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1.
J Neurol Neurosurg Psychiatry ; 90(5): 514-521, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30538138

RESUMEN

BACKGROUND: Autologous haematopoietic stem cell transplantation (AHSCT) has been explored as a therapeutic intervention in multiple sclerosis (MS) over the last two decades; however, prospective clinical trials of the most common myeloablative conditioning regimen, BEAM, are limited. Furthermore, patient selection, optimal chemotherapeutic regimen and immunological changes associated with disease response require ongoing exploration. We present the outcomes, safety and immune reconstitution (IR) of patients with active, treatment refractory MS. METHODS: This study was a single-centre, phase II clinical trial of AHSCT for patients with active relapsing remitting (RRMS) and secondary progressive MS (SPMS). Patients underwent AHSCT using BEAM (carmustine, etoposide, cytarabine, melphalan)+antithymocyte globulin chemotherapeutic regimen. OUTCOMES: The primary outcome was event-free survival (EFS); defined as no clinical or radiological relapses and no disability progression. Multiparameter flow cytometry was performed for evaluation of post-transplant IR in both MS and lymphoma patients receiving the same chemotherapy regimen. RESULTS: Thirty-five patients (20 RRMS, 15 SPMS) completed AHSCT, with a median follow-up of 36 months (range 12-66). The median Expanded Disability Status Scores (EDSS) was 6 (2-7) and patients had failed a median of 4 (2-7) disease modifying therapies. 66% failed treatment with natalizumab. EFS at 3 years was 60%, (70% RRMS). Sustained improvement in EDSS was seen in 15 (44%) of patients. There was no treatment-related mortality. A sustained rise in CD39+ T regulatory cells, immunosuppressive CD56hi natural killer cells and ablation of proinflammatory mucosal-associated invariant T cells was seen for 12 months following AHSCT in patients with MS. These changes did not occur in patients with lymphoma receiving the same chemotherapy for AHSCT. CONCLUSIONS: The EFS in our MS cohort is significantly greater than other high-efficacy immunosuppressive therapies and similar to other AHSCT studies despite a more heavily pretreated cohort. TRIAL REGISTRATION NUMBER: ACTRN12613000339752.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Esclerosis Múltiple Crónica Progresiva/terapia , Esclerosis Múltiple Recurrente-Remitente/terapia , Adulto , Suero Antilinfocítico/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carmustina/uso terapéutico , Citarabina/uso terapéutico , Etopósido/uso terapéutico , Femenino , Humanos , Inmunosupresores/uso terapéutico , Masculino , Melfalán/uso terapéutico , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Prospectivos , Trasplante Autólogo , Resultado del Tratamiento , Adulto Joven
2.
J Acquir Immune Defic Syndr ; 75(3): 328-337, 2017 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-28350553

RESUMEN

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) can lead to significant changes to the HIV reservoir and HIV immune responses, indicating that further characterization of HIV-infected patients undergoing HSCT is warranted. METHODS: We studied 3 patients who underwent HSCT after either reduced intensity conditioning or myeloablative conditioning regimen. We measured HIV antigens and antibodies (Ag/Ab), HIV-specific CD4 T-cell responses, HIV RNA, and DNA in plasma, peripheral blood mononuclear cells, isolated CD4 T cells from peripheral blood, and lymph node cells. The patients remained on antiretroviral therapy throughout the follow-up period. RESULTS: All patients have been in continued remission for 4-6 years post-HSCT. Analyses of HIV RNA and DNA levels showed substantial reductions in HIV reservoir-related measurements in all 3 patients, changes in immune response varied with pronounced reductions in 2 patients and a less dramatic reduction in 1 patient. One patient experienced unexpected viral rebound 4 years after HSCT. CONCLUSIONS: These 3 cases highlight the substantial changes to the HIV reservoir and the HIV immune response in patients undergoing allogeneic HSCT. The viral rebound observed in 1 patient indicates that replication competent HIV can re-emerge several years after HSCT despite these marked changes.


Asunto(s)
Infecciones por VIH/inmunología , Infecciones por VIH/terapia , Trasplante de Células Madre Hematopoyéticas , Carga Viral/inmunología , Adulto , Terapia Antirretroviral Altamente Activa , Linfocitos T CD4-Positivos/inmunología , ADN Viral/sangre , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Inducción de Remisión , Acondicionamiento Pretrasplante , Resultado del Tratamiento , Adulto Joven
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