Ten years after the first inspection of a candidate European centre, an EBMT registry analysis suggests that clinical is improved when hematopoietic SCT is performed in a Jacie accredited program

In 2010, JACIE, the Joint Accreditation Committee of ISCT (International Society for Cell Therapy) Europe and EBMT (European group for Blood and Marrow Transplantation) celebrated the tenth anniversary of the first inspection of a European hematopoietic SCT program. JACIE standards establish the criteria for a comprehensive quality management program that covers all three major domains of activity that are necessary for the delivery of HSCT: clinical, collection and processing, as well as their interactions with ancillary and supportive activities. Although more than 200 European programs have applied for JACIE accreditation, and more than 100 have been granted accreditation, a recent retrospective analysis of the large-size EBMT registry of autologous and allogenic hematopoietic HSCT demonstrates that one of the factors affecting the overall survival of recipients of allogenic transplantation is the status of the transplant program regarding JACIE accreditation. This provides one of the first demonstrations that introduction of a quality management system contributes to the overall survival of patients treated with a highly specific medical procedure, and represents a milestone in the implementation of JACIE

Essential requirements for setting up a stem cell processing laboratory

The Graft Processing subcommittee of the Worldwide Network for Blood and Marrow Transplantation wrote this guideline to assist physicians and laboratory technologists with the setting up of a cell processing laboratory (CPL) to support a hematopoietic stem cell transplant program, thereby facilitating the start-up of a transplant program in a new location and improving patient access to transplantation worldwide. This guideline describes the minimal essential features of designing such a laboratory and provides a list of equipment and supply needs and staffing recommendations. It describes the typical scope of services that a CPL is expected to perform, including product testing services, and discusses the basic principles behind the most frequent procedures. Quality management (QM) principles specific to a CPL are also discussed. References to additional guidance documents that are available worldwide to assist with QM and regulatory compliance are also provided. © 2014 Macmillan Publishers Limited All rights reserved

Secondary malignancies after high-dose chemotherapy in germ cell tumor patients: A 34-year retrospective study of the European Society for Blood and Marrow Transplantation (EBMT)

We aimed to assess the incidence and risk factors of secondary malignancy (SM) in the young adult patients who received high-dose chemotherapy (HDCT) for germ cell tumors (GCT). The EBMT database was interrogated. Criteria for patient selection included adult male GCT and HDCT administered in any line of therapy. Cumulative incidence methods were used to estimate the time-to-SM diagnosis. Univariable Fine and Gray proportional hazard regression evaluated risk factors of SM occurrence. From 1981 to 2015, 9153 autografts were identified. Among 5295 patients, 59 cases of SM, developed after a median follow-up of 3.8 years, were registered. Of these patients, 23 (39%) developed hematologic SM, 34 (57.6%) solid SM (two patients had uncoded SM). Twenty-year cumulative incidence of solid versus hematologic SM was 4.17% (95% CI: 1.78-6.57) versus 1.37% (95% CI: 0.47-2.27). Median overall survival after SM was significantly shorter for patients who developed hematologic SM versus solid SM (8.6 versus 34.4 months, p = 0.003). Age older than 40 years at the time of HDCT was significantly associated with hematologic, but not solid, SM development (p = 0.004 versus p = 0.234). SM occurrence post-HDCT showed different patterns of incidence and mortality in GCT. These data may be important to optimize patient selection, counseling and follow-up after HDCT

development of adaptive immune effector therapies in solid tumors

Abstract State-of-the-art treatment strategies have drastically ameliorated the outcome of patients affected by cancer. However, resistant and recurrent solid tumors are generally nonresponsive to conventional therapies. A central factor in the sequence of events that lead to cancer is an alteration in antitumor immune surveillance, which results in failure to recognize and eliminate the transformed tumor cell. A greater understanding of the dysregulation and evasion of the immune system in the evolution and progression of cancer provides the basis for improved therapies. Targeted strategies, such as T-cell therapy, not only generally spare normal tissues, but also use alternative antineoplastic mechanisms that synergize with other therapeutics. Despite encouraging success in hematologic malignancies, adaptive cellular therapies for solid tumors face unique challenges because of the immunosuppressive tumor microenvironment, and the hurdle of T-cell trafficking within scarcely accessible tumor sites. This review provides a brief overview of current cellular therapeutic strategies for solid tumors, research carried out to increase efficacy and safety, and results from ongoing clinical trials

JACIE accreditation for blood and marrow transplantation: past, present and future directions of an international model for healthcare quality improvement.

