scholarly journals Mogamulizumab for adult T-cell leukemia-lymphoma: a multicenter prospective observational study

2020 ◽  
Vol 4 (20) ◽  
pp. 5133-5145
Author(s):  
Kentaro Yonekura ◽  
Shigeru Kusumoto ◽  
Ilseung Choi ◽  
Nobuaki Nakano ◽  
Asahi Ito ◽  
...  
Keyword(s):  
T Cell ◽  
Observational Study ◽  
Cytotoxic T Lymphocytes ◽  
Prospective Observational Study ◽  
Cell Subset ◽  
Cd8 T Cell ◽  
Lymphocyte Population ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Multicenter Prospective Observational Study

Abstract Monitoring of Immune Responses Following Mogamulizumab-Containing Treatment in Patients with Adult T-Cell Leukemia-Lymphoma (ATL) (MIMOGA) is a multicenter prospective observational study to establish the most effective and safe treatment strategy using mogamulizumab for ATL patients (UMIN000008696). Mogamulizumab-naive patients were enrolled (n = 102), of whom 101 received mogamulizumab-containing treatment (68 acute, 18 lymphoma, 12 chronic, and 3 smoldering subtypes). At enrollment, there was a significant inverse correlation between serum soluble interleukin-2 receptor (sIL-2R) levels and percentages of Tax-specific cytotoxic T lymphocytes (Tax-CTLs) in the entire lymphocyte population or in the CD8+ T cell subset, but there was not a correlation with cytomegalovirus pp65–specific cytotoxic T lymphocytes (CMV-CTLs). The overall response rate was 65%, and median progression-free survival and overall survival (OS) were 7.4 and 16.0 months, respectively. A higher percentage of Tax-CTLs, but not CMV-CTLs, within the entire lymphocyte population or in the CD8+ T cell subset was significantly associated with longer survival. Multivariate analysis identified the clinical subtype (acute or lymphoma type), a higher sIL-2R level, and a lower percentage of CD2−CD19+ B cells in peripheral blood mononuclear cells as significant independent unfavorable prognostic factors for OS. This indicates that a higher percentage of B cells might reflect some aspect of a favorable immune status leading to a good outcome with mogamulizumab treatment. In conclusion, the MIMOGA study has demonstrated that mogamulizumab exerts clinically meaningful antitumor activity in ATL. The patient’s immunological status before mogamulizumab was significantly associated with treatment outcome. Further time series immunological analyses, in addition to comprehensive genomic analyses, are warranted.

scholarly journals Identification of Two New HLA-A*1101-Restricted Tax Epitopes Recognized by Cytotoxic T Lymphocytes in an Adult T-Cell Leukemia Patient after Hematopoietic Stem Cell Transplantation

2005 ◽  
Vol 79 (15) ◽  
pp. 10088-10092 ◽  
Author(s):  
Nanae Harashima ◽  
Ryuji Tanosaki ◽  
Yukiko Shimizu ◽  
Kiyoshi Kurihara ◽  
Takao Masuda ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
T Lymphocytes ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cytotoxic T Lymphocytes ◽  
Cell Leukemia ◽  
Hematopoietic Stem ◽  
Adult T Cell Leukemia

ABSTRACT We previously reported that Tax-specific CD8+ cytotoxic T lymphocytes (CTLs), directed to single epitopes restricted by HLA-A2 or A24, expanded in vitro and in vivo in peripheral blood mononuclear cells (PBMC) from some adult T-cell leukemia (ATL) patients after but not before allogeneic hematopoietic stem cell transplantation (HSCT). Here, we demonstrated similar Tax-specific CTL expansion in PBMC from another post-HSCT ATL patient without HLA-A2 or A24, whose CTLs equally recognized two newly identified epitopes, Tax88-96 and Tax272-280, restricted by HLA-A11, suggesting that these immunodominant Tax epitopes are present in the ATL patient in vivo.

Expression of PD-1 and PD-L1 on cytotoxic T lymphocytes and immune deficiency in a patient with adult T cell leukemia/lymphoma

2017 ◽  
Vol 97 (2) ◽  
pp. 359-360 ◽  
Author(s):  
Toyoshi Yanagihara ◽  
Yuki Ikematsu ◽  
Koji Kato ◽  
Akiko Yonekawa ◽  
Satoko Ideishi ◽  
...  
Keyword(s):  
Immune Deficiency ◽  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia

scholarly journals Elevation of Memory Cytotoxic T Lymphocytes, Including Human T Lymphotropic Virus Type 1 Tax-Specific and Hepatitis Virus Type C-Specific Cytotoxic T Lymphocytes, in a Patient with Adult T-Cell Leukemia/Lymphoma and Hepatocellular Carcinoma

2020 ◽  
Vol 13 (2) ◽  
pp. 802-806
Author(s):  
Tatsuro Jo ◽  
Yohei Kaneko ◽  
Takayuki Oishi ◽  
Kaori Matsuzaka ◽  
Haruna Shioya ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Virus Type ◽  
Hepatitis Virus ◽  
Cell Leukemia ◽  
T Lymphotropic Virus ◽  
Adult T Cell Leukemia ◽  
Type C

