A case of post-transplant adult T-cell leukemia/lymphoma presenting myelopathy similar to but distinct from human T-cell leukemia virus type I (HTLV- I)-associated myelopathy

Kawamata, Toyotaka; Ohno, Nobuhiro; Sato, Kota; Kobayashi, Masayuki; Jo, Norihide; Kikuchi, Yuji; Tanosaki, Ryuji; Yamano, Yoshihisa; Tojo, Arinobu; Uchimaru, Kaoru

doi:10.1186/2193-1801-3-581

Cited by 6 publications

(7 citation statements)

References 26 publications

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“…The emergence of these cells was apparently correlated with severity of infection. Another recent report [ 26 ] described a case of post-transplant adult T-cell leukemia/lymphoma in whom CXCR3+CCR4+ T cells were observed. As recently described by Becattini et al [ 13 ], the repertoire of memory CD4+ T cells includes not only cells polarized towards a single fate (conventional Th1, Th2, etc.…”

Section: Discussionmentioning

confidence: 99%

Neuroinvasive West Nile Infection Elicits Elevated and Atypically Polarized T Cell Responses That Promote a Pathogenic Outcome

et al. 2016

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Most West Nile virus (WNV) infections are asymptomatic, but some lead to neuroinvasive disease with symptoms ranging from disorientation to paralysis and death. Evidence from animal models suggests that neuroinvasive infections may arise as a consequence of impaired immune protection. However, other data suggest that neurologic symptoms may arise as a consequence of immune mediated damage. We demonstrate that elevated immune responses are present in neuroinvasive disease by directly characterizing WNV-specific T cells in subjects with laboratory documented infections using human histocompatibility leukocyte antigen (HLA) class II tetramers. Subjects with neuroinvasive infections had higher overall numbers of WNV-specific T cells than those with asymptomatic infections. Independent of this, we also observed age related increases in WNV-specific T cell responses. Further analysis revealed that WNV-specific T cell responses included a population of atypically polarized CXCR3+CCR4+CCR6- T cells, whose presence was highly correlated with neuroinvasive disease. Moreover, a higher proportion of WNV-specific T cells in these subjects co-produced interferon-γ and interleukin 4 than those from asymptomatic subjects. More globally, subjects with neuroinvasive infections had reduced numbers of CD4+FoxP3+ Tregs that were CTLA4 positive and exhibited a distinct upregulated transcript profile that was absent in subjects with asymptomatic infections. Thus, subjects with neuroinvasive WNV infections exhibited elevated, dysregulated, and atypically polarized responses, suggesting that immune mediated damage may indeed contribute to pathogenic outcomes.

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Section: Discussionmentioning

confidence: 99%

Neuroinvasive West Nile Infection Elicits Elevated and Atypically Polarized T Cell Responses That Promote a Pathogenic Outcome

et al. 2016

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“…Regarding HAM development, one case after allo-HSCT and 13 cases after organ transplantation, including 10 cases after renal transplantation, two cases after liver transplantation, and one case after heart transplantation have been reported (Table 5). 21 - 33 The majority of the cases were due to donor-derived HAM 22 , 23 , 28 …”

Section: Discussionmentioning

confidence: 99%

“…ATL development after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and organ transplantation has been reported in three and 13 cases, respectively 6 - 20 . Similarly, the development of HAM-mimicking myelitis after allo-HSCT and HAM after organ transplantation has been reported in one and 13 cases, respectively 21 - 33 . On the other hand, the clinical impact of HTLV-1 infection after allo-HSCT and organ transplantation is unclear and controversial.…”

Section: Introductionmentioning

confidence: 99%

The clinical impact of human T-lymphotrophic virus type 1 (HTLV-1) infection on the development of adult T-cell leukemia-lymphoma (ATL) or HTLV-1–associated myelopathy (HAM) / atypical HAM after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and renal transplantation

Kawano¹,

Yoshida²,

Kawano³

et al. 2018

J Clin Exp Hematopathol

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Because there are limited clinical reports on the impact of human T-lymphotropic virus type 1 (HTLV-1) on organ transplantation, its effects on the development of adult T-cell leukemia-lymphoma (ATL), post-transplantation lymphoproliferative disorder (PTLD) and HTLV-1-associated myelopathy (HAM) or atypical HAM after organ transplantation remain unclear.We retrospectively analyzed the impact of HTLV-1 in 54 allogeneic hematopoietic stem cell transplantation (allo-HSCT) cases and 31 renal transplantation cases between January 2006 and December 2016.Among the 54 allo-HSCT cases, nine recipients with ATL tested positive for HTLV-1, and one was found to be an HTLV-1 carrier. All donors tested negative for HTLV-1. Only one HTLV-1 carrier did not present with ATL or HAM development after allo-HSCT. Among nine ATL cases after allo-HSCT, four eventually relapsed due to proliferation of recipient-derived ATL cells. However, in one ATL case, atypical HAM developed rapidly at 5 months after allo-HSCT.Among the 31 renal transplantation cases, all donors tested negative for HTLV-1, and only recipients tested positive. Only one HTLV-1 carrier recipient did not present with ATL or HAM development after renal transplantation. However, one HTLV-1-negative recipient developed PTLD in the brain 10 years after renal transplantation.In clinical practice, careful follow-up of HTLV-1 infected recipients after organ transplantation is important because atypical HAM can develop in ATL patients after allo-HSCT. Furthermore, to clarify the risk of ATL or HAM development in HTLV-1 infected recipients, we prospectively followed up our cohort.

