Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 47
Filtrar
1.
Biol Blood Marrow Transplant ; 26(11): 2034-2039, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32712327

RESUMO

Sickle cell disease (SCD) is the most common inherited hemoglobinopathy. Hematopoietic stem cell transplantation (HCT) is the sole curative therapy for SCD, but few patients will have a matched sibling donor. Patients with SCD are mostly of African origin and thus are less likely to find a matched unrelated donor in international registries. Using HaploStats, we estimated HLA haplotypes for 185 patients with SCD (116 from a Brazilian center and 69 from European Society for Blood and Marrow Transplantation [EBMT] centers) and classified the ethnic origin of haplotypes. Then we assessed the probability of finding an HLA-matched unrelated adult donor (MUD), considering loci A, B, and DRB1 (6/6), in international registries. Most haplotypes were African, but Brazilians showed a greater ethnic admixture than EBMT patients. Nevertheless, the chance of finding at least one 6/6 potential allelic donor was 47% for both groups. Most potential allelic donors were from the US National Marrow Donor Program registry and from the Brazilian REDOME donor registry. Although the probability of finding a donor is higher than previously reported, strategies are needed to improve ethnic diversity in registries. Moreover, predicting the likelihood of having an MUD might influence SCD management.

2.
Bone Marrow Transplant ; 55(7): 1367-1378, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32286503

RESUMO

Graft-versus-host disease (GVHD) and cytomegalovirus (CMV)-related complications are leading causes of mortality after unrelated-donor hematopoietic cell transplantation (UD-HCT). The non-conventional MHC class I gene MICB, alike MICA, encodes a stress-induced polymorphic NKG2D ligand. However, unlike MICA, MICB interacts with the CMV-encoded UL16, which sequestrates MICB intracellularly, leading to immune evasion. Here, we retrospectively analyzed the impact of mismatches in MICB amino acid position 98 (MICB98), a key polymorphic residue involved in UL16 binding, in 943 UD-HCT pairs who were allele-matched at HLA-A, -B, -C, -DRB1, -DQB1 and MICA loci. HLA-DP typing was further available. MICB98 mismatches were significantly associated with an increased incidence of acute (grade II-IV: HR, 1.20; 95% CI, 1.15 to 1.24; P < 0.001; grade III-IV: HR, 2.28; 95% CI, 1.56 to 3.34; P < 0.001) and chronic GVHD (HR, 1.21; 95% CI, 1.10 to 1.33; P < 0.001). MICB98 matching significantly reduced the effect of CMV status on overall mortality from a hazard ratio of 1.77 to 1.16. MICB98 mismatches showed a GVHD-independent association with a higher incidence of CMV infection/reactivation (HR, 1.84; 95% CI, 1.34 to 2.51; P < 0.001). Hence selecting a MICB98-matched donor significantly reduces the GVHD incidence and lowers the impact of CMV status on overall survival.

4.
Bull Cancer ; 107(1S): S72-S84, 2020 Jan.
Artigo em Francês | MEDLINE | ID: mdl-31586527

RESUMO

Haploidentical hematopoietic stem cell transplantation has been growing steadily since 2012. The SFGM-TC has twice published guidelines concerning T-cell repleted haploidentical grafts with high dose cyclophosphamide post-transplantation. The 2013 workshop recommended using the non-myeloablative Baltimore protocol with bone marrow and developed prospective protocols to evaluate these transplantations. The 2015 workshop reported improved results of reduced conditioning regimens in Hodgkin's lymphoma and intensive conditioning in myeloid hemopathies, and a similar outcome with 10/10 HLA matched donor with the same disease-risk score thus raising the question of the qualifier "alternative" for haploidentical transplants. The current work concerns the criteria for selecting the donor. The main criterion remains the absence of anti-HLA antibodies directed against the donor present in the recipient sera (DSA - Donor Specific Antibodies). In case of DSA and in the absence of an alternative donor, desensitization protocols exist. The other criteria are impossible to prioritize: age, sex, CMV, and blood type. The degree of relatedness and the number of HLA incompatibilities do not seem to be a criterion of choice. The 'ideal' donor would be a young man, CMV-matched, without major ABO incompatibility with a marrow transplant. There is insufficient data for the KIR-ligand and NIMA/NIPA mismatch. Peripheral stem cell grafts appear to yield more acute GVHD than bone marrow grafts after intensive conditioning, but with comparable survival rates. Based on the literature review, the comparison of haploidentical with unrelated donors encourages inclusion in existing national protocols randomizing these different donors.


