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Although allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a curative therapy for high‐risk acute leukemia (AL), some patients still relapse. Since patients simultaneously have many prognostic factors, difficulties are associated with the construction of a patient‐based prediction algorithm of relapse. The alternating decision tree (ADTree) is a successful classification method that combines decision trees with the predictive accuracy of boosting. It is a component of machine learning (ML) and has the capacity to simultaneously analyze multiple factors. Using ADTree, we attempted to construct a prediction model of leukemia relapse within 1 year of transplantation. With the model of training data (n = 148), prediction accuracy, the AUC of ROC, and the κ‐statistic value were 78.4%, 0.746, and 0.508, respectively. The false positive rate (FPR) of the relapse prediction was as low as 0.134. In an evaluation of the model with validation data (n = 69), prediction accuracy, AUC, and FPR of the relapse prediction were similar at 71.0%, 0.667, and 0.216, respectively. These results suggest that the model is generalized and highly accurate. Furthermore, the output of ADTree may visualize the branch point of treatment. For example, the selection of donor types resulted in different relapse predictions. Therefore, clinicians may change treatment options by referring to the model, thereby improving outcomes. The present results indicate that ML, such as ADTree, will contribute to the decision‐making process in the diversified allo‐HSCT field and be useful for preventing the relapse of leukemia.

Erdheim–Chester disease (ECD), a rare form of non-Langerhans cell histiocytosis, is characterized by the infiltration of foamy CD68 + and CD1a - histiocytes into multiple organ systems. Central nervous system (CNS) involvement has recently been reported to be a poor prognostic factor when treating ECD with interferon alpha. We report the case of a 66-year-old Japanese patient with ECD involving the CNS who harbored the BRAF V600E mutation and also concomitantly developed polycythemia vera with the JAK2 V617F mutation. We confirmed 2-chlorodeoxyadenosine (cladribine) therapy to be effective for the patient in this case.

Summary The suppressors of cytokine signaling (SOCS) proteins are negative regulators of cytokine signaling required to prevent excessive cellular responses. In particular, SOCS3 is involved in the regulation of metabolic syndromes, such as obesity and diabetes, by suppressing leptin and insulin signals. SOCS3 also suppresses the inflammatory response associated with metabolic stress, but this specific role remains undefined. Wild-type mice on a high-fat diet (HFD) exhibited only fatty liver, whereas systemic deletion of SOCS3 resulted in excessive myeloid hematopoiesis and hepatic inflammation. In addition, depletion of the gut microbiota resulted in considerable improvement in excess granulopoiesis and splenomegaly, halting the progression of systemic inflammation in SOCS3KO mice on the HFD. This result suggests that intestinal dysbiosis is involved in inflammation associated with SOCS3KO. Although contributing to diet-induced obesity and fatty liver, SOCS3 is nevertheless critical to suppress excess myeloid hematopoiesis and severe systemic inflammation associated with intestinal dysbiosis on HFD.

No abstract

Cell culture media influence the characteristics of human osteogenic periosteal sheets. We have previously found that a stem cell medium facilitates growth and collagen matrix formation in vitro and osteogenesis in vivo. However, it has not yet been demonstrated which culture medium is superior for osteoclastogenesis, a prerequisite for reconstruction of normal bone metabolic basis. To address this question, we compared chemotaxis and osteoclastogenesis in tissue-engineered periosteal sheets (TPSs) prepared with two types of culture media. Periosteal tissues obtained from adult volunteers were expanded with the conventional Medium 199 or with the stem cell medium, MesenPRO. Hematopoietic enhanced-green-fluorescent-protein (EGFP)-nude mice were prepared by γ-irradiation of Balb/c nu/nu mice and subsequent transplantation of bone marrow cells from CAG-EGFP C57BL/6 mice. TPSs were implanted subcutaneously into the chimeric mice and retrieved after intervals for immunohistopathological examination. EGFP+ cells were similarly recruited to the implantation site in both the TPSs prepared, whereas the distribution of CD11b+ cells was significantly lower in the TPS prepared with the stem cell medium. Instead, osteoclastogenesis was higher in the TPS prepared with the stem cell medium than in the one prepared with the conventional medium. These findings suggest that the stem cell medium is preferable for the preparation of more functional TPSs.

Background: Increased physical activity is associated with improved survival in patients undergoing cancer treatment. However, the association of self-reported physical activity and activity intensity with HCT outcomes is less clear. Aims: The goal of this study is to evaluate the relationship of self-reported physical activity and HCT outcomes. Methods: Data was collected from the Moffitt Cancer Center Health Research Informatics and transplant databases. Between 01/01/2011 and 7/5/2018, 587 patients received an allogeneic HSCT and completed IPAQ short form. IPAQ scoring algorithm was used to ascertain metabolic equivalent of task-minutes (MET-minutes) per day. Based on MET-minutes/day aggregate score, patients were subsequently divided into three activity categories: low (n = 337), moderate (n = 52), and vigorous (n = 198). Results: Median follow-up was 41.7 months (range 11.4-267months). Patients with lower physical activity were older ] and had more comorbidities (HCT-CI = 3 [0-9]), in comparison to patients with moderate and vigorous activity. Males reported vigorous activity more commonly (66.7%) in comparison to females (33.3%) whereas low activity level was similar for each gender (females 51.3%, males 48.7%). There was no significant difference in Karnofsky performance status (KPS), Armand disease risk, conditioning intensity, number of prior chemotherapy regimens, and cardiopulmonary function amongst the three categories (Table 1). Patients with vigorous physical activity had lower risk of NRM in comparison to low and moderate activity (Figure 1). In multivariate modeling, after accounting for KPS, graft-versus host disease, and FEV1, physical activity level was an independent predictor of non-relapse mortality with lower activity levels associated with increased risk of NRM (HR: low 1.7 (95% CI: 1.07-2.93); moderate 2.11 (95% CI: 1.03-4.31); overall P = 0.049). However, no association was seen between activity level and overall survival or relapse free survival (P = NS).Summary/Conclusion: Self-reported vigorous activity prior to HCT is an independent predictor of NRM after HCT. This easy to employ tool can be of utility in the clinic to risk stratify HCT candidates. Further studies are warranted to evaluate impact of self-reported physical activity on HCT outcomes.

Donor T cell activation, proliferation, differentiation, and migration are the major steps involved in graft-versus-host disease (GVHD) development following bone marrow transplantation. Chondroitin sulfate (CS) proteoglycan is a major component of the extracellular matrix and causes immune modulation by interacting with cell growth factors and inducing cell adhesion. However, its precise effects on immune function are unclear than those of other proteoglycan families. Thus, we investigated the significance of CS within donor cells in acute GVHD development utilizing CSGalNAc T1-knockout (T1KO) mice. To determine the effects of T1KO, the mice underwent allogenic bone marrow transplantation from major histocompatibility complex-mismatched donors. While transplantation resulted in hepatic GVHD with inflammatory cell infiltration of both CD4+ and CD8+ effector memory T cells, transplantation in T1KO-donors showed milder cell infiltration and improved survival with fewer splenic effector T cells. In vitro T-cell analyses showed that the ratio of effector memory T cells was significantly lower via phorbol myristate acetate/ionomycin stimulation. Moreover, quantitative PCR analyses showed significantly less production of inflammatory cytokines, such as IFN-γ and CCL-2, in splenocytes of T1KO mice. These results suggest that reduction of CS in donor blood cells may suppress the severity of acute GVHD after hematopoietic stem cell transplantation.