Metabolism, including catabolism and anabolism, is a basic cellular process necessary for cell survival. T lymphocytes have a distinct metabolism that can determine both fate and function. T-cell activation depends on glycolysis to obtain materials and energy for proliferation and effector function. Importantly, T cells utilize different metabolic processes under different conditions and diseases. Allogeneic hematopoietic cell transplantation (allo-HCT) is a classic immunotherapy for hematological malignancies; however, the development of graft-versus-host disease (GVHD) is a major factor limiting the success of allo-HCT. T cells in the donor graft drive GVHD by mounting a robust immunological attack against recipient normal tissues. Hence, understanding T-cell metabolism after allo-HCT would provide potential metabolic targets for the control of GVHD and primary tumor relapse. The purpose of the current review is to highlight the key metabolic pathways involved in alloantigen-activated T cells and to discuss how manipulating these pathways can serve as potential new therapeutic strategies to induce immune tolerance after allo-transplantation. We will also summarize the recent progress in regulating T-cell metabolism in bone marrow transplantation by targeting novel metabolic regulators or immune checkpoint molecules.

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Purpose: Application of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with hematological disorders is limited by the development of graft-versus-host-disease (GVHD).Separation of GVHD and graft-versus-leukemia (GVL) remains a great challenge in the field. We investigated the contribution of individual pathways involved in the complement cascade in GVH and GVL responses in order to identify specific targets by which to separate these two processes. Experimental Design:We used multiple preclinical murine and human-to-mouse xenograft models involving allo-HCT recipients lacking components of the AP or CP/LP to dissect the role of each individual pathway in GVHD pathogenesis and the GVL effect. For translational purposes, we used the AP-specific complement inhibitor, CR2-fH, which localizes in injured target organs to allow specific blockade of complement activation at sites of inflammation.Results: Complement deposition was evident in intestines of mice and patients with GVHD. In a preclinical setting, ablation of the AP, but not the CL/LP, significantly improved GVHD outcomes.Complement activation through the AP in host hematopoietic cells, and specifically dendritic cells (DCs), was required for GVHD progression. AP-deficiency in recipients decreased donor T-cell migration and Th1/Th2 differentiation, while increasing the generation of regulatory T-cells (Tregs). This was due to decreased activation and stimulatory activity of recipient DCs in GVHD target organs. Treatment with CR2-fH effectively prevented GVHD while preserving GVL activity. Conclusion:This study highlights the AP as a new therapeutic target to prevent GVHD and tumor relapse after allo-HCT. Targeting the AP by CR2-fH represents a promising therapeutic approach for GVHD treatment.

The present study has identified parenting practices that need to be encouraged or excluded for improving parent-child relationships. Initiating these measures would help in the rehabilitation of children with SpLD.

Introduction. Sickle cell hemoglobin D disease (HbSD) is a rare variant of sickle cell disease (SCD). Incidence of pulmonary thromboembolism (PE) and deep venous thrombosis (DVT) in children with HbSD is unknown. PE and DVT are known complications of SCD in adults but have not been reported in the literature in children with HbSD. Case Report. We are reporting a case of a 12-year-old boy with HbSD with acute chest syndrome (ACS) complicated by complete thrombosis of the branch of the right pulmonary artery and multiple small pulmonary artery emboli seen on computed tomography (CT) pulmonary angiogram and thrombosis of the right brachial vein seen on Doppler ultrasound. Our patient responded to treatment with anticoagulant therapy. Conclusion. There are no cases reported in children with HbSD disease presenting as ACS with pulmonary thromboembolism. We suggest that PE should be suspected in patients presenting with ACS who do not show improvement with standard management. CT pulmonary angiogram should be utilized for early diagnosis and appropriate management as there is no current protocol for management of PE/DVT in pediatric patients with SCD.

Highlights d Lysosomal acid lipase (LAL) is required for donor T cells to induce GVHD d LAL regulates T cell immunity in GVHD target organs d Pharmacological blockade of LAL effectively ameliorates GVHD d Pharmacological blockade of LAL preserves GVL activity

Sclerosing epithelioid fibrosarcoma (SEF) is a rare and aggressive tumor for which no standardized treatment regimens are available. The occurrence of this tumor in children and adolescents has been rarely reported, especially in the head and neck region. Involvement of the neuraxis is reported only in a few patients. We report a case of a 13-year-old boy with SEF of the skull with intracranial extension. The tumor recurred after initial resection and rapidly spread to the brain parenchyma and the meninges with no response to surgery, chemotherapy and radiation therapy.

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