Adult T-Cell Leukemia/Lymphoma in London: Clinical Experience of 21 Cases

Pawson, Rachel; Richardson, Deborah; Pagliuca, Antonio; Kelsey, Stephen M.; Hoque, Selina; Breuer, Judith; Newland, Adrian C.; Mufti, Ghulam J.

doi:10.3109/10428199809057597

Cited by 27 publications

(14 citation statements)

References 28 publications

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“…A median age at diagnosis of 58 years, while higher than initial reports of ATLL in England and the Caribbean (11,15) is comparable both to more recent UK reports (16,17) and to Japanese data (12).…”

Section: Discussionsupporting

confidence: 55%

“…Almost twice as many cases of aggressive ATLL were lymphoma, in contrast to the original Shimoyama cohort (8) and previous British studies where acute ATLL was more frequent (15)(16)(17) and to a 2010 meta-analysis in which the ratio was approximately 1:1 (22).…”

Section: Discussionmentioning

confidence: 41%

“…Further UK experience is limited to two case series and two prospective studies. In both case series, including 52 and 21 patients respectively, median overall survival (OS) was only 6 months (15,16). In 2001 a prospective study assessed the tolerability and efficacy of zidovudine (ZDV) and interferon-α (IFN-α) in 15 subjects and compared to historical controls.…”

Section: Introductionmentioning

confidence: 99%

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Use of Zidovudine and Interferon Alfa With Chemotherapy Improves Survival in Both Acute and Lymphoma Subtypes of Adult T-Cell Leukemia/Lymphoma

Hodson

Crichton

Montoto

et al. 2011

JCO

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PurposeAdult T cell leukaemia/lymphoma (ATLL) is a mature (post-thymic) T cell lymphoma associated with human T-lymphotropic virus type 1 (HTLV-1) infection. Survival in aggressive subtypes remains poor and treatment resistance is frequent. Use of zidovudine (ZDV) and interferon-alpha (IFNα) has been associated with improved response rates in small studies and prolonged overall survival in leukaemic ATLL subtypes in a recent meta-analysis. Patients and methodsWe report the clinico-pathologic characteristics, treatment and outcome of 73 ResultsThe overall response rate ranged from 55% with chemotherapy alone to 81% with combined first line therapy (chemotherapy with concurrent/sequential ZDV/IFNα).Median overall survival (OS) was 9 months: 7.5 months for acute ATLL and 10 months for lymphoma ATLL. Use of ZDV/IFNα at any time prolonged survival in acute (p=0.0007) and lymphoma ATLL (p=0.0004) and was the sole factor associated with reduction in risk of death in aggressive ATLL (hazard ratio 0.23, 95%CI 0.09-0.60, p=0.002). Combined first line therapy prolonged median OS in acute (p=0.0081) and lymphoma ATLL (p=0.001) compared with chemotherapy alone. ConclusionThese data support the use of low dose ZDV/IFNα with chemotherapy in the first line treatment of acute and lymphoma ATLL.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 41%

Section: Introductionmentioning

confidence: 99%

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Use of Zidovudine and Interferon Alfa With Chemotherapy Improves Survival in Both Acute and Lymphoma Subtypes of Adult T-Cell Leukemia/Lymphoma

Hodson

Crichton

Montoto

et al. 2011

JCO

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“…These data accord with the results of the Lymphoma Study Group in which CR was obtained in 17-18% of patients treated with CHOP (LSG-1) (Lymphoma Study Group, 1982;Shimoyama et al, 1988); in 37% of patients treated with CHOP plus methotrexate (Shimoyama et al, 1988). A similar response (63% CR þ PR) was found in 21 patients treated with combination chemotherapy in London, UK over a 15-year period (1981-1995), but the median survival was only 5.5 months (Pawson et al, 1998). Intensification of CHOP with etoposide, vindesine, ranimustine, and mitoxantrone resulted in CR in 35.8% of the 83 patients (Taguchi et al, 1996) and in 43% when part of a nine-agent cycle (LSG-4) (Tobinai et al, 1994).…”

Section: Chemotherapymentioning

confidence: 52%

Natural history of adult T-cell leukemia/lymphoma and approaches to therapy

2005

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After cell-to-cell transmission, HTLV-I increases its viral genome by de novo infection and proliferation of infected cells. Proliferation of infected cells is clonal and persistent in vivo. During the carrier state, infected cells are selected in vivo by the host's immune system, the genetic and epigenetic environment of proviral integration sites, and other factors. In leukemic cells, tax gene expression is frequently impaired by genetic and epigenetic mechanisms. Such loss of Tax expression enables ATL cells to escape the host immune system. On the other hand, ATL cells acquire the ability to proliferate without Tax by intracellular genetic and epigenetic changes. Despite advances in support and the development of novel treatment agents, the prognosis for ATLL remains poor. A number of therapies, however, do appear to improve prognosis compared to CHOP (VEPA). These include interferon-a plus zidovudine (probably after 1-2 cycles of CHOP), intensive chemotherapy as in LSG-15 with G-CSF support and Allo-SCT (which includes the potential for cure). Emerging novel approaches include HDAC inhibitors, monoclonal antibodies, and proteasome inhibitors. Comparison between different therapeutic approaches is complicated by the range of natural history of ATLL, different recruitments of naı¨ve-to-therapy, refractory or relapsed patients, and variations in the reporting of outcome that frequently excludes difficultto-evaluate patients. Moreover, results from relatively small proof-of-principle studies have not been extended with randomized, controlled trials. As a result, currently, there is no clear evidence to support the value of any particular treatment approach over others. To avoid further unnecessary patient suffering and to identify optimal therapy as rapidly as possible, large randomized, controlled trials encompassing multicenter, international collaborations will be necessary.

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“…The existing 'diagnostic markers' for ATL currently are immunoassay for HTLV-I gene products, HTLV-I-specific antibody production, and detection of HTLV-I DNA. 5 These parameters have little discriminating value among HTLV-I diseases, clinical subtypes, or severity of disease. There has been some utility of immune activation markers as predictors of outcome, which, although effective within ATL, are not diagnostic for HAM/TSP or other HTLV-I-related diseases as a whole.…”

Section: Introductionmentioning

confidence: 99%