[Progressive multifocal leukoencephalopathy during the treatment for mycosis fungoides].

A 58-year-old man was diagnosed with mycosis fungoides (MF) confirmed by skin biopsy for systemic erythema that appeared in 2006 and had been on psoralen plus ultraviolet A (PUVA) therapy and topical steroids. In September 2017, he had diffuse large B-cell lymphoma and received chemotherapy. Since March 2019, tumor stage MF with large cell transformation was observed, and chemotherapy containing brentuximab vedotin (BV) was performed, which yielded a remarkable response. During the preparation for allogeneic hematopoietic stem cell transplantation, bradykinesia, delayed response, and cognitive decline were observed. Head magnetic resonance imaging fluid-attenuated inversion recovery images showed hyperintensity in the deep white matter below the bilateral frontal cortex. The general cerebrospinal fluid test revealed no abnormalities and was below the sensitivity of JC virus (JCV) quantitative PCR. As progressive multifocal leukoencephalopathy (PML) was strongly suspected from clinical symptoms and radiographic signs, ultrasensitive JCV testing was performed. The test result was positive; hence, the patient was diagnosed with PML. Chemotherapy was discontinued, but his central nervous system symptoms worsened, and he died on the 135th day of illness. We considered that PML developed based on the underlying disease and immunodeficiency caused by chemotherapy such as BV.

Improved survival among elderly patients with aggressive adult T-cell leukemia/lymphoma: Impact of mogamulizumab-containing chemotherapy.

Due to the poor prognosis of adult T-cell leukemia/lymphoma (ATL), new treatments are urgently needed, especially for elderly patients with aggressive ATL. The anti-CCR4 antibody drug mogamulizumab (MOG) has been approved for the treatment of untreated ATL. To analyze the impact of MOG on elderly patients, we conducted a retrospective analysis of patients aged 70 years and older with aggressive ATL diagnosed at our institution between 2015 and 2021. Among 32 patients, including those who received best supportive care, the median survival time (MST) and 2-year overall survival (OS) rate were 14.6 months (range, 0.0-83.7), and 34.7% [95% confidence interval (CI), 18.2-51.9], respectively, which were better than outcomes in our previous study. The MST and 2-year OS for patients treated with MOG-containing chemotherapy were 18.1 months (range, 4.0-83.7) and 45.0% (95%CI, 23.1-64.7), respectively, demonstrating clear improvement. Adverse events observed with MOG-containing treatment, such as myelosuppression and skin rash, were similar to those reported previously. Univariate analysis identified comorbidity as a predictor of poor outcomes, but not intensity of MOG-containing treatment, suggesting a different mechanism of action than that of classical chemotherapy. Our study suggests that MOG-containing treatments are an option for elderly patients with ATL.

RUNX1 expression is regulated by a super-enhancer and is a therapeutic target in adult T-cell leukemia/lymphoma.

Super-enhancers (SEs) play an important role in regulating tumor-specific gene expression. JQ1, a Bromodomain-containing protein 4 (BRD4) inhibitor, exerts antitumor effects by disrupting SE-mediated regulation of gene expression. We investigated the anti-adult T-cell leukemia/lymphoma (ATL) effects of JQ1. JQ1 induced apoptosis and inhibited ATL cell proliferation. JQ1 suppressed RUNX1expression through the disruption of SE-mediated gene regulation. In the previous reports, it was shown that IC50s of AI-10-104 and Ro5-3335, RUNX1 inhibitors were 1-10 µM for lymphoblastic leukemia cell lines carrying RUNX1 mutations. In the present study, we demonstrated that IC50s of AI-10-104 and Ro5-3335 were also 1-10 µM or lower for ATL cell lines. Simultaneously, AI-10-104 suppressed MYC proto-oncogene (c-MYC) expression. RUNX1 is a potential therapeutic target for ATL that promotes c-MYC expression. We showed that RUNX1 expression is regulated via SEs in ATL and that RUNX1 may be a novel therapeutic target for ATL.

The level of bone marrow WT1 message is a useful marker to differentiate myelodysplastic syndromes with low blast percentage from cytopenia due to other reasons.

OBJECTIVE: Myelodysplastic syndromes (MDS) are a group of hematological neoplasms associated with ineffective hematopoiesis and that transform to acute leukemia. Distinguishing MDS from other cytopenias is sometimes difficult even for trained hematologists. WT1, the gene mutated in Wilms' tumor, was found expressed in acute myeloid leukemia and MDS. The amount of WT1 in peripheral blood and bone marrow (BM) is low in low-risk MDS subtypes, and is high in high-risk MDS subtypes. However, the role of WT1 in the differential diagnosis between MDS and other diseases showing cytopenia has not been fully addressed. The present study evaluated whether WT1 expression level can assist in the differential diagnosis of MDS from other cytopenias. METHODS: The amount of WT1 message was evaluated among 56 MDS patients and 47 patients with cytopenia for various other reasons (cytopenia VR) at the Nagasaki University Hospital. RESULTS: The level of WT1 was significantly related to the percentage of blasts in BM among MDS cases, and the type of French-American-British classification of MDS; refractory anemia (RA) cases showed significantly lower WT1 level than patients with RA with excess blasts. WT1 level was significantly related to the prognostic risk categories of MDS by the International Prognostic Scoring System (IPSS) and the revised IPSS. Although the blast percentage in the BM of RA and cytopenia VR were both less than 5%, there was a significant difference in the level of WT1 between MDS and cytopenia VR. CONCLUSION: WT1 might be a good marker to differentiate low blast percentage MDS and cytopenia VR.

Long-term outcome of immunosuppressive therapy for Japanese patients with lower-risk myelodysplastic syndromes.

To investigate the long-term usefulness of immunosuppressive therapy (IST) for Japanese patients with lower-risk myelodysplastic syndromes, we retrospectively analyzed 29 MDS patients who were treated with cyclosporine A alone or with anti-thymocyte globulin at a single institute in Japan. A total of 58.6 % of patients showed hematological response to IST. Overall survival of all patients was 74.5 % at 5 years and 48.3 % at 10 years. The major adverse event was the elevation of creatinine level (grade 1 and 2). Eleven patients were still on IST at the time of analysis with, at least, some clinical benefits. Pneumonia was the most frequent cause of death (eight of 12 deaths), followed by bleeding (three of 12); most of the patients who died were non-responders. The presence of paroxysmal nocturnal hemoglobinuria-type cells was significantly associated with both response to IST and long-term survival by univariate analysis. The 10-year overall survival of responders (72.2 %) was significantly superior to that of non-responders (15.6 %, P < 0.0001). These results suggest that IST using cyclosporine A provides long-term benefit for Japanese patients with lower-risk MDS.