Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 69
Filtrar
Más filtros

Bases de datos
Tipo del documento
Intervalo de año de publicación
1.
N Engl J Med ; 386(1): 11-23, 2022 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-34986284

RESUMEN

BACKGROUND: A single-group, phase 1-2 study indicated that eltrombopag improved the efficacy of standard immunosuppressive therapy that entailed horse antithymocyte globulin (ATG) plus cyclosporine in patients with severe aplastic anemia. METHODS: In this prospective, investigator-led, open-label, multicenter, randomized, phase 3 trial, we compared the efficacy and safety of horse ATG plus cyclosporine with or without eltrombopag as front-line therapy in previously untreated patients with severe aplastic anemia. The primary end point was a hematologic complete response at 3 months. RESULTS: Patients were assigned to receive immunosuppressive therapy (Group A, 101 patients) or immunosuppressive therapy plus eltrombopag (Group B, 96 patients). The percentage of patients who had a complete response at 3 months was 10% in Group A and 22% in Group B (odds ratio, 3.2; 95% confidence interval [CI], 1.3 to 7.8; P = 0.01). At 6 months, the overall response rate (the percentage of patients who had a complete or partial response) was 41% in Group A and 68% in Group B. The median times to the first response were 8.8 months (Group A) and 3.0 months (Group B). The incidence of severe adverse events was similar in the two groups. With a median follow-up of 24 months, a karyotypic abnormality that was classified as myelodysplastic syndrome developed in 1 patient (Group A) and 2 patients (Group B); event-free survival was 34% and 46%, respectively. Somatic mutations were detected in 29% (Group A) and 31% (Group Β) of the patients at baseline; these percentages increased to 66% and 55%, respectively, at 6 months, without affecting the hematologic response and 2-year outcome. CONCLUSIONS: The addition of eltrombopag to standard immunosuppressive therapy improved the rate, rapidity, and strength of hematologic response among previously untreated patients with severe aplastic anemia, without additional toxic effects. (Funded by Novartis and others; RACE ClinicalTrials.gov number, NCT02099747; EudraCT number, 2014-000363-40.).


Asunto(s)
Anemia Aplásica/terapia , Suero Antilinfocítico/uso terapéutico , Benzoatos/uso terapéutico , Ciclosporina/uso terapéutico , Hidrazinas/uso terapéutico , Terapia de Inmunosupresión , Inmunosupresores/uso terapéutico , Pirazoles/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anemia Aplásica/tratamiento farmacológico , Anemia Aplásica/genética , Suero Antilinfocítico/efectos adversos , Benzoatos/efectos adversos , Ciclosporina/efectos adversos , Quimioterapia Combinada , Femenino , Humanos , Hidrazinas/efectos adversos , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Prospectivos , Pirazoles/efectos adversos , Receptores de Trombopoyetina/agonistas , Inducción de Remisión , Adulto Joven
2.
Cancer ; 125(9): 1499-1506, 2019 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-30620383

RESUMEN

BACKGROUND: T cell-replete haploidentical stem cell transplantation (haplo-SCT) is a valid therapeutic option for adult patients with high-risk acute myeloid leukemia (AML) lacking an HLA-matched sibling or unrelated donor. METHOD: We retrospectively analyzed the outcomes of 912 AML patients ≥45 years of age who had undergone haplo-SCT with either myeloablative conditioning (MAC; n = 373) or reduced intensity conditioning (RIC; n = 539) regimens. RESULTS: The median follow-up was 31.1 and 25.7 months for MAC and RIC, respectively. The incidence of relapse and nonrelapse mortality (NRM) were 25.1% versus 28.7% and 31.0% versus 30.3% for MAC and RIC, respectively; 2-year leukemia-free survival (LFS) was 43.9% for MAC versus 41.0% for RIC. In multivariate analysis, the use of MAC versus RIC was not associated with a difference in the outcomes. Results were confirmed in the propensity score-weighted analysis. Disease status and performance status at transplantation were associated with outcomes. Notably, the use of posttransplantation cyclophosphamide was associated with reduced acute graft-versus-host disease (aGVHD) stage III-IV, and NRM and increased overall survival, LFS, and GVHD-free, relapse-free survival. The use of mobilized peripheral blood stem cells was associated with an increased risk of stage II-IV aGVHD. CONCLUSION: No differences were found between MAC and RIC regimens for haplo-SCT in adults with AML who were ≥45 years of age. The type of GVHD prophylaxis, disease status, and performance status were the major predictors of transplantation outcome. These results may serve as the background for randomized study comparing RIC versus MAC for haplo-SCT in adults with AML.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Acondicionamiento Pretrasplante/métodos , Trasplante Haploidéntico , Factores de Edad , Anciano , Anciano de 80 o más Años , Europa (Continente)/epidemiología , Femenino , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/epidemiología , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Pronóstico , Sistema de Registros , Estudios Retrospectivos , Hermanos , Acondicionamiento Pretrasplante/estadística & datos numéricos , Trasplante Haploidéntico/estadística & datos numéricos , Resultado del Tratamiento
3.
Haematologica ; 104(9): 1782-1788, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-30733269

