RESUMO
No disponible
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Venenos de Artrópodes/uso terapêutico , Linfo-Histiocitose Hemofagocítica/imunologia , Imunoterapia/métodos , Citocinas/análise , Insuficiência de Múltiplos Órgãos/complicaçõesRESUMO
The nephrotic syndrome is a rare complication of allogeneic stem cell transplantation (alloHSCT). We present two cases of nephrotic syndrome during chronic graft-versus-host disease (GvHD) involving altered cytokine gene expression in renal tissue. A patient with acute lymphatic leukemia demonstrated nephrotic syndrome due to minimal change disease as a marker of chronic GvHD. A patient with acute lymphoblastic leukemia suffered from severe nephrotic syndrome due to membranous glomerulopathy. In the two presented cases of GvHD-linked nephrotic syndrome, increased cytokine gene expression [tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), interferon gamma (IFN-gamma), interleukin 2 (IL-2), IL-6, and IL-10] assessed using semiquantitative evaluation with reverse transcriptase polymerase chain reaction (RT-PCR) in situ on renal biopsy was observed.
Assuntos
Citocinas/genética , Doença Enxerto-Hospedeiro/complicações , Nefrose Lipoide/etiologia , Síndrome Nefrótica/etiologia , Adulto , Citocinas/metabolismo , Diagnóstico Diferencial , Expressão Gênica , Doença Enxerto-Hospedeiro/genética , Humanos , Masculino , Nefrose Lipoide/diagnóstico , Nefrose Lipoide/genética , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
In the present study, two coding polymorphisms within the heat shock protein 70-hom gene (HSP70-hom) were analysed. One hundred and thirty-eight individuals were studied, including 42 Polish patients with sarcoidosis, 13 of which presented with Löfgren's syndrome (LS), and 94 control subjects. Dimorphisms at positions +2763 (A/G) and +2437 (C/T) of the HSP70-hom gene were typed using amplification refractory mutation system and polymerase chain reaction-restriction fragment length polymorphism technique, respectively. A significant prevalence of the HSP(+2437)-C allele and the HSP(+2437)-CC homozygous genotype was observed in patients with sarcoidosis and in those presenting with LS as compared to controls (P < 0.001 in all comparisons made). A majority of HLA-DRB1*03-positive patients with LS were carrying both HSP(+2437)-C and (+2763)-G alleles, and the concomitant presence of these three genetic factors was more frequent among patients with LS as compared to patients without LS (0.54 vs. 0.17, P < 0.05) and controls (0.54 vs. 0.01, P < 0.001). The association of the HSP(+2437)-C allele with sarcoidosis and LS appeared to be independent of the presence of DRB1*03, although this HLA specificity was associated with LS manifestation. The HSP(+2763)-G allele was independently associated with neither sarcoidosis nor LS. However, this HSP(+2763)-G allele was present with either DRB1*03 or HSP(+2437)-C within the same haplotypes in the patients and this might explain the observed prevalence of DRB1*03, HSP(+2437)-C and (+2763)-G in patients with LS. In conclusion, HSP(+2437)-C allele was found as a factor associating with susceptibility to sarcoidosis and LS.
Assuntos
Proteínas de Choque Térmico HSP70/genética , Homozigoto , Polimorfismo de Nucleotídeo Único , Sarcoidose/genética , Doença Aguda , Adulto , Feminino , Predisposição Genética para Doença , Genótipo , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Família Multigênica , Fenótipo , Sarcoidose/imunologia , Índice de Gravidade de Doença , SíndromeRESUMO
The present study sought to retrospectively assess risk factors for occurence of and mortality from severe acute graft-versus-host-disease (aGvHD) among 66 patients receiving hematopoietic stem cell transplants (HSCT) from matched sibling donors (MSD). Thirty-six patients were in early and 30 in intermediate or advanced stages of the disease. Twenty-six patients developed severe aGvHD grades II-IV. Thirty-five patients died after transplantation (15 due to aGvHD). There were 20 major ABO-mismatched transplants and 26 cases wherein donor and recipient differed with respect to sex (11: F-->M; 15: M-->F). These transplant characteristics as well as HLA class II specificities were chosen for discriminative analysis. HLA specificities were assessed in an independent analyses for as patients lacking (DR11) or having DR13 associated with aGvHD. It appeared that donor age increased the risk of aGvHD, but a fatal outcome of this complication was influenced by recipient age. Female to male transplantations were associated with a higher risk of aGvHD. Major ABO incompatibility tended to increase the risk of aGvHD and fatal outcomes. DR11 was associated with factors playing a protective role, while DR13 was the least of all significant factors influencing the development of severe and fatal aGvHD.
