role ◽  
Proteasome Inhibition ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Adult T Cell Leukemia

Abstract Abstract 2714 Poster Board II-690 Adult T cell leukemia (ATL) is one of the rare human cancers initiated by a transforming retrovirus, HTLV-I. After many years of controversy, it is now accepted that the viral transactivator protein Tax plays a critical role in initiating the leukemic process, because Tax transgenics develop a disease with striking ATL features. Long-term prognosis of ATL patients remains extremely poor, but we recently reported that the combination of As2O3, interferon-a (IFN), and zidovudine yielded unprecedented response rates. Indeed, in 10 chronic ATL patients, a 100% response rate was observed, including 7 complete remissions (CR), 2 CR but with more than 5% circulating atypical lymphocytes, and one partial response. We demonstrate that the As2O3/IFN combination, previously shown to degrade Tax, cures Tax-driven murine ATLs. Unexpectedly, this combination immediately abrogates leukemia transplantation into secondary recipients, while the primary tumor continues to grow and only exhausts much later. Leukemia initiating cell (LIC) clearance is reversed by proteasome inhibition, demonstrating that LICs are addicted to continuous Tax expression. Most anticancer treatments fail to target LIC. These results establish that As2O3/IFN/zidovudine acts through Tax targeting and predict a favorable long-term outcome for responsive patients. Thus, oncogene degradation can selectively target LICs, explaining this very recent success of a similar regimen in patients. Disclosures: No relevant conflicts of interest to declare.

How I treat adult T-cell leukemia/lymphoma

Blood ◽  
2011 ◽  
Vol 118 (7) ◽  
pp. 1736-1745 ◽  
Author(s):  
Ali Bazarbachi ◽  
Felipe Suarez ◽  
Paul Fields ◽  
Olivier Hermine
Keyword(s):  
T Cell ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Activated T Cells ◽  
Term Survival ◽  
Long Term Survival ◽  
Adult T Cell Leukemia ◽  
Human T Cell

AbstractAdult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy of mature activated T cells caused by human T-cell lymphotropic virus type I. ATL carries a bad prognosis because of intrinsic chemoresistance and severe immunosuppression. In acute ATL, Japanese trials demonstrated that although combinations of chemotherapy improved response rate, they failed to achieve a significant impact on survival. Patients with chronic and smoldering ATL have a better prognosis, but long-term survival is poor when these patients are managed with a watchful-waiting policy or with chemotherapy. Recently, a worldwide meta-analysis revealed that the combination of zidovudine and IFN-α is highly effective in the leukemic subtypes of ATL and should be considered as standard first-line therapy in that setting. This combination has changed the natural history of the disease through achievement of significantly improved long-term survival in patients with smoldering and chronic ATL as well as a subset of patients with acute ATL. ATL lymphoma patients still benefit from chemotherapy induction with concurrent or sequential antiretroviral therapy with zidovudine/IFN. To prevent relapse, clinical trials assessing consolidative targeted therapies such as arsenic/IFN combination or novel monoclonal antibodies are needed. Finally, allogeneic BM transplantation should be considered in suitable patients.

scholarly journals HTLV-1-Associated Lymphoma Presented as Massive Lymphadenopathy

2021 ◽  
Vol 9 ◽  
pp. 232470962110132
Author(s):  
Pei Ting Chen ◽  
David Onukogu ◽  
Gregory Gotlieb ◽  
Rashid Chaudhry ◽  
Vijay Jaswani ◽  
...  
Keyword(s):  
T Cell ◽  
Clinical Features ◽  
Bone Lesions ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Massive Lymphadenopathy ◽  
Human T Cell

Adult T-cell leukemia/lymphoma is an aggressive T-cell malignancy caused by the long-term infection of human T-cell lymphotropic virus type 1 (HTLV-1). Our understanding of clinical features still largely relies on the Shimoyama classification developed 30 years ago, which described the 4 clinical subtypes (the smoldering, chronic, lymphoma, and acute types) based on the manifestations of lymphocytosis, elevated lactate dehydrogenase, hypercalcemia, lymphadenopathy, and involvement of the skin, lung, liver, spleen, central nervous system, bone, ascites, pleural effusion, and gastrointestinal tract. HTLV-1-associated lymphoma has a variety of presentations but the presentation of massive lymphadenopathy and compression symptoms is rare and has not been emphasized in the literature. In this article, we describe 2 cases of adult T-cell leukemia/lymphomas that presented with massive cervical nodes or mediastinal nodes with compressing symptoms as the major presenting clinical features. Clinicians should remain aware of this type of presentation by HTLV-1-associated lymphoma, especially in patients who came from endemic areas, even if not all clinical features are present and particularly with hypercalcemia and lytic bone lesions.

Interferon-α and zidovudine for relapsed/refractory adult T cell leukemia/lymphoma: case reports of Japanese patients

2010 ◽  
Vol 92 (5) ◽  
pp. 762-764 ◽  
Author(s):  
Kenji Ishitsuka ◽  
Hiroo Katsuya ◽  
Tomona Toyota ◽  
Masanao Ishizu ◽  
Naoko Kunami ◽  
...  
Keyword(s):  
T Cell ◽  
Case Reports ◽  
Japanese Patients ◽  
Interferon Α ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia

scholarly journals Cord Blood Transplantation Provided Long-term Remission in a Case of Adult T-cell Leukemia-lymphoma (ATL) with Myelofibrosis

2016 ◽  
Vol 55 (2) ◽  
pp. 197-201
Author(s):  
Hidehiro Itonaga ◽  
Jun Taguchi ◽  
Takeharu Kato ◽  
Shinya Sato ◽  
Yasushi Sawayama ◽  
...  
Keyword(s):  
T Cell ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Blood Transplantation
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