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1.
Curr Res Transl Med ; 2018 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-30206045

RESUMO

PURPOSE: We developed a prognostic scoring system to evaluate the prognosis of myelodysplastic syndrome (MDS) patients surviving more than 100 days allogeneic hematopoietic cell transplantation after (allo-HCT). PATIENTS AND METHODS: We performed a landmark analysis on a derivation cohort of 393 cases to identify prognostic factors for 3-year overall survival. Potential predictor variables included demographic and clinical data, transplantation modalities and early post-transplant complications. The scoring system was tested against a validation cohort which included 391 patients. RESULTS: Complications occurring before day 100 such as relapse [HR = 6.7; 95%CI, 4.5-10.0] (4 points), lack of platelet recovery [HR, 3.6; 95%CI, 2.2-5.8] (2 points), grade-II acute GVHD [HR = 1.7; 95%CI, 1.2-2.5] (1 point) and grade-III/IV [HR = 2.6; 95%CI, 1.8 -3.8] (2 points) were the only independent predictors of 3-year OS. The 3-year OS associated with low (0), intermediate (1-3) and high (≥4) risk scores was respectively 70%, 46% and 6%. The model performed consistently in both cohorts, with good calibration. CONCLUSION: This post-transplant scoring system is a powerful predictor of outcome after allo-HCT for MDS, and can provide useful guidance for clinicians. Additional studies are required to evaluate this scoring system for other hematologic malignancies.

2.
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.

3.
Hum Immunol ; 77(11): 1008-1015, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26902994

RESUMO

In the absence of an HLA matched familial donor, a search for an unrelated donor or cord blood unit is initiated through worldwide registries. Although a first look-up on available HLA information of donors in the "book" at BMDW (Bone Marrow Donor Worldwide) can provide a good estimation of the number of compatible donors, the variety of resolution typing levels requires confirmatory typing (CT) which are expensive and time consuming. In order to help recipient centers in their work. The French donor registry (France Greffe de Moelle/Agence de la Biomedecine) has recently developed a software program called "EasyMatch®" that uses haplotype frequencies to compute the likelihood of phenotypic match in donors according to various typing resolution levels. The goal of our study is to report a single monocentric user-experience with EasyMatch®, demonstrating that its routine use reduced the cost and the delay of the donor search in our center, allowing the definition of a new strategy to search compatible unrelated donors. The strategy was first established on a retrospective cohort of 217 recipients (185 adults and 32 children=before score) and then validated on a prospective cohort of 171 recipients (160 adults and 11 children=after score). For all patients, we calculated the delay between the registration day and the donor identification day, and the number of CT requested to the donor centre. Considering both groups, we could observe a significant decrease of the number of CT from 8 to 2 (p<0,001), and a significant decrease of the median delay to identify a suitable donor from 43 to 31days (p<0.0001). EasyMatch® estimates the number of potentially identical donors, but doesn't foresee availability of the donors. It provides us an easy tracking of mismatches, an estimation of the number of potential donors, the selection of population following ethnic origin of patients and a high prediction when probability is high or low. It affords a new approach of donor search in our daily work and improves the efficiency in the great challenge of the compatible donor identification.


Assuntos
Transplante de Medula Óssea , Seleção do Doador/métodos , Antígenos HLA/metabolismo , Transplante de Células-Tronco Hematopoéticas , Doadores não Relacionados , Adulto , Criança , Estudos de Coortes , Análise Custo-Benefício , Estudos de Viabilidade , França , Histocompatibilidade , Teste de Histocompatibilidade , Humanos , Estudos Retrospectivos
4.
Hum Immunol ; 76(5): 381-4, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25637665

RESUMO

We have estimated human leukocyte antigen (HLA) haplotype frequencies using the maximum likelihood mode, which accommodates typing ambiguities. The results of the frequency distribution of the 7015 haplotypes obtained are presented here. These include a total of 114 HLA-A, 185 HLA-B, and 76 HLA-DRB1 unique alleles at each locus. Across all populations, although the most common individual HLA alleles were HLA-A(∗)02:01 (29.0%), HLA-B(∗)07:02 (11.4%), and HLA-DRB1(∗)07:01 (15.9%), the most frequent haplotype was found to be HLA-A(∗)01:01∼B(∗)08:01∼DRB1(∗)03:01.