Herein, we present the case of a patient who suffered from adult T-cell leukemia/lymphoma (ATLL) and hepatocellular carcinoma (HCC) after obtaining a sustained virological response following treatment with a direct-acting antiviral (DAA) at different points in time. The patient went into complete remission (CR) for ATLL. Unfortunately, subsequent relapse of ATLL was observed. This situation was overcome using chemotherapy with pegylated interferon alpha-2b. Human T lymphotropic virus type 1 Tax-specific cytotoxic T lymphocytes (CTLs) were recognized after obtaining second CR, and those CTLs have been maintained for many years. After 4 years from the second CR, chronic hepatitis type C was treated with a DAA, and sustained virological response was attained. However, the occurrence of HCC was detected. Surprisingly, the tumor disappeared spontaneously. Hepatitis virus type C-specific CTLs were also detected in the patient. T-cell receptor (TCR) V beta gene repertoire analyses revealed oligoclonal expansion of effector and memory CTLs. The number of CTLs expressing the TCR V beta 13.1 has increased over the years since HCC occurrence. The activation and maintenance of anticancer cellular immunity may have allowed the patient to obtain long-term survival and overcome two lethal neoplasms.

scholarly journals Robust CD8+ T-cell proliferation and diversification after mogamulizumab in patients with adult T-cell leukemia-lymphoma

2020 ◽  
Vol 4 (10) ◽  
pp. 2180-2191
Author(s):  
Masato Saito ◽  
Toshihiko Ishii ◽  
Itaru Urakawa ◽  
Asuka Matsumoto ◽  
Ayako Masaki ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Cd8 T Cell ◽  
Cell Depletion ◽  
T Cell Proliferation ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
T Cell Depletion ◽  
Adult T Cell Leukemia ◽  
Before And After

Abstract Skin-related adverse events (AEs) occur frequently in adult T-cell leukemia-lymphoma (ATL) patients treated with mogamulizumab, a humanized anti-CCR4 monoclonal antibody. This study was undertaken to elucidate the mechanisms of mogamulizumab-induced skin-related AEs. We analyzed the T-cell receptor β chain repertoire in ATL patients’ peripheral blood mononuclear cells (PBMCs) before and after mogamulizumab. Skin-related AEs were present in 16 patients and were absent in 8 patients. Additionally, we included 11 patients before and after chemotherapy without mogamulizumab. Immune-related gene expression in PBMCs before and after mogamulizumab was also assessed (n = 24). Mogamulizumab treatment resulted in CCR4+ T-cell depletion, and the consequent lymphopenia provoked homeostatic CD8+ T-cell proliferation, as evidenced by increased expressions of CD8B and CD8A, which were significantly greater in patients with skin-related AEs than in those without them. We hypothesize that proliferation is driven by the engagement of self-antigens, including skin-related antigens, in the face of regulatory T-cell depletion. Together with the observed activated antigen presentation function, this resulted in T-cell diversification that was significantly greater in patients with skin-related AEs than in those without. We found that the CD8+ T cells that proliferated and diversified after mogamulizumab treatment were almost entirely newly emerged clones. There was an inverse relationship between the degree of CCR4+ T-cell depletion and increased CD8+ T-cell proliferation and diversification. Thus, lymphocyte-depleting mogamulizumab treatment provokes homeostatic CD8+ T-cell proliferation predominantly of newly emerging clones, some of which could have important roles in the pathogenesis of mogamulizumab-induced skin-related AEs.

High Expression of Intestinal Homing Receptor CD103 in Adult T-Cell Leukemia/Lymphoma, Similar to 2 Other CD8+ T-Cell Lymphomas

2016 ◽  
Vol 40 (4) ◽  
pp. 462-470 ◽  
Author(s):  
Hideki Ishibashi ◽  
Satoshi Nimura ◽  
Kenji Ishitsuka ◽  
Yasuhito Mihashi ◽  
Mikio Mizoguchi ◽  
...  
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
High Expression ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Homing Receptor ◽  
Adult T Cell Leukemia ◽  
T Cell Lymphomas

scholarly journals Improved survival of patients with aggressive ATL by increased use of allo-HCT: A prospective observational study

2021 ◽  
Author(s):  
Ayumu Ito ◽  
Nobuaki Nakano ◽  
Takashi Tanaka ◽  
Shigeo Fuji ◽  
Junya Makiyama ◽  
...  
Keyword(s):  
Observational Study ◽  
Cord Blood ◽  
Treatment Outcomes ◽  
Prospective Observational Study ◽  
Hematopoietic Cell Transplantation ◽  
Curative Therapy ◽  
Adult T Cell Leukemia ◽  
Unrelated Donors ◽  
Multicenter Prospective Observational Study ◽  
Clinical Trials Registry

Aggressive adult T-cell leukemia/lymphoma (ATL) is a hematological malignancy that is difficult to treat with chemotherapy alone, and allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy. We conducted a multicenter, prospective, observational study to clarify the treatment outcomes of aggressive ATL in the current era. Between 2015 and 2018, 113 patients aged 70 years or younger with newly diagnosed aggressive ATL were enrolled. The median age at diagnosis was 61 years old. Treatment outcomes were compared with those of 1,792 ATL patients diagnosed between 2000 and 2013 in our previous retrospective study. The inclusion criteria were the same in both studies. The prospective cohort demonstrated better overall survival (OS) than the retrospective cohort (2-year OS, 45% versus 29%, respectively; P<0.001), with a much higher proportion of patients receiving allo-HCT (80% versus 34%, respectively; P<0.001) and a shorter interval from diagnosis to allo-HCT (median, 128 versus 170 days, respectively; P<0.001). Among the 90 patients who received allo-HCT (cord blood, n=30; HLA-haploidentical related donors, n=20; other related donors, n=14; other unrelated donors, n=26), the 2-year probabilities of OS, non-relapse mortality (NRM), and disease progression were 44%, 23%, and 46%, respectively. OS and NRM did not differ statistically according to donor type. Our results suggest that increased application of allo-HCT improved the survival of patients with aggressive ATL. The use of cord blood or HLA-haploidentical donors may be feasible for aggressive ATL when HLA-matched related donors are unavailable. This study was registered with the UMIN Clinical Trials Registry (UMIN 000017672).

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