Masatoshi Sakurai

Summary: Unrelated cord blood transplantation (CBT) is an important alternative donor option for adult patients with myelodysplastic syndrome (MDS); however, the prognostic significance of cord blood unit characteristics following CBT remains unclear and may vary according to disease risk. We conducted a nationwide retrospective study of 1767 adult patients with MDS who underwent first single‐unit CBT between 1999 and 2023, including 529 patients with low‐risk and 1238 with high‐risk disease at transplantation. Cord blood unit characteristics were not significantly associated with disease‐free survival (DFS) in patients with low‐risk MDS. In contrast, in patients with high‐risk MDS, higher cryopreserved cluster of differentiation (CD)34 ⁺ cell dose and higher colony‐forming unit–granulocyte/macrophage dose were associated with improved DFS, whereas human leucocyte antigen (HLA) serological one‐locus mismatch and female‐to‐male donor–recipient sex mismatch were independently associated with inferior DFS. Restricted cubic spline Cox regression demonstrated a significant non‐linear association between CD34 ⁺ cell dose and DFS, as well as relapse, in high‐risk MDS. These findings demonstrate that the prognostic impact of cord blood unit characteristics after single‐unit CBT differs according to MDS risk status and support a risk‐adapted approach to cord blood unit selection, particularly for patients with high‐risk MDS.

This study aimed to determine the clinical profile and disease burden of patients with paroxysmal nocturnal hemoglobinuria (PNH) in Japan using real-world data from the Adelphi Real World PNH Disease Specific Programme (DSP)™, a cross-sectional survey conducted between January and December 2022. Data included demographics, treatment, and clinical values (hemoglobin [Hb] and lactate dehydrogenase [LDH]). Patient-reported outcome measures included the EQ-5D-5L and the FACIT-Fatigue. Seventeen physicians provided information on 45 patients, among whom 86.7% were receiving treatment with complement 5 inhibitors (C5i). Median (IQR) age was 65.0 (54.5, 73.0) years; 55.6% were male. Among C5i-treated patients (n = 39), 51.3% received ravulizumab and 48.7% eculizumab, for a median (IQR) duration of 1.6 (1.0, 2.7) years. Median (IQR) Hb level was 7.2 (7.0, 8.1) g/dL at diagnosis and 10.0 (8.8, 10.6) g/dL at survey; 91.4% had LDH levels exceeding 1.5 times the upper limit of normal at diagnosis, 11.4% at survey. Twelve patients returned a self-completed questionnaire. Patient-reported symptoms included tiredness (83.3%), shortness of breath (75.0%), and anemia (58.3%). Mean (SD) EQ-5D-5L and FACIT-Fatigue scores were 0.73 (0.16) and 32.3 (7.1). Even C5i-treated patients continued to experience substantial disease burden, highlighting the need for more effective treatments to improve quality of life.

Pre‐engraftment syndrome (PES) is a unique complication of cord blood transplantation (CBT) whose risk factors and impact on transplant outcomes remain controversial. Using a nationwide database in Japan, we analyzed a total of 3734 patients who underwent single‐unit CBT. PES occurred in 18.3% of patients, and risk factors for PES included a higher hematopoietic cell transplantation‐specific comorbidity index, first transplantation, myeloablative conditioning (MAC), lower total nucleated cell (TNC) dose, and graft‐versus‐host disease (GVHD) prophylaxis regimens excluding tacrolimus with methotrexate. Patients who developed PES had significantly higher incidences of grade II–IV acute GVHD (53.1% vs. 31.3%, p < 0.001) and chronic GVHD (27.2% vs. 21.7%, p = 0.002) compared to those without PES. Landmark analysis with multivariable adjustment revealed that PES was independently associated with increased non‐relapse mortality (NRM, hazard ratio [HR] 1.46; 95% CI 1.22–1.75; p < 0.001), reduced relapse incidence (HR 0.78; 95% CI 0.63–0.96; p = 0.020), and a trend toward inferior overall survival (OS, HR 1.13; 95% CI 0.98–1.30; p = 0.088). Moreover, patients who experienced both PES and acute GVHD had the highest 2‐year NRM (31.7%; 95% CI 26.0%–37.6%) and the lowest 2‐year OS (55.9%; 95% CI 50.0%–62.4%), compared with those who experienced either PES (NRM 20.7%; OS 65.0%) or acute GVHD (NRM 19.5%; OS 62.8%) ( p < 0.001), highlighting the combined effects of these complications. This study, the largest to date on PES, demonstrates its clinical significance as an early complication with lasting effects on transplant outcomes.

Pleural effusion following chimeric antigen receptor (CAR) T-cell therapy is typically transient, bilateral, and associated with cytokine release syndrome (CRS). We herein report persistent unilateral massive pleural effusion with CAR T-cell infiltration in a 34-year-old man with refractory primary mediastinal large B-cell lymphoma involving pleural lesions treated with axicabtagene ciloleucel. Flow cytometry confirmed CAR T-cell infiltration into the pleural fluid. Although temporarily improved by corticosteroids, the effusion persisted for several months but eventually resolved spontaneously. Physicians should consider CAR T-cell infiltration in persistent unilateral pleural effusion after CAR T-cell therapy, emphasizing the importance of flow cytometry for the diagnosis and potential spontaneous resolution without corticosteroids.

Phlegmonous gastritis (PG) is a rare, life-threatening bacterial infection characterized by thickening of the gastric wall. We report a case of PG in a 17-year-old male following allogeneic hematopoietic stem cell transplantation for severe aplastic anemia. Seven months after transplantation, the patient presented with severe abdominal pain, fever, and significant gastric wall thickening on CT. Initial antibiotic therapy was initiated immediately. The patient developed multiple organ failure; however, his condition rapidly improved with intensive care. After two weeks, the patient improved and was successfully discharged. This is the first report of PG after transplantation, highlighting the need for an early diagnosis and treatment.

Clinically significant cytomegalovirus infection (csCMVi) is frequently observed after allogeneic hematopoietic stem cell transplantation (HSCT) and prophylaxis with letermovir is commonly adopted. However, the clinical benefit of letermovir prophylaxis according to graft sources has not been sufficiently elucidated. We retrospectively analyzed 2194 recipients of HSCT who were CMV-seropositive (236 with letermovir prophylaxis and 1958 without prophylaxis against CMV). csCMVi was significantly less frequent in patients with letermovir prophylaxis than in those without (23.7% vs 58.7% at 100 days after HSCT, P < .001) and the same trend was seen when recipients of bone marrow (BM), peripheral blood stem cell (PBSC), or cord blood (CB) transplantation were separately analyzed. In recipients of BM, nonrelapse mortality (NRM) was significantly lower in the letermovir group at 6 months after HSCT (5.0% vs 14.9%, P = .018), and the same trend was observed in recipients of PBSCs (14.7% vs 24.8%, P = .062); however, there was no statistical significance at 1 year (BM, 21.1% vs 30.4%, P = .67; PBSCs, 21.2% vs 30.4%, P = .096). In contrast, NRM was comparable between recipients of CB with and without letermovir prophylaxis throughout the clinical course (6 months, 23.6% vs 24.3%, P =.92; 1 year, 29.3% vs 31.0%, P = .77), which was confirmed by multivariate analyses. In conclusion, the impact of letermovir prophylaxis on NRM and csCMVi should be separately considered according to graft sources.

Chronic myelomonocytic leukaemia (CMML) is a haematological malignancy with a poor prognosis. Allogeneic haematopoietic stem cell transplantation remains the only curative approach. Without human leucocyte antigen-matched related sibling donors, the optimal alternative donor has yet to be established. Although unrelated bone marrow transplantation (UBMT) has been extensively studied, cord blood transplantation (CBT) for CMML remains largely unexplored. This nationwide retrospective study compared the outcomes of UBMT and single-unit umbilical CBT in patients with CMML. This study included 118 patients who underwent their first allo-HSCT during 2013–2021. Of these, 50 received BMT (UBMT group), while 68 underwent CBT (CBT group). The primary endpoint was the 3-year overall survival (OS). There were comparable 3-year OS rates between the UBMT (51.0%, 95% confidence interval [CI]: 34.1–65.5%) and CBT (46.2%, 95% CI: 33.2–58.1%; P = 0.60) groups. In the inverse probability of treatment weighting analysis, CBT did not show significantly improved outcomes compared with UBMT regarding the 3-year OS rate (hazard ratio 0.97 [95% CI: 0.57–1.66], P = 0.91). Thus, CBT may serve as an alternative to UBMT for patients with CMML. Further research is necessary to optimise transplantation strategies and enhance outcomes in patients with CMML undergoing CBT.