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1.
Clin Transplant ; 31(5)2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28256022

RESUMEN

Graft-versus-host disease (GVHD) is a major adverse effect associated with allogeneic stem cell transplant. Previous studies in mice indicated that administration of the probiotic Lactobacillus rhamnosus GG can reduce the incidence of GVHD after hematopoietic stem cell transplant. Here we report results from the first randomized probiotic enteric regimen trial in which allogenic hematopoietic stem cell patients were supplemented with Lactobacillus rhamnosus GG. Gut microbiome analysis confirmed a previously reported gut microbiome association with GVHD. However, the clinical trial was terminated when interim analysis did not detect an appreciable probiotic-related change in the gut microbiome or incidence of GVHD. Additional studies are necessary to determine whether probiotics can alter the incidence of GVHD after allogeneic stem cell transplant.


Asunto(s)
Microbioma Gastrointestinal/efectos de los fármacos , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Lacticaseibacillus rhamnosus/fisiología , Probióticos/administración & dosificación , Adulto , Anciano , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/dietoterapia , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Trasplante Homólogo
2.
Leuk Res ; 122: 106934, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36084368

RESUMEN

BACKGROUND: The excellent results of posttransplant cyclophosphamide in decreasing graft-versus-host disease (GVHD) after haploidentical (HI) allogeneic transplant have challenged current donor selection algorithms. PATIENTS AND METHODS: We compared outcomes after matched sibling (MSD) versus alternative donor transplant using identical graft-versus-host disease (GVHD) prophylaxis including posttransplant cyclophosphamide (PTCy. Endpoints included engraftment, time outside of the hospital in the first 100 days after transplant, overall survival (OS), non-relapse mortality (NRM) and percentage of patients disease-free and off immunosuppression (DFOI) at one year and at the last follow-up. RESULTS: There were significant differences at baseline between matched donor versus HI donor transplants with higher disease-risk index (DRI), more female-to-male donor recipient pairs and a higher percentage of Black patients in the HI group. Engraftment and time out of the hospital favored MSD and matched unrelated donor transplants. Multivariate analysis showed that high DRI and Black race were associated with decreased survival and Black race was associated with a higher NRM. CONCLUSIONS: With the use of PTCy, our results support current donor selection algorithms. The finding of decreased survival and increased NRM in Black patients requires confirmation in a larger number of patients as well as the development of mitigation strategies.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Acondicionamiento Pretrasplante/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Estudios Retrospectivos , Ciclofosfamida/uso terapéutico , Recurrencia , Aloinjertos
3.
Bone Marrow Transplant ; 56(5): 1099-1105, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33257777

RESUMEN

The addition of posttransplant cyclophosphamide (PTCy) to standard graft-versus-host disease (GVHD) prophylaxis following haploidentical blood stem transplants has resulted in relatively low rates of GVHD. As GVHD remains a major cause of morbidity and mortality in patients receiving transplants from matched donors, we began to use PTCy in all blood stem cell transplants in 2016 and compared our recent experience with PTCy after matched sibling and unrelated donor transplants (N = 49) to the earlier 2-year period (N = 41) when PTCy was not used. Endpoints included graft-versus-host, relapse-free-survival (GRFS), overall survival, non-relapse mortality, and percentage of patients disease-free and off immunosuppression (DFOI) at 1 year and at the last follow-up. The difference in GRFS between the standard and the PTCy cohort was not statistically significant. There was a statistically improved relapse-free and overall survival in the PTCY cohort that was due to a significant decrease in non-relapse mortality secondary to GVHD. There was also a borderline statistically improved DFOI at 1 year and at last follow-up in the PTCY group. These results suggest that PTCy after HLA-matched transplants provides at least comparable efficacy to other GVHD strategies and may allow more frequent discontinuation of immunosuppression.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Aloinjertos , Ciclofosfamida , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Estudios Retrospectivos
4.
Leuk Res ; 32(12): 1842-8, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18614230

RESUMEN

Allogeneic hematopoietic stem cell transplantation provides curative therapy for some patients with advanced hematologic malignancies. Disease response after allogeneic transplant is, at least in part, mediated by donor immune cells. In this report we describe a cellular therapy using haploidentical peripheral blood stem cells administered after very low dose total body irradiation (TBI) (100cGy). The donor cells were anticipated to be rejected, so no graft-versus-host (GVHD) prophylaxis was used. Patients with persistent disease beyond 8 weeks could be further treated with infusions of irradiated haploidentical donor cells. Of the 10 patients enrolled in the study, durable engraftment of allogeneic cells was seen in one patient. Two patients with resistant relapsed acute myelogenous leukemia (AML) had a disease response. Analysis of T cell reactivity from one patient who achieved a complete response but did not have durable engraftment of donor cells indicated that disease response was associated with the generation of host-derived anti-leukemic cytotoxic CD8+ T cells that reacted with an AML-associated proteinase 3 epitope. Results from this patient suggest that allogeneic therapy induced a host anti-tumor response associated with cytotoxic T cells reactive with a low affinity self-antigen.


