Schizophyllum commune sinusitis after allogeneic bone marrow transplantation for myelodysplastic syndrome: A case report and literature review.

Sinusitis is a serious infectious complication of allogeneic hematopoietic stem cell transplantation. Schizophyllum commune (S commune) is a common basidiomycete fungus that is rarely involved in human disease. We report herein a case of S commune sinusitis after allogeneic bone marrow transplantation. A 66-year-old man with myelodysplastic syndrome underwent allogeneic bone marrow transplantation and developed maxillary and ethmoid sinusitis. The sinusitis did not improve with liposomal amphotericin B after neutrophil engraftment, so we considered that surgical intervention was needed for the recovery of sinusitis. Endoscopic sinus surgery was performed. In the debridement tissue of paranasal mucosa, filamentous fungal elements were observed. Moreover, genetic analysis of the tissue revealed the presence of S commune. Schizophyllum commune should be recognized as a fungal pathogen that causes sinusitis after allogeneic hematopoietic stem cell transplantation. This case suggests the effectiveness of prompt surgical intervention with liposomal amphotericin B treatment for S commune sinusitis and the usefulness of genetic diagnosis for cases under antifungal treatment. (160 words).

Intestinal Behçet's Disease with Primary Myelofibrosis Involving Trisomy 8.

Behçet's disease (BD) is a disorder characterized by systemic inflammation of multiple organs, including the intestines. Several studies have reported a relationship between myelodysplastic syndrome and BD, and trisomy 8 was frequently seen, especially in intestinal BD. However, the association of BD with primary myelofibrosis (PMF) has not been well documented. A 58-year-old Japanese female was diagnosed with PMF in 2014. The symptoms of PMF resolved with ruxolitinib. However, she developed fever and intestinal perforation due to multiple ulcers in the terminal ileum in 2017. Intestinal perforation recurred 1 month later, and the dose of ruxolitinib was tapered. After discontinuation of ruxolitinib, she presented with recurrent oral aphthous ulcers and uveitis. Subsequently, intestinal perforation recurred, and she was diagnosed with intestinal BD. Trisomy 8 was identified in her peripheral blood. She underwent steroid therapy, azathioprine, and infliximab. This case suggests relationships between PMF, trisomy 8, and BD.

Upshaw-Schulman syndrome diagnosed during pregnancy complicated by reversible cerebral vasoconstriction syndrome.

Upshaw-Schulman syndrome (USS) is an inherited type of thrombotic thrombocytopenic purpura (TTP) that is extremely rare, but often diagnosed during pregnancy. Reversible cerebral vasoconstriction syndrome (RCVS) is the transient stenosis of several cerebral arteries that is frequently diagnosed post-partum. We describe a 28-year-old woman with USS complicated by RCVS after delivery that was treated by plasma exchange with a good outcome. She was referred to our hospital with thunderclap headache, anemia and thrombocytopenia that occurred immediately postpartum. She was diagnosed with TTP and multiple cerebral infarctions. Plasma exchange promptly improved her symptoms on hospital day 3. Moreover, multiple stenoses of cerebral arteries indicating RCVS were resolved. Since her sister also had an episode of thrombocytopenia during pregnancy, inherited TTP was suspected and genetic analyses confirmed USS. Pregnancy is a risk for not only TTP, but also RCVS. Endothelial damage might be an underlining cause and vasospasm after delivery is a trigger of RCVS. Plasma exchange was effective against both TTP and RCVS.

Serum immunoglobulin G as a discriminator of infection in follicular lymphoma patients undergoing chemotherapy with bendamustine in combination with rituximab.

OBJECTIVES: Chemotherapy, including bendamustine, usually causes lymphocytopaenia and hypogammaglobulinaemia as side effects in patients with haematological malignancies. Therefore, the possibility has been considered that these immunological adverse events induced by bendamustine may lead to infectious diseases. However, lymphocytopaenia and/or hypogammaglobulinaemia have not yet been shown to have a statistically significant association with infection in cancer patients who receive bendamustine. METHODS: We retrospectively studied 27 patients with relapsed or refractory indolent follicular lymphoma who were treated with bendamustine and rituximab (BR). In order to elucidate relationships between immune-related laboratory parameters (i.e. peripheral blood leukocyte, neutrophil, lymphocyte and immunoglobulin G [IgG]) and infectious events, receiver operating characteristic (ROC) curve and multivariate logistic regression analyses were performed. RESULTS: Infectious diseases occurred in 11 patients (11/27, 41%), including 3 (3/27, 11%) with severe diseases. The area under the ROC curve (AUC) showed that the lowest IgG level during and after BR discriminated infectious events (cut-off value, 603 mg/dL) with 81.8% sensitivity and 68.8% specificity (AUC, 0.76; 95% CI, 0.52-0.90). Furthermore, a multivariate regression analysis revealed that the minimal serum IgG value during and after BR therapy was the only variable that was significantly associated with infection (odds ratio, 8.29; 95% CI, 1.19-57.62; p value, 0.03). CONCLUSION: Serum IgG ≤603 mg/dL during and after BR therapy was independently associated with an increased risk of infection. The monitoring of serum IgG during chemotherapy may help to predict the development of infection in blood cancer patients undergoing chemotherapy with bendamustine in combination with rituximab.

