[Ruptured mycotic cerebral aneurysm in an adult T-cell leukemia/lymphoma patient undergoing allogeneic stem cell transplantation].

A 63-year-old man with adult T-cell leukemia-lymphoma underwent allogeneic bone marrow transplantation from an HLA-matched unrelated donor. On day 17 after transplantation, chest computed tomography (CT) showed nodules in the lower lobes of both lungs, and invasive pulmonary aspergillosis (IPA) was suspected. Treatment with liposomal amphotericin B was started, and improvement of infectious lesions was confirmed with CT on day 28. The antifungal agent was changed to voriconazole on day 52 because of progressive renal dysfunction. Disorders of consciousness and paralysis of the left upper and lower extremities developed on day 61. Brain CT showed subcortical hemorrhage in the right parietal and occipital lobes, and the patient died on day 62. An autopsy revealed filamentous fungi, suspected to be Aspergillus, in the pulmonary nodules and a ruptured cerebral aneurysm. Although IPA occurs in 10% of transplant recipients, vigilant monitoring for mycotic cerebral aneurysms is required to prevent hematogenous dissemination of Aspergillus, which is associated with a high mortality rate.

[Fatal invasive pneumococcal disease developed 14 years after allogeneic hematopoietic stem cell transplantation in a patient with myelodysplastic syndrome].

Invasive pneumococcal diseases (IPDs) after allogeneic hematopoietic stem cell transplantation have high fatality rates and often develop late after transplantation. The patient was a 58-year-old female. Fourteen years ago, she underwent bone marrow transplantation from a HLA-DR 1-antigen mismatched unrelated donor for myelodysplastic syndrome. She developed pneumonia, chronic graft-versus-host disease, and hypogammaglobulinemia. She received 23-valent pneumococcal capsular polysaccharide vaccine 11 and 6 years earlier. She was presented to our emergency room with fever. Her blood culture was positive for pneumococcus, and she was diagnosed with an IPD. The patient received antibiotic treatment but died on the third day of hospitalization. Because of its seriousness, pneumococcal infection should receive attention even 10 or more years after transplantation. Preventive approaches such as vaccination and early intervention at the time of diagnosis are important.

Development of a Prognostic Scoring System using MYC Expression and Soluble Interleukin Receptor -2 level for Diffuse Large B-cell Lymphoma.

Background: Diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), is the most frequent type of lymphoid neoplasm. Methods: We investigated the relationships between clinical factors of DLBCL-NOS and MYC immunohistochemistry (IHC) staining. Results: A total of 110 patients diagnosed with DLBCL-NOS from 2012 to 2020 at Tottori University Hospital and treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy were included. IHC staining of MYC in formalin-fixed, paraffin-embedded tumor specimens was performed, and ROC-curve analysis revealed the cut-off value of the MYC positive rate as 55%. The 2-year overall survival (OS) rates of the MYC-negative and -positive groups were 84.7% vs 57.7% (P = 0.0091), and the progression-free survival rates were 77.8% vs 54.7% (P = 0.016), respectively. Multivariate analysis for OS showed prognostic significance of MYC positivity [hazards ratio (HR): 2.496; P = 0.032], and serum levels of soluble interleukin-2 receptor (sIL-2R) > 2000 U/mL (HR: 3.950; P = 0.0019), as well as age > 75 (HR: 2.356; P = 0.068). The original scoring system was developed based on these findings. By assigning one point to each item, age (> 75), MYC positivity, and sIL-2R level (> 2000), all patients were classified into three risk categories: group 1 (0 points), group 2 (1 point), and group 3 (2-3 points). The 2-year survival rates were 100%, 83.0%, and 47.1% for the groups 1, 2, and 3, respectively (P < 0.0001). Conclusion: We suggest that a prognostic scoring system using MYC expression and soluble interleukin receptor -2 level is useful for the prediction of prognosis, contributing to further stratification in DLBCL-NOS.

Successful HLA-haploidentical stem cell transplantation with post-transplant cyclophosphamide in an older patient with chronic active Epstein-Barr virus infection.

