Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the central nervous system (CNS) observed in immunocompromised individuals. We retrospectively evaluated the clinical courses of PML in patients with hematological malignancies at North Japan Hematology Study Group institutions, using patients with human immunodeficiency virus (HIV) infection as a reference. Eight PML patients had hematological malignancies and 9 had HIV infection. CD4 + T cell counts were markedly low in patients with hematological malignancies (median 168/μl, range 48.4–330/μl) and did not differ significantly from those in patients with HIV infection (median 28/μl, range 8–225.4/μl). IgG levels were significantly lower in patients with hematological malignancies (median 643.5 mg/dL, range 205–2478 mg/dL) than in patients with with HIV infection (median 1691.5 mg/dL, range 1304–3014 mg/dL) (p < 0.01). Almost all patients with hematological malignancies died after progression of PML (median time from onset to death, 136 days). In contrast, seven patients with HIV infection were alive at the end of follow-up. The incidence of PML in patients with hematological malignancies may increase with the introduction of new antibody drugs and cellular therapies in future. Considering the poor prognosis, greater caution is warranted regarding this serious complication.
Background:Although ustekinumab (UST) is effective in Crohn's disease (CD), long-term real-world data beyond 5 years and its effects on extraintestinal manifestations remain limited. We evaluated UST's long-term effectiveness and safety in CD. Methods:This multicenter retrospective study enrolled 317 CD patients who initiated UST between May 2017 and February 2023 at seven institutions in Japan. The primary outcome was the UST continuation rate. The secondary outcomes included factors affecting the continuation rates, surgery-free survival, endoscopic remission rates, improvement in perianal and extraintestinal manifestations, and adverse events. Results:UST continuation rates at 1, 3, and 5 years were 87.6%, 69.6%, and 66.8%, respectively, with 43 patients followed beyond 5 years (maximum 6.1 years). Multivariate analysis identified week-8 albumin ≥3.3 g/dL (HR 0.30; 95% CI, 0.12-0.72; P = .007) and week-8 C-reactive protein (CRP) ≥0.33 mg/dL (HR 2.05; 95% CI, 1.14-3.69; P = .016) as independent predictors of continuation. Endoscopic remission rates improved significantly from baseline (10%) to week 52 (19%, P < .01) and week 104 (30%, P < .01). Among perianal fistula cases (n = 60), 28% achieved clinical fistula remission and 37% showed improvement. Resolution or improvement was observed in 76% of arthritis and 86% of psoriasis-like lesion cases. The surgery-free survival rate at 5 years was 85.1%. The adverse event rate was 10.7%. Conclusions:UST demonstrated favorable medium- to long-term effectiveness and safety in CD patients with limited follow-up data beyond 5 years. Week-8 albumin and CRP levels may serve as early predictive biomarkers but require external validation in independent cohorts.
Venetoclax (VEN), a BCL-2 inhibitor, was approved in Japan in March 2021, for acute myeloid leukemia (AML). We retrospectively analyzed the impact of VEN approval on treatment patterns and outcomes in older AML patients aged 65–74 years unfit for intensive chemotherapy in Japan. Using the Hokkaido Leukemia Net database, we categorized 101 patients into pre-VEN (n = 46) and post-VEN (n = 55) cohorts, excluding those who had acute promyelocytic leukemia or received intensive chemotherapy. Following VEN approval, VEN + azacitidine (AZA) became the most frequently used initial regimen (56
In the era of immune checkpoint inhibitors for cancers, the need for prognostic biomarkers to identify patients most likely to achieve a durable response has become increasingly more relevant. Tumour-infiltrating lymphocytes (TILs) have gained significant interest, as they can be evaluated using standard haematoxylin and eosin-stained slides, making it a widely accessible and cost-effective biomarker. In addition to their practicality, TILs provide prognostic insights into the interplay between the immune system and tumour cells. While the morphological assessment of TILs has been standardised in breast cancer, comprehensive guidelines for their evaluation in gastro-oesophageal carcinomas (GEC) are still lacking. This narrative review examines the current literature on the composition, clinical implications and therapeutic utility of TILs in GEC. These insights are used to propose a framework with recommendations for standardised evaluation and reporting of TILs in GEC, while also highlighting pitfalls specific to GEC pathology. These recommendations serve as a vital first step towards the widespread use and validation of TILs as a biomarker.