Efficacy and Safety of the Modified EPOCH Regimen (Etoposide, Vincristine, Doxorubicin, Carboplatin, and Prednisolone) for Adult T-cell Leukemia/Lymphoma: A Multicenter Retrospective Study.

BACKGROUND: We retrospectively analyzed patients with untreated aggressive adult T-cell leukemia/lymphoma who received the modified EPOCH (mEPOCH) regimen. PATIENTS AND METHODS: Patients received up to 6 mEPOCH cycles. Etoposide (50 mg/m2/day), doxorubicin (10 mg/m2/day), and vincristine (0.4 mg/m2/day) were each given as a continuous 96-hour infusion on days 1 to 4. Prednisolone (40 mg/m2/day) was given intravenously or orally on days 1 to 4 and then tapered and stopped on day 7, and carboplatin (dose calculated for each patient individually using Calvert's formula according to a target under the curve of 3 mg/mL/min) was given as a 2-hour intravenous infusion on day 6. RESULTS: In 103 patients, overall response rate and complete response rate were 58% and 25%, respectively. With a median follow-up of 8.9 months, the median survival time was 9.8 months (95% confidence interval, 7.2-13.9 months). The median progression-free survival (PFS) was 4.2 months (95% confidence interval, 3.4-5.7 months). Patients who completed ≥ 4 cycles experienced significantly better overall survival and PFS compared with those who completed < 4 cycles. Twenty-eight patients underwent allogeneic hematopoietic stem cell transplantation after mEPOCH and demonstrated significantly prolonged overall survival and PFS compared with those who did not undergo transplantation. CONCLUSION: The mEPOCH regimen is effective with tolerable adverse effects and may be an alternative treatment option for adult T-cell leukemia/lymphoma.

Transformation of follicular lymphoma to double-hit lymphoma during adjuvant chemotherapy for concurrent ovarian carcinoma.

The frequency of multiple primary malignant neoplasms (MPMN) is increasing due to population aging. Since consensus guidelines for the treatment of MPMN are lacking, treatment strategies are determined by disease status on a per-patient basis. In this report, we describe a case of MPMN with follicular lymphoma (FL) grade 1 that transformed to double-hit lymphoma during adjuvant chemotherapy for concurrent ovarian carcinoma. A 64-year-old woman was diagnosed with MPMN of FL and endometrioid carcinoma by staging laparotomy and lymph node biopsy. She received four cycles of adjuvant chemotherapy (carboplatin and paclitaxel) for endometrioid carcinoma, but during chemotherapy, the FL grade 1 transformed to double-hit lymphoma. We speculate that adjuvant chemotherapy for endometrioid carcinoma may have triggered the transformation of FL in the present case.

Acquired hemophilia A associated with autoimmune pancreatitis with serum IgG4 elevation.

A case of acquired hemophilia A (AHA) that developed in a patient with autoimmune pancreatitis (AIP) is presented. A 64-year-old woman was diagnosed with AIP in 2007. The symptoms resolved with prednisolone (PSL). Although the dose of PSL was tapered to 7.5 mg/day for maintenance, serum IgG4 levels remained high. She suddenly presented with subcutaneous bleeding in 2015. Her activated partial thromboplastin time was prolonged (80.0 s). A mixing test showed an inhibitor pattern, factor VIII (FVIII) activity was less than 1%, and FVIII inhibitor was 290 BU/mL. She was diagnosed with AHA. Her serum IgG4 was elevated to 133 mg/dL. She was treated first with PSL alone, but she developed bladder tamponade. Cyclophosphamide and activated prothrombin complex concentrate were combined with PSL. She then achieved hemostasis, and FVIII inhibitor disappeared. FVIII inhibitor had been detected since PSL was tapered and AHA recurred two months later. An enzyme-linked immunosorbent assay showed that the inhibitor was mainly IgG4 and IgG1. This case suggests that elevation of IgG4 may be associated with the development of both AHA and AIP.