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Background: Hematopoietic stem cell transplantation (HSCT) is a procedure with high morbidity and mortality. Identifying patients for maximum benefit and risk assessment is crucial in the decision‐making process. This has led to the development of predictive risk models for HSCT in adults, which have limitations when applied to pediatric population. Our goal was to develop an automatic learning algorithm to predict survival in children with malignant disorders undergoing HSCT. Methods: We studied allogenic HSCTs performed on children with malignant disorders at a third‐level hospital between 1991 and 2021. Survival was analyzed using the Kaplan–Meier method, log‐rank test for the univariate analysis, and Cox regression for the multivariate analysis. A prognostic index was constructed based on these findings. Lastly, we constructed a predictive model using a random forest algorithm to forecast 1‐year survival after HSCT. Results: We analyzed 229 HSCTs in 201 patients with a median follow‐up of 1.64 years. Variables that impacted on the multivariate analysis were older age (hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.12–1.76, p =.003), oldest period of HSCT (HR 0.46, 95% CI 0.29–0.73, p <.001), and mismatched donor (HR 2.65, 95% CI 1.51–4.65, p =.001). Our prognostic index was associated with 3‐year overall survival (OS; p <.001). A random forest was developed using as variables: diagnosis, age, year of HSCT, time from diagnosis to HSCT, disease stage, donor type, and conditioning. This achieved 72% accuracy in predicting 1‐year OS. Conclusions: Our index and random forest was effective in predicting 1‐year survival. However, further validation in diverse populations is necessary to establish their generalizability. [ABSTRACT FROM AUTHOR]

The Fences: A webcomic on collective debt and ruination in Paraguay is a production of the Australian‐Paraguayan comics studio CómicsClub comprised of anthropologist and writer Caroline E. Schuster and artists Enrique Bernardou and David Bueno. This webcomic began as an anthropological fieldwork study of climate financing ‐ that is, novel financial arrangements that address the emerging weather‐related risks to human communities of global warming, deforestation, and mass extinction. As we enter an era of 'global weirding' characterised by strange and extreme weather, insurance companies have welcomed the opportunity to cast themselves as financial 'first responders,' offering coverage for drought, floods, bushfires, and other so‐called secondary perils that cost billions of dollars annually in property damage and reconstruction costs. The webcomic tells this story through interactive sequential art. Through branching timelines and 'what if?' scenarios, the project recuperates a critical speculative imagination and offers alternatives to financial modes of 'buying the future.' [ABSTRACT FROM AUTHOR]

Objectives: To compare the outcomes of treosulfan‐based vs busulfan‐based conditioning regimens in allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients. Methods: Retrospective study of all consecutive patients (2012–2019) treated with allogenic HSCT and treosulfan‐ or busulfan‐based conditioning regimens at a single center. Results: A total of 101 HSCT were included: 66 HSCT with busulfan and 35 with treosulfan. In malignant diseases (n = 62), busulfan‐based conditioning was more commonly employed than treosulfan: 82.3% vs 17.7%. However, the use of treosulfan for malignant diseases increased over time: 6.5% of HSCT in 2012–2015 vs 29% of HSCT in 2015–2019 (p =.02). The cohort of treosulfan had more children under 1‐year of age than the busulfan cohort (31 vs 13%; p =.033). The percentage of patients who received serotherapy was 73 and 89% in the nonmalignant and malignant groups, respectively. The engraftment, time to neutrophil, and platelet engraftment were not significantly different between the busulfan and the treosulfan cohorts. Rate of grade II‐IV acute GvHD was significantly higher in the busulfan cohort than the treosulfan cohort (39% vs 15%; p =.016). No differences were observed in endothelial damage complications, chronic GvHD, relapse, overall survival, and transplant‐related mortality. Conclusions: Busulfan‐based conditioning regimens are used more frequently for children undergoing allogenic HSCT, but treosulfan‐based conditioning is gaining acceptance. Treosulfan‐based conditioning is associated with lower rates of acute GvHD, and no significant differences on overall survival were observed compared with busulfan. [ABSTRACT FROM AUTHOR]

Background: Acantholytic cutaneous squamous cell carcinomas (aCSCCs) have been classically considered as a high‐risk variant of CSCC. However, more recent studies show that aCSCC does not confer more aggressiveness. This study aims to establish whether the prognosis of the aCSCC is worse than that of the non‐acantholytic (naCSCC) or not. Methods: Retrospective case‐control study with 50 aCSCCs and 50 naCSCCs. For each aCSCC, an naCSCC with similar high‐risk features to the aCSCC but with no acantholysis was selected. Prognosis between both groups was compared. Results: The mean age was 86 years (SD 9.61). Sixty‐one patients were men. Thirty‐nine CSCCs were located in high‐risk head and neck areas. Twenty CSCCs exhibited a poor degree of differentiation, and 36 showed an infiltrative growth pattern. The tumor diameter was 18.71 mm (interquartile range, IQR 35), and the tumor thickness was 6.72 mm (IQR 15.50). Twelve CSCCs exhibited perineural infiltration, and eight CSCCs exhibited invasion beyond the subcutaneous fat. Positive margins after excision of the tumor in 22 aCSCCs vs eight naCSCCs (P < 0.02). Nineteen poor‐prognosis events were observed (local recurrence, lymph node metastasis, and death from CSCC). However, no differences were observed between both groups when comparing poor‐prognosis events. Conclusion: The proportion of unfavorable events is similar in aCSCC and naCSCC. The acantholytic histopathological subtype is not associated with a poorer prognosis than the non‐acantholytic CSCC in our cohort. [ABSTRACT FROM AUTHOR]

