Masao Ogata’s research while affiliated with Oita University and other places

Genetic factors, inflammatory cytokines such as interleukin (IL)‐6 and tumor necrosis factor‐α (TNF‐α), and uremic substances such as 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid (CMPF) have been reported to affect organic anion transporting polypeptide (OATP)1B1 transport activity. However, the relationship between OATP1B1 transport activity and these factors in patients with cancer cachexia has not been reported. This study aimed to identify the factors contributing to individual differences in OATP1B1 transport activity in patients with cancer cachexia, using coproporphyrin‐I (CP‐I) as an endogenous biomarker of OATP1B1 transport activity. The study recruited 114 patients with cancer cachexia who satisfied the selection criteria. The subjects were classified into pre‐cachexia, cachexia, and refractory cachexia. Median [interquartile range] plasma CP‐I level was higher in patients with pre‐cachexia (0.91 [0.67–1.12] ng/mL) compared with the data in the general population reported previously and tended to be higher in patients with refractory cachexia (1.06 [0.78–1.64] ng/mL) than in those with cachexia (0.87 [0.62–1.07] ng/mL), suggesting that OATP1B1 transport activity may decrease with the progression of cancer cachexia. Plasma CP‐I correlated positively with IL‐6 and TNF‐α concentrations but did not correlate with OATP1B1 polymorphisms or CMPF concentration, which have been reported to reduce transport activity. Multiple regression analysis using the forced entry method identified refractory cachexia as a significant factor independently affecting plasma CP‐I concentration. These findings suggest that the reduction in OATP1B1 transport activity in patients with cancer cachexia may be attributed to inflammatory cytokines or some other factors that are elevated by cancer cachexia progression, rather than OATP1B1 polymorphisms and CMPF.

Introduction Understanding differences in clinical outcomes between PBSCT and BMT is important, and this study compared outcomes of HLA‐matched related PBSCT and BMT using reduced‐intensity conditioning (RIC) in adult acute myeloid leukemia (AML) patients. Methods Data from 402 patients who underwent either PBSCT ( n = 294) or BMT ( n = 108) between 2000 and 2022 were analyzed using the Japanese nationwide registry database. The primary endpoint was overall survival (OS), and secondary endpoints included disease‐free survival (DFS), non‐relapse mortality (NRM), and GVHD. Results Results indicated no significant difference in 3‐year OS (44.6% for PBSCT vs. 46.9% for BMT, HR 1.173, P = 0.299) and DFS (42.1% vs. 41.8%, HR 1.073, P = 0.639). PBSCT was more beneficial for avoiding relapse (20.3% vs. 12.4%, HR, 0.715, P = 0.059). However, PBSCT was associated with higher NRM (20.3% vs. 12.4%, HR 1.801, P = 0.025) due to more frequent, chronic GVHD (HR 1.889, P = 0.035). Subgroup analysis did not reveal specific patient groups that benefited more from PBSCT or BMT. Incidence of extensive chronic GVHD and NRM has improved in PBSCT recipients in recent years (2014–2022). Conclusions We conclude that related PBSCT with RIC regimens offers comparable prognosis to BMT for adult AML patients. Further optimization of prophylactic strategies for chronic GVHD is required to improve outcomes after PBSCT.

Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) provides durable remission for patients with adult T‐cell leukemia/lymphoma (ATL); however, few studies have focused on post‐transplant outcomes in ATL patients ≤49 years. To clarify prognostic factors in ATL among patients <40 years (adolescents and young adult [AYA]; n = 73) and 40–49 years (Young; n = 330), we conducted a nationwide retrospective study. Estimated 3‐year overall survival (OS) rates were 61.8% and 43.1% in AYA and Young patients, respectively (p = 0.005). In the multivariate analysis, Young patients showed worse OS (Hazard ratio (HR) [95% confidential interval] 1.62 [1.10–2.39], p = 0.015), chronic graft‐versus‐host disease (GVHD)‐free and relapse‐free survival (CRFS) (HR 1.54 [1.10–2.14], p = 0.011), and GVHD‐free and relapse‐free survival (GRFS) (HR 1.40 [1.04–1.88], p = 0.026) than AYA patients. No significant differences were observed in OS, CRFS, or GRFS between the myeloablative conditioning (MAC) and reduced‐intensity conditioning (RIC) regimens; however, non‐relapse mortality was significantly lower in patients with the RIC regimen than those with the MAC regimen (HR 0.46 [0.24–0.86], p = 0.015). In summary, OS was worse in Young patients than in AYA patients in the allo‐HSCT setting for ATL. Furthermore, the RIC regimen has potential as an alternative treatment option for ATL patients ≤49 years.