RESUMEN

Allogeneic hematopoietic stem cell transplant remains the only curative treatment for myelofibrosis. Most post-transplantation events occur during the first two years and hence we aimed to analyze the outcome of 2-year disease-free survivors. A total of 1055 patients with myelofibrosis transplanted between 1995 and 2014 and registered in the registry of the European Society for Blood and Marrow Transplantation were included. Survival was compared to the matched general population to determine excess mortality and the risk factors that are associated. In the 2-year survivors, disease-free survival was 64% (60-68%) and overall survival was 74% (71-78%) at ten years; results were better in younger individuals and in women. Excess mortality was 14% (8-21%) in patients aged <45 years and 33% (13-53%) in patients aged ≥65 years. The main cause of death was relapse of the primary disease. Graft-versus-host disease (GvHD) before two years decreased the risk of relapse. Multivariable analysis of excess mortality showed that age, male sex recipient, secondary myelofibrosis and no GvHD disease prior to the 2-year landmark increased the risk of excess mortality. This is the largest study to date analyzing long-term outcome in patients with myelofibrosis undergoing transplant. Overall it shows a good survival in patients alive and in remission at two years. However, the occurrence of late complications, including late relapses, infectious complications and secondary malignancies, highlights the importance of screening and monitoring of long-term survivors.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mielofibrosis Primaria/terapia , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia , Sistema de Registros , Inducción de Remisión , Factores de Riesgo , Trasplante Homólogo , Resultado del Tratamiento
4.
Am J Hematol ; 94(1): 80-86, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30328134

RESUMEN

We retrospectively analyzed the outcomes of 1837 adults and children with severe aplastic anemia (SAA) who underwent matched sibling donor (MSD) and matched unrelated donor (MUD) hemopoietic stem cell transplantation (HSCT) between 2000 and 2013. Patients were grouped by transplant conditioning containing either anti-thymocyte globulin (ATG) (n = 1283), alemtuzumab (n = 261), or no serotherapy (NS) (n = 293). The risks of chronic GvHD were significantly reduced when ATG or alemtuzumab were compared with NS (P = .021 and .003, respectively). Acute GVHD was significantly reduced in favor of alemtuzumab compared with ATG (P = .012) and NS (P < .001). By multivariate analysis, when compared with ATG, alemtuzumab was associated with a lower risk of developing acute (OR 0.262; 95% CI 0.14-0.47; P < .001) and chronic GVHD (HR 0.58; 95% CI 0.35-0.94; P = .027). OS was significantly better in ATG and alemtuzumab patients compared with NS (P = .010 and .025). Our data shows inclusion of serotherapy in MSD and MUD HSCT for patients with SAA reduces chronic GVHD and provides a survival advantage over patients not receiving serotherapy. Notably, alemtuzumab reduced the risk of acute and chronic GvHD compared with ATG and indicates that alemtuzumab might be the serotherapy of choice for MSD and MUD transplants for SAA.


Asunto(s)
Anemia Aplásica/terapia , Trasplante de Células Madre Hematopoyéticas , Depleción Linfocítica , Linfocitos T/inmunología , Adolescente , Adulto , Anciano , Alemtuzumab/uso terapéutico , Anemia Aplásica/inmunología , Suero Antilinfocítico/uso terapéutico , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Inmunización Pasiva , Lactante , Donadores Vivos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Acondicionamiento Pretrasplante , Resultado del Tratamiento , Adulto Joven
5.
Biol Blood Marrow Transplant ; 24(12): 2501-2508, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30041010

