Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 49
Filtrar
Más filtros

Banco de datos
Tipo del documento
Intervalo de año de publicación
1.
Biol Blood Marrow Transplant ; 26(4): 665-671, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31881283

RESUMEN

The gain/amplification CKS1B gene at chromosome region 1q21 (1q+) is one of the most common genetic aberrations in multiple myeloma (MM). Amplification of CKS1B is frequently associated with the deletion of the CDKN2C gene at chromosome region 1p32 (1p-), which is also associated with inferior outcomes. In this retrospective study, we evaluated the outcomes of patients with 1q+ and/or 1p- after high-dose therapy and autologous hematopoietic cell transplantation (auto-HCT). From January 2006 to December 2015, 1491 newly diagnosed patients with MM underwent upfront high-dose therapy and auto-HCT at our institution. Of those, 899 had the fluorescent in situ hybridization (FISH) data available. FISH was performed at diagnosis and before the start of induction in 686 (76%) patients and after the initiation of induction therapy in 213 (24%) patients. We identified 100 patients with 1q+ and/or 1p- by FISH from the cohort of 899 patients. A control group (n = 287) with diploid cytogenetics and normal FISH panel was selected from the same cohort. From the above 2 cohorts, using a propensity score matched analysis, we identified matched controls for 85 of the 100 patients with 1q+/1p-. Patients were matched for age at auto-HCT, sex, International Staging System stage, induction regimen, creatinine level, disease status at auto-HCT, conditioning regimen, and maintenance therapy. Sixty-seven (79%), 4 (5%), and 14 (16%) patients had 1q+, 1p-, or both 1q+ and 1p-, respectively. There was no significant difference in induction therapy, preparative regimen, or maintenance therapy between the 1q+/1p- and the control group. The median follow-up time for all patients was 29.2 months (range, 0.29 to 84.96). The cumulative incidence of 100-day nonrelapse mortality was 1.2% and 0% for the 1q+/1p- and the control group, respectively. Forty-two patients (50%) in the 1q+/1p- group achieved complete response compared with 40 patients (47%) in the control group. The estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 41% and 79% for the 1q+/1p- group and 56% and 86% for the control group. Patients in the 1q+/1p- group were at significantly increased risk of progression or death compared to the control group (hazard ratio [HR], 2.21; confidence interval [CI], 1.18 to 4.16; P = .014). No significant association between OS in the 2 groups was observed. The outcome of the 1q+/1p- alone (with no additional high-risk cytogenetics) and the propensity score matched control groups was also compared. Median PFS for the 1q+/1p- alone subgroup was 26.6 months, compared with 38.8 months for the control group (HR, 1.9; CI, 0.9 to 4.08; P = .09). The median OS had not been reached for the 1q+/1p- alone subgroup and was 81.1 months for the control group (HR, 1.25; CI, 0.3 to 4.6; P= .73). 1q+/1p- abnormalities with amplification of CKS1B and deletion ofCDKN2Cgenes were associated with shorter PFS compared with a propensity score matched group of patients with diploid cytogenetics and normal a FISH panel. The outcomes of 1q+/1p- patients with MM have improved with the use of more effective induction, conditioning, and maintenance therapy compared with historical controls, but we still need more effective therapeutic approaches to fully overcome the negative impact of 1q+/1p-.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Cromosomas , Humanos , Hibridación Fluorescente in Situ , Mieloma Múltiple/genética , Mieloma Múltiple/terapia , Puntaje de Propensión , Estudios Retrospectivos , Trasplante Autólogo , Resultado del Tratamiento
2.
Biol Blood Marrow Transplant ; 25(7): 1340-1346, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30763728

RESUMEN

We analyzed 186 patients with lymphoma who underwent allogeneic stem cell transplantation (ASCT) with fludarabine-melphalan (FM) conditioning and different types of donors (25 haploidentical [HD], 98 matched unrelated [MUD], and 63 matched related [MRD]) at our institution between September 2009 and January 2018. Patients received fludarabine 160 mg/m2 (40 mg/m2/day for 4 days) in combination with 1 dose of melphalan 140 mg/m2 (FM140) or 100 mg/m2 (FM100). Engraftment was similar among the 3 groups (92%, 89%, and 98%, respectively; P = .7). The 6-month cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) was 4% in the HD group, 14% in the MUD group, and 8% in the MRD group (P not significant), and the respective 3-year cumulative incidence of chronic GVHD was 5%, 16%, and 26% (P not significant). The respective 3-year nonrelapse mortality and relapse rates were 31%, 32%, and 10% (HD versus MUD, P = .9; HD versus MRD, P = .02) and 15%, 21%, and 39% (HD versus MUD, P = .4; HD versus MRD, P = .04). At 3 years, progression-free survival (PFS) was 59%, 44%, and 46% (P not significant); overall survival (OS) was 52%, 54%, and 67% (P not significant); and GVHD-free, relapse-free survival was 39%, 31%, and 24% (P not significant). No differences in the 3-year PFS (57% versus 43%; P = .3) and OS (64% versus 58%; P = .7) were seen between patients receiving FM100 and those receiving FM140. Our data demonstrate that in patients with lymphoma, ASCT with HD transplants have similar outcomes as ASCT with HLA-matched transplants, and the FM100 conditioning regimen appears to be at least as effective as the FM140 regimen.


