Successful bridge therapy of gilteritinib to cord blood transplantation in relapsed acute myeloid leukemia after bone marrow transplantation.

The FMS-related tyrosine kinase 3 (FLT3) internal tandem duplication mutations (FLT3-ITD) positive acute myeloid leukemia (AML) is a disease with a dismal outcome. Gilteritinib is a second-generation FLT3 inhibitor with activity against ITD and high affinity toward the FLT3 receptor, thereby showing therapeutic potential for relapsed/refractory FLT3-mutated AML. Bone marrow transplantation (BMT) from a human leukocyte antigen (HLA) identical sibling donor was performed in a 38-year-old Japanese male with FLT3-ITD positive AML. Neutrophil engraftment (>0.5 × 109/L) was achieved on day 16, and bone marrow remission was revealed on day 32. The patient's AML relapsed hematologically four months after BMT and was resistant to salvage chemotherapy. Gilteritinib was administered and the patient achieved non-remission but 'stable disease' status according to the response criteria. During administration, liver damage was observed but controllable. The patient received cord blood transplantation (CBT) as the second hematopoietic stem cell transplantation (HSCT) three months after relapse and achieved second remission. There was no evidence of recurrence of AML four months after CBT. This case demonstrates that gilteritinib can control FLT3-ITD positive AML that relapsed early after initial HSCT and can bridge to second HSCT.

[Outcomes of primary central nervous system lymphoma patients treated with high-dose methotrexate and rituximab].

Primary central nervous system lymphoma (PCNSL) is a rare, aggressive type of non-Hodgkin lymphoma with a poor prognosis and no defined optimal therapeutic strategies. We retrospectively analyzed the survival of six PCNSL patients who were treated with high-dose methotrexate (HDMTX) -based chemotherapy combined with rituximab. The median age at diagnosis was 71 (range, 54-75) years, and the ECOG performance status was ≥3 in four patients. The histopathological findings revealed that all patients had diffuse large B-cell lymphoma. Objective response was obtained in all patients (five, complete response; one, partial response). Three patients had severe non-hematological toxicities: one had pulmonary thromboembolism, one had sepsis, and one developed acute epididymitis. However, each patient recovered and their symptoms could be managed. The median follow-up was 28.8 (range, 13.4-65.5) months. Five patients were still alive and disease-free, and one patient relapsed 62.2 months after the diagnosis. Therefore, the addition of rituximab to HDMTX may improve outcomes. Further clinical investigation is necessary to establish standardized initial therapies for PCNSL, particularly in elderly patients.

Myelodysplastic syndrome with myelofibrosis in which azacitidine therapy was effective and cord blood transplantation was carried out.

Myelodysplastic syndrome with myelofibrosis (MDS-F) is a disease with a poor prognosis, and patients with this condition are at an increased risk of engraftment failures after allogeneic hematopoietic stem cell transplantation (SCT). Azacitidine (AZA) is effective in high-risk MDS patients. However, the effects of AZA on MDS-F have not been elucidated. AZA was administered to a 62-year-old male with MDS-F for 7 days at a dose of 75 mg/m2. Hematological improvements were observed after only 1 course of treatment. No suitable donor was found through the Japan Marrow Donor Program; therefore, the patient underwent umbilical cord blood transplant (UCBT). Neutrophil engraftment was observed on day 21 after the transplant procedure. He developed acute graft versus host disease (GVHD) of the skin (stage 3/grade II), but it could be controlled using prednisolone. Chronic GVHD was not observed and he was discharged in good general condition on day 68. While treatment prior to allogeneic SCT of MDS-F has not been established, in the present case, the hematological improvement brought about by AZA likely contributed to the patient's positive response to UCBT.

Methylmercury exposure at dosage conditions that do not affect growth can impair memory in adolescent mice.

Methylmercury is an environmental pollutant that can induce serious central nervous system damage. Its ubiquitous presence in the environment in trace amounts has raised concerns about potential adverse effects on human health. Although many studies have evaluated the effects of methylmercury on neural development in fetal and neonatal mice, there has been less focus on studies using adolescent mice. Therefore, in this study, the effects of methylmercury on brain neurodevelopment and maturation were evaluated by various neurobehavioral trials using adolescent mice exposed to 30 ppm methylmercuric chloride (approximately 24 ppm methylmercury) for up to 8 weeks. Under these administration conditions, weight gain in adolescent mice was unaffected by methylmercury exposure. Furthermore, methylmercury exposure in adolescent mice had no effect on sociability as assessed by the social interaction test, impulsivity as assessed by the cliff avoidance reaction test, depressive behavior as assessed by the tail-suspension test, or locomotor activity as assessed using the Supermex system. In contrast, short-term memory assessed by the Y-maze test, as well as long-term memory assessed by novel object recognition and passive avoidance tests, revealed impairments induced by methylmercury exposure in adolescent mice. These results suggest that long-term exposure to methylmercury during adolescence potentially impairs memory function, and the nervous pathway of brain areas involved in learning and memory are particularly vulnerable to the adverse effects of methylmercury. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-024-00239-y.

Comparative analyses of immune cells and alpha-smooth muscle actin-positive cells under the immunological microenvironment between with and without dense fibrosis in primary central nervous system lymphoma.