RESUMEN

Disease relapse remains an unmet medical need for patients with Hodgkin lymphoma (HL) receiving an allogeneic hematopoietic cell transplantation (HCT). With the aim of identifying patients at high risk for post-transplant relapse, we retrospectively reviewed 41 HL patients who had received haploidentical (haplo) nonmyeloablative (NMA) HCT with high dose post-transplant cyclophosphamide (PT-Cy) for graft-versus-host (GVHD) prophylaxis. Primary refractory disease, relapse within 6 months from autologous stem cell transplantation, age, pretransplant chemotherapy, HCT comorbidity index (HCT-CI), sex mismatch, tumor burden and pretransplant fluorodeoxyglucose positron emission tomography (FDG-PET) status, assessed by Deauville score, were analyzed as variables influencing outcomes. All but 1 patient engrafted: median time to neutrophil and platelet recovery was 15 (interquartile range, 13 to 23) days and 19 (interquartile range, 12 to 28) days, respectively. Cumulative incidence of severe (grade III to IV) acute graft-versus-host disease (GVHD) and 3-year moderate-severe chronic GVHD was 2.4% and 11.8%, respectively. The 3-year overall (OS), progression free (PFS), and graft relapse-free survival (GRFS) were 75.6%, 43.9%, and 39%, respectively. On multivariate analysis, 3-year OS was significantly worse in patients with HCT-CI ≥3 (hazard ratio [HR], 5.0; 95% confidence interval [CI], 1.1 to 21.8; P = .03). Three-year relapse rate, 3-year PFS, and 3-year GRFS were significantly worse in patients with HCT-CI ≥3 (HR, 3.5; 95% CI, 1.3 to 9.3; P = .01; HR, 3.3; 95% CI, 1.2 to 9.0; P = .02; and HR, 4.2; 95% CI, 1.7 to 9.9; P = .001, respectively) and in patients with a Deauville score ≥4 on pretransplant FDG-PET (HR, 4.4; 95% CI, 1.6-12.4; P = .005, HR, 3.8; 95% CI, 1.5 to 9.7; P = .005; and 3.2; 95% CI, 1.3 to 7.9; P = .01, respectively). On univariate analysis, 3-year NRM was significantly worse only in patients with a HCT-CI ≥3 (HR, 17.6; 95% CI, 1.4 to 221.0). Among relapsed or refractory HL patients undergoing haplo NMA HCT with PT-Cy, pretransplant FDG-PET with a Deauville score ≥4 and HCT-CI ≥3 identified patients at high risk of relapse. Moreover, an HCT-CI ≥3 was associated with higher NRM and lower OS.


Asunto(s)
Ciclofosfamida/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/cirugía , Inmunosupresores/uso terapéutico , Tomografía de Emisión de Positrones/métodos , Trasplante Haploidéntico/métodos , Adulto , Comorbilidad , Ciclofosfamida/farmacología , Femenino , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/patología , Humanos , Inmunosupresores/farmacología , Masculino , Recurrencia Local de Neoplasia
6.
Biol Blood Marrow Transplant ; 24(6): 1243-1249, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29421292

RESUMEN

We report a modified post-transplant cyclophosphamide (PT-CY) regimen, for unmanipulated haploidentical marrow transplants, in 150 patients with acute myeloid leukemia (AML). All patients received a myeloablative regimen, cyclosporine A (CsA) on day 0, mycophenolate on day +1, and PT-CY 50 mg/kg on days +3 and +5. The median age was 51 (range, 17-74) years, 51 (34%) patients had active disease at transplant, and the median follow-up of surviving patients 903 (range, 150-1955) days. The cumulative incidence (CI) of engraftment, acute graft-versus-host disease (GVHD) grade II to IV, and moderate/severe chronic GVHD was 92%, 17%, and 15%, respectively. The 4-year CI of transplant-related mortality (TRM) and relapse was 20% and 24%, respectively. Four-year survival for remission patients was 72% (74% versus 67% for <60 or ≥60 years of age) and 26% for advanced patients (17% versus 41% for <60 or ≥60 years of age). In a multivariate analysis, active disease at transplant was the only negative predictor of survival, TRM and relapse. The original PT-CY regimen can be modified with CsA on day 0, still providing protection against GVHD, low toxicity, and encouraging low relapse incidence in AML patients, also over 60 years of age.


Asunto(s)
Trasplante de Médula Ósea/métodos , Ciclofosfamida/uso terapéutico , Leucemia Mieloide Aguda/terapia , Trasplante Haploidéntico/métodos , Adolescente , Adulto , Anciano , Ciclosporina/uso terapéutico , Esquema de Medicación , Supervivencia de Injerto , Enfermedad Injerto contra Huésped , Humanos , Leucemia Mieloide Aguda/mortalidad , Persona de Mediana Edad , Análisis Multivariante , Agonistas Mieloablativos/administración & dosificación , Valor Predictivo de las Pruebas , Análisis de Supervivencia , Adulto Joven
7.
Biol Blood Marrow Transplant ; 24(1): 119-126, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29024804

RESUMEN

We studied the impact of HLA mismatching on the outcome of 318 consecutive patients who received an unmanipulated haploidentical bone marrow transplant, followed by post-transplant cyclophosphamide (PTCy). The number of HLA-mismatched antigens was tested for its impact on overall survival (OS) and nonrelapse mortality (NRM), whereas HLA mismatches in the graft-versus-host (GVH) direction were tested for prediction of graft-versus-host disease (GVHD and relapse. Finally, we studied whether graft rejection correlated with the number of HLA mismatched antigens in host-versus-graft (HVG) direction. Two hundred thirty-one donor-recipient pairs (72%) had 4/8 mismatches at the -A, -B, -C, -DRB1 HLA loci. HLA mismatches did not predict the 2-year OS (hazard ratio, .83; P = .58) and NRM (subhazard ratio, 1.08; P = .93). The cumulative incidence of acute GVHD (P = .13), 1-year chronic GVHD (P = .84), and relapse rate (P = .26) did not correlate with univectorial GVH mismatches. Similarly, no correlation was observed between the amount of HLA mismatch in the HVG direction and graft rejection. In multivariate analysis advanced disease at transplant was the strongest predictor of survival, NRM, relapse, and graft rejection. In conclusion, the degree of HLA mismatching should not be used as a criterion to select family haploidentical donors when using bone marrow as stem cell source and PTCy for GVHD prophylaxis.


Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Ciclofosfamida/uso terapéutico , Antígenos HLA/inmunología , Histocompatibilidad/inmunología , Trasplante Haploidéntico/efectos adversos , Trasplante de Médula Ósea/mortalidad , Rechazo de Injerto/inmunología , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Análisis de Supervivencia , Trasplante Haploidéntico/mortalidad
8.
Haematologica ; 103(8): 1317-1328, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29748438

RESUMEN

Allogeneic hematopoietic stem cell transplantation is the optimal care for patients with high-risk or intermediate - acute myeloid leukemia. In patients lacking matched sibling donor, haploidentical donors are an option. We compared outcomes of unmanipulated (Haplo) to matched sibling donor transplant in acute myeloid leukemia patients in first complete remission. Included were intermediate and high-risk acute myeloid leukemia in first complete remission undergoing Haplo and matched sibling donor transplant from 2007-2015, and reported to the ALWP of the EBMT. A propensity score technique was used to confirm results of main analysis: 2 matched sibling donors were matched with 1 Haplo. We identified 2654 pts (Haplo =185; matched sibling donor =2469), 2010 with intermediate acute myeloid leukemia (Haplo=122; matched sibling donor =1888) and 644 with high-risk acute myeloid leukemia (Haplo =63; matched sibling donor =581). Median follow up was 30 (range 1-116) months. In multivariate analysis, in intermediate - acute myeloid leukemia patients, Haplo resulted in lower leukemia-free survival (Hazard Ratio 1.74; P<0.01), overall-survival (HR 1.80; P<0.01) and GvHD-free-relapse-free survival (Hazard Ratio 1.32; P<0.05) and higher graft-versus-host disease (GvHD) non-relapse mortality (Hazard Ratio 3.03; P<0.01) as compared to matched sibling donor. In high-risk acute myeloid leukemia, no differences were found in leukemia-free survival, overall-survival, and GvHD-free- relapse-free survival according to donor type. Higher grade II-IV acute GvHD was observed for Haplo in both high-risk (Hazard Ratio 2.20; P<0.01) and intermediate risk (Hazard Ratio 1.84; P<0.01). A trend for a lower Relapse-Incidence was observed in Haplo among high-risk acute myeloid leukemia (Hazard Ratio 0.56; P=0.06). The propensity score analysis confirmed results. Our results underline that matched sibling donor is the first choice for acute myeloid leukemia patients in first complete remission. On the other hand, results of Haplo transplants are similar to matched sibling donor transplants in acute myeloid leukemia patients with high risk cytogenetics.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Donantes de Tejidos , Adolescente , Adulto , Anciano , Citogenética , Femenino , Enfermedad Injerto contra Huésped , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Medición de Riesgo , Hermanos , Análisis de Supervivencia , Trasplante Haploidéntico , Resultado del Tratamiento , Adulto Joven
9.
Am J Hematol ; 93(5): 643-648, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29498107