Background: Naïve T-cell-depleted grafts have been employed as an ex vivo T-cell depletion (TCD) platform to prevent graft-versus-host disease (GvHD) and improve immune reconstitution by providing rapid donor memory T-cell reconstitution after allogenic hematopoietic stem cell transplantation (allo-HSCT). CD45RA- memory T cells confer protection against viruses such as cytomegalovirus, Epstein-Barr virus, and adenovirus; however, reports have shown an unexpectedly high incidence of human herpesvirus (HHV)-6B encephalitis among pediatric allo-HSCT patients.Methods: We report the first 18 consecutive allo-HSCT, 16 haplo-HSCT, and two human leukocyte antigen-matched related donors implanted with naïve TCD grafts. All donors were administered three cell products: first, a CD34+ stem cell product; second, a CD45RA+ TCD graft, followed by an adoptive natural killer (NK) cell infusion within 10 days after HSCT. The study's primary endpoint was the incidence of HHV-6B encephalitis.Results: Engraftment was achieved in 94.5% of cases; 2-year overall survival, event-free survival, and GvHD/relapse-free survival were 87.2% (95% CI 78.6-95.8), 67.3% (95% CI 53.1-81.5), and 64% (95% CI 50.5-78.1), respectively. HHV-6B reactivation occurred in 7 of the haplo-HSCT patients, six of who received a cell infusion with an NK/CD4 ratio <2. None of the patients developed encephalitis.Conclusions: In this clinical study, we show that early adoptive NK cell infusion after a 45RA+ TCD allo-HSCT graft is safe and can prevent HHV-6B encephalitis. We recommend infusing adoptive NK cells after allo-HSCT using CD45RA+ TCD grafts. [ABSTRACT FROM AUTHOR]

Objective: Describe the GETH haploidentical stem cell transplantation (haplo‐HSCT) activity in non‐malignant disease (NMDs). Methods: We retrospectively analyzed data from children with NMDs who underwent haplo‐HSCT. Results: From January 2001 to December 2016, 26 pediatric patients underwent 31 haplo‐HSCT through ex vivo T cell‐depleted (TCD) graft platforms or post‐transplantation cyclophosphamide (PT‐Cy) at 7 Spanish centers. Five cases employed unmanipulated PT‐Cy haplo‐HSCT, 16 employed highly purified CD34+ cells, and 10 employed ex vivo TCD grafts manipulated either with CD3+CD19+ depletion, TCRαβ+CD19+ selection or naive CD45RA+ T‐cell depletion. Peripheral blood stem cells were the sole source for patients following TCD haplo‐HSCT, and bone marrow was the source for one PT‐Cy haplo‐HSCT. The most common indications for transplantation were primary immunodeficiency disorders (PIDs), severe aplastic anemia, osteopetrosis, and thalassemia. The 1‐year cumulative incidence of graft failure was 27.4%. The 1‐year III‐IV acute graft‐versus‐host disease (GvHD) and 1‐year chronic GvHD rates were 34.6% and 16.7%, respectively. The 2‐year overall survival was 44.9% for PIDs, and the 2‐year graft‐versus‐host disease‐free and relapse‐free survival rate was 37.6% for the other NMDs. The transplantation‐related mortality at day 100 was 30.8%. Conclusion: Although these results are discouraging, improvements will come if procedures are centralized in centers of expertise. [ABSTRACT FROM AUTHOR]

Background: Cancer immunotherapy involving natural killer (NK) cells has gained interest. Here we report two methods to obtain interleukin (IL)-15-activated NK cells for clinical use.Study Design and Methods: IL-15-activated NK cell products were obtained after 1) enrichment from healthy haploidentical donors' peripheral blood mononuclear cells (PBMNCs) collected by nonmobilized apheresis by a two-step magnetic procedure, depletion of CD3+ cells followed by selection of CD56+ cells and ex vivo overnight stimulation with IL-15 (NKIL15); and 2) expansion using the K562-mb15-41BBL cell line (NKAE), from autologous PBMNCs from patients with multiple myeloma or expansion from healthy haploidentical PBMNCs obtained from whole blood using the same previous cell line. We analyzed the NK cell recovery and expansion, T cell depletion, phenotype, cytotoxicity, safety, and genomic stability of two good manufacturing practices (GMP)-grade IL-15-activated NK cell products.Results: The number of NK cells obtained from NKIL15 cell and NKAE cell products was similar; however, there were significantly fewer T cells in the NKIL15 cell product. The haploidentical NKAE cell product contained more T cells than the autologous NKAE cell product. The surface expression of the activating receptors CD69, CD25, natural killer group-2 member D receptor, NKp44, NKp46, NKp30, and DNA accessory molecule 1 was up regulated in both NK cell products. NKIL15 cell and NKAE cell products had significantly higher lytic activity than unstimulated NK cells and showed no lytic activity against PBMNCs from healthy donors. No genetic alterations or potential oncogenic effects were found.Conclusion: Different GMP-grade procedures can be used to obtain large numbers of highly IL-15-activated NK cells with extremely low T cell content for clinical use. [ABSTRACT FROM AUTHOR]