Blood and marrow transplantation (BMT) is a complex and evolving medical speciality that makes substantial demands on healthcare resources. To meet a professional responsibility to both patients and public health services, the European Society for Blood and Marrow Transplantation (EBMT) initiated and developed the Joint Accreditation Committee of the International Society for Cellular Therapy and EBMT-better known by the acronym, JACIE. Since its inception, JACIE has performed over 530 voluntary accreditation inspections (62% first time; 38% reaccreditation) in 25 countries, representing 40% of transplant centres in Europe. As well as widespread professional acceptance, JACIE has become incorporated into the regulatory framework for delivery of BMT and other haematopoietic cellular therapies in several countries. In recent years, JACIE has been validated using the EBMT registry as an effective means of quality improvement with a substantial positive impact on survival outcomes. Future directions include development of Europe-wide risk-adjusted outcome benchmarking through the EBMT registry and further extension beyond Europe, including goals to faciliate access for BMT programmes in in low- and middle-income economies (LMIEs) via a 'first-step' process

Integrating biological HLA-DPB1 mismatch models to predict survival after unrelated hematopoietic cell transplantation

Non peer reviewe

CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines.

INTRODUCTION: Metastasis is a complex process involving loss of adhesion, migration, invasion and proliferation of cancer cells. Cell adhesion molecules play a pivotal role in this phenomenon by regulating cell-cell and cell-matrix interactions. CD146 (MCAM) is associated with an advanced tumor stage in melanoma, prostate cancer and ovarian cancer. Studies of CD146 expression and function in breast cancer remain scarce except for a report concluding that CD146 could act as a tumor suppressor in breast carcinogenesis. METHODS: To resolve these apparent discrepancies in the role of CD146 in tumor cells, we looked at the association of CD146 expression with histoclinical features in human primary breast cancers using DNA and tissue microarrays. By flow cytometry, we characterized CD146 expression on different breast cancer cell lines. Using siRNA or shRNA technology, we studied functional consequences of CD146 downmodulation of MDA-MB-231 cells in migration assays. Wild-type, mock-transfected and downmodulated transfected cells were profiled using whole-genome DNA microarrays to identify genes whose expression was modified by CD146 downregulation. RESULTS: Microarray studies revealed the association of higher levels of CD146 with histoclinical features that belong to the basal cluster of human tumors. Expression of CD146 protein on epithelial cells was detected in a small subset of cancers with histoclinical features of basal tumors. CD146+ cell lines displayed a mesenchymal phenotype. Downmodulation of CD146 expression in the MDA-MB-231 cell line resulted in downmodulation of vimentin, as well as of a set of genes that include both genes associated with a poor prognosis in a variety of cancers and genes known to promote cell motility. In vitro functional assays revealed decreased migration abilities associated with decreased CD146 expression. CONCLUSIONS: In addition to its expression in the vascular compartment, CD146 is expressed on a subset of epithelial cells in malignant breast. CD146 may directly or indirectly contribute to tumor aggressiveness by promoting malignant cell motility. Changes in molecular signatures following downmodulation of CD146 expression suggest that CD146 downmodulation is associated with the reversal of several biological characteristics associated with epithelial to mesenchymal transition, and the phenomenon associated with the metastatic process.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Impact of the SARS-CoV-2 pandemic on hematopoietic cell transplantation and cellular therapies in Europe 2020: a report from the EBMT activity survey

In 2020, 45,364 HCT in 41,016 patients, 18,796 (41%) allogeneic and 26,568 (59%) autologous in 690 centers were reported. Changes observed were as follows: total number of HCT −6.5%, allogeneic HCT −5.1%, autologous HCT −7.5%, and were more pronounced in non-malignant disorders for allogeneic HCT and in autoimmune disease for autologous HCT. Main indications were myeloid malignancies 10,441 (25%), lymphoid malignancies 26,120 (64%) and non-malignant disorders 2532 (6%). A continued growth in CAR-T cellular therapies to 1874 (+65%) patients in 2020 was observed. In allogeneic HCT, the use of haploidentical donors increased while use of unrelated and sibling donors decreased. Cord blood HCT increased by 11.7% for the first time since 2012. There was a significant increase in the use of non-myeloablative but a drop in myeloablative conditioning and in use of marrow as stem cell source. We interpreted these changes as being due to the SARS-CoV-2 pandemic starting early in 2020 in Europe and provided additional data reflecting the varying impact of the pandemic across selected countries and larger cities. The transplant community confronted with the pandemic challenge, continued in providing patients access to treatment. This annual report of the EBMT reflects current activities useful for health care planning