Asunto(s)
Enfermedad Injerto contra Huésped , Linfoma , Melfalán/administración & dosificación , Trasplante de Células Madre , Donantes de Tejidos , Adolescente , Adulto , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/terapia , Humanos , Incidencia , Linfoma/mortalidad , Linfoma/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Vidarabina/administración & dosificación , Vidarabina/análogos & derivados
3.
Mol Ther ; 25(1): 285-295, 2017 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-28129122

RESUMEN

Outcomes for patients with refractory diffuse large B cell lymphoma (DLBCL) are poor. In the multicenter ZUMA-1 phase 1 study, we evaluated KTE-C19, an autologous CD3ζ/CD28-based chimeric antigen receptor (CAR) T cell therapy, in patients with refractory DLBCL. Patients received low-dose conditioning chemotherapy with concurrent cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) for 3 days followed by KTE-C19 at a target dose of 2 × 106 CAR T cells/kg. The incidence of dose-limiting toxicity (DLT) was the primary endpoint. Seven patients were treated with KTE-C19 and one patient experienced a DLT of grade 4 cytokine release syndrome (CRS) and neurotoxicity. Grade ≥3 CRS and neurotoxicity were observed in 14% (n = 1/7) and 57% (n = 4/7) of patients, respectively. All other KTE-C19-related grade ≥3 events resolved within 1 month. The overall response rate was 71% (n = 5/7) and complete response (CR) rate was 57% (n = 4/7). Three patients have ongoing CR (all at 12+ months). CAR T cells demonstrated peak expansion within 2 weeks and continued to be detectable at 12+ months in patients with ongoing CR. This regimen of KTE-C19 was safe for further study in phase 2 and induced durable remissions in patients with refractory DLBCL.


Asunto(s)
Antígenos CD19/inmunología , Antígenos CD28/metabolismo , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/terapia , Complejo Receptor-CD3 del Antígeno de Linfocito T/metabolismo , Proteínas Recombinantes de Fusión , Linfocitos T/inmunología , Linfocitos T/metabolismo , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Antígenos CD28/genética , Terapia Combinada , Progresión de la Enfermedad , Resistencia a Antineoplásicos , Femenino , Estudios de Seguimiento , Humanos , Inmunofenotipificación , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/terapia , Linfoma no Hodgkin/diagnóstico , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Complejo Receptor-CD3 del Antígeno de Linfocito T/genética , Resultado del Tratamiento
4.
Biol Blood Marrow Transplant ; 23(12): 2166-2171, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28844946

RESUMEN

Fluid overload (FO) commonly occurs during hospitalization for allogeneic hematopoietic stem cell transplantation. We hypothesized that FO is associated with transplantation outcomes and evaluated this complication in 2 cohorts of patients. FO was graded based on post-transplantation weight gain, symptoms, and need for treatment, scored in real time by an independent team. The first cohort (study cohort; n = 145) underwent haploidentical transplantation for hematologic malignancies following a melphalan-based conditioning regimen. In univariate analysis, factors associated with day +100 nonrelapse mortality (NRM) were FO grade ≥2 (hazard ratio [HR], 15; 95% confidence interval [CI], 4.2 to 55; P < .001), creatinine >1 mg/dL (HR, 4.7; 95% CI, 1.6 to 14; P = .005), and age >55 years (HR, 4.5; 95% CI, 1.5 to 13; P = .008). In multivariate analysis, factors associated with day +100 NRM were FO grade ≥2 (HR, 13.1; 95% CI, 3.4 to 50; P < .001) and serum creatinine level >1 mg/dL at transplantation admission (HR, 3.5; 95% CI, 1.1 to 11; P = .03). These findings were verified in a separate cohort (validation cohort) of patients with acute myelogenous leukemia/myelodysplastic syndrome who underwent HLA-matched transplantation with busulfan-based conditioning (n = 449). In multivariate analysis, factors associated with day +100 NRM were FO grade ≥2 (HR, 34; 95% CI, 7.2 to 158; P < .001) and, in patients with FO grade <2, advanced disease status (HR, 5; 95% CI, 1.1 to 22; P = .03). A higher NRM translated to significantly poorer 1-year overall survival rates for patients with FO ≥2 than for patients without FO (70% versus 42%, P < .001 in the study cohort and 64% versus 38%, P < .001 in the validation cohort). In conclusion, FO grade ≥2 is strongly associated with higher NRM and shorter survival and should be considered an important prognostic factor in transplantation.


