Since the late 1990s, Stenotrophomonas maltophilia (S. maltophilia) has become one of the most common nonfermenting Gram-negative bacilli that cause opportunistic infection. Patients with hematologic diseases are the most risky candidate for S. maltophilia pneumonia or sepsis because of chemotherapy-induced neutropenia or immunodeficiency. Frequent exposure to broad-spectrum antibiotics and prolonged insertion of central venous catheter further enhance the risk of S. maltophilia infection. One of the most severe S. maltophilia infections is hemorrhagic pneumonia. This type of infection is mostly fatal because of pulmonary alveolar hemorrhage that leads to acute respiratory failure. Furthermore, S. maltophilia exhibits a high-level intrinsic resistance to conventional antibiotics such as β-lactams and aminoglycosides and, more recently, the increasing acquired resistance to co-trimoxazole and quinolones. According to our experienced and previously reported cases, all of the patients with hemorrhagic pneumonia caused by S. maltophilia had a fatal course within a few days after the onset of the pneumonia. In this article, we perform a systematic review on a total 30 cases of hemorrhagic pneumonia induced by S. maltophilia from our institutions and the literature, and we describe its early diagnosis, prophylaxis, and recommended therapeutic strategy for the infection in the treatment of hematologic disease.

Objective While unexplained liver dysfunction is common, it is sometimes difficult to identify its exact cause. One cause is viral infections. The identification of viruses other than hepatitis B and C that cause liver dysfunction is difficult because no methods to simultaneously identify these viruses have been established. The aim of this study was to quickly and simultaneously identify multiple virus species. Methods A total of 49 patients with unexplained liver dysfunction and undetermined inflammation were examined. The majority of patients had hematologic malignancies, and some had undergone bone marrow transplantation. Qualitative polymerase chain reactions (PCR) were performed to detect 12 species of DNA virus in whole blood. Quantitative real-time PCR was performed when a specific virus was amplified. In addition, 6 RNA hepatitis viruses were directly assayed by real-time PCR. These 2 PCR steps were completed within 1 hour. Results The most frequently detected virus in 37 patients with liver dysfunction, was transfusion transmitted virus (38%), which was followed by human herpes virus (HHV) type 6 (35%), Epstein-Barr virus (14%), cytomegalovirus (8%), and rarely hepatitis G virus and HHV-7 (3%). Similar viremia was observed in 12 patients with mild liver dysfunction. The results of the PCR assay were mostly consistent with those of routine virus serological tests. Conclusion A multiplex viral PCR assay was a useful tool for quickly identifying viruses that possibly cause liver dysfunction. It was also important that liver dysfunction acted as a proband that led to the discovery of serious viremia.

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A 78-year-old woman with multiple tumors in the liver and spleen was diagnosed with follicular dendritic cell (FDC) sarcoma based on the histological picture of splenectomized specimen and its expression of CD21 and CD 23. As a paraneoplastic immune disorder, Coombs' test was positive although hemolysis was not obvious. Since systemic chemotherapies were ineffective for residual liver tumors, transcatheter arterial chemoembolization (TACE) was performed with subsequent tumor reduction. Currently, the patient is alive 27 months after the diagnosis with residual hepatic tumors favorably controlled by repeated TACE. Our experience suggests that TACE is useful for the management of hepatic FDC sarcoma.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, so far, no large cohort study determined the risk factors and the most effective therapeutic strategies for TA-TMA. Thus, the present study aimed to clarify these clinical aspects based on a large multicenter cohort. This retrospective cohort study was performed by the Kyoto Stem Cell Transplantation Group (KSCTG). A total of 2425 patients were enrolled from 14 institutions. All patients were aged ≥16 years, presented with hematological diseases, and received allo-HSCT after the year 2000. TA-TMA was observed in 121 patients (5.0%) on day 35 (median) and was clearly correlated with inferior overall survival (OS) (hazard ratio [HR], 4.93). Pre- and post-HSCT statistically significant risk factors identified by multivariate analyses included poorer performance status (HR, 1.69), HLA mismatch (HR, 2.17), acute graft-versus-host disease (aGVHD; grades 3-4) (HR, 4.02), Aspergillus infection (HR, 2.29), and veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS; HR, 4.47). The response rate and OS significantly better with the continuation or careful reduction of calcineurin inhibitors (CNI) than the conventional treatment strategy of switching from CNI to corticosteroids (response rate, 64.7% vs 20.0%). In summary, we identified the risk factors and the most appropriate therapeutic strategies for TA-TMA. The described treatment strategy could improve the outcomes of patients with TA-TMA in the future.

Scedosporium prolificans (S. prolificans) is a type of mold, which rarely affects immunocompromised people. We treated a 71-year-old woman with acute myeloid leukemia (AML-M5a) with low-dose cytarabine, acralubicin, and filgrastim as the induction therapy. On day 7 after the initiation of chemotherapy, she became febrile and agranulocytic, and developed anal pain ; therefore, we discontinued the chemotherapy on day 8. Broad-spectrum antibiotics, micafungin, and then liposomal amphotericin B were ineffective. The serum concentration of β-D-glucan was 525 pg/mL. She died of multiple organ failure on day 17. S. prolificans was detected from the blood culture on day 13. Physicians should consider Scedosporium spp. infection when principal antifungal agents are ineffective and fungal infection is strongly suspected.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a new clinical entity that was reclassified from enteropathy-associated T-cell lymphoma in the 2016 WHO classification. An 83-year-old man with fever and diarrhea was referred to our hospital because of free air in the abdominal cavity and wall thickening of the large intestine on CT. Colonofiberscopic examination revealed mucosal edema and multiple ulcers at the sigmoid colon, splenic flexure, and transverse colon. Histopathological examination of the mucosal biopsy specimen demonstrated dense infiltration of small lymphocytes with nuclear atypia, some of which exhibited intraepithelial invasion. Immunohistologically, these lymphocytes were positive for CD3, CD56, and perforin. Regarding CD3 expression, the antigen was found to only be expressed in the cytoplasm and not on the surface membrane on flow cytometric analysis. PCR examination of the T-cell receptor (TCR) gene revealed monoclonal gene rearrangements of TCR-γ and TCR-β. Based on these findings, a diagnosis of colonal MEITL with cyCD3 expression at Lugano clinical stage 1 was made. After conservative management of the peritonitis, we treated the patient with CHOP and DeVIC regimens, but he developed progressive disease and died. The cyCD3 expression in MEITL may be novel, suggesting a thymocyte origin of the tumor cells.

Although G-CSF-producing tumor is well-known, co-production of IL-8 by such tumor and IL-8-induced neutrophil chemotaxis to tumor tissue have not been recognized. A 65-year-old male was diagnosed with papillary renal cell carcinoma accompanied by marked intratumoral neutrophil infiltration after left radical nephrectomy. At presentation, laboratory tests showed a white blood cell count of 47.8×10 9 /l with 84.1% neutrophils and a high CRP of 18.3 mg/dl. Serum concentrations of G-CSF, IL-6, and IL-8 were elevated to 143 pg/ml, 474 pg/ml, and 1,260 pg/ml, respectively. After the operation, the white cell count and serum concentrations of these cytokines returned to normal levels. Real-time quantitative PCR of the tumor tissue revealed high gene expressions of G-CSF and IL-8, which appeared to be the cause of the leukocytosis and intratumoral neutrophil infiltration.