RESUMO
The human leukocyte antigen (HLA) distribution in donor registry data is typically nonrandom as, mostly for economical reasons, typing additional loci or resolving ambiguities is selectively performed based on the previously known HLA type. Analyzing a sample of over 1 million German stem cell donors, we practically show the extent of the bias caused by the restriction of the input data for HLA haplotype frequency (HF) estimation to subsets selected according to their higher HLA typing resolution and, conversely, the correctness of estimates based on unselected data with a methodology suitable for heterogeneous resolution. We discuss algorithmic aspects of this approach and, also because of the sample size, provide some new insights into the distribution of HLA-DRB1 alleles in the German population and the application of HFs in unrelated donor search.
Assuntos
Antígenos HLA/genética , Transplante de Células-Tronco Hematopoéticas , Doadores de Tecidos , Algoritmos , Alelos , Feminino , Frequência do Gene , Genes MHC Classe I , Genes MHC da Classe II , Alemanha , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Haplótipos , Humanos , Masculino , Sistema de Registros/estatística & dados numéricosRESUMO
We analyzed regional differences in human leukocyte antigen (HLA)-A, -B, and -DR antigen and haplotype frequencies based on a sample of approximately 320,000 German donors in order to identify regions that are especially suited for ongoing stem cell donor recruitment. Geographic partitioning was carried out by postal code regions. Analysis of genetic distances suggests the existence of three regional clusters in South (regions 6-9), East (0-1), and Northwest (2-5) Germany. The southern cluster shows most favorable characteristics with respect to haplotypic and phenotypic diversity and the occurrence of rare HLA antigens. The opposite behavior is shown by regions 2-4 of the northwestern cluster. As a result of lower HLA diversity, completeness of a regional donor file in region 4 with 100,000 donors would be higher than that of a file in region 7 with 170,000 donors. This fact shows the relevance of regional HLA differences for practical donor registry planning. Results such as those presented in this work can be used to diminish the problem of decreasing marginal benefit of donor recruitment, as more than 13 million donors are registered worldwide today.
Assuntos
Antígenos HLA/genética , Transplante de Células-Tronco Hematopoéticas , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Alelos , Feminino , Frequência do Gene , Genes MHC Classe I , Genes MHC da Classe II , Alemanha , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Haplótipos , Heterozigoto , Humanos , Masculino , Sistema de Registros/estatística & dados numéricosRESUMO
Minority donor programs aim to improve access to unrelated hematopoietic SCT for specific ethnic groups through directed donor recruitment. We have developed criteria for initiation and evaluation of such programs and applied them to the situation of donors of Turkish descent in Germany, as well as a program by DKMS German Bone Marrow Center that targets this group. Criteria for program initiation include the number of accessible minority donors, potential impact on the chances of finding matching donors, and general access to unrelated transplantation for patients of the targeted group. Success criteria comprise number and availability of recruited donors, the effect of these donors on the HLA phenotype distribution of a donor file, and the number of donations resulting from the program. More than 40 000 donors of Turkish descent have been recruited within the analyzed program to date. Recruited minority donors show more favorable demographic characteristics but lower availability rates than do German donors. Although HLA haplotype distributions of Turkish and German donors differ considerably, patients with common Turkish HLA phenotypes should benefit from the German donor pool even without a specific minority program. The analysis of donations from minority donors, however, shows specific benefits for patients with rare HLA phenotypes.
