Background: Several commercial and academic autologous chimeric antigen receptor T-cell (CAR-T) products targeting CD19 have been approved in Europe for relapsed/refractory B-cell acute lymphoblastic leukemia, high-grade B-cell lymphoma and mantle cell lymphoma. Products for other diseases such as multiple myeloma and follicular lymphoma are likely to be approved by the European Medicines Agency in the near future. Design: The European Society for Blood and Marrow Transplantation (EBMT)-Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association collaborated to draft best practice recommendations based on the current literature to support health care professionals in delivering consistent, high-quality care in this rapidly moving field. Results: Thirty-six CAR-T experts (medical, nursing, pharmacy/laboratory) assembled to draft recommendations to cover all aspects of CAR-T patient care and supply chain management, from patient selection to long-term followup, post-authorisation safety surveillance and regulatory issues.

The online version of this article contains a supplementary appendix. BackgroundThe risk for donors of allogeneic hematopoietic stem cells transplants is generally considered negligible. Scattered reports of severe complications and a recent controversy on hematopoietic malignancies after granulocyte colony-stimulating factor administration have challenged this opinion. Design and MethodsThree hundred and thirty-eight allogeneic transplant teams from 35 primarily European countries were asked to report numbers of fatalities, severe adverse events and hematologic malignancies occurring among their hematopoietic stem cell donors. ResultsTwo hundred and sixty-two of the 338 teams (77.5%) responded to a first survey (1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002) and 169 of the 262 responder teams (65%) to a second survey (2003)(2004)(2005). They had performed a total of 51,024 first allogeneic hematopoietic stem cell transplantations, of which 27,770 were bone marrow and 23,254 peripheral blood. They observed five donor fatalities, one after a bone marrow donation and four after peripheral blood donation (incidence 0.98 per 10,000 donations; 95% CI 0.32-2.29), 37 severe adverse events (7.25/10,000; 95% CI 5.11-9.99), of which 12 in bone marrow donors (4.32/10,000; 95% CI 2.24-7.75) and 25 in peripheral blood donors (10.76/10,000; 95% CI 6.97-15.85; p<0.05) and 20 hematologic malignancies (3.92/10,000; 95% CI 2.39-6.05), of which 8 after donating bone marrow and 12 after donating peripheral blood stem cells. The observed incidence rate of hematologic malignancies did not exceed the expected incidence in an age-and sex-adjusted general population. ConclusionsHematopoietic stem cell donation is associated with a small but definite risk of fatalities and serious adverse events. True incidences might be higher, due to potential underreporting by study design. A continuous, standardized donor follow-up is needed to define donor risk groups and to monitor intermediate and long-term sequelae.Key words: hematopoietic stem cell donation, adverse event, hematologic malignancies, donor fatality. Haematologica 2009; 94:94-101. doi: 10.3324/haematol.13668 ©2009 Ferrata Storti Foundation. This is an open-access paper. Citation: Halter J, Kodera Y, Urbano Ispizua A, Greinix HT, Schmitz N, Favre G, Baldomero H, Niederwieser D, Apperley JF, and Gratwohl A, for the European Group for Blood and Marrow Transplantation (EBMT) activity survey office. Severe events in donors after allogeneic hematopoietic stem cell donation. Severe events in donors after allogeneic hematopoietic stem cell donation

We compared outcomes of patients with severe aplastic anemia (SAA) who received G-CSF stimulated bone marrow (G-BM) (n=78), unstimulated bone marrow (BM) (n=547), or peripheral blood progenitor cells (PBPC) (n=134) from an HLA-matched sibling. Transplantations occurred in 1997–2003. Rates of neutrophil and platelet recovery were not different among the three treatment groups. Grade 2–4 acute graft-versus-host disease (GVHD) (RR 0.82, p=0.539), grade 3–4 acute GVHD (RR 0.74, p=0.535) and chronic GVHD (RR 1.56, p=0.229) were similar after G-BM and BM transplants. Grade 2–4 acute GVHD (RR 2.37, p=0.012) but not grade 3–4 acute GVHD (RR 1.66, p=0.323) and chronic GVHD (RR 5.09, p<0.001) were higher after PBPC transplants compared to G-BM. Grade 2–4 (RR 2.90, p<0.001), grade 3–4 (RR 2.24, p=0.009) acute GVHD and chronic GVHD (RR 3.26, p<0.001) were higher after PBPC transplants compared to BM. Mortality risks were lower after transplantation of BM compared to G-BM (RR 0.63, p=0.05). These data suggest no advantage to using G-BM and the observed higher rates of acute and chronic GVHD in PBPC recipients warrants cautious use of this graft source for SAA. Taken together, BM is the preferred graft for HLA matched sibling transplants for SAA.

JACIE (Joint Accreditation Committee of the ISCT and the EBMT) launched its first official inspection programme in January 2004. Since then, 35 centres in Europe have been inspected. Almost all were found to be functioning at a high level of excellence, with the majority having only minor deficiencies in compliance with the standards. In one-third of centres there were more significant deficiencies. The most common deficiencies were in quality management, and a survey of the applicant centres confirmed this was the area where centres experienced most difficulty in preparation for accreditation. Following correction of deficiencies, 28 centres have at the time of writing achieved full accreditation. Implementation of JACIE required a significant investment of time and resources by applicant centres. The majority required at least 18 months to prepare for accreditation and 85% needed to employ a quality manager and/or data manager on an ongoing basis. However, all centres felt their programme had benefited from the implementation of JACIE. In addition to the inspection and accreditation of individual centres, JACIE maintains an educational programme including training courses for inspectors and for centre preparation. JACIE is also working closely with other international organisations working in cellular therapy to develop international standards for all aspects of stem cell transplant. IntroductionJACIE is a nonprofit body established for the purposes of assessment and accreditation in the field of haematopoietic stem cell transplantation (HSCT). The committee was founded in 1998 by the European Group for Blood and Marrow Transplantation (EBMT) and the International Society for Cellular Therapy (ISCT), the two leading scientific organisations involved with HSCT in Europe. JACIE modelled itself on the US-based Foundation for the Accreditation of Cellular Therapy (FACT), established in 1996 by the ISCT and the American society for Blood and Marrow Transplantation (ASBMT). JACIE actively collaborates with FACT in establishing standards for the provision of quality medical and laboratory practice in HSCT. JACIE conducts inspections, accredits programmes and encourages health institutions and facilities performing HSCT to meet these standards voluntarily in order to demonstrate their high levels of quality of care. The current organisation of JACIE is shown in Figure 1. The structure ensures wide consultation, with 20 European countries now represented on the Board in addition to nursing, paediatrics and cord-blood representatives.The primary aim of JACIE is to improve the quality of HSCT in Europe by providing a means whereby transplant centres, cell collection facilities and processing facilities can demonstrate high-quality practice. This is supported by coordinating training courses in quality management for applicant centres and courses for inspectors. An additional and wider aim is to ensure harmonisation between JACIE standards and other national/international standards, including the EU Tissues & Cells Direc...

A morphometric and immunohistochemical study was performed to assess the spleen's alterations in patients with autoimmune thrombocytopenia and in drug abusers with thrombocytopenia (DAT) related to human immunodeficiency virus (HIV) infection. A total of 34 patients were included in the study: 20 DAT patients and 14 with idiopathic thrombocytopenic purpura (ITP). Twenty HIV-negative splenectomy patients without thrombocytopenia were included as controls. Spleen weight in DAT patients (323.25 +/- 149.96 g, mean + standard deviation) was significantly increased compared with the ITP (164.28 +/- 29.79 g, P < 0.0001) and control (175.50 +/- 49.14 g, P < 0.0001) groups. The mean diameter of lymphoid follicles in the spleens of DAT patients (446.83 +/- 99.16 microns, was significantly higher than in those of the control patients (370.87 +/- 55.30 microns, P = 0.019). In control patients' spleens, the number of platelets in Billroth's cords was significantly higher (59.54 +/- 32.72/10(4) microns 2) than in those of the DAT (2.13 +/- 1.42/10(4) microns 2, P < 0.0001) and ITP (P < 0.0001) patients. The number of macrophages and ceroid histiocytes per 10(4) microns 2 of red pulp was significantly increased in both DAT (5.14 +/- 1.90) and ITP (7.48 +/- 4.38) patients compared with the control patients (3.66 +/- 1.10, P < 0.0001) and P = 0.06, respectively), and in ITP patients compared with DAT patients (P = 0.0136). The number of granulopoietic precursors per 10(4) microns 2 of red pulp was higher in the spleens of DAT (1.41 +2- 1.46, P < 0.0001) and ITP (0.92 +/- 0.75, P < 0.0001) patients compared with those of the control group. Transmission electron microscopy studies demonstrated platelet phagocytosis by macrophages of Billroth's cords and presence of myeloid metaplasia in spleens of DAT and ITP patients. Immunohistochemical studies showed a depletion of CD4+ lymphocytes in the T zone of splenic white pulp and an increased number of CD8+ lymphocytes in red pulp of DAT patients' spleens compared with those of ITP and control patients. There were no significant alterations in dendritic reticular cell network in the DAT group compared with the ITP and control groups.