Mixed T cell CHIMERISM in bone marrow at day+30 after allogeneic stem cell transplantation: Correlation with acute GVHD grades III-IV and no impact on relapse and overall survival.

OBJECTIVES: Early chimerism analysis is important to assess engraftment in allogeneic hematopoietic stem cell transplantations. METHODS: We retrospectively investigated the impact of T-cell chimerism at day 30 in bone marrow on acute graft-versus-host disease (aGVHD), relapse, and overall survival in 142 adult allo-transplanted patients. RESULTS: The majority of patients (89%) received myeloablative conditioning and 90% have undergone T-cell replete donor graft. At day 30, 103 patients showed T-complete chimerism with prevalence in haploidentical transplants, whereas 39 cases had CD3+ mixed chimerism, including 30 patients transplanted with HLA identical donors, and 21 with T-cell donors<90%. T-cell chimerism at day 30 was weakly inversely related to aGVHD grades II-IV (p = .078) with no cases of grades III-IV aGVHD in patients with CD3+ <95%. Mixed T-cell chimerism did not impact on relapse (p = .448) and five of the seven patients who relapsed had T-cell chimerism ≤90%. Older age and active disease at transplant had a statistically significant negative effect on overall survival (p = .01 and p = .0001, respectively), whereas mixed CD3+ chimerism did not. CONCLUSIONS: T lymphocyte chimerism analysis at day +30 in bone marrow could identify allo-transplanted patients at major risk of aGVHD grades III-IV (CD3+ donors >95%) mainly post-myeloablative conditioning regimen.

Emilia-Romagna Regional Blood System accreditation as an example of improvement through application of specific requirements: a retrospective analysis.

BACKGROUND: Institutional accreditation in Italy represents the license given by a region to a public or private facility to provide services in the name and on behalf of the National Health Service. This study aims to evaluate the improvement of the Emilia-Romagna Regional Blood System and to highlight its unresolved issues, analysing non-conformities observed during accreditation and maintenance inspections between 2013 and 2018. METHODS: All the Emilia-Romagna Regional Blood facilities were invited to participate in this study voluntarily and anonymously. Participants had to access a web application that we developed specifically. For each of the three inspections evaluated in this study, they had to enter data about the state of their organisation branches and non-conformities observed by regional inspectors. All data entered were finally exported from the web application database and analysed with spreadsheets. Statistical analysis was performed using Wilcoxon signed-rank test with continuity correction. RESULTS: 17 structures took part in the study, with a total of 174 organisation branches. The number of branches changed over the years because of new openings and closures due to reorganisations or non-conformities that were too difficult to correct. Inspectors observed 2381 non-conformities (291 structural, 611 technological and 1479 organisational). As a result of accreditation inspections and consequent improvement actions, non-conformities were reduced by 88%. The most frequent non-conformities concerned the management software and the transportation of blood and blood components. CONCLUSION: An improvement in the Emilia-Romagna Regional Blood System over time is evident: institutional accreditation certainly pushed it to change and overcome its problems to comply with specific requirements. The remaining non-conformities after the three inspections were mostly organisational and management software was the most critical issue. Despite these non-conformities, all currently active structures are accredited and guarantee high standards of quality and safety of products and services.

Retinoic acid inhibits the growth of bone marrow mesenchymal stem cells and induces p27Kip1 and p16INK4A up-regulation.

The importance of bone marrow mesenchymal stem cells in hemopoiesis has been definitely demonstrated. Thus, their impairment might cause profound alteration on production and maturation of blood cells. In the present paper, we investigated, for the first time, the effect of retinoic acid, an important antileukemic molecule, on the proliferation of primary cultures of human bone marrow mesenchymal stem cells. We demonstrated that retinoic acid, at a pharmacological concentration, hampers strongly the growth of the cells, without inducing osteoblastic differentiation. The analysis of cell division cycle machinery showed that the antiproliferative effect is associated with (i) the up-regulation of two cyclin-dependent kinase inhibitors, namely p27Kip1 and p16INK4A, and (ii) the down-regulation of cyclin-dependent kinase 2 activity and pRB phosphorylation. The reported findings represent novel insights into the antileukemic effects of the drug and contribute in clarifying the molecular mechanism of its pharmacological activity.