Assuntos
Haplótipos , Histocompatibilidade , Doadores de Tecidos , Adulto , Fatores Etários , Aloenxertos , Transplante de Medula Óssea , Ciclofosfamida/uso terapêutico , Infecções por Citomegalovirus/complicações , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Antígenos HLA/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Teste de Histocompatibilidade , Humanos , Imunossupressores/uso terapêutico , Depleção Linfocítica , Masculino , Fatores Sexuais , Linfócitos T , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos
5.
Cancer Immunol Immunother ; 68(10): 1561-1572, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31494742

RESUMO

Preclinical and clinical studies have suggested that cancer treatment with antitumor antibodies induces a specific adaptive T cell response. A central role in this process has been attributed to CD4+ T cells, but the relevant T cell epitopes, mostly derived from non-mutated self-antigens, are largely unknown. In this study, we have characterized human CD20-derived epitopes restricted by HLA-DR1, HLA-DR3, HLA-DR4, and HLA-DR7, and investigated whether T cell responses directed against CD20-derived peptides can be elicited in human HLA-DR-transgenic mice and human samples. Based on in vitro binding assays to recombinant human MHC II molecules and on in vivo immunization assays in H-2 KO/HLA-A2+-DR1+ transgenic mice, we have identified 21 MHC II-restricted long peptides derived from intracellular, membrane, or extracellular domains of the human non-mutated CD20 protein that trigger in vitro IFN-γ production by PBMCs and splenocytes from healthy individuals and by PBMCs from follicular lymphoma patients. These CD20-derived MHC II-restricted peptides could serve as a therapeutic tool for improving and/or monitoring anti-CD20 T cell activity in patients treated with rituximab or other anti-CD20 antibodies.


Assuntos
Antígenos CD20/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfoma/tratamento farmacológico , Animais , Feminino , Cadeias HLA-DRB1/imunologia , Humanos , Interferon gama/biossíntese , Linfoma/imunologia , Camundongos , Rituximab/uso terapêutico
6.
Am J Hematol ; 2018 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-29726580

RESUMO

Matching for HLA-A, -B, -C, and -DRB1 loci (8/8 match) is currently the gold standard for unrelated donor hematopoietic cell transplantation (HCT). In Europe, patients are also matched at the HLA-DQB1 loci (10/10 match). However, there is increasing evidence that matching at HLA-DRB3/4/5 loci may help to lower transplant-related morbidity and mortality. We therefore investigated the impact of HLA-DRB3/4/5 mismatches on outcomes in 1975 patients who received a first 10/10 matched unrelated donor (MUD) HCT in France from 2000 to 2012 for a hematological malignancy. High-resolution typing was performed at HLA-A, -B, -C, -DRB1, -DQB1, -DPB1, and -DRB3/4/5 loci for all donor/recipient pairs. Compared with DRB3/4/5-matched pairs, patients who received a MUD HCT from a DRB3/4/5 mismatched donor had a significantly increased risk of grade II-IV acute graft-versus-host disease (aGVHD) (Adjusted Hazard Ratio (HR) 1.43 (1.07 to 1.90)) associated with lower graft-versus-host disease-free and relapse-free survival (GRFS) (Adjusted HR 1.20 (1.02 to 1.42)). Conversely, we observed no differences in terms of chronic GVHD, nonrelapse mortality, relapse and overall survival. However, we believe that patients stand to benefit from DRB3/4/5 loci being considered for unrelated donor selection to improve GRFS and then quality of life after unrelated HCT.