Histopathologic examinations of primary central nervous system lymphoma (PCNSL) reveal concentric accumulation of lymphocytes in the perivascular area with fibrosis. However, the nature of this fibrosis in "stiff" PCNSL remains unclear. We have encountered some PCNSLs with hard masses as surgical findings. This study investigated the dense fibrous status and tumor microenvironment of PCNSLs with or without stiffness. We evaluated by silver-impregnation nine PCNSLs with stiffness and 26 PCNSLs without stiffness. Six of the nine stiff PCNSLs showed pathological features of prominent fibrosis characterized by aggregation of reticulin fibers, and collagen accumulations. Alpha-smooth muscle actin (αSMA)-positive spindle cells as a cancer-associated fibroblast, the populations of T lymphocytes, and macrophages were compared between fibrous and control PCNSLs. Fibrous PCNSLs included abundant αSMA-positive cells in both intra- and extra-tumor environments (5/6, 87% and 3/6, 50%, respectively). Conversely, only one out of the seven control PCNSL contained αSMA-positive cells in the intra-tumoral area. Furthermore, the presence of extra-tumoral αSMA-positive cells was associated with infiltration of T lymphocytes and macrophages. In conclusion, recognizing the presence of dense fibrosis in PCNSL can provide insights into the tumor microenvironment. These results may help stratify patients with PCNSL and improve immunotherapies for these patients.

Clinical significance of the lymphocyte-to-monocyte ratio in multiple myeloma patients with negative minimal residual disease: a single-center retrospective analysis.

Minimal residual disease (MRD) is a surrogate marker for survival in multiple myeloma (MM), while the lymphocyte-to-monocyte ratio (LMR) is a prognostic factor associated with the patients' immunological status. We retrospectively evaluated the clinical impact of MRD negativity and LMR. MRD was analyzed by multicolor flowcytometry (threshold, 1 × 10-5). Fifty-eight patients (median age 70 years) who achieved complete response were included in this study. Twenty-two patients received autologous stem cell transplantation, 14 received daratumumab-based chemotherapy, and 22 received another treatment. Forty-one (70.7%) patients achieved MRD negativity. Over the median follow-up time of 15.1 months, PFS in MRD-negative patients was significantly longer than in MRD-positive patients (P = 0.020). In addition, a high LMR at MRD assessment was associated with MRD negativity (P = 0.019) and long PFS (P = 0.009). Finally, neither MRD negativity nor high LMR at MRD assessment was associated with significantly shorter PFS compared with MRD positivity or low LMR (P = 0.002). In conclusion, high LMR was associated with MRD negativity and can be used as a predictor of long PFS. Change of treatment strategy might be essential for patients with MRD positivity and high LMR at MRD assessment due to their short PFS.

A retrospective analysis of combination chemotherapy consisting cyclophosphamide, vincristine, prednisolone and procarbazine (C-MOPP) for pretreated aggressive non-Hodgkin lymphoma.

The C-MOPP regimen, consisting cyclophosphamide, vincristine, prednisolone and procarbazine, has been used for treatment of non-Hodgkin lymphoma; however, there are few reports of this therapy against aggressive lymphoma. We performed a retrospective analysis of previously treated 89 patients who had received C-MOPP therapy from 1999 to 2013 at our institution. Median age was 67 (range, 22-81) years. Twenty-eight patients obtained CR, 5 obtained PR, and overall response rate was 37% (33/89). The estimated 1-year overall survival and progression-free survival rates were 61 and 33%, respectively. Major grade > 2 toxicities were leucopenia (55%) and neutropenia (52%). Efficacy and toxicity were in line with other recent studies involving new agents, given that the subjects mainly consisted of elderly outpatients. These data provide a rationale for the use of C-MOPP as a current control treatment arm when the response to new cancer therapy agents is evaluated.

A study on Borna disease virus infection in domestic cats in Japan.

Borna disease virus (BDV) infection causes neurological disease in cats. Here, we report BDV infection in 199 hospitalized domestic cats in the Tokyo area. BDV infection was evaluated by detection of plasma antibodies against BDV-p24 or -p40. BDV-specific antibodies were detected in 54 cats (27.1%). Interestingly, the percentage of seropositive cats was not significantly different among the three clinical groups, i.e., healthy (29.8%), neurologically asymptomatic disease (22.2%) and neurological disease (33.3%). The specific antibodies were present even in cats aged below one year. The seropositive ratio was constant, irrespective of age and sampling season. The present study suggests that additional factors are required for onset of Borna disease in naturally infected cats and that BDV is transmitted through vertical routes in cats.

Clinical features of suicide attempts in adults with autism spectrum disorders.

OBJECTIVE: The objective of this study was to investigate the frequency and clinical features of suicide attempts in adults with autism spectrum disorders (ASDs). METHODS: We enrolled 587 consecutive patients aged 18 or over who attempted suicide and were hospitalized for inpatient treatment. Psychiatric diagnoses, suicide attempt frequency and clinical features were compared between ASD and non-ASD patients. RESULTS: Forty-three (7.3%) of the 587 subjects who attempted suicide had ASDs. The incidence of patients with mood disorders was significantly lower (Fisher's Exact Test, P=.043) and that of those with an adjustment disorder was significantly higher (Fisher's Exact Test, P<.001) in the ASD group than in the non-ASD group. The average length of stay at both the hospital and intensive care unit in the ASD group was longer than that in the non-ASD group (z=-2.031, P=.042; z=-2.322, P=.020, respectively). CONCLUSIONS: ASDs should always be a consideration when dealing with suicide attempts in adults at the emergency room.