Asunto(s)
Neoplasias Hematológicas/cirugía , Anciano , Anciano de 80 o más Años , Antígenos CD/sangre , Antígenos CD34/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Complejo CD3/sangre , Linfocitos T CD8-positivos/inmunología , Trasplante de Células , Femenino , Citometría de Flujo , Neoplasias Hematológicas/inmunología , Humanos , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/cirugía , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/cirugía , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/cirugía , Masculino , Persona de Mediana Edad , Proyectos Piloto , Donantes de Tejidos , Expansión de Tejido/métodos , Recolección de Tejidos y Órganos/métodos , Trasplante Homólogo
5.
Cancer Chemother Pharmacol ; 57(6): 789-95, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16231182

RESUMEN

Phorbol esters activate protein kinase C and modulate a variety of downstream cell signaling pathways. 12-O-tetradecanoylphorbol-13-acetate (TPA) is a phorbol ester that induces differentiation or apoptosis in a variety of cell lines at low concentrations. A phase I dose escalation trial of TPA was undertaken for patients with relapsed or refractory malignancies. The starting dose was 0.063 mg/m2 and most patients were treated with an intravenous infusion of TPA on days 1-5 and 8-12 followed by a 2-week rest period prior to retreatment. Thirty-five patients were treated. A biological assay was used to monitor levels of TPA-like activity in the blood after treatment. Serious adverse events included individual episodes of gross hematuria, a grand mal seizure, syncope, and hypotension. Many patients had transient fatigue, mild dyspnea, fever, rigors, and muscular aches shortly after the infusion. Dose-limiting toxicities included syncope and hypotension at a dose of 0.188 mg/m2. Only a single patient had evidence of tumor response. These studies establish 0.125 mg/m2 as the maximally tolerated dose when TPA is administered on this schedule.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Acetato de Tetradecanoilforbol/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Antineoplásicos/sangre , Antineoplásicos/farmacocinética , Femenino , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Neoplasias/metabolismo , Acetato de Tetradecanoilforbol/efectos adversos , Acetato de Tetradecanoilforbol/sangre , Acetato de Tetradecanoilforbol/farmacocinética
6.
J Clin Oncol ; 21(20): 3785-91, 2003 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-14551297

RESUMEN

PURPOSE: Vaccines, cytokines, and other biologic-based therapies are being developed as antineoplastic agents. Many of these agents are designed to induce an autologous immune response directed against the malignancy. In contrast, hematopoietic stem-cell transplantation is being developed as a form of allogeneic immunotherapy. This study tests the tolerance and antineoplastic activity of sequential infusions of partially HLA-matched allogeneic blood mononuclear cells (obtained from relatives) when administered outside of the context of a hematopoietic stem-cell transplantation. The cells are irradiated to prevent graft-versus-host disease. PATIENTS AND METHODS: Fifteen patients with relapsed or refractory malignancies for which no standard therapy was available were enrolled onto a clinical trial designed to assess the tolerability and antineoplastic effects of irradiated partially HLA-matched blood mononuclear cells obtained from relatives. RESULTS: There was disease regression in three patients with metastatic renal cell carcinoma during treatment. There was disease progression in six patients with metastatic renal cell carcinoma and two patients with metastatic melanoma during treatment. There was no change in disease state in several other patients. CONCLUSION: Irradiated allogeneic blood mononuclear cells administered outside the context of hematopoietic stem-cell transplantation may induce disease responses in patients with relapsed or refractory malignancies. Transfusion of irradiated allogeneic blood mononuclear cells should be developed further as a novel therapeutic antineoplastic approach.


Asunto(s)
Carcinoma de Células Renales/terapia , Trasplante de Células , Neoplasias Renales/terapia , Células Asesinas Naturales/inmunología , Linfocitos T/inmunología , Adulto , Anciano , Femenino , Antígenos HLA , Humanos , Células Asesinas Naturales/efectos de la radiación , Masculino , Persona de Mediana Edad , Linfocitos T/efectos de la radiación
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