7.
Bull Cancer ; 104(12S): S65-S70, 2017 Dec.
Artigo em Francês | MEDLINE | ID: mdl-29128085

RESUMO

As part of the 7th Annual francophone workshop series on the harmonization of clinical practices in allogeneic stem cell transplantation held in Lille in September 2016, our workgroup discussed how transplant centers might follow a collective approach to coding data. This was done mainly by analyzing the study results found in the literature that do not provide clear answers. In addition, we discuss practical ways of coding for both donor and recipient HLA typing in the European bone marrow transplantation database called ProMISe which is managed by the European Society for Blood and Marrow Transplantation (EBMT).


Assuntos
Transplante de Medula Óssea/normas , Bases de Dados Factuais , Antígenos HLA/classificação , Teste de Histocompatibilidade/normas , Alelos , Terapia Baseada em Transplante de Células e Tecidos/normas , França , Antígenos HLA/imunologia , Teste de Histocompatibilidade/métodos , Humanos , Sociedades Médicas
9.
Haematologica ; 102(11): 1833-1841, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28751567

RESUMO

Acquired thrombotic thrombocytopenic purpura is a rare and severe disease characterized by auto-antibodies directed against "A Disintegrin And Metalloproteinase with Thrombospondin type 1 repeats, 13th member" (ADAMTS13), a plasma protein involved in hemostasis. Involvement of CD4+ T cells in the pathogenesis of the disease is suggested by the IgG isotype of the antibodies. However, the nature of the CD4+ T-cell epitopes remains poorly characterized. Here, we determined the HLA-DR-restricted CD4+ T-cell epitopes of ADAMTS13. Candidate T-cell epitopes were predicted in silico and binding affinities were confirmed in competitive enzyme-linked immunosorbent assays. ADAMTS13-reactive CD4+ T-cell hybridomas were generated following immunization of HLA-DR1 transgenic mice (Sure-L1 strain) and used to screen the candidate epitopes. We identified the ADAMTS131239-1253 peptide as the single immunodominant HLA-DR1-restricted CD4+ T-cell epitope. This peptide is located in the CUB2 domain of ADAMTS13. It was processed by dendritic cells, stimulated CD4+ T cells from Sure-L1 mice and was recognized by CD4+ T cells from an HLA-DR1-positive patient with acute thrombotic thrombocytopenic purpura. Interestingly, the ADAMTS131239-1253 peptide demonstrated promiscuity towards HLA-DR11 and HLA-DR15. Our work paves the way towards the characterization of the ADAMTS13-specific CD4+ T-cell response in patients with thrombotic thrombocytopenic purpura using ADAMTS131239-1253-loaded HLA-DR tetramers.


Assuntos
Proteína ADAMTS13/imunologia , Linfócitos T CD4-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Antígeno HLA-DR1/imunologia , Epitopos Imunodominantes/imunologia , Fragmentos de Peptídeos/imunologia , Proteína ADAMTS13/química , Alelos , Sequência de Aminoácidos , Animais , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Epitopos de Linfócito T/química , Antígeno HLA-DR1/química , Antígeno HLA-DR1/metabolismo , Humanos , Imunização , Epitopos Imunodominantes/química , Imunoglobulina G/imunologia , Camundongos , Camundongos Transgênicos , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Ligação Proteica/imunologia , Púrpura Trombocitopênica Trombótica/genética , Púrpura Trombocitopênica Trombótica/imunologia , Púrpura Trombocitopênica Trombótica/metabolismo
11.
Sci Rep ; 7: 41125, 2017 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-28117403

RESUMO

Allogeneic human cardiac-derived stem/progenitor cells (hCPC) are currently under clinical investigation for cardiac repair. While cellular immune response against allogeneic hCPC could be part of their beneficial-paracrine effects, their humoral immune response remains largely unexplored. Donor-specific HLA antibodies (DSA-HLA-I/DSA-HLA-II), primary elements of antibody-mediated allograft injury, might present an unidentified risk to allogeneic hCPC therapy. Here we established that the binding strength of anti-HLA monoclonal antibodies delineates hCPC proneness to antibody-mediated injury. In vitro modeling of clinical setting demonstrated that specific DSA-HLA-I of high/intermediate binding strength are harmful for hCPC whereas DSA-HLA-II are benign. Furthermore, the Luminex-based solid-phase assays are suitable to predict the DSA-HLA risk to therapeutic hCPC. Our data indicate that screening patient sera for the presence of HLA antibodies is important to provide an immune-educated choice of allogeneic therapeutic cells, minimize the risk of precipitous elimination and promote the allogeneic reparative effects.


