Allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia/lymphoma with HTLV-1-associated myelopathy

Sakamoto, Hikaru; Itonaga, Hidehiro; Sawayama, Yasushi; Kojima, Akira; Chiwata, Masahiko; Fujioka, Machiko; Kitanosono, Hiroko; Horai, Makiko; Miyazaki, Tatsuhiko; Shiraishi, Hiroaki; Imaizumi, Yoshitaka; Yoshida, Shinichiro; Hata, Tomoko; Yamano, Yoshihisa; Miyazaki, Yasushi

doi:10.1007/s12185-020-03075-6

Cited by 5 publications

(4 citation statements)

References 42 publications

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“…15 In the phase 2 study of lenalidomide, only 2 patients with SD to prior therapy were included. 14 The shorter time since last ATL treatment (median, 60 days) in the current study compared with those in the phase 2 studies for other agents (234.5 days for lenalidomide and 89 days for tucidinostat) reflects the inclusion of patients with refractory disease and more aggressive features. Furthermore, the higher median of 3 prior lines of therapy (range, 1-8) in this study compared with 2 for lenalidomide (range, 1-4) and 2 for tucidinostat is similarly reflective of aggressive ATL.…”

Section: Discussionmentioning

confidence: 76%

“…10,11 However, the median age at diagnosis (68 years), donor availability, patient comorbidities, and infectious complications during induction treatment severely limit eligibility for allo-HSCT. 10,[12][13][14] In addition, more than half of patients who receive allo-HSCT cannot achieve long-term survival owing to relapse and/or treatment-related toxicities, requiring further treatment. 9 Recently, new agents have been incorporated into the armamentarium for relapsed or refractory (R/R) ATL.…”

Section: Regular Articlementioning

confidence: 99%

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An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma

Izutsu

Makita

Nosaka

et al. 2023

Blood

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Adult T-cell leukemia/lymphoma (ATL) is an aggressive non-Hodgkin lymphoma with poor prognosis and few treatment options for patients with relapsed, recurrent, or refractory disease. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. This multicenter phase 2 trial (NCT04102150; https://clinicaltrials.gov/ct2/show/NCT04102150; DS3201-A-J201) enrolled patients with R/R aggressive ATL (acute, lymphoma, unfavorable chronic type). Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity. The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. The primary endpoint was met with a centrally reviewed ORR of 48.0% (90% CI, 30.5% to 65.9%), including 5 complete and 7 partial remissions. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). Treatment-emergent adverse events (TEAEs) were manageable. TEAEs that occurred in ≥20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. Grade ≥3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL.

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Section: Discussionmentioning

confidence: 76%

Section: Regular Articlementioning

confidence: 99%

An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma

Izutsu

Makita

Nosaka

et al. 2023

Blood

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“…According to previous research experience [ 21 , 22 ], it needed to query documents in multiple databases. Because there was no database that could record all the literature, it needed to supplement the related literature in another database [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

PET/CT Evaluation of the Effect of Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of T‐Cell Lymphoblastic Lymphoma

Zhao

Guo

et al. 2022

Contrast Media & Molecular Imaging

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The aim of this study was to investigate the clinical value of positron emission tomography/computerized tomography scanning (PET/CT) in the evaluation of the effect of allogeneic hematopoietic stem cell transplantation in the treatment of T lymphoblastic lymphoma. 12 relevant research articles were collected through layer-by-layer screening in large databases such as Pubmed, Baidu Scholar, and China How Net, and analyzed and summarized using indicators such as progression-free survival (PFS), overall survival (OS), hazard ratio (HR), maximum standardized uptake value (SUV max), total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), elevated lactate dehydrogenase (LDH), and β2-microglobulin (β2-MG). The results showed that before treatment, 18F-FDG PET/CT baseline diagnosis could accurately stage the patients; during treatment, 18F-FDG PET/CT detection could provide effective treatment information; and after treatment, complications were found during 18F-FDG PET/CT detection. In summary, 18F-FDG PET/CT can monitor and evaluate treatment prognosis at baseline, middle, and late stages, and 18F-FDG PET/CT has become an indispensable and important examination technique in clinical work.

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“…263 Several other treatments have been proposed for various conditions, including monoclonal antibodies, immunoglobulins, probiotics, vitamins, and plasmaphaeresis, 103 and there have also been attempts at bone marrow transplantation or maybe stem cell therapy. 264…”

Section: Therapeutic Approaches For Ham/tspmentioning

confidence: 99%

Novel insights into human T‐lymphotropic virus type‐1 (HTLV‐1) pathogenesis‐host interactions in the manifestation of HTLV‐1‐associated myelopathy/tropical spastic paraparesis

Ahmadi Ghezeldasht,

Mosavat,

Rezaee

2024

Reviews in Medical Virology

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Human T‐lymphotropic virus type‐1 (HTLV‐1) was the first discovered human oncogenic retrovirus, the etiological agent of two serious diseases have been identified as adult T‐cell leukaemia/lymphoma malignancy and HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP), a debilitating chronic neuro‐myelopathy. Despite more than 40 years of molecular, histopathological and immunological studies on HTLV‐1‐associated diseases, the virulence and pathogenicity of this virus are yet to be clarified. The reason why the majority of HTLV‐1‐infected individuals (∼95%) remain asymptomatic carriers is still unclear. The deterioration of the immune system towards oncogenicity and autoimmunity makes HTLV‐1 a natural probe for the study of malignancy and neuro‐inflammatory diseases. Additionally, its slow worldwide spreading has prompted public health authorities and researchers, as urged by the WHO, to focus on eradicating HTLV‐1. In contrast, neither an effective therapy nor a protective vaccine has been introduced. This comprehensive review focused on the most relevant studies of the neuro‐inflammatory propensity of HTLV‐1‐induced HAM/TSP. Such an emphasis on the virus‐host interactions in the HAM/TSP pathogenesis will be critically discussed epigenetically. The findings may shed light on future research venues in designing and developing proper HTLV‐1 therapeutics.

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Allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia/lymphoma with HTLV-1-associated myelopathy

Cited by 5 publications

References 42 publications

An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma

An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma

PET/CT Evaluation of the Effect of Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of T‐Cell Lymphoblastic Lymphoma

Novel insights into human T‐lymphotropic virus type‐1 (HTLV‐1) pathogenesis‐host interactions in the manifestation of HTLV‐1‐associated myelopathy/tropical spastic paraparesis

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