Assuntos
Antígenos HLA-A/genética , Antígenos HLA-B/genética , Cadeias HLA-DRB1/genética , Transplante de Células-Tronco Hematopoéticas , Sistema de Registros , Medula Óssea/metabolismo , França , Frequência do Gene , Haplótipos , Teste de Histocompatibilidade , Humanos , Doadores de Tecidos
5.
Hum Immunol ; 76(5): 374-80, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25637668

RESUMO

High-resolution haplotype frequency estimations and descriptive metrics are becoming increasingly popular for accurately describing human leukocyte antigen diversity. In this study, we compared sample sets of publically available haplotype frequencies from different populations to characterize the consequences of unequal sample size on haplotype frequency estimation. We found that for low samples sizes (a few thousand), haplotype frequencies were overestimated, affecting all descriptive metrics of the underlying distribution, such as most frequent haplotype, the number of haplotypes, and the mean/median frequency. This overestimation was a result of random sample fluctuation and truncation of the tail end of the frequency distribution that comprises the least frequent haplotypes. Finally, we simulated balanced datasets through resampling and contrasted the disparities of descriptive metrics among equal and unequal datasets. This simulation resulted in the global description of the most frequent human leukocyte antigen haplotypes worldwide.


Assuntos
Grupos Étnicos , Antígenos HLA/genética , Viés de Seleção , Conjuntos de Dados como Assunto , Frequência do Gene , Haplótipos , Humanos , Polimorfismo Genético , Sistema de Registros , Análise de Regressão , Tamanho da Amostra , Doadores de Tecidos
6.
Haematologica ; 99(9): 1509-15, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24972767

RESUMO

Umbilical cord blood transplant recipients are exposed to an increased risk of graft failure, a complication leading to a higher rate of transplant-related mortality. The decision and timing to offer a second transplant after graft failure is challenging. With the aim of addressing this issue, we analyzed engraftment kinetics and outcomes of 1268 patients (73% children) with acute leukemia (64% acute lymphoblastic leukemia, 36% acute myeloid leukemia) in remission who underwent single-unit umbilical cord blood transplantation after a myeloablative conditioning regimen. The median follow-up was 31 months. The overall survival rate at 3 years was 47%; the 100-day cumulative incidence of transplant-related mortality was 16%. Longer time to engraftment was associated with increased transplant-related mortality and shorter overall survival. The cumulative incidence of neutrophil engraftment at day 60 was 86%, while the median time to achieve engraftment was 24 days. Probability density analysis showed that the likelihood of engraftment after umbilical cord blood transplantation increased after day 10, peaked on day 21 and slowly decreased to 21% by day 31. Beyond day 31, the probability of engraftment dropped rapidly, and the residual probability of engrafting after day 42 was 5%. Graft failure was reported in 166 patients, and 66 of them received a second graft (allogeneic, n=45). Rescue actions, such as the search for another graft, should be considered starting after day 21. A diagnosis of graft failure can be established in patients who have not achieved neutrophil recovery by day 42. Moreover, subsequent transplants should not be postponed after day 42.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro/terapia , Leucemia Mieloide Aguda/terapia , Agonistas Mieloablativos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Humanos , Lactente , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Neutrófilos/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Indução de Remissão , Análise de Sobrevida , Fatores de Tempo , Transplante Homólogo
7.
Haematologica ; 99(3): 535-40, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24143000