Assuntos
Anticorpos/análise , Antígenos HLA/imunologia , Teste de Histocompatibilidade , Transplante de Células-Tronco/métodos , Células-Tronco/imunologia , Anticorpos/imunologia , Humanos , Imunidade Humoral , Miocárdio/citologia , Miocárdio/imunologia
12.
Bull Cancer ; 103(11S): S243-S247, 2016 Nov.
Artigo em Francês | MEDLINE | ID: mdl-27855950

RESUMO

In an attempt to harmonize clinical practices among French hematopoietic stem cell transplantation centers, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held its sixth annual workshop series in September 2015 in Lille. This event brought together practitioners from across the country with the purpose of offering careful analysis of published studies on clinical practice issues that remain to be disputed. This article addresses the impact of HLA and KIR gene polymorphism on the outcome of the transplantation in order to optimize unrelated donor selection.


Assuntos
Seleção do Doador/normas , Transplante de Células-Tronco Hematopoéticas , Antígenos de Histocompatibilidade/genética , Histocompatibilidade/genética , Polimorfismo Genético , Receptores KIR/genética , Alelos , França , Genótipo , Histocompatibilidade/imunologia , Antígenos de Histocompatibilidade/imunologia , Humanos , Receptores KIR/imunologia , Sociedades Médicas , Resultado do Tratamento
13.
Front Immunol ; 7: 307, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27570526

RESUMO

Allogeneic hematopoietic stem cell transplantation (AHSCT) is a curative treatment for a wide variety of hematological diseases. In 30% of the cases, a geno-identical donor is available. Any other situation displays some level of human leukocyte antigen (HLA) incompatibility between donor and recipient. Deleterious effects of anti-HLA immunization have long been recognized in solid organ transplant recipients. More recently, anti-HLA immunization was shown to increase the risk of primary graft failure (PGF), a severe complication of AHSCT that occurs in 3-4% of matched unrelated donor transplantation and up to 15% in cord blood transplantation and T-cell depleted haplo-identical stem cell transplantation. Rates of PGF in patients with DSA were reported to be between 24 and 83% with the highest rates in haplo-identical and cord blood transplantation recipients. This led to the recommendation of anti-HLA antibody screening to detect donor-specific antibodies (DSA) in recipients prior to AHSCT. In this review, we highlight the role of anti-HLA antibodies in AHSCT and the mechanisms that may lead to PGF in patients with DSA, and discuss current issues in the field.

14.
Blood ; 128(15): 1979-1986, 2016 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-27549307

RESUMO

Graft-versus-host disease (GVHD) is among the most challenging complications in unrelated donor hematopoietic cell transplantation (HCT). The highly polymorphic MHC class I chain-related gene A, MICA, encodes a stress-induced glycoprotein expressed primarily on epithelia. MICA interacts with the invariant activating receptor NKG2D, expressed by cytotoxic lymphocytes, and is located in the MHC, next to HLA-B Hence, MICA has the requisite attributes of a bona fide transplantation antigen. Using high-resolution sequence-based genotyping of MICA, we retrospectively analyzed the clinical effect of MICA mismatches in a multicenter cohort of 922 unrelated donor HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 10/10 allele-matched HCT pairs. Among the 922 pairs, 113 (12.3%) were mismatched in MICA MICA mismatches were significantly associated with an increased incidence of grade III-IV acute GVHD (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.50-2.23; P < .001), chronic GVHD (HR, 1.50; 95% CI, 1.45-1.55; P < .001), and nonelapse mortality (HR, 1.35; 95% CI, 1.24-1.46; P < .001). The increased risk for GVHD was mirrored by a lower risk for relapse (HR, 0.50; 95% CI, 0.43-0.59; P < .001), indicating a possible graft-versus-leukemia effect. In conclusion, when possible, selecting a MICA-matched donor significantly influences key clinical outcomes of HCT in which a marked reduction of GVHD is paramount. The tight linkage disequilibrium between MICA and HLA-B renders identifying a MICA-matched donor readily feasible in clinical practice.


