Dataset Information

Treatment advances and prognosis for patients with adult T-cell leukemia-lymphoma.

ABSTRACT: A classification for adult T-cell leukemia-lymphoma (ATL) based on clinical features was proposed in 1991: acute, lymphoma, chronic, and smoldering types, and their median survival times (MSTs) were reported to be 6.2, 10.2, 24.3 months, and not reached, respectively. Several new therapies for ATL have since been developed, i.e. dose-intensity multi-agent chemotherapies, allogeneic hematopoietic stem cell transplantation (allo-HSCT), monoclonal antibodies, and anti-viral therapy. The monoclonal antibody to CCR4, mogamulizumab, clearly improved response rates in patients with treatment-naïve and relapsed aggressive ATL, and has the potential to provide a survival advantage. The outcomes of allo-HSCT have been reported since the early 2000s. High treatment-related mortality was initially the crucial issue associated with this treatment approach; however, reduced intensity conditioning regimens have decreased the risk of treatment-related mortality. The introduction of allo- HSCT has had a positive impact on the prognosis of and potential curability with treatments for ATL. A meta-analysis of a treatment with interferon-? and zidovudine (IFN/AZT) revealed a survival benefit in patients with the leukemic subtype. A phase 3 study comparing IFN/AZT with watchful waiting in patients with indolent ATL is ongoing in Japan. Several clinical trials on novel agents are currently being conducted, such as the histone deacetylase inhibitors, alemtuzumab, brentuximab vedotin, nivolumab, and an EZH1/2 dual inhibitor.

SUBMITTER: Katsuya H

PROVIDER: S-EPMC6144188 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Treatment advances and prognosis for patients with adult T-cell leukemia-lymphoma.

Katsuya Hiroo H Ishitsuka Kenji K

Journal of clinical and experimental hematopathology : JCEH 20170608 3

A classification for adult T-cell leukemia-lymphoma (ATL) based on clinical features was proposed in 1991: acute, lymphoma, chronic, and smoldering types, and their median survival times (MSTs) were reported to be 6.2, 10.2, 24.3 months, and not reached, respectively. Several new therapies for ATL have since been developed, i.e. dose-intensity multi-agent chemotherapies, allogeneic hematopoietic stem cell transplantation (allo-HSCT), monoclonal antibodies, and anti-viral therapy. The monoclonal ...[more]

PMID: 28592744

Similar Datasets

Project description:BackgroundAdult T-cell leukemia/lymphoma (ATLL), a peripheral T-cell leukemia/lymphoma associated with the human T-cell lymphotropic virus type-1 (HTLV-1), has been classified following the clinical forms defined by Shimoyama in 1991. A suggestion to modify Shimoyama's classification was proposed in 2007 to differentiate within the smoldering patients those who presented nodules or tumors in the skin without lung involvement, which was named the primary cutaneous tumoral (PCT) form of ATLL. In the present study, according to their clinicopathological characteristics, we estimated the mortality rates of 143 ATLL patients from Bahia, Brazil. We also evaluated the importance of classifying PCT/ATLL separately from the smoldering type on disease prognosis.Methodology/principal findingsDiagnosis of ATLL was established based on a positive serology for HTLV-1, histopathological and/or cytological diagnosis of peripheral T-cell leukemia/lymphoma. Patients were clinically grouped according to Shimoyama's classification, considering PCT variants separately from the smoldering cases. Bivariate and multivariable survival analyses were applied to identify factors associated with disease prognosis. Significant differences in the median survival time were observed between the clinical types, with the smoldering type presenting the longest median survival (109 months) compared to the other forms (<50 months); the median survival for PCT/ATLL was 20 months. Multivariable analysis confirmed that ATLL clinical types were associated with survival, with a better prognosis for patients with the smoldering and chronic types. Furthermore, skin involvement was related to a worse outcome in the multivariable analysis, regardless of the clinical form and presence of lymphadenopathy.Conclusions/significanceOur results reinforce the importance of considering the PCT/ATLL separately from the smoldering type when classifying ATLL to better define prognosis and treatment, given the significant difference in the survival of patients between the smoldering form and PCT/ATLL. Skin involvement should also be considered an independent prognostic factor in patients with ATLL.

Project description:Adult T cell leukemia-lymphoma (ATL) is an aggressive malignancy secondary to chronic infection with the human T cell leukemia virus type I (HTLV-I) retrovirus. ATL carries a dismal prognosis. ATL classifies into four subtypes (acute, lymphoma, chronic, and smoldering) which display different clinical features, prognosis and response to therapy, hence requiring different clinical management. Smoldering and chronic subtypes respond well to antiretroviral therapy using the combination of zidovudine (AZT) and interferon-alpha (IFN) with a significant prolongation of survival. Conversely, the watch and wait strategy or chemotherapy for these indolent subtypes allies with a poor long-term outcome. Acute ATL is associated with chemo-resistance and dismal prognosis. Lymphoma subtypes respond better to intensive chemotherapy but survival remains poor. Allogeneic hematopoietic stem cell transplantation (HSCT) results in long-term survival in roughly one third of transplanted patients but only a small percentage of patients can make it to transplant. Overall, current treatments of aggressive ATL are not satisfactory. Prognosis of refractory or relapsed patients is dismal with some encouraging results when using lenalidomide or mogamulizumab. To overcome resistance and prevent relapse, preclinical or pilot clinical studies using targeted therapies such as arsenic/IFN, monoclonal antibodies, epigenetic therapies are promising but warrant further clinical investigation. Anti-ATL vaccines including Tax peptide-pulsed dendritic cells, induced Tax-specific CTL responses in ATL patients. Finally, based on the progress in understanding the pathophysiology of ATL, and the risk-adapted treatment approaches to different ATL subtypes, treatment strategies of ATL should take into account the host immune responses and the host microenvironment including HTLV-1 infected non-malignant cells. Herein, we will provide a summary of novel treatments of ATL in vitro, in vivo, and in early clinical trials.

Dataset Information

Treatment advances and prognosis for patients with adult T-cell leukemia-lymphoma.

Publications

Treatment advances and prognosis for patients with adult T-cell leukemia-lymphoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets