Nobuaki Nakano

Summary: Cutaneous T‐cell lymphoma is staged by the degree of skin, lymph node, viscera and blood involvement. Skin response is a determinant of treatment decisions. Mogamulizumab, an anti‐CC chemokine receptor 4 antibody, is approved for mycosis fungoides and Sézary syndrome after ≥1 systemic therapy. Longitudinal changes in modified Severity‐Weighted Assessment Tool (mSWAT) score, and cluster of differentiation (CD)4 ⁺ CD7 ⁻ /CD26 ⁻ cell subsets during mogamulizumab treatment were investigated as an exploratory post‐hoc analysis. While chronological differences in mSWAT scores were not interpreted by a linear mixed model (LMM) due to a statistically significant interaction term, significant differences based on responses in CD7 ⁻ (−690.5/μL; 95% confidence interval [CI], −1195 to −186.2; p = 0.0076) and CD26 ⁻ (−1029/μL; 95% CI, −1705 to −353.7; p = 0.0030) cell counts were identified. Actual values of mSWAT scores decreased for responders at Week (W) 12 and 24 from baseline (BL) (mean ± standard error: BL: 97.57 ± 6.52; W12: 52.34 ± 6.16; W24: 34.89 ± 4.93) following a rapid decrease of CD7 ⁻ cells in blood at W4 (BL: 2809 ± 650.3/μL; W4: 204.4 ± 50.76/μL; W12: 101.9 ± 28.81/μL; W24: 152.8 ± 54.98/μL). Monitoring both blood and skin improvements is important for effective mogamulizumab treatment in patients with advanced stage disease.

Donor polymorphisms in killer-cell immunoglobulin-like receptor (KIR) and HLA shape natural killer (NK) cell activity, which may influence relapse risk after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, association studies have been limited by insufficient allele-level KIR genotyping. Using high-resolution, long-read genotyping of 15 KIR genes, we performed an unbiased discovery analysis in 219 patients with T-cell leukemia/lymphoma (ATL) who underwent allo-HSCT to identify relapse-associated donor KIR/HLA polymorphisms. We comprehensively tested associations between donor KIR/HLA amino acid–level combinations and relapse risk, accounting for linkage disequilibrium across KIR haplotypes, and validated the findings in independent cohorts. In ATL, KIR3DL1∗005 or KIR3DS1∗013 with glutamic acid at position 62 in the HLA-B α2 domain (HLA-B-D2-62E) and KIR3DL1∗001/∗007/∗015/∗020 with HLA-B-D2-62V (valine) were high-risk (H) combinations. Meanwhile, KIR3DL1∗015 with isoleucine at position 80 in the HLA-B α1 domain (HLA-B-D1-80I) and KIR3DL1∗001/∗005/∗007/∗020 with HLA-B-D1-80T (threonine) were low-risk (L) combinations. Compared with L-/H+ donors (n = 119), L+/H-, L-/H-, and L+/H+ donors (n = 80) showed reduced relapse (adjusted hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.19-0.65; P = 7.5 × 10-4) and improved overall survival (adjusted HR, 0.67; 95% CI, 0.45-0.98; P = .038). Those donors were associated with reduced relapse in other T-cell malignancies (n = 145; adjusted HR, 0.37; 95% CI, 0.16-0.89; P = .026) but not in acute myeloid leukemia (n = 965; P = .77), suggesting disease specificity. Low-risk combinations increased CD107a degranulation of KIR3DL1+ NK cells against HLA class I–deficient targets, consistent with enhanced NK cell education. These findings support KIR/HLA-based donor selection and underscore the role of antitumor NK cell immunity.

Purpose Physical function frequently declines after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the influence of disease status and general condition at the time of transplantation on longitudinal functional changes remains unclear. Methods This retrospective study included 135 adult patients with hematological malignancies who underwent their first allo-HSCT and completed physical function assessments before transplantation and at discharge. Handgrip strength and 6-min walk distance (6MWD) were evaluated. Patients were stratified according to disease status (complete remission [CR] vs. non-CR) and general condition (performance status [PS]). Results Both handgrip strength and 6MWD decreased significantly after transplantation in all groups. No significant differences in functional changes were observed between the CR and non-CR groups. In contrast, patients with poor PS at transplantation tended to show a greater decline in 6MWD than those with good PS. Multiple regression analysis identified PS at transplantation, age, sex, and change in the hemoglobin level as significant factors associated with changes in 6MWD. Conclusion Pre-transplant PS was associated with a greater post-transplant decline in endurance capacity, regardless of disease status. PS may serve as a practical clinical indicator for identifying patients at higher risk of physical function deterioration and guiding early targeted rehabilitation interventions.

Fludarabine/busulfan and fludarabine/melphalan are viable options as conditioning regimens. However, the optimal fludarabine‐based conditioning in cord blood transplantation (CBT) remains unclear. Therefore, this retrospective, registry‐based study aimed to analyze the impact of five fludarabine‐containing conditioning regimens on 1395 adult patients (median age, 61 years) with acute myeloid leukemia, myelodysplastic syndrome, and chronic myeloid leukemia who underwent their first CBT. Treatment outcomes of fludarabine combined with melphalan (100–140 mg/m²) and low‐dose total body irradiation (TBI; FM140T); melphalan (80–99 mg/m²) and TBI (FM80T); busulfan (12.8 mg/kg) and melphalan (FB4M); busulfan (12.8 mg/kg) and TBI (FB4T); and busulfan (6.4 mg/kg) and TBI (FB2T) were compared. The 3‐year survival rate was 67%, 53%, 44%, 36%, and 39%, respectively (p < .0001). The FM140T survival rate was the most favorable after adjusting for confounders, and the hazard ratios (vs. FM140T) for overall mortality were as follows: FM80T, 1.6 (95% confidence interval [CI], 1.2–2.2); FB4M, 2.1 (95% CI, 1.6–2.8); FB4T, 2.7 (95% CI, 2.0–3.7); and FB2T, 2.2 (95% CI, 1.6–3.1). The better survival observed with FM140T, regardless of the disease, disease risk, age, or transplant year, was attributed to the lower relapse rate and lower non‐relapse mortality (NRM) associated with fewer infectious deaths. Conversely, FB4T was associated with a higher relapse rate and higher NRM. The findings indicate that the outcomes of CBT in myeloid malignancies were highly dependent on both the alkylating agent and its dose in combination with fludarabine. Therefore, compared with fludarabine/busulfan‐based conditioning, FM140T may be the preferred regimen.

This Japanese nationwide retrospective study investigated the impact of HLA-mismatched unrelated transplantation for adult T-cell leukemia-lymphoma (ATL) patients who received transplantation between 2000 and 2018. We compared 6/6 antigen-matched related donor (MRD), 8/8 allele-matched unrelated donor (8/8MUD), and 1 allele-mismatched unrelated donor (7/8MMUD) in the graft-versus-host direction. We included 1191 patients; 449 (37.7%) were in the MRD group, 466 (39.1%) in the 8/8MUD group, and 276 (23.7%) in the 7/8MMUD group. In the 7/8MMUD group, 97.5% of patients received bone marrow transplantation, and no patients received post-transplant cyclophosphamide. The cumulative incidences of non-relapse mortality (NRM) and relapse at 4 years, and the probabilities of overall survival at 4 years in the MRD group were 24.7%, 44.4%, 37.5%, in the 8/8MUD group were 27.2%, 38.2%, and 37.9%, and in the 7/8MMUD group were 34.0%, 34.4%, and 35.3%, respectively. The 7/8MMUD group had a higher risk of NRM (hazard ratio (HR) 1.50 [95% CI, 1.13–1.98; P = 0.005]) and a lower risk of relapse (HR 0.68 [95% CI, 0.53–0.87; P = 0.003]) than the MRD group. The donor type was not a significant risk factor for overall mortality. These data suggest that 7/8MMUD is an acceptable alternative donor when an HLA-matched donor is unavailable.

Differentially expressed mRNAs, significantly enriched pathways, and differentially expressed ADTs between clusters or subclusters