RESUMO

Double cord blood transplantation extends the use of cord blood to adults for whom a single unit is not available, but the procedure is limited by its cost. To evaluate outcomes and cost-effectiveness of double compared to single cord blood transplantation, we analyzed 134 transplants in adults with acute leukemia in first remission. Transplants were performed in France with reduced intensity or myeloablative conditioning regimens. Costs were estimated from donor search to 1 year after transplantation. A Markov decision analysis model was used to calculate quality-adjusted life-years and cost-effectiveness ratio within 4 years. The overall survival at 2 years after single and double cord blood transplants was 42% versus 62%, respectively (P=0.03), while the leukemia-free-survival was 33% versus 53%, respectively (P=0.03). The relapse rate was 21% after double transplants and 42% after a single transplant (P=0.006). No difference was observed for non-relapse mortality or chronic graft-versus-host-disease. The estimated costs up to 1 year after reduced intensity conditioning for single and double cord blood transplantation were € 165,253 and €191,827, respectively. The corresponding costs after myeloablative conditioning were € 192,566 and € 213,050, respectively. Compared to single transplants, double cord blood transplantation was associated with supplementary costs of € 21,302 and € 32,420 up to 4 years, but with increases in quality-adjusted life-years of 0.616 and 0.484, respectively, and incremental cost-effectiveness ratios of € 34,581 and €66,983 in the myeloablative and reduced intensity conditioning settings, respectively. Our results showed that for adults with acute leukemia in first complete remission in France, double cord transplantation is more cost-effective than single cord blood transplantation, with better outcomes, including quality-adjusted life-years.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Análise Custo-Benefício , Leucemia/terapia , Doença Aguda , Adolescente , Adulto , Idoso , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/economia , França , Doença Enxerto-Hospedeiro/etiologia , Humanos , Leucemia/diagnóstico , Leucemia/mortalidade , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
8.
Exp Hematol ; 41(11): 924-33, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23831606

RESUMO

Allogeneic hematopoietic stem cell (HSC) transplantation is a curative treatment for many hematologic malignancies for which umbilical cord blood (UCB) represents an alternative source of HSCs. To overcome the low cellularity of one UCB unit, double UCB transplantation (dUCBT) has been developed in adults. We have analyzed the outcome of 136 patients who underwent dUCBT reported to the SFGM-TC registry between 2005 and 2007. Forty-six patients received myeloablative regimens, and 90 patients received reduced-intensity conditioning regimens. There were 84 cases of leukemia, 17 cases of non-Hodgkin lymphoma, 11 cases of myeloma, and 24 other hematologic malignancies. At transplantation, 40 (29%) patients were in complete remission. At day 60 after transplantation, the cumulative incidence of neutrophil recovery was 91%. We observed one UCB unit domination in 88% of cases. The cumulative incidence of day 100 acute graft-versus-host disease, chronic graft-versus-host disease, transplant-related mortality, and relapse at 2 years were 36%, 23%, 27%, and 28% respectively. After a median follow-up of 49.5 months, the 3-year probabilities of overall and progression-free survival were 41% and 35%, respectively, with a significant overall survival advantage when male cord engrafted male recipients. We obtained a long-term plateau among patients in complete remission, which makes dUCBT a promising treatment strategy for these patients.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Neoplasias Hematológicas/cirurgia , Sistema de Registros/estatística & dados numéricos , Adolescente , Adulto , Idoso , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
9.
J Clin Oncol ; 30(36): 4533-40, 2012 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-23109707

RESUMO

PURPOSE: To investigate the impact of prior-to-transplantation azacitidine (AZA) on patient outcome after allogeneic stem-cell transplantation (alloSCT) for myelodysplastic syndrome (MDS). PATIENTS AND METHODS: Of the 265 consecutive patients who underwent alloSCT for MDS between October 2005 and December 2009, 163 had received cytoreductive treatment prior to transplantation, including induction chemotherapy (ICT) alone (ICT group; n = 98), AZA alone (AZA group; n = 48), or AZA preceded or followed by ICT (AZA-ICT group; n = 17). At diagnosis, 126 patients (77%) had an excess of marrow blasts, and 95 patients (58%) had intermediate-2 or high-risk MDS according to the International Prognostic Scoring System (IPSS). Progression to more advanced disease before alloSCT was recorded in 67 patients. Donors were sibling (n = 75) or HLA-matched unrelated (10/10; n = 88). They received blood (n = 142) or marrow (n = 21) grafts following either myeloablative (n = 33) or reduced intensity (n = 130) conditioning. RESULTS: With a median follow-up of 38.7 months, 3-year outcomes in the AZA, ICT, and AZA-ICT groups were 55%, 48%, and 32% (P = .07) for overall survival (OS); 42%, 44%, and 29% (P = .14) for event-free survival (EFS); 40%, 37%, and 36% (P = .86) for relapse; and 19%, 20%, and 35% (P = .24) for nonrelapse mortality (NRM), respectively. Multivariate analysis confirmed the absence of statistical differences between the AZA and the ICT groups in terms of OS, EFS, relapse, and NRM. CONCLUSION: With the goal of downstaging underlying disease before alloSCT, AZA alone led to outcomes similar to those for standard ICT.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/cirurgia , Antimetabólitos Antineoplásicos/efeitos adversos , Azacitidina/efeitos adversos , Terapia Combinada , Feminino , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/etiologia , Estudos Retrospectivos , Transplante Homólogo/métodos , Resultado do Tratamento
11.
Transplantation ; 80(5): 634-42, 2005 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-16177638

