PCR-positivity in harvested bone marrow predicts relapse after transplantation with autologous purged bone marrow in children in second remission of precursor B-cell acute leukaemia

Purging of autologous bone marrow (BM) grafts of children in second remission after a relapse of precursor B acute lymphoblastic leukaemia (ALL) in the BM has been carried out in our laboratory since 1987, initially by complement mediated cell lysis. This protocol was extended by performing an immunorosette depletion before lysis with complement. The aim of the present study was to assess by polymerase chain reaction the presence of residual leukaemic cells in the BM grafts before and after purging. The results were then correlated to clinical outcome. In 24/28 patients a PCR product was obtained by amplification of IgH and/or TcR junctional regions. BM before purging was available for analysis in 13 patients. We found that leukaemic cells could be detected in 8/13 (62%) of these grafts before purging . All these eight patients experienced a relapse, regardless of whether the purging procedure had been successful (defined as achievement of PCR-negativity) or not. In contrast, none of the five patients with PCR-negative grafts before purging relapsed ( P  = 0.0008). One patient died due to transplant-related toxicity. Of the remaining 23 patients, nine patients received a PCR-positive BM graft after purging. All these nine patients experienced a relapse as compared to 6/14 whose BM was PCR-negative after purging ( P  = 0.0072). Two of eight PCR-positive BM grafts could be purged to PCR-negativity. Thus, improvements both in treatment of leukaemia and in purging efficacy are still needed.     

Role for CCG-trinucleotide repeats in the pathogenesis of chronic lymphocytic leukemia

Chromosome 11q deletions are frequently observed in chronic lymphocytic leukemia (CLL) in association with progressive disease and a poor prognosis. A minimal region of deletion has been assigned to 11q22-q23. Trinucleotide repeats have been associated with anticipation in disease, and evidence of anticipation has been observed in various malignancies including CLL. Loss of heterozygosity at 11q22-23 is common in a wide range of cancers, suggesting this is an unstable area prone to chromosome breakage. The location of 8 CCG-trinucleotide repeats on 11q was determined by Southern blot analysis of a 40-Mb YAC and PAC contig spanning 11q22-qter. Deletion breakpoints in CLL are found to co-localize at specific sites on 11q where CCG repeats are located. In addition, a CCG repeat has been identified within the minimal region of deletion. Specific alleles of this repeat are associated with worse prognosis. Folate-sensitive fragile sites are regions of late replication and are characterized by CCG repeats. The mechanism for chromosome deletion at 11q could be explained by a delay in replication. Described here is an association between CCG repeats and chromosome loss suggesting that in vivo "fragile sites" exist on 11q and that the instability of CCG repeats may play an important role in the pathogenesis of CLL.     

Cancellous bone changes in the radius of patients with rheumatoid arthritis: a cross-sectional quantitative macroradiographic study

OBJECTIVE: Fractal signature analysis (FSA), a computerized method of textural analysis, permits the separate measurement of changes in vertical and horizontal trabeculae based on the fractal dimension over a range of trabecular widths (fractal signature). We determined whether the FSA of high-definition macroradiographs (x5 magnification) quantified radiographic changes at sites of osteopenia and erosion formation in the rheumatoid arthritis (RA) hand. METHODS: Sixty-seven RA patients had macroradiographs of the left wrist and hand. The distal radius was scored and grouped from very mild (RA1) to moderate (RA4) disease. Macroradiographs were digitized and FSA of horizontal and vertical trabecular organization was performed in the radius at sites of periarticular osteopenia, erosion formation and at a mid-metaphyseal site. The RA groups were compared with 11 healthy non-arthritic subjects using ANOVA and Dunnett's tests. RESULTS: Compared to the non-arthritic hands, FSA at the distal radius in groups RA1 to RA4 measured significantly lower (P<0.05) fractal signatures. The fractal signatures were lowest in RA4 involving small, medium to large sized vertical trabeculae at the periarticular osteopenic (0.18 to 0.84 mm, P<0.01) and mid-metaphyseal sites (0.12 to 0.60 and 0.84 to 1.02 mm, P 相似文献   

In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation

A novel nonmyeloablative conditioning regimen was investigated in 44 patients with hematologic malignancies. The median patient age was 41 years. Many of the patients had high-risk features, including 19 patients with a previous failed transplant. Recipient conditioning consisted of CAMPATH-1H, 20 mg/day on days -8 to -4; fludarabine, 30 mg/m(2) on days -7 to -3; and melphalan, 140 mg/m(2) on day -2. Thirty-six recipients received unmanipulated granculocyte colony-stimulating factor-mobilized peripheral blood stem cells from HLA-identical siblings, and 8 received unmanipulated marrow from matched unrelated donors. GVHD prophylaxis was with cyclosporine A alone for 38 patients and cyclosporine A plus methotrexate for 6 sibling recipients. Forty-two of the 43 evaluable patients had sustained engraftment. Results of chimerism analysis using microsatellite polymerase chain reaction indicate that 18 of 31 patients studied were full-donor chimeras while the other patients were mixed chimeras in one or more lineages. At a median follow-up of 9 months (range 3 to 29 months), 33 patients remain alive in complete remission or with no evidence of disease progression. Seven patients relapsed or progressed post-transplantation, and 4 of them subsequently died. Four patients died of regimen-related complications. There were no cases of grades III-IV acute GVHD. Only 2 patients developed grade II acute GVHD, and only 1 had chronic GVHD. The estimated probability of nonrelapse mortality was 11%. Although longer follow-up is needed to establish the long-term remission rates, this study demonstrates that this nonmyeloablative preparative regimen is associated with durable engraftment, minimal toxicity, and low incidence of GVHD.     

Evolving beyond antiracism: Reflections on the experience of developing a cultural safety curriculum in a tertiary education setting

There is an inextricable link between cultural and clinical safety. In Australia high-profile Aboriginal deaths in custody, publicised institutional racism in health services and the international Black Lives Matter movement have cemented momentum to ensure culturally safe care. However, racism within health professionals and health professional students remains a barrier to increasing the number of Aboriginal and Torres Strait Islander Health professionals. The Australian Health Practitioner Regulation Agency's Aboriginal and Torres Strait Islander Health Strategy's objective to ‘eliminate racism from the health system’, and the recent adoption of the Aboriginal and Torres Strait Islander peoples led cultural safety definition, has instigated systems level reflections on decolonising practice. This article explores cultural safety as the conceptual antithesis to racism, examining its origins, and contemporary evolution led by Aboriginal and Torres Strait Islander peoples in Australia, including its development in curriculum innovation. The application of cultural safety is explored using in-depth reflection, and the crucial development of integrating critical consciousness theory, as a precursor to culturally safe practice, is discussed. Novel approaches to university curriculum development are needed to facilitate culturally safe and decolonised learning and working environments, including the key considerations of non-Indigenous allyship and collaborative curriculum innovations and initiatives.     

Specialized Inpatient Psychiatry for Serious Behavioral Disturbance in Autism and Intellectual Disability

Psychiatric hospitalization of children with autism spectrum disorder and/or intellectual disability is common, however, the effectiveness of this intervention is largely unknown. Thirty-eight clinically-referred children 8–19 years old admitted to a specialized inpatient psychiatry unit were assessed by a consistent caregiver on the Aberrant Behavior Checklist-Irritability (ABC-I) subscale at admission, discharge and 2 months post discharge. There was a decrease in the mean ABC-I score from admission (27.3, SD 7.4) to discharge (11.9, SD 8.8), which was sustained at 2 months post discharge (14.8, SD 9.3) (p < 0.001). Seventy-eight percent of the subjects were rated as “Improved” on the clinician Clinical Global Impressions Improvement scale at discharge. The study is limited by lack of a control group, but offers preliminary evidence for specialized inpatient psychiatry as an intervention for serious behavioral disturbance in this population.     

Ethnicity,self-care,and use of medical care among the elderly with joint symptoms

Elderly individuals with self-reported joint symp-toms representing three ethnic groups (i.e., blacks [n = 105], Hispanics[n = 100], and whites of Eastern European origin [n = 112] answered questions about their use of self-care and medical care for these symptoms. Ethnic groups differed in both self-care practices and their use of medical care for joint symptoms. Multiple regression analyses demonstrated that arthritis-specific and general health status were better predictors than ethnicity of the tendency to rely on self-care and medical care. There was no evidence that self-care served as a substitute for medical care.