RESUMEN

The aim of this study was to assess the outcome of patients with aplastic anemia (AA), receiving rabbit anti-thymocyte globulin (Thymoglobulin, SANOFI) and cyclosporin, as first line treatment. Eligible were 955 patients with AA, treated first line with Thymoglobulin, between 2001 and 2008 (n = 492), or between 2009 and 2012 (n = 463). The median age of the patients was 21 years (range 1-84). Mortality within 90 days was 5.7% and 2.4%, respectively in the two time periods (P = .007).The actuarial 10-year survival for the entire population was 70%; transplant free survival was 64%. Predictors of survival in multivariate analysis, were severity of the disease, patients age and the interval between diagnosis and treatment. Survival was 87% vs 61% for responders at 6 months versus nonresponders (P < .0001). The 10-year survival of nonresponders at 6 months, undergoing a subsequent transplant (n = 110), was 64%, vs 60% for patient not transplantated (n = 266) (P = .1). The cumulative incidence of response was 37%, 52%, 65% respectively, at 90, 180, and 365 days. In multivariate analysis, negative predictors of response at 6 months, were older age, longer interval diagnosis treatment, and greater severity of the disease. In conclusion, early mortality is low after first line treatment of AA with Thymoglobulin, and has been further reduced after year 2008. Patients age, together with interval diagnosis-treament and severity of the disease, remain strong predictors of response and survival.


Asunto(s)
Anemia Aplásica/tratamiento farmacológico , Suero Antilinfocítico/uso terapéutico , Ciclosporina/uso terapéutico , Quimioterapia Combinada/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anemia Aplásica/mortalidad , Asia , Niño , Preescolar , Europa (Continente) , Humanos , Lactante , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Adulto Joven
10.
Am J Hematol ; 93(6): 736-744, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29498106

RESUMEN

Acute myeloid leukemia (AML) patients harboring the FLT3-ITD mutation are considered a high risk patient subset preferentially allocated for allogeneic stem cell transplantation in first remission. Whether FLT3-ITD retains a prognostic role in haploidentical stem cell transplantation (haplo-SCT) is unknown. To analyze the prognostic impact of FLT3-ITD in haplo-SCT, we performed a retrospective analysis of the multicenter registry of the acute leukemia working party of the European Society for Blood and Marrow Transplantation. We included all adult AML patients with known FLT3 status who underwent a first T-cell replete related haplo-HCT in first complete remission from 2005 to 2016. We evaluated 293 patients of whom 202 were FLT3wt and 91 were FLT3-ITD mutated. FLT3-ITD patients were more likely to be NPM1 mutated as well as be in the intermediate risk cytogenetic risk category. In multivariate analysis, patients with FLT3-ITD had comparable rates of relapse incidence [Hazard ratio (HR) = 1.34, confidence interval (CI) 95%, 0.67-2.7; P = .9] and leukemia-free survival (HR = 0.99, CI 95%, 0.62-1.57; P = .9) to those of FLT3wt patients. Overall survival, the incidence of nonrelapse mortality, and graft versus host disease-free/relapse-free survival were not significantly impacted by FLT3-ITD status. Furthermore, relapse and overall survival were comparable between FLT3-ITD patients transplanted from various donor pools, namely matched siblings, unrelated donors, haplo-SCT). Finally, subset analysis of patients with intermediate risk cytogenetics confirmed the absence of a prognostic impact of FLT3-ITD also for this patient segment. In AML patients undergoing T-cell replete haplo-SCT, the FLT3-ITD mutation possibly does not retain its prognostic significance.


Asunto(s)
Leucemia Mieloide Aguda/diagnóstico , Trasplante Haploidéntico , Tirosina Quinasa 3 Similar a fms/genética , Adulto , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Mutación , Nucleofosmina , Pronóstico , Sistema de Registros , Estudios Retrospectivos
11.
Am J Hematol ; 93(2): 246-253, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29114918

RESUMEN

Haploidentical hematopoietic cell transplantation (haplo-HCT) is being increasingly used in acute leukemia patients as an alternative transplant modality when matched sibling or matched unrelated donors are unavailable. As several potential haploidentical relative donors are typically available for a given patient, optimizing donor selection to improve clinical outcome is crucial. The impact of donor age and kinship on the outcome of acute leukemia patients is not clearly established in this setting. Using the multinational registry of the acute leukemia working party of the European society for blood and marrow transplantation we retrospective analyzed the clinical outcome of 1270 acute myeloid leukemia and acute lymphoblastic leukemia patients who underwent haplo-HCT between 2005 and 2015. Patients over the age of 40 were significantly affected by increasing donor age resulting in higher non-relapse mortality (NRM) [Hazard ratio (HR)=1.86, confidence interval (CI) 95%, 1.18-2.94; P = .007], inferior leukemia-free survival (LFS) (HR = 1.59, CI 95%, 1.13-2.24; P = .007), and overall survival (OS) (HR = 1.74, CI 95%, 1.22-2.47; P = .002) when donors were over the age of 40. Additionally, kinship was found to be prognostically significant as patients transplanted from children donors over the age of 35 experienced an increased rate of NRM (HR = 1.82, CI 95%, 1.13-2.9; P = .01), inferior LFS (HR = 1.5, CI 95%, 1.05-2.13; P = .03), and OS (HR = 1.5, CI 95%, 1.04-2.15; P = .03). For patients younger than 40 years, donor age and kinship were mostly not clinically impactful. Our data establish donor age and kinship as significant determinants of outcome following haplo-HCT for acute leukemia patients.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia/terapia , Donante no Emparentado , Enfermedad Aguda , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Leucemia/mortalidad , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Análisis de Supervivencia , Trasplante Haploidéntico , Resultado del Tratamiento
12.
Am J Hematol ; 93(12): 1532-1542, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30218444