Chronic active Epstein-Barr virus infection (CAEBV) is a subtype of EBV-associated T/NK cell lymphoproliferative disease and is only curable by allogeneic hematopoietic stem cell transplantation. However, finding a human leukocyte antigen (HLA)-matched donor at a suitable time can sometimes be difficult. We report the case of a 60-year-old woman who received prednisolone (PSL) after being diagnosed with autoimmune hepatitis 3 years earlier. She suddenly developed high fever and impaired liver function. Based on a high EBV DNA load in the peripheral blood, CAEBV was diagnosed. The patient was started on cooling therapy with PSL, cyclosporine, and etoposide, which reduced symptoms. Subsequently, she received HLA-haploidentical stem cell transplantation (haplo-SCT) with reduced-intensity conditioning (fludarabine 25 mg/m2 for 5 days, melphalan 50 mg/m2 for 2 days, and total body irradiation at 2 Gy) and post-transplant cyclophosphamide (PTCy) because she lacked an HLA-matched donor. Liver function was restored, and EBV DNA load in peripheral white blood cells became undetectable. The patient is alive without relapse or severe complications over 1 year after transplantation. To our knowledge, this is the first report of successful haplo-SCT with PTCy for CAEBV. This approach may be an alternative therapeutic option for CAEBV patients lacking an HLA-matched donor.

[Successful outcome of allogeneic hematopoietic stem cell transplantation for systemic mastocytosis complicated with acute myeloid leukemia].

A 60-year-old woman developed a fifth thoracic spine fracture with progressive paraplegia and underwent posterior spine fusion in June 2018. Based on the histopathological analysis of the surgical specimen, she was diagnosed with KIT D816V-positive systemic mastocytosis (SM). In June 2019, peripheral blood examination revealed remarkable eosinophilia. She was given prednisolone, which resulted in the resolution of eosinophilia. In May 2020, she developed acute myeloid leukemia (AML). Induction therapy was initiated and complete remission achieved. Subsequently, she received one course of consolidation therapy and allogeneic hematopoietic stem cell transplantation (allo-SCT). Although the residual mast cell tumor aggravated during chemotherapy for AML, the tumor regressed after allo-SCT, suggesting a graft-versus-mastocytosis effect. Nine months after the transplantation, the patient is alive and healthy without recurrence of AML and SM.

Regression Analysis to Estimate the Factor VIII Activity of Patients with Hemophilia A Without Inhibitor who Received Emicizumab Therapy.

BACKGROUND: Emicizumab, a bispecific monoclonal antibody for hemophilia A (HA), has strong pharmacodynamic effects in several coagulation assays resulting in dosing difficulties with Factor VIII (FVIII) concentrates during bleeding emergencies. MATERIALS AND METHODS: Single and multiple regression models were studied to estimate FVIII activity using 27 archived plasma samples from three patients with HA without inhibitor under emicizumab treatment. Explanatory variables were FVIII chromogenic assay (CSA), Ad|min1|, Ad|min2|, the number of seconds of APTT, and the FVIII one-stage assay (OSA), which were measured without idiotype antibodies. The response variable was FVIII OSA measured with idiotype antibodies. RESULTS: In the simple linear model, the FVIII CSA regression coefficient was 1.04 and the intercept was -14.55 (r2 = 0.95; p < 0.001). In the multiple regression model, FVIII OSA and FVIII CSA were selected based on the Akaike Information Criterion, with regression coefficients of 1.74 and 1.15, respectively, and an intercept of -92.03 (r2 = 0.96, p < 0.001). CONCLUSIONS: The regression models can estimate the FVIII:C levels in patients with HA receiving emicizumab and would be useful in a bleeding emergency and/or surgery.

Comparison of Prognostic Indices in Japanese Patients with Diffuse Large B-cell Lymphoma in the Yonago Area.

BACKGROUND: Several prognostic indices for diffuse large B-cell lymphoma (DLBCL) have been developed. Which index is appropriate for Japanese patients with DLBCL treated in real-world practice is unknown. METHODS: The prognostic performances of the original international prognostic index (IPI), age-adjusted IPI, National Comprehensive Cancer Network-IPI, elderly IPI and revised IPI were compared using patients with DLBCL treated in a single institute in the Yonago area in Japan. RESULTS: From 2005 through 2015, 182 patients with de novo DLBCL were treated with chemotherapy in Tottori University Hospital; 154 (85%) patients received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) although full dose was administered in 63 (35%) patients. The median age of the patients was 71 years (range 18 to 91). Three-year overall survival rate was 71.8% (95% CI, 64.1% to 78.2%). All indices significantly discriminate risk groups for overall survival of the patients (P < 0.001). Although no statistical difference of performance was found among these indices, the best scores of model fit/discrimination measures were beaten out by age-adjusted IPI, the simplest and three-factor model. CONCLUSION: Age-adjusted IPI is still usable in real-world practice while a better predictive model is desired for Japanese patients with DLBCL.

Efficacy of bendamustine on thrombocytopenia and hemolytic anemia secondary to CD5-positive B-cell lymphoma with massive splenomegaly in a patient with rheumatoid arthritis.

Chemotherapy for lymphoma may be avoided in the presence of coincident cytopenia. In case of immune cytopenia secondary to lymphoma, treatment of cytopenia is the same for primary cases, however, chemotherapy for lymphoma may be effective at the cost of severe hematological toxicity. The present study reports a complex case of thrombocytopenia and direct antiglobulin test-negative hemolytic anemia, thus mimicking Evans syndrome, secondary to cluster of differentiation 5-positive B-cell lymphoma with massive splenomegaly, in a patient suffering from rheumatoid arthritis for two decades. Treatment with prednisolone, high-dose dexamethasone, eltrombopag and rituximab for cytopenia were not effective. Chemotherapy with bendamustine subsequently resolved the cytopenia, additionally resulting in a complete remission of lymphoma. Thus, bendamustine may have a role in the management of lymphoma complicated with severe cytopenia.

Pulmonary intravascular large B-cell lymphoma successfully treated with rituximab, cyclophosphamide, vincristine, doxorubicin and prednisolone immunochemotherapy: Report of a patient surviving for over 1 year.

A 73-year-old man with a history of lethargy, fever and dyspnea was admitted to Tottori University Hospital. A computed tomography (CT) scan revealed splenomegaly and diffusely spreading ground-glass opacities (GGOs) in both lungs. A video-assisted thoracoscopic surgery (VATS)-guided lung biopsy revealed intravascular proliferation of large atypical lymphoid cells in the arteries, veins and alveolar walls. The patient was diagnosed with intravascular large B-cell lymphoma (IVLBCL); he received 6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) immunochemotherapy and has remained in complete remission for >1 year. Although IVLBCL is a rare disease, it should be considered in the differential diagnosis of pulmonary diffuse lesions that present with GGOs on CT scans.

Development of Reverse Transcription Loop-Mediated Isothermal Amplification for Simple and Rapid Detection of Promyelocytic Leukemia-Retinoic Acid Receptor α mRNA.

BACKGROUND: Acute promyelocytic leukemia (APL) is a disease characterized by expression of Promyelocytic Leukemia-Retinoic Acid Receptor α (PML-RARα) chimeric mRNA. Although APL is curable, early death due to hemorrhage is a major problem. Here, we report the development of a simple and rapid diagnostic method for APL based on reverse transcription loop-mediated isothermal amplification (RT-LAMP). METHODS: An RT-LAMP primer set was designed to detect three types of PML-RARα mRNA in a single reaction. Serial dilutions of plasmid DNA containing bcr1, bcr2, or bcr3 PML-RARα sequences and RNA extracted from bone marrow aspirates of 6 patients with APL were used to compare the results of RT-LAMP and nested PCR assays. RESULTS: Plasmid DNA was amplified by RT-LAMP, for which the reaction time was > 4 h shorter and the lower detection limit was higher than for nested RT-PCR. Six of 7 samples tested positive by both methods. CONCLUSION: We developed an RT-LAMP assay for simple and rapid PML-RARα mRNA detection that may be clinically useful for point-of-care testing and APL diagnosis.