‘SeaStats’: hard figures on sea and coast

Looking for reliable figures on our seas and coasts? In need of that particular number to finish your introduction or presentation? ‘SeaStats’ offers interesting facts, each with a direct link to the source document and author(s). The primary criteria for selection are 1) reliability and quality of the source and 2) relevance of the figures. ‘SeaStats’ is a bilingual product that allows for a thematic search through 9 topics and 40 subtopics that are relevant marine, coastal and estuarine themes. ‘SeaStats’ wishes to a) facilitate the search for reliable anecdotic information on seas and coasts, with a focus on figures and numbers and 2) provide an additional exposure of marine and coastal research results to a wider public. Figures can be looked up through the 9 different symbols in the start-screen www.vliz.be/cijfers_beleid/zeecijfers (Dutch and English) or by filling in specific search terms. Take this example; you want to know the exact length of the Belgian coastline? Follow the symbol ‘Sea of space’ on the start-screen, click on ‘geography’, or use the search term ‘coastline’. The result of your search will inform you that there are 3 different and www.vliz.be/docs/Zeecijfers/seabordernl.pdf, where each alternative is explained. Source documents are by preference full texts of publications documented in IMIS, on relevant Belgian research or relating to the Belgian part of the North Sea, the Scheldt Estuary and the Belgian coastal zone

Long-Term Immune Recovery After Hematopoietic Stem Cell Transplantation for ADA Deficiency: a Single-Center Experience

Unconditioned hematopoietic stem cell transplantation (HSCT) is the recommended treatment for patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency with an HLA-matched sibling donor (MSD) or family donor (MFD). Improved overall survival (OS) has been reported compared to the use of unrelated donors, and previous studies have demonstrated that adequate cellular and humoral immune recovery can be achieved even in the absence of conditioning. Detailed insight of the long-term outcome is still limited. We aim to address this by studying a large single-center cohort of 28 adenosine deaminase-deficient patients who underwent a total of 31 HSCT procedures, of which more than half were unconditioned. We report an OS of 85.7% and event-free survival of 71% for the entire cohort, with no statistically significant differences after procedures using related or unrelated HLA-matched donors. We find that donor engraftment in the myeloid compartment is significantly diminished in unconditioned procedures, which typically use a MSD or MFD. This is associated with poor metabolic correction and more frequent failure to discontinue immunoglobulin replacement therapy. Approximately one in four patients receiving an unconditioned procedure required a second procedure, whereas the use of reduced intensity conditioning (RIC) prior to allogeneic transplantation improves the long-term outcome by achieving better myeloid engraftment, humoral immune recovery, and metabolic correction. Further longitudinal studies are needed to optimize future management and guidelines, but our findings support a potential role for the routine use of RIC in most ADA-deficient patients receiving an HLA-identical hematopoietic stem cell transplant, even when a MSD or MFD is available

Effect of stem cell source on long-term chimerism and event-free survival in children with primary immunodeficiency disorders after fludarabine and melphalan conditioning regimen

BACKGROUND: Reduced-intensity conditioning (RIC) regimens are increasingly being used in the transplantation of patients with primary immunodeficiency disorders (PIDs), but there are no large studies looking at long-term lineage-specific chimerism. OBJECTIVES: We sought to analyze long-term chimerism and event-free survival in children undergoing transplantation for PIDs using RIC with fludarabine and melphalan (Flu/Melph) and to study the effect of donor type and stem cell source. METHODS: One hundred forty-two children underwent transplantation with RIC by using Flu/Melph and for PIDs by using bone marrow (n = 93) or peripheral blood stem cells (PBSCs; n = 49). Donors were matched unrelated donors (n = 72), mismatched unrelated donors (n = 37), matched sibling donors (n = 14), matched family donors (n = 12), and mismatched family donors (n = 7). RESULTS: Overall survival at a median follow-up of 7.5 years was 78%, irrespective of stem cell source or donor type. When bone marrow was used as the stem cell source, 26% of patients ended up with very low levels of donor chimerism (50% donor chimerism) in all lineages. CONCLUSIONS: On the basis of our experience, we would suggest that PBSCs should be the stem cell source of choice in children with PIDs undergoing transplantation with Flu/Melph RIC from a matched donor source. This is most likely to ensure sustained high-level donor chimerism

Excellent overall and chronic graft-versus-host-disease-free event-free survival in Fanconi anaemia patients undergoing matched related- and unrelated-donor bone marrow transplantation using alemtuzumab–Flu–Cy: the UK experience

Haematopoietic stem cell transplantation (HSCT) remains the only curative option in Fanconi anaemia (FA). We analysed the outcome of children transplanted for FA between 1999 and 2018 in the UK. A total of 94 transplants were performed in 82 patients. Among the donors, 51·2% were matched related donors (MRD) while the remainder were alternative donors. Most patients received a fludarabine–cyclophosphamide (Flu–Cy)‐based conditioning regimen (86·6%) and in vivo T‐cell depletion with alemtuzumab (69·5%). Five‐year overall survival (OS) was 85·4% [70·4–93.2] with MRD, 95·7% [72·9–99.4] with matched unrelated donors (MUD), 44·4% [6·6–78.5] with mismatched unrelated donors (MMUD) and 44·4% [13·6–71.9] with mismatched related donors (MMRD) (P < 0·001). Other factors significantly impacting OS were pre‐transplant bone marrow status, source of stem cells, cytomegalovirus (CMV) serostatus, preparation with Flu–Cy, use of total body irradiation (TBI) and alemtuzumab as serotherapy. In multivariate analysis, absence of myelodysplastic syndrome (MDS) or leukaemia, bone marrow as source of stem cells, cytomegalovirus (CMV) other than +/− (Recipient/Donor) and Flu–Cy were protective factors for five‐year OS. Five‐year chronic graft‐versus‐host‐disease (cGVHD)‐free event‐free survival was 75·4% with the same risk factors except for CMV serostatus. Five‐year non‐relapse mortality was 13·8% [7·3–22.3]. Only five patients (6·1%) developed grade II–IV acute GVHD and two patients chronic GVHD. These data confirm the excellent outcome of matched related or unrelated HSCT in children with FA

Treatment dilemmas in asymptomatic children with primary hemophagocytic lymphohistiocytosis

Asymptomatic carriers (ACs) of pathogenic biallelic mutations in causative genes for primary hemophagocytic lymphohistiocytosis (HLH) are at high risk of developing life-threatening HLH, which requires allogeneic hematopoietic stem cell transplantation (HSCT) to be cured. There are no guidelines on the management of these asymptomatic patients. We analyzed the outcomes of pairs of index cases (ICs) and subsequently diagnosed asymptomatic family members carrying the same genetic defect. We collected data from 22 HSCT centers worldwide. Sixty-four children were evaluable. ICs presented with HLH at a median age of 16 months. Seven of 32 ICs died during first-line therapy, and 2 are alive after chemotherapy only. In all, 23/32 underwent HSCT, and 16 of them are alive. At a median follow-up of 36 months from diagnosis, 18/32 ICs are alive. Median age of ACs at diagnosis was 5 months. Ten of 32 ACs activated HLH while being observed, and all underwent HSCT: 6/10 are alive and in complete remission (CR). 22/32 ACs remained asymptomatic, and 6/22 have received no treatment and are in CR at a median follow-up of 39 months. Sixteen of 22 underwent preemptive HSCT: 15/16 are alive and in CR. Eight-year probability of overall survival (pOS) in ACs who did not have activated HLH was significantly higher than that in ICs (95% vs 45%; P = .02), and pOS in ACs receiving HSCT before disease activation was significantly higher than in ACs receiving HSCT after HLH activation (93% vs 64%; P = .03). Preemptive HSCT in ACs proved to be safe and should be considered

Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells

Autologous T cells engineered to express chimeric antigen receptor against the B cell antigen CD19 (CAR19) are achieving marked leukemic remissions in early-phase trials but can be difficult to manufacture, especially in infants or heavily treated patients. We generated universal CAR19 (UCART19) T cells by lentiviral transduction of non-human leukocyte antigen-matched donor cells and simultaneous transcription activator-like effector nuclease (TALEN)-mediated gene editing of T cell receptor α chain and CD52 gene loci. Two infants with relapsed refractory CD19(+) B cell acute lymphoblastic leukemia received lymphodepleting chemotherapy and anti-CD52 serotherapy, followed by a single-dose infusion of UCART19 cells. Molecular remissions were achieved within 28 days in both infants, and UCART19 cells persisted until conditioning ahead of successful allogeneic stem cell transplantation. This bridge-to-transplantation strategy demonstrates the therapeutic potential of gene-editing technology