Assuntos
Doença Enxerto-Hospedeiro/epidemiologia , Antígenos HLA-DR/sangue , Transplante de Células-Tronco/efeitos adversos , Transplante Homólogo/imunologia , Sistema ABO de Grupos Sanguíneos , Doença Aguda , Fatores Etários , Incompatibilidade de Grupos Sanguíneos , Análise Discriminante , Feminino , Subtipos Sorológicos de HLA-DR , Humanos , Masculino , Valores de Referência , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo/efeitos adversosRESUMO
We analysed the treatment outcome of primary refractory HD patients managed with high-dose chemotherapy and haematopoietic cell transplantation. Data of 65 adult patients who underwent HDC/ASCT in nine Polish centres for primary resistant Hodgkin's disease between June 1991 and July 2000 were collected retrospectively. Response rate to HDC/ASC: CR, 54%; PR, 20%; less than PR, 15%; early deaths, 11%. Actuarial 3-year OS and PFS were 55% and 36%, respectively. In multivariate analysis, lack of bulky lymph nodes and use of immunotherapy were favourable factors for both OS and PFS. IPF <3 at the time of transplantation was predictive for PFS. However, the prognostic impact of immunotherapy should be interpreted with caution since this group included more patients who achieved CR after HDC/ASCT. The results of HDC/ASCT are encouraging and confirm earlier findings. The role of immunotherapy should be further investigated in prospective trials.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/mortalidade , Doença de Hodgkin/terapia , Adolescente , Adulto , Análise de Variância , Criança , Feminino , Doença de Hodgkin/mortalidade , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Terapia de Salvação , Análise de Sobrevida , Taxa de Sobrevida , Transplante Autólogo/mortalidade , Resultado do TratamentoRESUMO
Determination of DRB1 and DRB3 specificities in sarcoidosis patients identified that the presence of DRB1*03 and the absence of DRB1*11 and/or DRB1*12 favors a course of disease that is associated positively with Löfgren's syndrome (DRB1*03) and negatively with stage I disease (DRB1*11 and/or 12). In common with normal controls, DRB1*03 was associated with DRB3*0101 and DRB1*11/12 with DRB3*0201/2. An analysis of DRB1 and DRB3 associations in variants of sarcoidosis revealed that DRB1*03 and DRB3*0101 were associated with Löfgren's syndrome in a combined association fashion. Conversely, a lack of DRB1*11 and/or DRB1*12 but not DRB3*0201/2 favored the clinical course of sarcoidosis.
Assuntos
Alelos , Antígenos HLA-DR/genética , Sarcoidose/genética , Adolescente , Adulto , Feminino , Predisposição Genética para Doença/genética , Variação Genética/genética , Cadeias HLA-DRB1 , Cadeias HLA-DRB3 , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Twenty-five G-CSF-mobilized leukapheresis products (mLP) were screened for cellular composition, including CD34+DR-, CD34+DR+ and leukocyte profile, to compare with 5 native (unstimulated) LP (nLP) and 16 BM inoculi. G-CSF stimulation led to an increase in CD34+ cells and CD15+ cells but did not influence the lymphocyte content of mLP. Two groups of 14 and 16 patients were allografted with phenotypically defined mLP (1-4 mLP were used for each patient) and BM, respectively. mLP used for allografting had significantly more CD34+ cells, including CD34+DR- cells, monocytes, T cells, and B cells as compared with BM inoculi. Patients were followed for median observation time of 289 days and 409 days for the mLP (PBPC) and BM groups, respectively. The two groups were well matched in regard to age, sex, and stage of disease, with a slight prevalence of major blood group incompatibility (7 of 14 versus 3 of 16) and a lower donor/recipient weight ratio (0.8+/-0.2 vs 1.5+/-0.6, p = 0.002) in the PBPC group. Granulocyte and platelet recovery was faster in the PBPC group than in the BM group. The time of reaching 20,000/microl platelets but not 500/microl granulocytes correlated with the number of CD34+ cells in each inoculum. The survival curves of the PBPC and BM groups were similar, as was the incidence of acute GvHD (aGvHD). This was also valid for aplastic anemia cases (7 and 5 patients in the PBPC and BM group, respectively), who benefited from a high number of CD34+ grafted cells but did not experience aGvHD. Thus, mLP do not appear to elicit aGvHD with higher frequency than BM and may be preferable for hematotherapy.
Assuntos
Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Antígenos CD34 , Contagem de Células Sanguíneas , Criança , Feminino , Mobilização de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/patologia , Humanos , Leucaférese , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/farmacologia , Transplante HomólogoAssuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia/terapia , Adulto , Criança , Quimera , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Repetições de Microssatélites , Polônia , Recidiva , Condicionamento Pré-Transplante , Resultado do TratamentoRESUMO
Biallelic polymorphisms in the promoter region of the TNF-alpha gene (TNFA) and in the first intron of the TNF-beta gene (TNFB) have been associated with variation in TNF-alpha production and with susceptibility to severe diseases. Among other functions, TNF-alpha plays a pivotal role in regulatory aspects of granuloma formation and sustenance. In sarcoidosis, a systemic granulomatous disorder of unknown aetiology, the clinical course of the disease has been associated with the patient's individual capacity of spontaneous TNF-alpha production by alveolar macrophages. We determined the TNFA and TNFB polymorphisms in 101 patients with pulmonary sarcoidosis and 216 healthy blood donors. A highly significant shift to the more uncommon TNFA2 allele was found in the Löfgren syndrome patient group, which represents the acute form of the disease with frequent spontaneous remission. The results show that gene frequencies of the TNFA gene variation are significantly different within the clinical forms of sarcoidosis, indicating that genetic predisposition for TNF-alpha production may play a role in the pathogenesis of the disease.
Assuntos
Polimorfismo Genético , Regiões Promotoras Genéticas , Sarcoidose Pulmonar/genética , Fator de Necrose Tumoral alfa/genética , Humanos , Linfotoxina-alfa/genéticaAssuntos
Transplante de Medula Óssea , Proteína C-Reativa/biossíntese , Doença Enxerto-Hospedeiro/diagnóstico , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Interferon gama/biossíntese , Adolescente , Adulto , Biomarcadores/sangue , Proteína C-Reativa/análise , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/imunologia , Neoplasias Hematológicas/imunologia , Humanos , Interferon gama/sangue , Masculino , Pessoa de Meia-Idade , Núcleo Familiar , Reação em Cadeia da Polimerase , Pele/imunologia , Doadores de Tecidos , Transcrição Gênica , Transplante HomólogoRESUMO
The results of allogenic bone marrow transplantation (allo-BMT) in 26 children with ALL treated with the same initial- and relapse-BFM-protocols, but transplanted in different centers (Poznan, Wroclaw, Hannover) after conditioning with two different regimens have been compared. Ten children (6 in Poznan, 4 in Wroclaw) were conditioned for BMT with busulfan and cyclophosphamide when fractionated TBI (FTBI) was not available there. Sixteen children obtained FTBI and etoposide (11 in Hannover, where in children with ALL exclusively chemoradioconditioning regimen has been employed, and 5 in Poznan). It has been found, that the chemoconditioning procedure was probably less effective (5-year EFS 18%) than the regimen with FTBI (7-year EFS 60%). Therefore, TBI seems to be at this point still mandatory in pediatric ALL patients, unless combinations of chemotherapeutic drugs might be able to substitute the radiation in the future.
Assuntos
Transplante de Medula Óssea/métodos , Bussulfano/administração & dosagem , Imunossupressores/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Irradiação Corporal Total , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Ciclofosfamida/administração & dosagem , Etoposídeo/administração & dosagem , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Terapia de Imunossupressão/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Recidiva , Taxa de SobrevidaRESUMO
Analysis of skin biopsy specimens for the presence of adhesion molecules, composition of cellular infiltrates, Ki-67 antigen expression, and examination of serum for interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) levels, wes performed in patients after allogeneic bone marrow transplantation (alloBMT), to study the pathomechanism of acute graft-versus-host disease (aGvHD). It was found that: 1) early hematological recovery constitutes a risk factor for grade IV GvHD, 2) vascular cell adhesion molecule-1 (VCAM-1) is present in the matrix organizing the cells in the bone marrow and in aGvHD infiltrates, 3) HLA DR antigens aberrant expression in epithelial cells, as well as 4) strong expression of Ki-67 is seen in early stages of aGvHD. These immunopathomorfological lesions are cytokine-dependent. High levels of IL-6 and TNF-alpha were found in sera of patients affected with the aGvHD process and infectious complications. An increase of IL-6 in the course of aGvHD is a sign of poor prognosis. These data support the notion that cytokines facilitate the cell accumulation at the site of aGvHD at the beginning of this process and again, at the final stage of the disease, cytokines high levels are associated with the organ damage.