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1.
Int J Hematol ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31993940

RESUMO

Regulatory T-cells (Tregs) are major mediators of mammalian self-tolerance via cytotoxic T-lymphocyte antigen 4 (CTLA4) signaling pathways. An immune dysregulation syndrome associated with heterozygous germline mutations in CTLA4 was recently reported. Clinical features include recurrent infections, systemic lymphadenopathy, various autoimmune conditions, hypogammaglobulinemia, and autosomal dominant inheritance, characteristic of primary immunodeficient disease (PID). PID symptoms are variable and few patients with sporadic de novo CTLA4 germline mutations have been described. Here, we report the case of a 26-year-old man with an immune dysregulation syndrome and a de novo CTLA4 germline mutation. The patient exhibited several clinical features associated with PID. Next-generation sequencing revealed a CTLA4 germline mutation, c.436G>A; p.G146R, in exon 2 of CTLA4. Sanger sequencing confirmed the patient was the only member of his family with this germline mutation. The patient was diagnosed with an immune dysregulation syndrome associated with de novo germline CTLA4 mutation, complicated by steroid-refractory rheumatoid arthritis. Treatment with abatacept, a CTLA4-immunoglobulin fusion molecule, was initiated, resulting in dramatic resolution of the patient's clinical symptoms. As PID with CTLA4 germline mutation is rare and patients may be under-diagnosed, physicians should be aware of the features of PID.

2.
Ann Hematol ; 99(1): 113-119, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31768678

RESUMO

Novel anti-myeloma drugs have significantly improved the overall survival (OS) of patients with multiple myeloma (MM). However, not all MM patients treated with these drugs show survival benefits, and biologic and genetic prognostic factors are insufficient to predict the response to treatment. Decreasing treatment-related complications is important to improve the efficacy of treatment in patients with MM. The Controlling Nutritional Status (CONUT) score is a screening method for poor nutritional status, which is associated with poor prognosis in several cancers because it increases the rate of treatment-related complications. We retrospectively analyzed the OS of 64 patients with symptomatic MM and evaluated the correlation between the CONUT score and patient prognosis in MM. The median age at diagnosis was 66 years, and multivariate analysis showed that a high CONUT score (≥ 5; hazard ratio, 3.937; 95% confidence interval, 1.214-12.658; P = 0.022) was an independent prognostic risk factor. Subgroup analysis was performed according to patient age because the choice of treatment strategy, particularly autologous peripheral blood stem cell transplantation (auto-PBSCT), can vary depending on age in MM patients. Younger patients (< 65 years old) who received auto-PBSCT and had a lower CONUT score (0-3) showed a significantly better survival outcome than those with a higher CONUT score (≥ 4) (median OS, not reached vs. 64.1 months; P = 0.011). The CONUT score is simple to calculate and provides a useful prognostic indicator in patients with MM, especially transplant-eligible patients.


Assuntos
Mieloma Múltiplo , Estado Nutricional , Transplante de Células-Tronco de Sangue Periférico , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Mieloma Múltiplo/fisiopatologia , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
4.
Clin Lymphoma Myeloma Leuk ; 19(6): 326-331, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30981611

RESUMO

Mogamulizumab, a defucosylated humanized monoclonal antibody against the C-C chemokine receptor 4 (CCR4), has been approved for the treatment of relapsed adult T-cell leukemia/lymphoma (ATL). Compared with conventional chemotherapy, mogamulizumab monotherapy displayed more efficacy in relapsed ATL, making mogamulizumab a promising therapeutic agent. However, mogamulizumab could increase graft-versus-host disease, resulting in poor survival outcome in the allogenic stem cell transplant (allo-SCT) setting. It is possible that the efficacy of mogamulizumab could be established by the occurrence of skin rashes and/or CCR4 mutational status. Hence, this study reviews the current treatment strategies for patients with ATL and focuses on the safety and efficacy (single-agent and combined with chemotherapy or allo-SCT) of mogamulizumab.

5.
Intern Med ; 58(14): 2073-2077, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30918199

RESUMO

Primary chest wall lymphoma is rare and typically associated with chronic pleural inflammation. Double-hit lymphoma (DHL), which is defined as aggressive mature B-cell lymphoma with MYC and BCL2 or BCL6 rearrangements, is a highly aggressive malignancy that tends to have extranodal involvement and is resistant to standard immunochemotherapy. We herein report a 55-year-old man with no history of chronic pleural inflammation, diagnosed with primary chest wall DHL with MYC/BCL6 rearrangement, and harboring a unique BCL6 translocation, t (3;7) (q27;p12). After six courses of intensive chemotherapy, he has achieved complete remission. To our knowledge, this is the first case report of primary chest wall DHL.


Assuntos
Antineoplásicos/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Parede Torácica/patologia , Translocação Genética , Humanos , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
6.
Int J Hematol ; 109(2): 221-227, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30368656

RESUMO

Adult T-cell leukemia (ATL) is an aggressive mature T-cell malignancy with a poor prognosis. The anti-C-C motif chemokine receptor 4 (CCR4) antibody mogamulizumab (moga) reduces ATL cells and induces reconstitution of polyclonal T cells; however, ATL cases often remain resistant and moga sometimes causes fatal immunopathology. Epstein-Barr virus (EBV)-related B-cell lymphoma develops in severely immunocompromised subjects, and is particularly associated with impaired T-cell immunity. Here, we report an ATL patient who had received conventional chemotherapy plus moga, and subsequently developed EBV-related diffuse large B-cell lymphoma (DLBCL) of the central nervous system. Next-generation sequencing-based T-cell receptor repertoire analyses identified residual abnormal clones and revealed that reconstitution of polyclonal T cells was incomplete, even after moga treatment. Furthermore, a skin rash that developed after moga treatment was found to contain ATL clones. This case suggests that the limited therapeutic effects of moga and incomplete T-cell reconstitution are associated with severely impaired T-cell immunity and subsequent development of EBV-related DLBCL.


Assuntos
Herpesvirus Humano 4 , Linfoma Difuso de Grandes Células B/etiologia , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias do Sistema Nervoso Central , Criança , Células Clonais/patologia , Humanos , Leucemia-Linfoma de Células T do Adulto/complicações , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Linfoma Difuso de Grandes Células B/virologia , Linfócitos T/imunologia , Linfócitos T/patologia
8.
Oncoimmunology ; 7(3): e1405204, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29399406

RESUMO

Although the anti-CCR4 antibody mogamulizumab (moga) shows striking antitumor activity against adult T cell leukemia (ATL), it can also cause fatal immunological pathology such as severe skin rash and graft-versus-host disease, which might be attributed to depletion of CCR4+ regulatory T cells. We previously showed that next generation sequencing enables precise analysis of the T cell receptor (TCR) repertoire, and we here used the technique to reveal the immunological dynamics in moga-treated ATL patients. Treatment with moga resulted in remarkable reduction or elimination of clonal cells, and enhanced reconstitution of non-tumor polyclonal CD4+ T cells and oligoclonal CD8+ T cells. Interestingly, cutaneous T cells infiltrating moga-related skin rashes did not share the same major clones in peripheral blood, which minimizes the possibility of cross-reaction. Thus, deep sequencing of the TCR can reveal the immune reconstitution of moga-treated ATL and provides powerful insights into its mode of action.

9.
Intern Med ; 57(6): 855-860, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29151530

RESUMO

Solitary bone plasmacytoma (SBP) tends to progress to multiple myeloma (MM); however, progression to multiple solitary plasmacytomas (MSP) is rare. We report a case of CD138-low MSP with 17p deletion in a patient with relapsed SBP. 17p deletion is associated with a poor outcome in patients with MM, and the low expression of CD138 in myeloma cells is associated with drug resistance and a poor prognosis. The patient was successfully treated with bortezomib plus dexamethasone induction therapy and autologous hematopoietic stem cell transplantation followed by bortezomib maintenance therapy. Consequently, bortezomib treatment was stopped and a stringent complete response has been maintained.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Recidiva Local de Neoplasia/terapia , Transplante Autólogo/métodos , Deleção Cromossômica , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Resultado do Tratamento
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