RESUMEN

Patients with acute myeloid leukemia (AML) who relapse after autologous stem cell transplantation (ASCT) can be rescued by allogeneic SCT. We identified 537 adult patients with AML allografted in second complete remission (CR2) or first relapse after ASCT in the European Society for Blood and Marrow Transplantation (EBMT) registry. At 3 years post allograft, leukemia free survival (LFS) was 31.4% [95%CI 27.3-35.6], overall survival (OS) 39.5% [95%CI 35.1-43.9], relapse incidence (RI) 34.6% [95%CI 30.4-38.8], and nonrelapse mortality (NRM) 33.7% [95%CI 29.6-37.9]. RI was higher in patients transplanted in relapse in comparison to those transplanted in CR2 (HR 1.76, P = .004) and in patients who relapsed later after ASCT (HR 0.97 per month, P < 10-3 ), both translating into better LFS/ OS. Relapse was also lower in patients undergoing allogeneic stem cell transplantation (allo-HSCT) from an unrelated donor (UD) in comparison to those transplanted from a matched sibling donor (MSD) (HR 0.49, P < 10-3 ). NRM was increased in patients who received total body irradiation (TBI) pre-ASCT (HR 2.43; P < 10-4), translating into worse LFS/OS. LFS/OS did not differ between patients allotransplanted with reduced intensity (RIC) or myeloablative (MAC) conditioning. In conclusion, one third of adult patients with AML relapsing post ASCT can be rescued with allo-HSCT, with better LFS/OS in patients who relapsed later post ASCT, those transplanted in CR2 and those who had not received TBI pre-ASCT.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Adulto , Humanos , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Acondicionamiento Pretrasplante/métodos , Trasplante Autólogo/efectos adversos , Trasplante Homólogo , Irradiación Corporal Total
13.
Haematologica ; 102(12): 2125-2133, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28971905

RESUMEN

Patients with acute graft-versus-host disease (GvHD) grade I were randomized to an observation arm (n=85) or to a treatment arm (n=86) consisting of 6-methylprednisolone 1 mg/kg/day, after stratification for age and donor type. The primary end point was development of grade II-IV GvHD. The cumulative incidence of grade II-IV GvHD was 50% in the observation arm and 33% in the treatment arm (P=0.005). However, grade III-IV GvHD was comparable (13% vs 10%, respectively; P=0.6), and this was true for sibling and alternative donor transplants. Moderate/severe chronic GvHD was also comparable (17% vs 9%). In multivariate analysis, an early interval between transplant and randomization (

Asunto(s)
Enfermedad Injerto contra Huésped/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Enfermedad Aguda , Adolescente , Adulto , Anciano , Niño , Preescolar , Progresión de la Enfermedad , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/patología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Lactante , Recién Nacido , Metilprednisolona/efectos adversos , Persona de Mediana Edad , Pronóstico , Esteroides/efectos adversos , Esteroides/uso terapéutico , Análisis de Supervivencia , Adulto Joven
14.
Biol Blood Marrow Transplant ; 22(2): 324-329, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26456259

