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Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) has a wide range of clinical presentations and is sometimes life-threatening. It is often treated with systemic corticosteroids and etoposide, but no optimal treatment has been identified. Dexamethasone palmitate (DP) contains a combination of dexamethasone and a lipid emulsion and is selectively taken up by activated macrophages. Recently, a small case series reported the efficacy of dexamethasone palmitate (DP) in HLH. Here, we present the results of a nationwide survey in Japan detailing 14 cases of EBV-HLH treated with DP in children. One week after DP initiation, fever, cytopenia, and splenomegaly resolved in 77%, 38%, and 77% of patients (10, 5, and 10 of 13 patients, 1 missing). A 50% or greater reduction in ferritin levels was observed in 62% of patients (8 of 13 patients, 1 missing). In addition, the attending physician judged DP to be effective or partially effective in 12/14 (86%) patients. DP-related adverse events were uncommon, with only two infectious events reported. Thus, DP can be a therapeutic option for EBV-HLH.

We report a case of acquired dysfibrinogenemia with monoclonal gammopathy of undetermined significance presenting λ-type IgA M protein. The patient showed lower functional (0.4 g/dL) and normal immunological fibrinogen (2.9 g/dL). To examine the cause of the false lower value of fibrinogen, we performed experiments using the patient’s purified fibrinogen and IgA. Fibrinogen was purified from the patient’s plasma; IgA was purified from plasma or serum by immunoaffinity chromatography. We performed thrombin-catalyzed fibrin polymerization, scanning electron microscopy (SEM), immunoblotting analysis, and enzyme-linked immunosorbent assays (ELISAs). Fibrin polymerization in the patient’s plasma was markedly reduced and SEM showed no fiber bundles or sponge-like structures. Purified IgA did not influence polymerization, whereas immunoprecipitated plasma with an anti-IgA (α-chain) antibody indicated normalization of polymerization and clot structure. Western blotting analysis revealed the presence of monoclonal λ-type IgA-bound fibrinogen, the proportion of which was significantly higher than normal control plasma using ELISA. Our results suggest that IgA M protein-bound fibrinogen is not normally converted into fibrin, but rather leads to formation of an aberrantly structured fragile clot. The patient’s reduced plasma fibrinogen level was caused by the presence of IgA M protein-bound fibrinogen, not by IgA M protein alone.

The incidence of severe adverse events (SAEs) and associated risk factors in hematopoietic cell transplantation donors needs to be clarified for related donors (relatives of the transplant recipient), whose criteria for donation are more lenient than for unrelated donors. Data from related donors registered in the Japanese national data registry database between 2005 and 2021 were evaluated to determine the association of short-term SAE incidence with donor characteristics at registration. Fourteen of 4339 bone marrow (BM) donors (0.32%) and 54 of 10,684 peripheral blood stem cell (PBSC) donors (0.51%) experienced confirmed SAEs during the short donation period. No deaths were observed. Past medical history was a common risk factor for SAEs in both BM and PBSC donors. Age of 60 years or older and female sex were identified as risk factors for SAEs in PBSC donors. Female sex was also a risk factor for poor mobilization, which resulted in discontinuation of PBSC collection. Although donors should be selected carefully, a certain level of safety is ensured for related donors in Japan. Donor safety should be further increased by improving the selection method for related donors and extending the follow-up period.

Recent advances in intensive chemo- and immunotherapy have contributed to the outcome of hemophagocytic lymphohistiocytosis (HLH); however, the prognosis of HLH in children differs by HLH subtype. In Japan, secondary HLH, particularly Epstein–Barr virus-associated HLH (EBV-HLH), is the most common HLH subtype. The prognosis of HLH has improved in recent years. We here conducted a prospective study of 73 patients who were treated with HLH-2004 protocol in Japan. EBV-HLH, familial HLH (FHL), and HLH of unknown etiology were seen in 41, 9, and 23 patients, respectively. Patients with resistant or relapsed disease after HLH-2004 treatment and those with FHL received hematopoietic stem cell transplantation (HSCT). The induction rate after initial therapy was 58.9%, and the 3-year overall survival (OS) rate of all patients was 73.9% and differed significantly among those with EBV-HLH, FHL, and HLH of unknown etiology. Of the 17 patients who received HSCT, the 3-year OS rates of those with and without complete resolution before HSCT were 83.3% and 54.5%, respectively. Outcomes in children with HLH who were treated with the same protocol differed among HLH subtypes. Appropriate strategy for each subtype should be established in future studies.

Although clinical trials have reported an improvement in the prognosis of hemophagocytic lymphohistiocytosis (HLH), current treatment outcomes are unsatisfactory, especially in severe cases. Most clinical trial patients with severe disease discontinue participation due to complications associated with HLH or treatment-related toxicity. A retrospective survey of patients who discontinued participation in the JPLSG HLH-2004 clinical trial was conducted to review the detailed course of these cases to optimize HLH treatment and supportive care. Findings in these patients were compared with those of 45 patients who completed the protocol treatment. The 3 year overall survival rate of patients who completed treatment was 86.7%, versus 50.7% for those who did not complete treatment. Incidence of serious adverse events, such as infections, coagulopathy, and posterior reversible encephalopathy syndrome, during the initial 8 weeks of treatment was much higher in patients who did not complete treatment than in patients who completed treatment. To improve overall outcomes of patients with HLH, it is important to not only optimize HLH-directed therapy but also provide appropriate supportive care.

Post-transplant early immune disorders and engraftment failure/delay are major issues in unrelated umbilical cord blood transplantation (UCBT). We evaluated graft-versus-host disease (GVHD) prophylaxis approaches after UCBT by comparing UCBT outcomes with GVHD prophylaxis using tacrolimus plus methylprednisolone (Tac/mPSL, n = 32) to that with Tac plus methotrexate (Tac/MTX, n = 31) at a single pediatric transplantation center. The 30-day cumulative incidence rates of neutrophil engraftment and median neutrophil engraftment times in the Tac/mPSL and Tac/MTX groups were 70.1% and 90.3% and 19 and 17 days, respectively (p = 0.09). Pre-engraftment immune reactions (PIR) and acute GVHD were improved with Tac/MTX; PIR incidence (p = 0.020) and cumulative incidence of 100-day acute GVHD (grade II–IV, 38.7% vs 68.8%, p = 0.045; grade III–IV, 9.7% vs 34.4%, p = 0.021) were significantly lower in the Tac/MTX group than in the Tac/mPSL group. However, the incidence rates of relapse (p = 0.921) and cytomegalovirus reactivation (p = 0.908), and the estimated overall (p = 0.87) and event-free survival (p = 0.88) were comparable between the two groups. These data indicate that GVHD prophylaxis with Tac/MTX is associated with favorable results, including reduced PIR and acute GVHD incidence after UCBT, without adverse effects.

This paper proposes a framework on Sustainable Development Goal (SDG) evaluation, arguing that attainment of the 17 goals and 169 related targets depends significantly on practice-based monitoring and evaluation. The SDGs’ 15-year time frame can helpfully be divided into three 5-year phases: a planning phase driven by proactive evaluation and evaluability assessment, an improvement phase characterized by formative evaluation and monitoring, and a completion phase involving outcome and impact evaluations. Under these phases, in order not to miss the SDGs’ fundamental philosophy of “no one left behind,” local relevance must be considered when evaluating SDG programs, particularly to capture the overarching concepts applicable across the 17 goals, such as educational dynamics and resilience.

IntroductionAlthough the prognosis of Langerhans cell histiocytosis (LCH) is excellent, the high recurrence rate and permanent consequences, such as central diabetes insipidus and LCH-associated neurodegenerative diseases, remain to be resolved. Based on previous reports that patients with high-risk multisystem LCH show elevated levels of inflammatory molecules, we hypothesised that dexamethasone would more effectively suppress LCH-associated inflammation, especially in the central nervous system (CNS). We further hypothesised that intrathecal chemotherapy would effectively reduce CNS complications. We administer zoledronate to patients with multifocal bone LCH based on an efficacy report from a small case series.Methods and analysisThis phase II study (labelled the LCH-19-MSMFB study) is designed to evaluate the significance of introducing dexamethasone and intrathecal chemotherapy for multisystem disease and zoledronate for multifocal bone disease in previously untreated, newly diagnosed children, adolescents (under 20 years) and adults under 40 years. The primary endpoint is the 3-year event-free survival rate by risk group of under 20 years and the 3-year event-free survival rate of 20 years and over.Ethics and disseminationThis study was approved by the Central Review Board of the National Hospital Organisation Nagoya Medical Centre (Nagoya, Japan) on 21 January 2022 and was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp/en-latest-detail/jRCTs041210027). Written informed consent will be obtained from all patients and/or their guardians.Trial registration numberjRCTs041210027.