RESUMO

BACKGROUND: Half of the patients with chronic graft-versus-host disease (GvHD) do not achieve a complete remission with first-line therapy. No clear recommendations are available regarding second-line treatments. METHODS: We retrospectively report our single-center experience of low-dose thoracoabdominal irradiation (1-Gy TAI) in 41 patients with refractory extensive chronic GvHD from 1983 to 2000. Median time from extensive chronic GvHD to TAI was one year (median GvHD episodes before TAI, n = 4). RESULTS: Eighty-two percent of the patients achieved a clinical response at a median of 34 days after TAI (range, 15-180). Best response rates were observed in fasciitis (79%), and oral GvHD lesions (73%). A complete clinical response was achieved in 11 patients by 2 years postTAI. Fifty-seven percent of the patients had at least a 50% reduction of their corticosteroid daily dose by 6 months postTAI. Probability of corticosteroid discontinuation was 38% by 2 years postTAI (95% CI, 23-56%). Two-year chronic GvHD relapse incidence was 34%. Ten-year survival from irradiation was 57% (95% CI, 42-78%); patients with fasciitis, lymphocytes >1.0 x 10/L, and platelets >200 x 10/L had a better outcome. CONCLUSIONS: TAI is a safe and efficient option in patients with refractory chronic GvHD, leading to a significant tapering of systemic corticosteroid dose in most cases.


Assuntos
Doença Enxerto-Hospedeiro/radioterapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Radioterapia/métodos , Abdome , Adolescente , Adulto , Criança , Doença Crônica , Terapia Combinada , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Radioterapia/efeitos adversos , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Tórax , Transplante Homólogo
12.
Blood ; 105(6): 2608-13, 2005 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-15546951

RESUMO

Thymic function is critical for immune reconstitution after hematopoietic stem cell transplantation (HSCT). We evaluated recipient thymic function before HSCT by quantifying T-cell receptor excision circles (TRECs) in pretransplantation peripheral blood lymphocytes from 102 patients who received HSCs from an HLA-identical sibling for malignant (n = 87) or nonmalignant diseases (n = 15). Median TREC value before transplantation was 257 TRECs per 150,000 CD3+ cells (range, 0-42,746). We assessed 172 TRECs per 150,000 CD3+ cells as the most discriminating TREC value for survival in a first cohort of patients (n = 62). This cut-off was validated in a second independent prospective group of 40 patients. In the 102 patients, a TREC value greater than or equal to 172 was associated with a better survival (P < .000 01), a decreased incidence of grade II-IV acute graft-versus-host disease (GVHD; P = .017), chronic GVHD (P = .023), and bacterial (P = .003) and cytomegalovirus (CMV) infection (P = .024). In a multivariate analysis, low pretransplantation TREC values were associated with a higher incidence of CMV infection (hazard ratio [HR] = 2.0, P = .06) and severe bacterial infections (HR = 2.8, P = .036). Finally, high TREC values (HR = 6.6, P = .002) and ABO compatibility (HR = 2.7, P = .02) were associated with a better survival. Therefore, recipient host thymic function assessment could be helpful in predicting HSCT outcome and identifying patients who require a close immunologic monitoring.