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“…The development of HAM-mimicking myelitis following treatment with allo-HSCT has been rarely reported. Kawamata et al 30 first reported a post-transplant ATL case with HAM-mimicking myelitis. 31 Furthermore, these results suggest the possible involvement of a certain immunological mechanism, such as HAM, in the patient's symptoms, irrespective of the lack of anti-HTLV-1 antibody in the patient's CSF.…”

Section: Referencesmentioning

confidence: 99%

“…However, Kanda et al also reported that the development of mild-to-moderate acute GVHD confers a lower risk of disease progression and a beneficial influence on survival of ATL patients treated with allo-HSCT. 30 In addition to the development of acute GVHD, the selective depletion of effector T-reg by mogamulizumab may also contribute to the increase of cytotoxic T-cells in ATL patients through immune check point inhibition. 18,22 In a basic setting, Sugiyama et al reported that mogamulizumab selectively depleted effector T-reg, evoking an anti-tumor immune response in humans.…”

Section: Referencesmentioning

confidence: 99%

The Impact of a Humanized CCR4 Antibody (Mogamulizumab) on Patients with Aggressive-Type Adult T-Cell Leukemia-Lymphoma Treated with Allogeneic Hematopoietic Stem Cell Transplantation

Kawano

Kuriyama

Yoshida

et al. 2017

J Clin Exp Hematopathol

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Although a humanized CCR4 antibody (mogamulizumab) was reported to be effective for refractory adult T-cell leukemia-lymphoma (ATL), several reports regarding the use of mogamulizumab before allo-hematopoietic stem cell transplantation (HSCT) strongly indicated a high incidence of severe acute graft-versus-host-disease (GVHD) and treatment-related mortality (TRM). We retrospectively analyzed nine aggressive-type ATL patients who underwent allo-HSCT at a single institution in Miyazaki from 2006.1.1 to 2015.7.31. Among nine ATL patients, three had used mogamulizumab before treatment with allo-HSCT because of the poor control of refractory ATL. All three patients were treated with four to eight cycles of mogamulizumab. The interval from last administration of mogamulizumab to allo-HSCT was two to five months. All three patients with prior mogamulizumab treatment developed mild-moderate acute GVHD (grade 2) 28, 34, or 40 days after allo-HSCT. Acute GVHD was controlled by prednisolone treatment. Two patients in complete remission before allo-HSCT exhibited relatively prolonged survival (survival rate, 66%). Moreover, one patient developed human T-cell leukemia virus type 1-associated myelopathy-mimicking myelitis at five months after allo-HSCT. In contrast, two of six ATL patients without a history of mogamulizumab use survived (survival rate 33%). Thus, in cases of mogamulizumab use before treatment with allo-HSCT for refractory ATL, an appropriately long interval from the last administration of mogamulizumab to allo-HSCT may be one of factors to reduce TRM by acute GVHD, and to subsequently enhance graft-versus-tumor effects in ATL cases. Furthermore, caution is needed when administering mogamulizumab before allo-HSCT for severe GVHD and TRM. 〔J Clin Exp Hematop 56(3):135-144, 2017〕

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A case of post-transplant adult T-cell leukemia/lymphoma presenting myelopathy similar to but distinct from human T-cell leukemia virus type I (HTLV- I)-associated myelopathy

Cited by 6 publications

References 26 publications

Neuroinvasive West Nile Infection Elicits Elevated and Atypically Polarized T Cell Responses That Promote a Pathogenic Outcome

Neuroinvasive West Nile Infection Elicits Elevated and Atypically Polarized T Cell Responses That Promote a Pathogenic Outcome

The clinical impact of human T-lymphotrophic virus type 1 (HTLV-1) infection on the development of adult T-cell leukemia-lymphoma (ATL) or HTLV-1–associated myelopathy (HAM) / atypical HAM after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and renal transplantation

The Impact of a Humanized CCR4 Antibody (Mogamulizumab) on Patients with Aggressive-Type Adult T-Cell Leukemia-Lymphoma Treated with Allogeneic Hematopoietic Stem Cell Transplantation

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