Asunto(s)
Líquidos Corporales , Edema/patología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Aumento de Peso , Adolescente , Adulto , Anciano , Femenino , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/patología , Neoplasias Hematológicas/terapia , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/patología , Síndromes Mielodisplásicos/terapia , Acondicionamiento Pretrasplante/métodos , Adulto Joven
5.
Cancer ; 123(12): 2329-2337, 2017 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-28178369

RESUMEN

BACKGROUND: Human metapneumovirus (hMPV) causes upper and lower respiratory tract infections (URIs and LRIs, respectively) in healthy and immunocompromised patients; however, its clinical burden in patients with cancer remains unknown. METHODS: In a retrospective study of all laboratory-confirmed hMPV infections treated at the authors' institution between April 2012 and May 2015, clinical characteristics, risk factors for progression to an LRI, treatment, and outcomes in patients with cancer were determined. RESULTS: In total, 181 hMPV infections were identified in 90 patients (50%) with hematologic malignancies (HMs), in 57 (31%) hematopoietic cell transplantation (HCT) recipients, and in 34 patients (19%) with solid tumors. Most patients (92%) had a community-acquired infection and presented with URIs (67%), and 43% developed LRIs (59 presented with LRIs and 19 progressed from a URI to an LRI). On multivariable analysis, an underlying HM (adjusted odds ratio [aOR], 3.11; 95% confidence interval [CI], 1.12-8.64; P = .029), nosocomial infection (aOR, 26.9; 95% CI, 2.79-259.75; P = .004), and hypoxia (oxygen saturation [SpO2], ≤ 92%) at presentation (aOR, 9.61; 95% CI, 1.98-46.57; P = .005) were identified as independent factors associated with LRI. All-cause mortality at 30 days from hMPV diagnosis was low (4%), and patients with LRIs had a 10% mortality rate at day 30 from diagnosis; whereas patients with URIs had a 0% mortality rate. CONCLUSIONS: hMPV infections in patients with cancer may cause significant morbidity, especially for those with underlying HM who may develop an LRI. Despite high morbidity and the lack of directed antiviral therapy for hMPV infections, mortality at day 30 from this infection remained low in this studied population. Cancer 2017;123:2329-2337. © 2017 American Cancer Society.


Asunto(s)
Infecciones Comunitarias Adquiridas/epidemiología , Neoplasias/epidemiología , Infecciones por Paramyxoviridae/epidemiología , Neumonía Viral/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Causas de Muerte , Niño , Preescolar , Infecciones Comunitarias Adquiridas/virología , Infección Hospitalaria/epidemiología , Infección Hospitalaria/virología , Femenino , Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Humanos , Hipoxia/epidemiología , Lactante , Masculino , Metapneumovirus , Persona de Mediana Edad , Mortalidad , Análisis Multivariante , Oportunidad Relativa , Infecciones por Paramyxoviridae/virología , Neumonía Viral/virología , Infecciones del Sistema Respiratorio/virología , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos/epidemiología , Adulto Joven
6.
Br J Haematol ; 177(4): 567-577, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28295181