The impact of letermovir (LTV)—an anti-cytomegalovirus (CMV) drug—on human herpesvirus-6 (HHV-6) encephalitis is unclear. We hypothesized that LTV prophylaxis may increase the incidence of HHV-6 encephalitis by reducing anti-CMV therapies after allogeneic hematopoietic stem cell transplantation (HSCT). To evaluate the association between HHV-6 encephalitis and antiviral prophylaxis, 7985 adult patients from a nationwide registry who underwent their first HSCT between January 2019 and December 2021 were analyzed. The incidence of HHV-6 encephalitis on day 100 after HSCT was 3.6%; 11.5% for the broad-spectrum antiviral group (foscarnet, ganciclovir, or valganciclovir); 2.8% for the LTV group, and 3.8% for the other antiviral group (p < 0.001). These differences persisted when cord blood transplantation (CBT) was analyzed separately (14.1%, 5.9%, and 7.4%, p < 0.001). In the multivariate analysis, CBT (hazard ratio [HR]: 2.90), broad-spectrum antiviral prophylaxis (HR: 1.91), and grade II–IV acute graft-versus-host disease requiring systemic corticosteroids (HR: 2.42) were independent risk factors for encephalitis (all p < 0.001). The findings of this large modern database study indicate that broad-spectrum antiviral prophylaxis, rather than LTV prophylaxis, is paradoxically associated with HHV-6 encephalitis in the LTV era. This paradoxical finding needs to be further explored in future studies. Graphical abstract

Patients with hematological malignancies (HM) often receive tazobactam/piperacillin (TAZ/PIPC) and glycopeptide antibiotics for febrile neutropenia. The effect of concomitant use of TAZ/PIPC on risk of teicoplanin (TEIC)-associated acute kidney injury (AKI) remains unclear. We investigated the impact of concomitant TAZ/PIPC use on TEIC-associated AKI in HM patients and identified the risk factors. In this retrospective, single-center, observational cohort study, 203 patients received TEIC, 176 of whom satisfied the selection criteria and were divided into TEIC cohort (no TAZ/PIPC; n = 118) and TEIC + TAZ/PIPC cohort (n = 58). AKI was defined as serum creatinine increase ≥0.3 mg/dL within 48 h or ≥50% from baseline. Incidence of AKI in TEIC cohort before and after propensity score matching was 9.3 and 5.9%, respectively, and that in TEIC + TAZ/PIPC cohort was 10.3 and 11.8%. AKI incidence and risk were not significantly different between two cohorts before (p = 0.829; odds ratio (OR) 1.122, 95% confidence interval (CI) 0.393–3.202) and after matching (p = 0.244; OR 2.133, 95% CI 0.503–9.043). Logistic regression analysis with factors clinically or mechanistically potentially related to TEIC-associated AKI, including concomitant TAZ/PIPC use, as independent variables identified baseline hemoglobin level as the only significant risk factor for TEIC-associated AKI (p = 0.011; OR 0.484, 95% CI 0.276–0.848). In HM patients treated with TEIC, concomitant TAZ/PIPC use did not increase AKI risk whereas lower hemoglobin levels had higher risk for TEIC-associated AKI development, suggesting the necessity to monitor serum creatinine when using TEIC in patients with anemia. Fullsize Image