三﨑 柚季子

Th17, a subset of helper T cells that produce interleukin-17 (IL-17), is thought to play a pivotal role in the pathogenesis of chronic graft-versus-host disease (GVHD). However, the kinetics of Th17 following allogeneic haematopoietic stem cell transplantation (allo-HSCT) have not been elucidated. In this study, we evaluated the temporal dynamics and diversity of peripherally circulating Th17 after allo-HSCT. The study included 86 patients who survived without disease relapse for 1 year or more, and for whom peripheral blood samples 3 months after allo-HSCT were available. Th17 was detected and sorted by flow cytometry, and T-cell receptor (TCR) repertoire was analysed by a next-generation sequencing (NGS) method. Patients with chronic GVHD showed a higher TCR repertoire diversity, while those with severe chronic GVHD showed a lower TCR diversity and Th17/Cluster of Differentiation (CD) 4 ratio. The amino acid sequence in complementarity determining region 3 of Th17-TCR was not apparently different between patients with and without chronic GVHD. Additionally, a higher Th17/CD4 ratio at 3 months was related to a lower incidence of subsequent chronic GVHD. The current study explored the kinetics of peripherally circulating Th17 after allo-HSCT, which might be associated with the development of chronic GVHD.

BACKGROUND: Cytomegalovirus reactivation (CMVR) after allogeneic hematopoietic cell transplantation (allo-HCT) is a reversible event, and conventional indicators such as the simple cumulative incidence cannot reflect transitional CMVR states. We propose a novel indicator, current CMVR (cCMVR), which visualizes both the occurrence and remission of CMVR over time. METHODS: To evaluate the utility of cCMVR, we analyzed 389 CMV seropositive patients who had received their first allo-HCT. cCMVR was defined as the probability of the state where anti-CMV drugs were administered for CMVR or CMV disease without relapse or death at any time. RESULTS: We compared two groups with or without letermovir prophylaxis (LTV and no-LTV groups). The 1-, 2-, 3-, and 6-month cCMVR values were 0.0%, 0.0%, 2.9%, and 2.9% in the LTV group, and 7.1%, 31.9%, 11.0%, and 0.8% in the no-LTV group. In the LTV group, cCMVR never exceeded 10%, while in the no-LTV group, cCMVR peaked at approximately 2 months after allo-HCT, and fewer than 5% of patients developed CMVR after 4 months post-HCT. Next, in the no-LTV group, we assessed cCMVR stratified according to the presence of risk factors for the simple cumulative incidence of CMVR, and this revealed that patients grafted from HLA-mismatched related donors and those who received alemtuzumab for GVHD prophylaxis appeared to experience repeated episodes of CMVR, whereas the early difference in cCMVR according to pretransplant CMV-IgG titer diminished over time. CONCLUSION: cCMVR could be a valuable indicator for visualizing recurrent CMV infection and illustrating differences in the time course of CMVR.

Thioredoxin (TXN) is a component of a major reductive system in various eukaryotes. Although oxidative stress is considered to contribute to the development of acute graft-versus-host disease (GVHD), the clinical significance of TXN remains to be elucidated. The current study included 118 patients who had undergone their first allogeneic haematopoietic stem cell transplantation (allo-HSCT) between 2022 and 2025, and their serum samples at day 0 were sequentially collected (training cohort). The study also assessed 47 patients who had undergone their first allo-HSCT between 2012 and 2015 and whose serum at around day 0 had previously been cryopreserved and was available (validation cohort). The high-TXN group showed a lower cumulative incidence of grade II-IV acute GVHD (100-day incidence: 47.5% vs. 59.2%), although the difference did not reach statistical significance (p = 0.058). The validation cohort demonstrated similar results (0% vs. 35.8%, p = 0.053). However, multivariate analysis revealed that high-TXN group was significantly associated with a reduced risk of acute GVHD (hazard ratio [HR] 0.48, p = 0.031). In addition, the combination of TXN with clinical factors enhanced the predictive potential for acute GVHD compared with that of clinical factors alone (p = 0.0039). TXN might be useful for predicting acute GVHD and could contribute to the establishment of a prediction model.

A 19-year-old woman with acute myeloid leukemia who had received a subcutaneous implantable cardioverter defibrillator (SICD) was scheduled to undergo allogeneic hematopoietic stem cell transplantation (HSCT). The conditioning regimen included total body irradiation (TBI) at a dose of 12 Gy, under which the SICD was considered at high risk for malfunction. We planned to deactivate and reactivate the SICD before and after each TBI session to mitigate the risk of device malfunction. Additionally, SICD shielding measures were implemented during TBI to minimize the risk of malfunction. Through these procedures, HSCT could be performed without significant adverse events linked to the SICD.

Systemic corticosteroids are the standard initial therapy for gastrointestinal graft-versus-host disease (GI-GVHD), but are associated with increased infectious risk and potential attenuation of graft-versus-leukemia effects. Beclomethasone dipropionate (BDP) has minimal gastrointestinal absorption and may provide localized efficacy, but evidence for monotherapy is limited. We retrospectively analyzed 37 patients who underwent first allogeneic hematopoietic cell transplantation and received oral BDP as initial monotherapy for acute GI-GVHD. Treatment response was assessed at days 28 and 56, and treatment failure was defined as initiation of systemic corticosteroids. All patients had stage 0-1 disease. Upper and lower GI-GVHD were observed in 24 (64.9%) and 13 (35.1%) patients, respectively. Response rates at days 28 and 56 were 62.9% and 65.6%. Treatment failure occurred more frequently in patients with lower GI-GVHD, female-to-male transplantation, and reduced-intensity conditioning. BDP monotherapy may be effective for selected patients with mild GI-GVHD, although careful monitoring is required in high-risk populations.