RESUMEN

There is limited information regarding the immunological predictors of post-allogeneic stem cell transplant (alloSCT) outcome in chronic lymphocytic leukaemia (CLL), such as mixed T-cell chimerism. We analysed 143 consecutive patients with relapsed/refractory CLL, transplanted between 2000 and 2012, to determine the prognostic relevance of mixed chimerism post-alloSCT and the ability of post-transplant immunomodulation to treat relapse. Mixed T-cell chimerism occurred in 50% of patients at 3 months and 43% at 6 months post-alloSCT; upon 3- and 6-month landmark analysis, this was associated with inferior progression-free survival (PFS) [Hazard ratio (HR) 1·93, P = 0·003 and HR 2·58, P < 0·001] and survival (HR 1·66, P = 0·05 and HR 2·17, P < 0·001), independent of baseline patient characteristics, and a lower rate of grade II-IV acute graft-versus-host disease (GHVD) (16% vs. 52%, P < 0·001). Thirty-three patients were treated with immunomodulation for relapse post-alloSCT (immunosuppression withdrawal, n = 6, donor lymphocyte infusion, n = 27); 17 achieved complete response (CR), which predicted superior PFS (53 months vs. 10 months, P < 0·001) and survival (117 months vs. 30 months, P = 0·006). Relapsed patients with mixed chimerism had inferior response to immunomodulation; conversion to full donor chimerism was highly correlated both with CR and with the development of severe acute GVHD, which was fatal in 3/8 patients. Novel therapeutic strategies are required for patients with mixed T-cell chimerism post-alloSCT for CLL.


Asunto(s)
Quimerismo , Leucemia Linfocítica Crónica de Células B/terapia , Trasplante de Células Madre/métodos , Linfocitos T/fisiología , Adulto , Cuidados Posteriores/métodos , Anciano , Métodos Epidemiológicos , Femenino , Supervivencia de Injerto/genética , Enfermedad Injerto contra Huésped/etiología , Humanos , Inmunosupresores/uso terapéutico , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/mortalidad , Transfusión de Linfocitos/efectos adversos , Masculino , Persona de Mediana Edad , Recurrencia , Trasplante de Células Madre/mortalidad , Trasplante Homólogo , Resultado del Tratamiento
9.
Biol Blood Marrow Transplant ; 22(7): 1333-1337, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27064056

RESUMEN

Forty patients (median age, 31 years; range, 20 to 63) with Hodgkin lymphoma underwent an allogeneic stem cell transplant with the gemcitabine-fludarabine-melphalan reduced-intensity conditioning regimen. Thirty-one patients (77%) had undergone a prior autologous stem cell transplant, with a median time to progression after transplant of 6 months (range, 1 to 68). Disease status at transplant was complete remission/complete remission, undetermined (n = 23; 57%), partial remission (n = 14; 35%), and other (n = 3; 8%). Twenty-six patients (65%) received brentuximab vedotin before allotransplant. The overall complete response rate before allotransplant was 65% in brentuximab-treated patients versus 42% in brentuximab-naive patients (P = .15). At the latest follow-up (October 2015) 31 patients were alive. The median follow-up was 41 months (range, 5 to 87). Transplant-related mortality rate at 3 years was 17%. Pulmonary, skin toxicities, and nausea were seen in 13 (33%), 11 (28%), and 37 (93%) patients, respectively. At 3 years, estimates for overall and progression-free survival were 75% (95% CI, 57% to 86%) and 54% (95% CI, 36% to 70%). Overall incidence for disease progression was 28% (95% CI, 16% to 50%). We believe the gemcitabine-fludarabine-melphalan regimen allows moderate dose intensification with acceptable morbidity and mortality. The inclusion of gemcitabine affected nausea, pulmonary, and likely skin toxicity. Exposure to brentuximab vedotin allowed more patients to reach allogeneic stem cell transplantation in complete remission. With over 50% of patients progression-free at 3 years, allogeneic stem cell transplantation with reduced-intensity conditioning remains an effective and relevant treatment option for Hodgkin lymphoma in the brentuximab vedotin era.


Asunto(s)
Desoxicitidina/análogos & derivados , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad de Hodgkin/terapia , Melfalán/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Vidarabina/análogos & derivados , Adulto , Brentuximab Vedotina , Desoxicitidina/uso terapéutico , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/mortalidad , Humanos , Inmunoconjugados/uso terapéutico , Enfermedades Pulmonares/inducido químicamente , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Inducción de Remisión , Terapia Recuperativa/efectos adversos , Terapia Recuperativa/métodos , Terapia Recuperativa/mortalidad , Enfermedades de la Piel/inducido químicamente , Análisis de Supervivencia , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/mortalidad , Trasplante Homólogo , Vidarabina/uso terapéutico , Adulto Joven , Gemcitabina
13.
Blood ; 122(17): 2965-73, 2013 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-24030379