Assuntos
Doença Enxerto-Hospedeiro , Antígenos HLA/genética , Transplante de Células-Tronco Hematopoéticas , Antígenos de Histocompatibilidade Classe I/genética , Teste de Histocompatibilidade , Desequilíbrio de Ligação , Doença Aguda , Adolescente , Adulto , Idoso , Aloenxertos , Criança , Pré-Escolar , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Estudos Retrospectivos
15.
PLoS One ; 11(7): e0156679, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27383202

RESUMO

Black people are at increased risk of thrombotic thrombocytopenic purpura (TTP). Whether clinical presentation of TTP in Black patients has specific features is unknown. We assessed here differences in TTP presentation and outcome between Black and White patients. Clinical presentation was comparable between both ethnic groups. However, prognosis differed with a lower death rate in Black patients than in White patients (2.7% versus 11.6%, respectively, P = .04). Ethnicity, increasing age and neurologic involvement were retained as risk factors for death in a multivariable model (P < .05 all). Sixty-day overall survival estimated by the Kaplan-Meier curves and compared with the Log-Rank test confirmed that Black patients had a better survival than White patients (P = .03). Salvage therapies were similarly performed between both groups, suggesting that disease severity was comparable. The comparison of HLA-DRB1*11, -DRB1*04 and -DQB1*03 allele frequencies between Black patients and healthy Black individuals revealed no significant difference. However, the protective allele against TTP, HLA-DRB1*04, was dramatically decreased in Black individuals in comparison with White individuals. Black people with TTP may have a better survival than White patients despite a comparable disease severity. A low natural frequency of HLA-DRB1*04 in Black ethnicity may account for the greater risk of TTP in this population.


Assuntos
Afro-Americanos/genética , Grupo com Ancestrais do Continente Africano/genética , Púrpura Trombocitopênica Trombótica/etnologia , Púrpura Trombocitopênica Trombótica/genética , Adulto , Alelos , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Frequência do Gene , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Trombótica/mortalidade , Sistema de Registros , Fatores de Risco , Resultado do Tratamento
16.
Haematologica ; 101(7): 884-90, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27056924

RESUMO

Unrelated allogeneic transplantation for severe aplastic anemia is a treatment option after immunosuppressive treatment failure in the absence of a matched sibling donor. Age, delay between disease diagnosis and transplantation, and HLA matching are the key factors in transplantation decisions, but their combined impact on patient outcomes remains unclear. Using the French Society of Bone Marrow Transplantation and Cell Therapies registry, we analyzed all consecutive patients (n=139) who underwent a first allogeneic transplantation for idiopathic severe aplastic anemia from an unrelated donor between 2000 and 2012. In an adjusted multivariate model, age over 30 years (Hazard Ratio=2.39; P=0.011), time from diagnosis to transplantation over 12 months (Hazard Ratio=2.18; P=0.027) and the use of a 9/10 mismatched unrelated donor (Hazard Ratio=2.14; P=0.036) were independent risk factors that significantly worsened overall survival. Accordingly, we built a predictive score using these three parameters, considering patients at low (zero or one risk factors, n=94) or high (two or three risk factors, n=45) risk. High-risk patients had significantly shorter survival (Hazard Ratio=3.04; P<0.001). The score was then confirmed on an independent cohort from the European Group for Blood and Marrow Transplantation database of 296 patients, with shorter survival in patients with at least 2 risk factors (Hazard Ratio=2.13; P=0.005) In conclusion, a simple score using age, transplantation timing and HLA matching would appear useful to help physicians in the daily care of patients with severe aplastic anemia.


Assuntos
Anemia Aplástica/diagnóstico , Anemia Aplástica/terapia , Transplante de Medula Óssea , Doadores não Relacionados , Adolescente , Adulto , Idoso , Anemia Aplástica/mortalidade , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/métodos , Criança , Pré-Escolar , Feminino , França , Doença Enxerto-Hospedeiro/etiologia , Humanos , Lactente , Depleção Linfocítica , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença , Análise de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
17.
Hum Immunol ; 77(11): 1092-1100, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27060781

RESUMO

During solid organ transplantation, interactions between recipient and donor immune cells occur chiefly in the allograft microvasculature. All three HLA class II antigens, DR, DP and DQ, have been detected on renal EC with a markedly increased expression of HLA class II observed in renal allografts undergoing rejection. Recent studies of donor-specific antibodies (DSA) have exposed the prevalence of de novo DSA directed against HLA-DQ, as well as a strong association between these antibodies and allograft damage. The HLA-DQ molecule can be distinguished from the other class II antigens by its transcription, expression and peptide repertoire. The distinct intragraft expression and immunogenicity of HLA-DQ may contribute to the incidence of HLA-DQ DSA, as well as directing the DSA-mediated damage. The possibility of HLA class II antigen-specific signaling in EC may reveal different mechanisms of allograft damage that act in tandem with complement-dependent injury. This review addresses the features of the HLA-DQ heterodimer that may underlie the high incidence of HLA-DQ directed DSA and their association with allograft damage. We also consider existing data in hematopoietic stem cell transplantation concerning HLA directed DSA.


Assuntos
Rejeição de Enxerto/imunologia , Antígenos HLA-DP/imunologia , Antígenos HLA-DQ/imunologia , Antígenos HLA-DR/imunologia , Transplante de Células-Tronco Hematopoéticas , Citotoxicidade Celular Dependente de Anticorpos , Epitopos , Sobrevivência de Enxerto/imunologia , Teste de Histocompatibilidade , Humanos , Imunidade Humoral , Isoanticorpos/metabolismo , Transplante de Rim , Imunologia de Transplantes
20.
Am J Hematol ; 90(10): 897-903, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26149659

RESUMO

In absence of available matched-related or unrelated donor (MUD), mismatched unrelated donors (MMUD) and unrelated cord blood (UCB) are both considered to be suitable donors, with similar post-transplant overall survival. In most of these retrospective comparisons, HLA typing of adult donors was performed at eight loci. The aim of this study was to compare the outcome of patients transplanted from UCB (N = 64) with those transplanted from 9/10-HLA MMUD (N = 84) or 10/10-HLA MUD (N = 196). In multivariate analysis, UCB was associated with less Grade II-IV acute GVHD in comparison with MUD (aHR 1.97, 95% CI 1.19-3.27, P = 0.009) and MMUD transplants (aHR 1.79, 95% CI 1.02-3.15, P = 0.042), while the cumulative incidence of chronic GVHD was not significantly different between the three groups. Overall survival (OS), non-relapse mortality, and relapse were not different between MMUD and UCB transplantation, whereas OS was impaired after UCB in comparison with MUD (aHR 0.65, 95% CI 0.43-0.99, P = 0.043). Factors also impacting OS were the donor/recipient CMV serostatus (Donor-/Recipient+ aHR 1.76, 95% CI 1.23-2.52, P = 0.002 compared with D-/R-), the donor/recipient gender combination (Female/Male versus other combinations aHR 1.57, 95% CI 1.11-2.22, P = 0.012) and disease risk (aHR 1.58, 95% CI 1.05-2.38, P = 0.027 for high vs. low risk disease). Our data confirm that UCB and 9/10-HLA MMUD are both relevant alternative options when no 10/10-HLA donor is available. Donor/recipient gender combination and CMV serostatus had a significant impact on survival and may be taken into account, along with donor type, in the setting of MMUD and UCB transplants.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas , Doadores não Relacionados , Doença Aguda , Adolescente , Adulto , Fatores Etários , Criança , Feminino , Doença Enxerto-Hospedeiro/etiologia , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...