RESUMO
BACKGROUND: Chronic lymphocytic leukaemia (CLL) is a common haematological malignancy that mainly occurs in the elderly population. Patients frequently have comorbidities compromising the use of old and new systemic therapies. METHODS AND RESULTS: We report the prevalence of comorbidities in patients with CLL as present in the southern region of the Netherlands Cancer Registry. Comorbid conditions were present in 67% of the male and 63% of the female patients, and became more common with increasing age. Furthermore, we describe the beneficial local and abscopal effects of splenic irradiation in four patients with CLL who were not suitable for systemic chemoimmunotherapy because of severe comorbidities, or who were unwilling to undergo systemic therapy. CONCLUSION: Our results show that, although an old tool, splenic irradiation should not be forgotten as a potentially effective palliative treatment option in frail patients with symptomatic CLL.
Assuntos
Idoso Fragilizado , Leucemia Linfocítica Crônica de Células B/radioterapia , Baço/efeitos da radiação , Adulto , Idoso , Feminino , Seguimentos , Humanos , Incidência , Leucemia Linfocítica Crônica de Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do TratamentoRESUMO
Immunosuppressive therapy (IST), consisting of antithymocyte globulin and cyclosporine A, is effective in refractory cytopenia of childhood (RCC), suggesting that, similar to low-grade myelodysplastic syndromes in adult patients, T lymphocytes are involved in suppressing hematopoiesis in a subset of RCC patients. However, the potential role of a T-cell-mediated pathophysiology in RCC remains poorly explored. In a cohort of 92 RCC patients, we prospectively assessed the frequency of T-cell receptor (TCR) ß-chain variable (Vß) domain skewing in bone marrow and peripheral blood by heteroduplex PCR, and analyzed T-cell subsets in peripheral blood by flow cytometry. TCRVß skewing was present in 40% of RCC patients. TCRVß skewing did not correlate with bone marrow cellularity, karyotype, transfusion history, HLA-DR15 or the presence of a PNH clone. In 28 patients treated with IST, TCRVß skewing was not clearly related with treatment response. However, TCRVß skewing did correlate with a disturbed CD4(+)/CD8(+) T-cell ratio, a reduction in naive CD8(+) T cells, an expansion of effector CD8(+) T cells and an increase in activated CD8(+) T cells (defined as HLA-DR(+), CD57(+) or CD56(+)). These data suggest that T lymphocytes contribute to RCC pathogenesis in a proportion of patients, and provide a rationale for treatment with IST in selected patients with RCC.
Assuntos
Síndromes Mielodisplásicas/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Subpopulações de Linfócitos T/química , Linfócitos T Citotóxicos/imunologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Terapia de Imunossupressão , Lactente , Masculino , Síndromes Mielodisplásicas/patologia , Pancitopenia/imunologia , Estudos ProspectivosAssuntos
Citometria de Fluxo , Pancitopenia/diagnóstico , Adolescente , Antígenos CD/metabolismo , Células da Medula Óssea/metabolismo , Criança , Pré-Escolar , Citometria de Fluxo/métodos , Humanos , Imunofenotipagem , Lactente , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/metabolismo , Pancitopenia/metabolismo , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Patients with a microscopically visible deletion of the distal part of the long arm of chromosome 1 have a recognisable phenotype, including mental retardation, microcephaly, growth retardation, a distinct facial appearance and various midline defects including corpus callosum abnormalities, cardiac, gastro-oesophageal and urogenital defects, as well as various central nervous system anomalies. Patients with a submicroscopic, subtelomeric 1qter deletion have a similar phenotype, suggesting that the main phenotype of these patients is caused by haploinsufficiency of genes in this region. OBJECTIVE: To describe the clinical presentation of 13 new patients with a submicroscopic deletion of 1q43q44, of which nine were interstitial, and to report on the molecular characterisation of the deletion size. RESULTS AND CONCLUSIONS: The clinical presentation of these patients has clear similarities with previously reported cases with a terminal 1q deletion. Corpus callosum abnormalities were present in 10 of our patients. The AKT3 gene has been reported as an important candidate gene causing this abnormality. However, through detailed molecular analysis of the deletion sizes in our patient cohort, we were able to delineate the critical region for corpus callosum abnormalities to a 360 kb genomic segment which contains four possible candidate genes, but excluding the AKT3 gene.
Assuntos
Agenesia do Corpo Caloso , Deleção Cromossômica , Cromossomos Humanos Par 1/genética , Adolescente , Adulto , Criança , Pré-Escolar , Família , Feminino , Humanos , Lactente , Masculino , SíndromeRESUMO
1. Bacteroids of Rhizobium leguminosarum (strain PRE) purified from root nodules of Pisum sativum (var. 'Rondo') by the standard procedure of differential centrifugation contained considerable contamination of mitochondrial material. This could be removed by incubation of the bacteroid preparation with 1 M KCl/1% deoxycholate. 2. The DNA content of bacteroid cells of R. leguminosarum was found to have increased about three fold in comparison with the DNA content of free living R. leguminosarum bacteria. 3. No significant difference in DNA composition of free living R. leguminosarum bacteria and bacteroids could be detected by CsCl equilibrium centrifugation, RNA - DNA hybridization and DNA - DNA reassociation studies.