RESUMEN

Autologous T cells expressing a CD19-specific chimeric antigen receptor (CD19.CAR) are active against B-cell malignancies, but it is unknown whether allogeneic CD19.CAR T cells are safe or effective. After allogeneic hematopoietic stem cell transplantation (HSCT), infused donor-derived virus-specific T cells (VSTs) expand in vivo, persist long term, and display antiviral activity without inducing graft-vs-host disease; therefore, we determined whether donor VSTs, engineered to express CD19.CAR, retained the characteristics of nonmanipulated allogeneic VSTs while gaining antitumor activity. We treated 8 patients with allogeneic (donor-derived) CD19.CAR-VSTs 3 months to 13 years after HSCT. There were no infusion-related toxicities. VSTs persisted for a median of 8 weeks in blood and up to 9 weeks at disease sites. Objective antitumor activity was evident in 2 of 6 patients with relapsed disease during the period of CD19.CAR-VST persistence, whereas 2 patients who received cells while in remission remain disease free. In 2 of 3 patients with viral reactivation, donor CD19.CAR-VSTs expanded concomitantly with VSTs. Hence CD19.CAR-VSTs display antitumor activity and, because their number may be increased in the presence of viral stimuli, earlier treatment post-HSCT (when lymphodepletion is greater and the incidence of viral infection is higher) or planned vaccination with viral antigens may enhance disease control.


Asunto(s)
Antígenos CD19/inmunología , Linfocitos B/inmunología , Trasplante de Células Madre Hematopoyéticas , Leucemia Linfocítica Crónica de Células B/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Linfocitos T/trasplante , Adenoviridae/inmunología , Adulto , Antígenos CD19/genética , Antineoplásicos/uso terapéutico , Linfocitos B/patología , Niño , Citomegalovirus/inmunología , Femenino , Expresión Génica , Herpesvirus Humano 4/inmunología , Humanos , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/patología , Leucemia Linfocítica Crónica de Células B/virología , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/virología , Ingeniería de Proteínas , Recurrencia , Linfocitos T/inmunología , Linfocitos T/virología , Trasplante Homólogo
14.
Haematologica ; 100(10): 1361-70, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26250579

RESUMEN

Cord blood transplant requires less stringent human leukocyte antigen matching than unrelated donors. In 133 patients with hematologic malignancies who engrafted after double cord blood transplantation with a dominant unit, we studied the effect of high resolution testing at 4 loci (-A, -B, -C, -DRB1) for its impact on 2-year transplant-related mortality. Ten percent of the dominant cord blood units were matched at 7-8/8 alleles using HLA-A, -B, -C, and -DRB1; 25% were matched at 6/8, 40% at 5/8, and 25% at 4/8 or less allele. High resolution typing at 4 loci showed that there was no 2-year transplant-related mortality in 7-8/8 matched patients. Patients with 5-6/8 matched dominant cord blood units had 2-year transplant-related mortality of 39% while patients with 4/8 or less matched units had 60%. Multivariate regression analyses confirmed the independent effect of high resolution typing on the outcome when adjusted for age, diagnosis, CD34(+) cell dose infused, graft manipulation and cord to cord matching. The worst prognostic group included patients aged over 32 years with 4/8 or less matched cord blood units compared with patients who were either younger than 32 years old independent of allele-level matching, or aged over 32 years but with 5-6/8 matched cord blood units (Hazard Ratio 2.2; 95% confidence interval: 1.3-3.7; P<0.001). Patients with 7-8/8 matched units remained the group with the best prognosis. Our data suggest that high resolution typing at 4 loci and selecting cord blood units matched at at least 5/8 alleles may reduce transplant-related mortality after double cord blood transplantation.


Asunto(s)
Alelos , Trasplante de Células Madre de Sangre del Cordón Umbilical , Histocompatibilidad/genética , Histocompatibilidad/inmunología , Mortalidad , Adolescente , Adulto , Anciano , Niño , Preescolar , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Femenino , Sangre Fetal/citología , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/etiología , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Antígenos de Histocompatibilidad/genética , Antígenos de Histocompatibilidad/inmunología , Prueba de Histocompatibilidad , Humanos , Lactante , Masculino , Persona de Mediana Edad , Retratamiento , Análisis de Supervivencia , Resultado del Tratamiento , Adulto Joven
15.
Biol Blood Marrow Transplant ; 20(12): 1975-81, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25263628

RESUMEN

Allogeneic stem cell transplantation for patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) has been performed primarily with an HLA-matched donor. Outcomes of haploidentical transplantation have recently improved, and a comparison between donor sources in a uniform cohort of patients has not been performed. We evaluated outcomes of 227 patients with AML/MDS treated with melphalan-based conditioning. Donors were matched related (MRD) (n = 87, 38%), matched unrelated (MUD) (n = 108, 48%), or haploidentical (n = 32, 14%). No significant differences were found between haploidentical and MUD transplantation outcomes; however, there was a trend for improved outcomes in the MRD group, with 3-year progression-free survival for patients in remission of 57%, 45%, and 41% for MRD, MUD, and haploidentical recipients, respectively (P = .417). Recovery of T cell subsets was similar for all groups. These results suggest that haploidentical donors can safely extend transplantation for AML/MDS patients without an HLA-matched donor. Prospective studies comparing haploidentical and MUD transplantation are warranted.