RESUMEN

This is a retrospective analysis of 95 patients with myelofibrosis who were allografted between 2001 and 2014. The aims of the study were to assess whether the outcome of alternative donor grafts has improved with time and how this compares with the outcome of identical sibling grafts. Patients were studied in 2 time intervals: 2000 to 2010 (n = 58) and 2011 to 2014 (n = 37). The Dynamic International Prognostic Scoring System score was comparable in the 2 time periods, but differences in the most recent group included older age (58 versus 53 years, P = .004), more family haploidentical donors (54% versus 5%, P < .0001), and the introduction of the thiotepa-fludarabine-busulfan conditioning regimen (70% of patients versus 2%, P < .0001). Acute and chronic graft-versus-host disease were comparable in the 2 time periods. The 3-year transplantation-related mortality (TRM) in the 2011 to 2014 period versus the 2000 to 2010 period is 16% versus 32% (P = .10), the relapse rate 16% versus 40% (P = .06), and actuarial survival 70% versus 39% (P = .08). Improved survival was most pronounced in alternative donor grafts (69% versus 21%, P = .02), compared with matched sibling grafts (72% versus 45%, P = .40). In conclusion, the outcome of allografts in patients with myelofibrosis has improved in recent years because of a reduction of both TRM and relapse. Improvement is most significant in alternative donor transplantations, with modifications in donor type and conditioning regimen.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Mielofibrosis Primaria/terapia , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mielofibrosis Primaria/mortalidad , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Donante no Emparentado , Adulto Joven
15.
Biol Blood Marrow Transplant ; 22(7): 1242-1246, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26970379

RESUMEN

Minimal residual disease (MRD) was monitored by Wilms tumor 1 (WT1) expression in 207 patients with acute myeloid leukemia (AML) after an allogeneic hemopoietic stem cell transplantation (HSCT) as a trigger to initiate pre-emptive immunotherapy (IT) with cyclosporin discontinuation and/or donor lymphocyte infusion. The trigger for IT was WT1 ≥ 180 copies/10(4) Abelson cells in marrow cells in the first group of 122 patients (WT1-180) and ≥ 100 copies in a subsequent group of 85 patients (WT1-100). Forty patients received IT. The cumulative incidence (CI) of relapse was 76% in WT1-180 (n = 17) versus 29% in WT1-100 patients (n = 23) receiving IT (P = .006); the leukemia-free survival from MRD positivity was 23% versus 74%, respectively (P = .003). We then looked at the entire AML patient population (n = 207). WT1-180 and WT1-100 patients were comparable for disease phase and age. The overall 4-year CI of transplantation-related mortality was 13% in both groups; the CI of leukemia relapse was 38% in the WT1-180 and 28% in the WT1-100 patients (P = .05) and leukemia-free survival was 56% versus 48%, respectively (P = .07). In conclusion, we suggests that WT1-based pre-emptive immunotherapy is feasible in patients with undergoing an allogeneic HSCT. The protective effect on relapse is greater when IT is triggered at lower levels of WT1.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Inmunoterapia/métodos , Leucemia Mieloide Aguda/terapia , Premedicación/métodos , Proteínas WT1/análisis , Adolescente , Adulto , Anciano , Células de la Médula Ósea/metabolismo , Femenino , Humanos , Inmunoterapia Adoptiva , Leucemia Mieloide Aguda/mortalidad , Transfusión de Linfocitos , Masculino , Persona de Mediana Edad , Trasplante Homólogo , Adulto Joven
16.
Blood ; 123(15): 2333-42, 2014 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-24558201

RESUMEN

Approximately one-third of patients with myelodysplastic syndrome (MDS) receiving allogeneic hematopoietic stem cell transplantation (HSCT) are cured by this treatment. Treatment failure may be due to transplant complications or relapse. To identify predictive factors for transplantation outcome, we studied 519 patients with MDS or oligoblastic acute myeloid leukemia (AML, <30% marrow blasts) who received an allogeneic HSCT and were reported to the Gruppo Italiano Trapianto di Midollo Osseo registry between 2000 and 2011. Univariate and multivariate survival analyses were performed using Cox proportional hazards regression. High-risk category, as defined by the revised International Prognostic Scoring System (IPSS-R), and monosomal karyotype were independently associated with relapse and lower overall survival after transplantation. On the other hand, older recipient age and high hematopoietic cell transplantation-comorbidity index (HCT-CI) were independent predictors of nonrelapse mortality. Accounting for various combinations of patient's age, IPSS-R category, monosomal karyotype, and HCT-CI, the 5-year probability of survival after allogeneic HSCT ranged from 0% to 94%. This study indicates that IPSS-R risk category and monosomal karyotype are important factors predicting transplantation failure both in MDS and oligoblastic AML. In addition, it reinforces the concept that allogeneic HSCT offers optimal eradication of myelodysplastic hematopoiesis when the procedure is performed before MDS patients progress to advanced disease stages.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos/cirugía , Adolescente , Adulto , Anciano , Aloinjertos , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Recurrencia , Factores de Riesgo , Resultado del Tratamiento , Adulto Joven
18.
Biol Blood Marrow Transplant ; 20(10): 1573-9, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24910379