Assuntos
Transplante de Células-Tronco Hematopoéticas/etnologia , Doadores Vivos , Saúde das Minorias , Obtenção de Tecidos e Órgãos/normas , Feminino , Alemanha , Haplótipos/genética , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Teste de Histocompatibilidade/estatística & dados numéricos , Humanos , Internacionalidade , Doadores Vivos/provisão & distribuição , Masculino , Turquia/etnologiaRESUMO
With more than 11 million registered stem cell donors worldwide and limited resources for health systems, it seems questionable if investments in ongoing donor recruitment are useful. Since there is evidence that transplant outcomes are better with younger donors, the age distribution of registered donors is highly relevant in this context. One might argue that the usefulness of a donor file decreases if there is no new donor recruitment not only as a result of loss of donors who reach the age limit for donation but also since those donors who remain in the file get older. We established a multivariate model to quantify this effect and to estimate the number (designated R) of donors who must be recruited annually to keep donor file usefulness constant. The model is applied to real data from DKMS German Bone Marrow Donor Center. R exceeds the number of donors who reach the age limit by factors up to 7.3. The model can serve as an easy-to-use tool for strategic donor registry planning. Our results suggest that analyses regarding optimal size of donor registries should also include the age distribution of registered donors.
Assuntos
Células-Tronco Hematopoéticas , Sistema de Registros , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos , Adolescente , Adulto , Fatores Etários , Definição da Elegibilidade , Alemanha , Transplante de Células-Tronco Hematopoéticas , Humanos , Pessoa de Meia-IdadeRESUMO
Many patients in need of a hematopoietic stem cell transplant do not find a fully matching donor although more than 11,000,000 potential donors are registered worldwide. Therefore, it is relevant to recruit donors who add diversity to the donor pool. We present the 'Roots' approach that includes the selection of already registered donors with rare HLA phenotypes and the recruitment of relatives of these donors. Two projects (Roots A and B) with different donor selection criteria were carried out. HLA phenotype frequency distributions of new donors differ significantly from the respective control groups: 2.7% of Roots A donors versus 1.1% of the control group have an HLA-AB phenotype that is unique in the DKMS file (P=0.001). Additionally, 39.5% of Roots B donors but only 18.3% of the control group have a unique HLA-ABDR phenotype (P<0.001). Similar results are found when phenotypes that are at most available 10 times in the DKMS donor file are analyzed. The results show that the Roots approach is generally suited to increasing the ratio of donors with rare HLA phenotypes in a donor file. Additional costs of Roots donor recruitment seem justified through the ratio of recruited donors with rare HLA phenotypes.
Assuntos
Antígenos HLA/imunologia , Células-Tronco Hematopoéticas/imunologia , Histocompatibilidade , Doadores de Tecidos/provisão & distribuição , Adulto , Família , Feminino , Antígenos HLA-A , Antígenos HLA-B , Antígenos HLA-DR , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Development of information systems to support research on environmental correlates of physical activity and nutrition has to date been largely ad hoc and driven by single research project requirements. In this rapidly growing field, research databases are becoming increasingly complex as researchers attempt to model the impact of multiple aspects of the environment such as neighborhood characteristics, site and building design, and nutritional environments on both aggregate and individual level measures of physical activity and weight. The presentation reports on the initial implementation of a logical data model in the context of an ongoing research program that is exploring the relation of neighborhood physical and demographic characteristics on physical activity levels measured in time and space.
Assuntos
Bases de Dados como Assunto , Atividade Motora , Obesidade , Pesquisa Biomédica/métodos , Meio Ambiente , Humanos , Modelos Teóricos , Saúde PúblicaRESUMO
A total of 50 unrelated marrow donors were examined by pelvic magnetic resonance imaging (MRI) to investigate the morphological sequelae of bone marrow harvesting (BMH). Signal increase in T2-weighted sequences and contrast media enhancement in T1 sequences at the operative sites were found as typical MRI morphology 4 weeks after harvest (group A, n=16), corresponding to edema, hyperemia and proliferative activity. Although tissue repair was completed in the majority of donors 1 year after BMH, about 36% of donors in group B (n=16) had abnormal findings. These included a persistence of the 'acute injury' signal pattern (2/16, 12%), and signal alterations due to fatty marrow conversion (4/16, 24%). The proportion of MRI abnormalities increased to over 70% in two-time donors (group C, n=11), which might indicate a cumulation of tissue damage after repetitive harvests. If donors had experienced prolonged discomfort after BMH (group D, n=7), MRI revealed pathological signals in 86%. In conclusion, the MRI morphology reflects the pathophysiological reactions after BMH, including inflammation and tissue repair. A further prospective evaluation in a larger number of donors is necessary to confirm these results and to identify the factors which influence the extent and duration of tissue damage.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Medula Óssea/patologia , Imageamento por Ressonância Magnética/métodos , Pelve , Doadores de Tecidos , Adulto , Medula Óssea/lesões , Feminino , Humanos , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Estudos Retrospectivos , CicatrizaçãoRESUMO
BACKGROUND: Recombinant human G-CSF is widely used to mobilize PBPCs in healthy donors for allogeneic transplantation. There have been concerns about donor safety because of splenic ruptures during G-CSF application. To address this problem, changes in splenic size in 91 healthy donors during G-CSF mobilization of allogeneic PBPCs were investigated. STUDY DESIGN AND METHODS: For mobilization, G-CSF in a dosage of 7.5 microg per kg per day was administered for 5 days and PBPC collection started Day 5. Splenic size was determined by ultrasound before G-CSF application was started and on the day of the first apheresis. RESULTS: The mean increase in splenic length was 11 mm (range, 0-28 mm; p<0.0001), whereas a mean increase of 5 mm in width (range, 0-14 mm; p<0.0001) was measured. No major side effects could be observed. There was no significant correlation between the increase in splenic size and the hematologic values, or the age and body-mass index. In a multivariant analysis, no independent risk factor for the development of a spleen enlargement over 19 mm in length and 9 mm in thickness was found in 20 percent of investigated donors. CONCLUSION: In this prospective trial, a significant spleen enlargement was observed in healthy donors during G-CSF mobilization of allogeneic PBPCs. Further investigations are needed to define the degree of spleen enlargement with higher G-CSF dosages to improve donor safety.
Assuntos
Doadores de Sangue , Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/metabolismo , Esplenomegalia/sangue , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Estudos Prospectivos , Baço/efeitos dos fármacosRESUMO
BACKGROUND AND OBJECTIVES: Allogeneic peripheral blood stem cell transplantation (PBSCT) from matched siblings has lead to clinical results comparable to those of standard bone marrow transplantation (BMT). We report the outcome of 79 patients transplanted with PBSC from unrelated donors. DESIGN AND METHODS: In 61 cases PBSC were used for primary transplantation whereas 18 patients were treated for relapse or graft-failure. In 35 patients receiving primary transplants, T-cell depletion (TCD) using CD34 positive selection of PBSC with or without additional T-cell depletion had been performed to reduce the risk of graft-versus-host-disease (GvHD). RESULTS: The rate of primary graft-failure was higher (20%) in the TCD group than in that receiving unmanipulated grafts (UM) (5%, p=0.007). Patients with standard risk (n=34) receiving first transplants had a significantly better overall (60.4% vs. 24%, p=0.02) and disease-free survival (57.2% vs. 22.3%, p=0.006) compared to a high risk group of patients (n=21). There were no differences in the speed of neutrophil and platelet engraftment between TCD and UM transplants. As expected, the cumulative risk for acute GvHD grade II.-IV was significantly higher in the patients who had received UM grafts (71.8% vs. 38.1%, p=0.005). Although a trend towards a better survival rate was observed after TCD transplantation (52.2%) compared to the UM group (38.1%), this difference was not statistically significant. The probability of relapse was significantly higher in patients after UM transplants (38.8% vs. 8. 4%). This apparent paradox is explained by the higher number of high-risk patients in this group (p=0.03). Multivariable analysis of disease-free survival revealed risk category (p=0.02) and use of ATG (p=0.03) to be of significant impact. All patients (n=6) with non-malignant diseases are alive with full donor chimerism. INTERPRETATION AND CONCLUSIONS: These data show that PBSC from unrelated donors can be transplanted either unmanipulated or CD34 selected. Prospective studies comparing BMT with PBSCT from unrelated donors are needed in defined disease categories.
Assuntos
Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas/métodos , Doadores de Tecidos , Transplante Homólogo/métodos , Adolescente , Adulto , Causas de Morte , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Doenças Genéticas Inatas/mortalidade , Doenças Genéticas Inatas/terapia , Alemanha/epidemiologia , Rejeição de Enxerto , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doenças Hematológicas/mortalidade , Doenças Hematológicas/terapia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Terapia de Imunossupressão/métodos , Lactente , Infecções/etiologia , Infecções/mortalidade , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Risco , Condicionamento Pré-Transplante , Transplante Homólogo/estatística & dados numéricos , Resultado do TratamentoRESUMO
The German bone marrow donor center (DKMS) hasrecruited over 732 500 donors during the first 9 years of its existence. Initially, donors were typed for HLA-A and B, and DR typing was only done on request for a patient-initiated search. In 1994, a project was started which led to the donor center-initiated DR typing (DCI-DRT) of >35,000 donors. These donors were selected by donor-specific criteria (age, sex, height and weight) and according to HLA-A and B phenotypes. The latter was done to avoid unnecessary DR typing of the most common A, B phenotypes With a follow up of >6 years, this strategy has led to a number of confirmatory typings (CT) (n=4588) and stem cell harvests (n=568), which is at least comparable to those ensuing after patient-initiated HLA-DR typing (126 000 DR typings, 8,213 CTs, 888 resulting in stem-cell donation). DCI-DRT seems to be a cost-effective strategy which may help to reduce search times and improve search outcome, and improve the overall efficiency of donor center operations
Assuntos
Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade/estatística & dados numéricos , Sistema de Registros , Doadores de Tecidos , Adolescente , Adulto , Algoritmos , Biologia Computacional , Feminino , Alemanha , Antígenos HLA-DR/genética , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Imunogenética , Masculino , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Doadores de Tecidos/estatística & dados numéricosRESUMO
Depressed inpatients (29 primary and 31 secondary) were blindly rated at several time points on 137 depressive symptoms. Of the 7 high-frequency symptoms or symptom clusters analyzed, significantly greater symptom persistence was seen for secondary depressives on low mood, pessimism, change in usual interests, and suicidal ideation. Day-to-day variability in symptoms did not differ between groups. Scalability of symptoms (Guttman scales) was acceptable for primary but not secondary depressives. Suicidal ideation tended to be the first symptom to remit in primary depression but persisted in the secondary group, even after remission of the most severe symptom. Implications for treatment are discussed.
Assuntos
Transtorno Depressivo/diagnóstico , Transtorno Depressivo/etiologia , Transtorno Depressivo/psicologia , Hospitalização , Humanos , Estudos Longitudinais , Transtornos Mentais/complicações , Escalas de Graduação Psiquiátrica , Suicídio/psicologiaRESUMO
Over a three-year period, we have seen in consultation four children whose mothers cited complaints referable to every organ system and which had persisted for many years. The parents had consulted a total of 99 physicians in eight states. Absence from school ranged from 40 to 200 days a year. Physical examinations of all patients and extensive and repeated laboratory studies were normal. On psychiatric examination the mothers exhibited paranoid thinking and a conviction of serious medical illness in their child which approached delusional proportions. They resisted psychiatric consultation and refused psychotherapy. The mother-child relationship was remarkably symbiotic, the two teen-age patients essentially voicing complaints which were indistinguishable from those reported by their mothers. The fathers invariably supported their wives' concerns. Subsequently, parents and children left treatment, continuing to "doctor shop." Long-standing multisystem complaints in a child with normal growth and maturation are incompatible with any known significant organic disease, but suggest a serious emotional problem within the family. Further, parents who take such children from doctor to doctor are frequently disturbed themselves and may use an offspring as a proxy patient. An accurate diagnosis depends on careful history-taking from parents, patient, health professionals, and schools.