Asunto(s)
Antígenos HLA , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Trasplante de Células Madre , Donante no Emparentado , Adulto , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Prueba de Histocompatibilidad , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/terapia , Estudios Retrospectivos , Tasa de Supervivencia
19.
Biol Blood Marrow Transplant ; 19(10): 1453-8, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23872222

RESUMEN

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potentially curative treatment for multiple myeloma (MM); however, because of high treatment-related mortality (TRM), its role is not well defined. Patients with newly diagnosed, relapsed, or primary refractory myeloma were enrolled in a randomized phase II trial of 2 reduced-intensity conditioning regimens: fludarabine 120 mg/m(2) + melphalan 100 mg/m(2) (FM100) versus fludarabine 120 mg/m(2) + melphalan 140 mg/m(2) (FM140) before allo-HCT from related or unrelated donors. Fifty patients underwent allo-HCT using FM100 (n = 23) or FM140 (n = 27) conditioning between April 2002 and 2011. There were no significant differences between FM100 and FM140 in time to neutrophil engraftment (P = .21), acute grade II to IV graft-versus-host disease (GVHD) (P = 1.0), chronic GVHD (P = .24), response rate (P = 1.0), TRM (13% versus 15%, P = 1.0), median progression-free survival (PFS), 11.7 versus 8.4 months, P = .12, and median overall survival (OS), 35.1 versus 19.7 months, P = .38. Cumulative incidence of disease progression in FM100 and FM140 was 43% and 70%, respectively (P = .08). Recurrent disease was the most common cause of death for both FM100 (26%) and FM140 (44%), P = .24. On multivariate analysis, disease status at allo-HCT, complete response or very good partial response (VGPR) was significantly associated with longer PFS (15.6 versus 9.6 months in patients with

Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/métodos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/cirugía , Acondicionamiento Pretrasplante/métodos , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia Combinada , Relación Dosis-Respuesta a Droga , Femenino , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Masculino , Melfalán/administración & dosificación , Melfalán/efectos adversos , Persona de Mediana Edad , Mieloma Múltiple/terapia , Trasplante Homólogo , Vidarabina/administración & dosificación , Vidarabina/efectos adversos , Vidarabina/análogos & derivados
20.
Transplant Cell Ther ; 29(3): 189-198, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36470579

RESUMEN

When multiple haploidentical donors are available for transplantation, those of younger generations are generally selected over those of older generations. However, it is unclear who is the optimal donor when selecting candidates from within a generation, such as father versus mother, son versus daughter, or brother versus sister. Although traditionally male donors are favored over female donors, particularly for male recipients, and significant associations of individual HLA mis(matches) on outcomes are being increasingly recognized, the hierarchy of factors for donor selection is indeterminate. To assess whether HLA factors take precedence over non-HLA factors and to isolate the influence of specific characteristics on outcomes, we analyzed 412 patients stratified by donor relationship: child donor (son [n = 202] versus daughter [n = 96]), parent (father [n = 28] versus mother [n = 29]), and sibling (noninherited maternal [NIMA; n = 29] versus paternal [NIPA; n = 28] mismatched). Among siblings, NIMA mismatch was associated with a lower risk of acute graft-versus-host disease (aGVHD); B-leader mismatch was associated with high nonrelapse mortality (NRM), poor progression-free survival, and a trend toward poor overall survival (OS), whereas A-mismatch was associated with lower aGVHD. Among parent donors, the relationship did not impact any outcome; B-leader mismatch was associated with higher NRM and a trend toward poor OS, whereas A-mismatch was associated with lower NRM and improved progression-free survival and OS. Among child donors, no individual HLA mismatch was predictive of any outcome, and daughter donors were not associated with any adverse outcomes in multivariate analyses. Our data suggest that certain HLA factors may be more significant in some cases and should be given priority over simply selecting a donor based on relationship/sex.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Niño , Humanos , Masculino , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Selección de Donante , Donantes de Tejidos , Madres
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA