Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
1.
Transplant Cell Ther ; 27(7): 614.e1-614.e8, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33775908

RESUMEN

One hundred and sixty-one patients underwent haploidentical stem cell transplantation (haploSCT) with thiotepa, busulfan, and fludarabine conditioning followed by post-transplantation cyclophosphamide (PTCy) (on days +3 and +4) and tacrolimus as graft-versus-host disease prophylaxis. Forty-two percent of patients had a high or very high revised Disease Risk Index (rDRI), 55% had an European Society for Blood and Marrow Transplantation risk score (EBMT-RS) ≥4, and 36% had an age-adjusted Hematopoietic Cell Transplant Comorbidity Index (HCT-CI-age) score ≥3. Each of these was considered an unfavorable score. Using the pretransplantation unfavorable scores that had an independent impact on each transplantation outcome studied in multivariate analysis allowed for better stratification of patient outcomes. Thus, the 3-year overall survival (OS) in patients with 0, 1, 2, and 3 unfavorable scores was 86%, 56%, 36%, and 24%, respectively. Nonrelapse mortality (NRM) was negatively impacted by the EBMT-RS and the HCT-CI-age score (3-year NRM in patients with 0, 1, and 2 unfavorable scores was 12%, 33%, and 43%, respectively), whereas the EBMT-RS and the rDRI had an impact on the 3-year relapse incidence (8%, 18%, and 41% in patients with 0, 1, and 2 unfavorable scores, respectively). In conclusion, our study shows that combining 2 or 3 of these well-defined pretransplantation scores improves the ability to predict transplantation outcomes in the setting of haploSCT with PTCy.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Busulfano/uso terapéutico , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Tiotepa/uso terapéutico , Acondicionamiento Pretrasplante , Vidarabina/análogos & derivados
2.
Clin Cancer Res ; 25(15): 4616-4623, 2019 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-31043390

RESUMEN

PURPOSE: The biologically active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3 (vit D), has immunoregulatory properties via binding vitamin D receptor (VDR). In a prospective trial, we previously reported a reduction in the incidence of chronic GvHD (cGvHD) among patients who received vit D after allogeneic stem cell transplantation (allo-HSCT; Clinical Trials.gov: NCT02600988). Here we analyze the role of patients and donors' VDR SNPs on the immunomodulatory effect of vit D. PATIENTS AND METHODS: Patients undergoing allo-HSCT were included in a prospective phase I/II clinical trial (Alovita) in three consecutive cohorts: control (without vit D), low-dose (1,000 IU/day), and high-dose (5,000 IU/day) groups. Vit D was given from day -5 until +100 after transplant. Genotyping of four SNPs of the VDR gene, FokI, BsmI, ApaI, and TaqI, were performed using TaqMan SNP genotyping assays. RESULTS: We observed a decrease in the incidence of overall cGvHD at 1 year after allo-HSCT depending on the use or not of vit D among patients with FokI CT genotype (22.5% vs 80%, P = 0.0004) and among those patients without BsmI/ApaI/TaqI ATC haplotype (22.2% vs 68.8%, P = 0.0005). In a multivariate analysis, FokI CT genotype significantly influenced the risk of cGvHD in patients treated with vit D as compared with the control group (HR 0.143, P interaction < 0.001). CONCLUSIONS: Our results show that the immunomodulatory effect of vit D depends on the VDR SNPs, and patients carrying the FokI CT genotype display the highest benefit from receiving vit D after allo-HSCT.


Asunto(s)
Colecalciferol/uso terapéutico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/epidemiología , Haplotipos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Polimorfismo de Nucleótido Simple , Receptores de Calcitriol/genética , Estudios de Casos y Controles , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/patología , Humanos , Incidencia , Estudios Prospectivos , España/epidemiología , Resultado del Tratamiento , Vitaminas/uso terapéutico
3.
Clin Cancer Res ; 22(23): 5673-5681, 2016 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-27358490

RESUMEN

PURPOSE: We describe the results of a prospective multicenter phase I/II trial evaluating the impact of the use of vitamin D (VitD) from day -5 to +100 on the outcome of patients undergoing allogeneic transplantation (EudraCT: 2010-023279-25; ClinicalTrials.gov: NCT02600988). EXPERIMENTAL DESIGN: A total of 150 patients were included in three consecutive cohorts of 50 patients each group: control group (CG, not receive VitD); low-dose group (LdD, received 1,000 IU VitD daily); and high-dose group (HdD, 5,000 IU VitD daily). We measured levels of VitD, cytokines, and immune subpopulations after transplantation. RESULTS: No significant differences were observed in terms of cumulative incidence of overall and grades 2-4 acute GVHD in terms of relapse, nonrelapse mortality, and overall survival. However, a significantly lower cumulative incidence of both overall and moderate plus severe chronic GVHD (cGVHD) at 1 year was observed in LdD (37.5% and 19.5%, respectively) and HdD (42.4% and 27%, respectively) as compared with CG (67.5% and 44.7%, respectively; P < 0.05). In multivariable analysis, treatment with VitD significantly decreased the risk of both overall (for LdD: HR = 0.31, P = 0.002; for HdD: HR = 0.36, P = 0.006) and moderate plus severe cGVHD (for LdD: HR = 0.22, P = 0.001; for HdD: HR = 0.33, P = 0.01). VitD modified the immune response, decreasing the number of B cells and naïve CD8 T cells, with a lower expression of CD40L. CONCLUSIONS: This is the first prospective trial that analyzes the effect of VitD postransplant. We observed a significantly lower incidence of cGVHD among patients receiving VitD. Interestingly, VitD modified the immune response after allo-SCT. Clin Cancer Res; 22(23); 5673-81. ©2016 AACR.


Asunto(s)
Enfermedad Injerto contra Huésped/inmunología , Factores Inmunológicos/inmunología , Vitamina D/inmunología , Adolescente , Adulto , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Trasplante Homólogo/métodos , Adulto Joven
4.
Leuk Lymphoma ; 56(3): 656-62, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24913510

RESUMEN

Strategies for reversing graft failure (GF) after allogeneic stem cell transplant (SCT) depend on the options available in each situation. GF was reported in 16 Spanish institutions from January 2006 to July 2011. Primary GF was defined as an absolute neutrophil count (ANC) > 0.5 × 10(9)/L not reached by day + 28 after SCT from peripheral blood (PB) or bone marrow (BM) progenitors and by day + 42 after SCT from unrelated cord blood (UCB) progenitors. Secondary GF was defined as a recurrent ANC < 0.5 × 10(9)/L. Eighty-nine patients with GF were reported, and 80 patients received a second SCT. The 5-year survival probability was 31% (95% confidence interval [CI]: 18-44%), and the incidences of non-relapse mortality and relapse estimated by competing risks were 47% (95% CI: 36-58%) and 21% (95% CI: 4-28%). The strategy adopted to treat GF was heterogeneous, and no approach could be unequivocally recommended for this situation. The prognosis of patients with GF was poor even after successful recovery from GF.


Asunto(s)
Rechazo de Injerto/prevención & control , Trasplante de Células Madre , Adolescente , Adulto , Anciano , Niño , Femenino , Rechazo de Injerto/etiología , Rechazo de Injerto/mortalidad , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Neutrófilos/citología , Tasa de Supervivencia , Trasplante Homólogo , Resultado del Tratamiento , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA