Satomi Matsuoka

α-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for various hematopoietic disorders. Graft-versus-host disease (GVHD) and infections are the major obstacles of HSCT, and their close relationship has been suggested. Although roles of bacterial and viral infections in the pathophysiology of GVHD are well described, impacts of fungal infection on GVHD remain to be elucidated. In mouse models of GVHD, injection of α-mannan (Mn), a major component of fungal cell wall, or heat-killed Candida albicans exacerbated GVHD, particularly in the lung. Mn-induced donor T-cell polarization toward Th17 and lung-specific chemokine environment in GVHD led to accumulation of Th17 cells in the lung. The detrimental effects of Mn on GVHD depended on donor IL-17A production and host C-type lectin receptor Dectin-2. These results suggest a previously unrecognized link between pulmonary GVHD and fungal infection after allogeneic HSCT.

R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease

The intestinal microbial ecosystem is actively regulated by Paneth cell–derived antimicrobial peptides such as &agr;-defensins. Various disorders, including graft-versus-host disease (GVHD), disrupt Paneth cell functions, resulting in unfavorably altered intestinal microbiota (dysbiosis), which further accelerates the underlying diseases. Current strategies to restore the gut ecosystem are bacteriotherapy such as fecal microbiota transplantation and probiotics, and no physiological approach has been developed so far. In this study, we demonstrate a novel approach to restore gut microbial ecology by Wnt agonist R-Spondin1 (R-Spo1) or recombinant &agr;-defensin in mice. R-Spo1 stimulates intestinal stem cells to differentiate to Paneth cells and enhances luminal secretion of &agr;-defensins. Administration of R-Spo1 or recombinant &agr;-defensin prevents GVHD-mediated dysbiosis, thus representing a novel and physiological approach at modifying the gut ecosystem to restore intestinal homeostasis and host–microbiota cross talk toward therapeutic benefits.

Ruxolitinib protects skin stem cells and maintains skin homeostasis in murine graft-versus-host disease

Graft-versus-host disease (GVHD) is the major complication after allogeneic stem cell transplantation (SCT). Emerging evidence indicates that GVHD leads to injury of intestinal stem cells. However, it remains to be investigated whether skin stem cells could be targeted in skin GVHD. Lgr5+ hair follicle stem cells (HFSCs) contribute to folliculogenesis and have a multipotent capacity to regenerate all epithelial cells in repair. We studied the fate of Lgr5+ HFSCs after SCT and explored the novel treatment to protect Lgr5+ HFSCs against GVHD using murine models of SCT. We found that GVHD reduced Lgr5+ HFSCs in association with impaired hair regeneration and wound healing in the skin after SCT. Topical corticosteroids, a standard of care for a wide range of skin disorders including GVHD, damaged HFSCs and failed to improve skin homeostasis, despite of their anti-inflammatory effects. In contrast, JAK1/2 inhibitor ruxolitinib significantly ameliorated skin GVHD, protected Lgr5+ HFSCs, and restored hair regeneration and wound healing after SCT. We, for the first time, found that GVHD targets Lgr5+ HFSCs and that topical ruxolitinib represents a novel strategy to protect skin stem cells and maintain skin homeostasis in GVHD.

Myasthenia gravis after allogeneic bone marrow transplantation: A case report and literature review

A 52-year-old man with acute myeloid leukemia underwent allogeneic hematopoietic stem cell transplantation and developed extensive chronic graft-versus-host disease and myasthenia gravis (MG), which became involved with oculobulbar and proximal upper and lower limb weakness in 677days. In the literature, we identified 24 cases where MG developed after allo-SCT. Graft-versus-host disease development and male recipients of female donors might be prone to the development of posttransplant MG (odds ratio, 3.75).

Disseminated toxoplasmosis after hematopoietic stem cell transplantation showing unusual magnetic resonance images

We herein report a patient who had disseminated toxoplasmosis after hematopoietic stem cell transplantation showing atypical clinical presentation and neuroimaging. Parkinsonism symptoms such as muscle rigidity, bradykinesia, tremor, and postural instability were initial manifestations. Magnetic resonance imaging showed diffuse symmetrical lesions of bilateral basal ganglia lacking ringed enhancement. Post‐mortem analysis revealed multiple tachyzoites of Toxoplasma gondii in the basal ganglia, mid brain, cerebellum, and cardiac muscle.

MALDI-TOF MS in post-transplant bloodstream infections: reliable identification of causative bacteria in the neutropenic phase

MALDI-TOF MS in post-transplant bloodstream infections: reliable identification of causative bacteria in the neutropenic phase

Successful treatment of immediate allogeneic myeloablative hematopoietic stem cell transplantation from a HLA-mismatched sibling donor for active systemic epstein-barr virus-positive T-cell lymphoproliferative disease of childhood following primary acute epstein-barr virus infection.

A 22‐year‐old female was admitted for sustained high fever and diagnosed with systemic Epstein–Barr virus‐positive T‐cell lymphoproliferative disease. As her clinical course was so aggressive, she immediately underwent allogeneic myeloablative bone marrow transplantation from an HLA‐mismatched sibling donor on hospital day 46. The patient has remained in complete remission for 3 years.

HCV Infection on Lymphoid Neoplasm

Since there is a suggested a link between HCV and liver cancer, attempts are currently being made to discover new drugs that can advance the treatment of hepatitis C and prevent it from progressing to liver cancer. On the other hand, in the treatment of lymphoma, it has been pointed out that HCV is associated with HCV reactivation and lymphoproliferative diseases such as lymphoma. In this review, we will summarize the relationship between lymphoproliferative diseases and hepatitis due to reactivation of HCV during treatment with rituximab.

Rituximab Maintenance Therapy and Bendamustine Containing Treatments may improve the Survival of Mantle Cell Lymphoma: Retrospective Analysis in Single Institute

Introduction: The prognosis for mantle cell lymphoma (MCL) has remained poor despite the current use of autologous transplantation and induction chemotherapy that includes high-dose cytarabine. The introduction of rituximab and bendamustine, however, has led to the improvement of prognosis of diffuse large B-Cell lymphoma and indolent lymphoma. For these reasons, we analyzed the effectivity of rituximab maintenance therapy and bendamustine against mantle cell lymphoma at our hospital.Methods: We selected 22 cases of MCL for which treatment was initiated between January 2004 and December 2016 at our hospital. We compared the cases based on the use of rituximab maintenance therapy or bendamustine, simplified Mantle Cell Lymphoma International Prognostic Index (sMIPI), staging, and treatment regimens to analyze the effect of rituximab maintenance therapy and bendamustine on prognosis.Results: Overall five-year survival rate was 67%. Significant difference (P=0.0432) was observed in the 5-year survival rate between the group treated with rituximab maintenance therapy (90.9%) and the group that was not (56.2%). Likewise, significant difference (P=0.0197) was observed in the 5-year survival rate between the group that received bendamustine during the course of treatment (90.9%) and the group that did not (50%). Majority of the cases in the group that received bendamustine, however, had been treated with rituximab maintenance therapy.Conclusion: Our study showed an improvement in prognosis of MCL due to the treatment with rituximab maintenance therapy and bendamustine. Although the analysis was conducted on a limited number of cases, we believe that rituximab maintenance therapy and treatments that include bendamustine are promising therapies for MCL.

Not Specific Cytokines but B Symptoms or C Reactive Proteins wereRelated the Infusion Reactions in Rituximab Treated B Cell Non-HodgkinâÂÂsLymphoma

Purpose: The purpose of this study is to analyze the risk factor for infusion related reaction (IRR) due to the rituximab treatment in patients with B cell non-Hodgkin’s lymphoma. Methods: A retrospective analysis was conducted the newly diagnosed B cell non-Hodgkin’s lymphoma patients who have received rituximab contained chemotherapy. Several factors with cytokines in patients were calculated. A P value <0.05 is significant. Results: 18 patients were included in the analysis. Most of patients were diffuse large B cell lymphoma or follicular lymphoma. Six patients had a IRR. TNF-α, IL6, IL8, sIL-2R, pre-administration of prednisolone were not observed significant differences. B symptom, CRP, gender was showed the significant differences in this analysis (B symptom: P=0.0139, gender: P=0.014, CRP: P=0.0354). Conclusion: B symptom, CRP, and gender might be important risk factors of the occurrence of IRR. Specific cytokines were not correlation with the IRR. Careful observation for IRR during rituximab administration is necessary for B cell non-Hodgkin’s lymphoma with B symptoms, and CRP positive patients.