Assuntos
Complexo CD3/sangue , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas , Linfócitos , Receptores de Antígenos de Linfócitos T/sangue , Irmãos , Sistema do Grupo Sanguíneo ABO , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/mortalidade , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Histocompatibilidade , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Receptores de Antígenos de Linfócitos T/análise , Transplante Homólogo
14.
Br J Haematol ; 125(3): 358-65, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15086417

RESUMO

Cord blood units (n = 5500) stored at the London Cord Blood Bank, including 59 units transplanted into a high risk and heterogeneous group of patients, were analysed. Transplant outcome data was available for 44 patients with a median clinical follow-up of 14 months (range 3-44 months). Over 40% of the collected units were of ethnic minority origin with a median volume of 79 ml (range 40-240 ml) and a median total nucleated cell (TNC) count of 11.9 x 10(9)/l (range 10.0-24.8 x 10(9)/l). The average patient's weight was 28 kg (range 5-80 kg) and the median age was 8 years (range 0.7-40 years). The median number of nucleated cells infused was 4 x 10(7)/kg (range 1.10-16 x 10(7)/kg). Neutrophil engraftment of 0.5 x 10(9)/l was observed in 33 (74+/-%) patients with an average time of 28 days (range 11-60). The Kaplan-Meier estimate of acute graft-versus-host disease (grade II >) at day 100 was 37 +/- 7% and in 27 (62%) patients, it was grade I or absent. The overall survival and disease-free survival at 2 years was 49 +/- 8% and 41 +/- 8%, respectively. Two years after transplantation the survival rate was 69% and 54% for patients receiving a 6/6 or 5/6 HLA matched units, respectively. Infection was the main cause of transplanted related mortality in these patients.


Assuntos
Bancos de Sangue/métodos , Sangue Fetal/transplante , Neoplasias Hematológicas/terapia , Adolescente , Adulto , Bancos de Sangue/organização & administração , Doadores de Sangue , Preservação de Sangue/métodos , Criança , Pré-Escolar , Criopreservação , Grupos Étnicos , Feminino , Seguimentos , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/prevenção & controle , Teste de Histocompatibilidade/métodos , Humanos , Lactente , Londres , Masculino , Resultado do Tratamento
15.
Exp Hematol ; 32(4): 397-407, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15050751

RESUMO

OBJECTIVE: Optimizing cord blood donor selection based mainly on cell dose and human leukocyte antigen (HLA) disparities may further improve results of unrelated cord blood transplants (UCBT). MATERIALS AND RESULTS: We analyzed 550 UCBTs for hematologic malignancies reported to the Eurocord Registry. Main outcomes and prognostic factors were analyzed in univariable and multivariable analyses incorporating center and period effects and using death and relapse as competitive risks for nonfatal endpoints. Nucleated cell (NC) dose before freezing and number of HLA disparities had a significant influence on outcome. Cumulative incidence (CI) of neutrophil and platelet recovery was associated with the number of HLA mismatches, number of NC before freezing, and use of granulocyte colony-stimulating factor. Coexistence of HLA class I and II disparities and high CD34 cell dose in the graft were associated with graft-vs-host disease grades III-IV. CI of disease relapse was higher in matched transplants showing a graft-vs-leukemia effect increased in HLA-mismatched transplants. Overall 3-year survival was 34.4%. Prognostic factors for survival were recipient age, gender, and disease status. CONCLUSION: Our results provide indications for a better choice of cord blood units according to cord blood cell content and HLA.


Assuntos
Contagem de Células Sanguíneas , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Neoplasias Hematológicas/terapia , Histocompatibilidade , Doadores de Tecidos , Adolescente , Adulto , Antígenos CD34/análise , Criança , Pré-Escolar , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/normas , Transplante de Células-Tronco de Sangue do Cordão Umbilical/estatística & dados numéricos , Intervalo Livre de Doença , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Efeito Enxerto vs Leucemia/imunologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Antígenos HLA/imunologia , Neoplasias Hematológicas/mortalidade , Humanos , Incidência , Recém-Nascido , Tábuas de Vida , Masculino , Defeitos do Tubo Neural/mortalidade , Defeitos do Tubo Neural/terapia , Prognóstico , Modelos de Riscos Proporcionais , Sistema de Registros/estatística & dados numéricos , Condicionamento Pré-Transplante/mortalidade , Condicionamento Pré-Transplante/estatística & dados numéricos , Resultado do Tratamento
16.
Blood ; 102(13): 4290-7, 2003 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-12920027

RESUMO

Results of unrelated cord blood transplantation (UCBT) in childhood acute myeloid leukemia (AML) have not been previously reported. We analyzed 95 children receiving UCB transplants for AML (20 in first complete remission [CR1], 47 in CR2, and 28 in more advanced stage). Poor prognosis cytogenetic abnormalities were identified in 29 cases. Most patients received a 1 or 2 HLA antigens-mismatched UCB transplants. The median number of collected nucleated cells (NCs) was 5.2 x 107/kg. Cumulative incidence (CI) of neutrophil recovery was 78% +/- 4%, acute graft-versus-host disease (GVHD) was 35% +/- 5%, and 100-day transplantation-related mortality (TRM) was 20% +/- 4%. In multivariable analysis, a collected NC dose higher than 5.2 x 107/kg was associated with a lower 100-day TRM. The 2-year CI of relapse was 29% +/- 5% and was associated with disease status. The 2-year leukemia-free survival (LFS) was 42% +/- 5% (59% +/- 11% in CR1, 50% +/- 8% in CR2, and 21% +/- 9% for children not in CR). Children with poor prognosis cytogenetic features had similar LFS compared with other patients (44% +/- 11% vs 40% +/- 8%). In CR2, LFS was not influenced by the length of CR1 (53% +/- 11% in CR1 < 9.5 months compared with 50% +/- 12% in later relapses). We conclude that UCBT is a therapeutic option for children with very poor-prognosis AML and who lack an HLA-identical sibling.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Leucemia Mieloide/terapia , Doença Aguda , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Contagem de Células Sanguíneas , Doadores de Sangue , Causas de Morte , Criança , Pré-Escolar , Terapia Combinada , Transplante de Células-Tronco de Sangue do Cordão Umbilical/mortalidade , Europa (Continente)/epidemiologia , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Lactente , Recém-Nascido , Leucemia Mieloide/tratamento farmacológico , Masculino , Sistema de Registros/estatística & dados numéricos , Indução de Remissão , Estudos Retrospectivos , Análise de Sobrevida
17.
Blood ; 101(6): 2137-43, 2003 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-12424197

RESUMO

Allogeneic bone marrow transplantation (BMT) from HLA-identical siblings is an accepted treatment for both thalassemia and sickle cell disease (SCD). However, it is associated with decided risk of both transplant-related mortality (TRM) and chronic graft-versus-host disease (GVHD). We analyzed 44 patients (median age, 5 years; range, 1-20 years) given an allogeneic related cord blood transplant for either thalassemia (n = 33) or SCD (n = 11). Thirty children were given cyclosporin A (CsA) alone as GVHD prophylaxis, 10 received CsA and methotrexate (MTX), and 4 patients received other combinations of immunosuppressive drugs. The median number of nucleated cells infused was 4.0 x 10(7)/kg (range, 1.2-10 x 10(7)/kg). No patient died and 36 of 44 children remain free of disease, with a median follow-up of 24 months (range, 4-76 months). Only one patient with SCD did not have sustained donor engraftment as compared with 7 of the 33 patients with thalassemia. Three of these 8 patients had sustained donor engraftment after BMT from the same donor. Four patients experienced grade 2 acute GVHD; only 2 of the 36 patients at risk developed limited chronic GVHD. The 2-year probability of event-free survival is 79% and 90% for patients with thalassemia and SCD, respectively. Use of MTX for GVHD prophylaxis was associated with a greater risk of treatment failure. Related CBT for hemoglobinopathies offers a good probability of success and is associated with a low risk of GVHD. Optimization of transplantation strategies could further improve these results.


Assuntos
Anemia Falciforme/terapia , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Talassemia/terapia , Doença Aguda , Plaquetas , Criança , Pré-Escolar , Doença Crônica , Ciclosporina/uso terapêutico , Intervalo Livre de Doença , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Lactente , Masculino , Metotrexato/uso terapêutico , Neutrófilos , Taxa de Sobrevida , Transplante Homólogo , Resultado do Tratamento
18.
Blood ; 99(8): 2726-33, 2002 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-11929759

RESUMO

Although CD34 cell dose is known to influence outcome of peripheral stem cell- and/or T-cell-depleted transplantation, such data on unmanipulated marrow transplantation are scarce. To study the influence of CD34(+) cell dose on hematopoietic reconstitution and incidence of infections after bone marrow transplantation, we retrospectively analyzed 212 patients from January 1994 to August 1999 who received a transplant of an unmanipulated graft from an HLA-identical sibling donor. Median age was 31 years; 176 patients had hematologic malignancies. Acute graft-versus-host disease prophylaxis consisted mainly in cyclosporin associated with methotrexate (n = 174). Median number of bone marrow nucleated cells and CD34(+) cells infused were 2.4 x 10(8)/kg and 3.7 x 10(6)/kg, respectively. A CD34(+) cell dose of 3 x 10(6)/kg or more significantly influenced neutrophil (hazard ratio [HR] = 1.37, P =.04), monocyte (HR = 1.47, P =.02), lymphocyte (HR = 1.70, P =.003), erythrocyte (HR = 1.77, P =.0002), and platelet (HR = 1.98, P =.00008) recoveries. CD34(+) cell dose also influenced the incidence of secondary neutropenia (HR = 0.60, P =.05). Bacterial and viral infections were not influenced by CD34 cell dose, whereas it influenced the incidence of fungal infections (HR = 0.41, P =.008). Estimated 180-day transplantation-related mortality (TRM) and 5-year survival were 25% and 56%, respectively, and both were highly affected by CD34(+) cell dose (HR = 0.55, P =.006 and HR = 0.54, P =.03, respectively). Five-year survival and 180-day TRM were, respectively, 64% and 19% for patients receiving a CD34(+) cell dose of 3 x 10(6)/kg or more and 40% and 37% for the remainders. In conclusion a CD34(+) cell dose of 3 x 10(6)/kg or more improved all hematopoietic recoveries, decreased the incidence of fungal infections and TRM, and improved overall survival.


Assuntos
Antígenos CD34/análise , Transplante de Medula Óssea/métodos , Células-Tronco Hematopoéticas/imunologia , Adolescente , Adulto , Transplante de Medula Óssea/imunologia , Transplante de Medula Óssea/mortalidade , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Hematopoese , Células-Tronco Hematopoéticas/citologia , Humanos , Infecção/etiologia , Infecção/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Transplante Isogênico/imunologia , Transplante Isogênico/métodos , Transplante Isogênico/mortalidade , Resultado do Tratamento
19.
Blood ; 99(4): 1458-64, 2002 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-11830500

RESUMO

Cord blood (CB) is used increasingly as a source of hematopoietic stem cells because of a lower risk of acute and chronic graft-versus-host disease (GVHD). However, there is some concern regarding the ability to adequately reconstitute host immune response due to the immaturity and naivety of CB T cells. This study was designed to evaluate T-cell reconstitution using combined approaches of phenotyping, analysis of alphabeta T-cell receptor (TCR) diversity, and assessment of ex vivo thymic function by measuring TCR rearrangement excision circles (TRECs). Ten patients who underwent CB transplantation for high-risk hematologic disorders were compared to a reference group of 19 age- and GVHD-matched patients who underwent transplantation with non-T cell-depleted bone marrow from an HLA-identical sibling donor. TREC values correlated with the relative number of naive T cells and with TCR repertoire polyclonality. During the first year after transplantation, TCR repertoires were highly abnormal and TREC values low in both groups. Notably, 2 years after transplantation onward TREC values as well as TCR diversity were higher in CB recipients than in recipients of bone marrow transplants. These data indicate an efficient thymic regeneration pathway from CB lymphoid progenitors despite the low number of cells infused compared to bone marrow, arguing for a complete clinical immune recovery after CB transplantation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Sistema Imunitário/citologia , Receptores de Antígenos de Linfócitos T alfa-beta/análise , Linfócitos T/imunologia , Timo/imunologia , Adolescente , Adulto , Transplante de Medula Óssea , Criança , Pré-Escolar , Feminino , Sangue Fetal , Seguimentos , Reação Enxerto-Hospedeiro/imunologia , Doenças Hematológicas/terapia , Humanos , Imunofenotipagem , Leucopoese , Masculino , Pessoa de Meia-Idade , Prognóstico , Linfócitos T/citologia , Timo/citologia , Resultado do Tratamento
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