RESUMEN

We studied 459 consecutive patients with hematologic malignancies, median age 44 years (range, 15 to 71 years), who underwent transplantation with grafts from identical sibling donors (SIB; n = 176), matched unrelated donors (MUD; n = 43), mismatched unrelated donors (mmUD; n = 43), unrelated cord blood (UCB; n = 105) or HLA-haploidentical family donors (HAPLO; n = 92). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate in the SIB recipients; antithymocyte globulin for the MUD, mmUD, and UCB recipients; and post-transplantation cyclophosphamide, cyclosporine, and mycophenolate in the HAPLO recipients. Conditioning regimens were mostly myeloablative (69%). Advanced disease phase was more frequent, but not significantly so, in the HAPLO and mmUD groups (P = .08). Acute GVHD grade II-IV was significantly less frequent in the HAPLO, UCB, and MUD groups (14% to 21%) compared with the SIB (31%) and mmUD (42%) groups (P < .001), and there was a trend toward less moderate-severe chronic GVHD in the HAPLO and UCB groups (P = .053). The proportion of patients off cyclosporine at 1 year ranged from 55% for the SIB group to 81% for the HAPLO group (P < .001). Transplantation-related mortality at 2 years was lower in the HAPLO and SIB groups (18% to 24%) compared with the MUD, mmUD, and UCB groups (33% to 35%; P = .10). Relapse rate was comparable in the 5 groups (P = .80). The 4-year actuarial survival was 45% in the SIB group, 43% in the MUD group, 40% in the mmUD group, 34% in the UCB group, and 52% in the HAPLO group (P = .10). In multivariate analysis, advanced disease was a negative predictor of survival (hazard ratio [HR], 2.4; P < .0001), together with a diagnosis of acute leukemia (HR, 1.8; P = .0001); HAPLO grafts were comparable to SIB (P = .80), whereas UCB had inferior survival (P = .03). In conclusion, unmanipulated haploidentical family donor transplants are an additional option for patients lacking a matched sibling donor.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Anciano , Femenino , Expresión Génica , Antígenos HLA/genética , Antígenos HLA/inmunología , Haplotipos , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/mortalidad , Prueba de Histocompatibilidad , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Estudios Prospectivos , Recurrencia , Hermanos , Análisis de Supervivencia , Trasplante Homólogo , Donante no Emparentado
19.
Biol Blood Marrow Transplant ; 20(9): 1440-3, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24862637

RESUMEN

Poor graft function (PGF) is characterized by pancytopenia and a hypoplastic marrow, with complete donor chimerism, usually without severe graft-versus-host disease (GVHD). We report 41 patients with PGF, treated with granulocyte colony-stimulating factor-mobilized CD34 selected cells, at a median interval from transplant of 140 days, without conditioning and without GVHD prophylaxis. Donors were HLA matched siblings (n = 12), unrelated donors (n = 18), or mismatched family members (n = 11). The median number of infused CD34(+) cells was 3.4 × 10(6)/kg. The rate of trilineage recovery was 75%: 83% for HLA matched siblings and 72% for unrelated and mismatched family members (P = .3). The cumulative incidence of acute grade II GVHD was 15%, and no patient developed de novo chronic GVHD. The actuarial 3-year survival is 63%: 76% and 25% for patients with or without trilineage recovery. These data confirm the role of CD34(+) selected cells from the same donor in the treatment of PGF and warrant the request for a second donation also when the donor is unrelated.


Asunto(s)
Supervivencia de Injerto/fisiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Acondicionamiento Pretrasplante/efectos adversos , Adolescente , Adulto , Antígenos CD34 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
20.
Rinsho Ketsueki ; 55(6): 607-32, 2014 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-24975331

RESUMEN

Advances in hematopoietic cell transplantation (HCT) technology and supportive care techniques have led to improvements in long-term survival after HCT. Emerging indications for transplantation, introduction of newer graft sources (eg, umbilical cord blood) and transplantation of older patients using less intense conditioning regimens have also contributed to an increase in the number of HCT survivors. These survivors are at risk for developing late complications secondary to pre-, peri-, and posttransplantation exposures and risk factors. Guidelines for screening and preventive practices for HCT survivors were published in 2006. An international group of transplantation experts was convened in 2011 to review contemporary literature and update the recommendations while considering the changing practice of transplantation and international applicability of these guidelines. This review provides the updated recommendations for screening and preventive practices for pediatric and adult survivors of autologous and allogeneic HCT.


Asunto(s)
Enfermedades Hematológicas/diagnóstico , Trasplante de Células Madre Hematopoyéticas , Enfermedades Hematológicas/terapia , Humanos , Prevención Secundaria , Sobrevivientes , Factores de Tiempo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA