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1.
Clin Microbiol Infect ; 29(6): 796.e7-796.e13, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36702399

RESUMO

OBJECTIVES: Chronic active Epstein-Barr virus infection (CAEBV) is a prototype of EBV-associated T-or NK-cell lymphoproliferative diseases. It is a disease with poor outcome. Almost all current therapies are ineffective except of allogeneic hematopoietic stem cell transplantation. METHODS: We investigated the efficacy and safety of programmed death 1 (PD-1) blockade (Sintilimab), combined with lenalidomide, which is an immunomodulatory drug, in an open-label, single-center, prospective study involving CAEBV patients. PD1 blockade 2mg/kg was given every two weeks by intravenous infusion on day 1, and lenalidomide 5mg (age<18 years)/10mg (age ≥ 18 years) was given orally once a day on day 1-14. RESULTS: As of Nov 15, 2020, 34 patients were enrolled. As of the Feb 1, 2021 analysis cut-off date, 24 cases completed at least 3 courses and were assessed for efficacy. The overall response rate is 54.2% (13/24, 45.8% complete response; 8.3% partial response). EBV-DNA copies in PBMC decreased significantly (p = 0.002). The proportion of CD8+T cells in lymphocytes increased (p = 0.007). The comparative analysis between response group and non-response group showed the proportion of Effector Memory CD8+ T cells and cytokines of CTLs activation (IFN-γ, CD27, CD30, MIG, IP-10) increased significantly in Response-group after treatment. Whole-exome sequencing generated from peripheral blood and saliva samples reveal that Non-Response group had a higher somatic mutational load of copy number variation in background. With a median follow-up time of 17.8 months, 22 of 24 patients were alive with an estimated survival probability of 91.3% at 1 year. All 34 patients were assessed for safety evaluation. The possible drug-related adverse events were reported in 17 (50%) patients. CONCLUSIONS: PD-1 blockade combined with lenalidomide was an effective and safe therapy for CAEBV patients. The significant therapeutic effect and the different characteristics between response and non-response group, provides a possible predictive value for CAEBV treatment option.


Assuntos
Infecções por Vírus Epstein-Barr , Humanos , Adolescente , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/genética , Lenalidomida/uso terapêutico , Receptor de Morte Celular Programada 1 , Leucócitos Mononucleares , Variações do Número de Cópias de DNA , Estudos Prospectivos , Doença Crônica
2.
Ann Hematol ; 101(11): 2471-2476, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36071294

RESUMO

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a common subtype of secondary HLH. EBV plays an important part in the course. EBV can cause central nervous system (CNS) infections, and there are few clinical studies on EBV-CNS infection in EBV-HLH patients. All patients who were diagnosed as EBV-HLH and underwent cerebrospinal fluid testing admitted to our center from January 2018 to December 2019 were retrospectively analyzed. Summarized the clinical data, evaluated treatment efficacy after intrathecal injection, and investigated the correlation between EBV-CNS infection with prognosis in EBV-HLH patients. Of 37 of 57 (64.9%) EBV-HLH patients has EBV-CNS infection. The survival of EBV-HLH patients without EBV-CNS infection was significantly better than that in EBV-CNS infection patients (P = 0.018). There were no statistically significant differences in sCD25, ferritin, ALT, AST, LDH, TB, WBC, Hb, and PLT counts between two groups (all P-values > 0.05). Higher EBV-DNA load in peripheral blood was correlated with EBV-CNS infection (P < 0.001). EBV-CNS infection is an independent risk factor affecting the survival of patients (P = 0.004). The CSF cell load of patients with and without EBV-CNS infection groups was significantly different (P = 0.024). Intrathecal injection with methotrexate combined with dexamethasone can effectively decrease CSF EBV-DNA load (P = 0.017) and CSF cell load (P = 0.025). EBV-CNS infection is an independent risk factor affecting prognosis in EBV-HLH patients. Therefore, EBV-CNS infection should cause concern for EBV-HLH patients. Cerebrospinal fluid testing is necessary for all patients. Methotrexate combined with dexamethasone intrathecal injection can be an effective treatment for EBV-CNS infection.


Assuntos
Infecções por Vírus Epstein-Barr , Linfo-Histiocitose Hemofagocítica , Sistema Nervoso Central , Dexametasona/uso terapêutico , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Ferritinas , Herpesvirus Humano 4 , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Metotrexato/uso terapêutico , Estudos Retrospectivos
3.
Cell Transplant ; 30: 9636897211057077, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34743574

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a severe or even fatal inflammatory status. Lymphoma associated hemophagocytic lymphohistiocytosis (LAHS) is a kind of secondary HLH (sHLH). It suffers the worst outcome among sHLH. Allo-HSCT is often considered necessary. Autologous stem cell transplantation (auto-SCT) is widely used in the treatment of lymphoma, especially for high-risk NHL. There have been no clinical reports on the use of auto-SCT in LAHS in the past 20 years. METHODS: We retrospectively evaluated 12 LAHS patients who received auto-SCT at our center from January 2013 to January 2020. Follow-up started at the date of LAHS diagnosis and ended at the date of death or last examination. Overall survival (OS) was calculated from the diagnosis of HLH to death of any cause. RESULTS: The median period between diagnosis and auto-SCT is 6.7 months. All 12 patients achieved remission after transplantation. Follow-up to 1 January 2021, 8 patients remained disease-free, 4 patients relapsed and 2 of them died eventually. The median follow-up time is 20.9 months, and the median overall survival time has not been reached yet. The 3-year OS rates was 71%. Compared with LAHS patients who did not undergo transplantation during the same period (median OS time is 3.4 months), patients who underwent auto-SCT had a significantly better prognosis (P=0.001). Even if the lymphoma reaches CR after treatment, auto-SCT still provides a better prognosis compared to CR patients without transplantation (P=0.037). Compared with lymphoma patients without HLH who underwent auto-SCT during the same period, they had a similar prognosis (P=0.350). CONCLUSION: LAHS, as a common type in secondary HLH, may have a better prognosis after removing the trigger of HLH. In this study, the autologous transplantation in LAHS can significantly improve the prognosis, and provide LAHS a similar prognosis as high-risk lymphoma without HLH.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Linfo-Histiocitose Hemofagocítica/terapia , Linfoma/terapia , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Adolescente , Adulto , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/patologia , Linfoma/mortalidade , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
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