Koji Kawamura

Graft-versus-leukemia (GVL) effect is mainly mediated by alloreactive T and NK cells through human leukocyte antigen (HLA). Although most HLA genes are located on the short arm of chromosome 6, the clinical significance of deletion of the short arm of chromosome 6 (del6p) which could attenuate the GVL effect has not been elucidated. We investigated impact of del6p at the diagnosis of hematological malignancies on allogeneic cell transplantation, using a Japanese registry database. Del6p was highly associated with additional chromosomal abnormalities. In the univariate analysis, the del6p group showed a higher incidence of relapse at 2 years among the entire cohort (2y-relapse 48.3% vs 25.7%, P <0.001). Multivariate analysis confirmed that del6p was significantly associated with an increased risk of relapse (HR 1.30 [95% CI: 1.02-1.65], P = 0.036). The del6p group also tended to be associated with relapse, when focusing on patients with complex karyotype (HR 1.25 [95% CI: 0.97-1.60], P = 0.079). Additionally, the impact of del6p on relapse was more evident in the HLA-mismatched than in the HLA-matched cohort. These results suggest that del6p at diagnosis might attenuate the GVL effect through HLA status.

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.

Despite recent advances, data on allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients aged ≥70 years remain limited. We identified prognostic factors and developed a risk score to guide transplant eligibility. Using the Japanese Transplant Registry Unified Management Program, we retrospectively analyzed 929 patients aged ≥70 years who underwent their first allo-HSCT for hematologic malignancies between 2000 and 2022. Prognostic factors were identified by multivariate Cox regression to construct a scoring system. The median patient age was 71 years (range, 70-88), with acute myeloid leukemia being the most common disease. The 2-year overall survival (OS) rate was 34.2%. Multivariate analysis identified age ≥75 years, ATL, lymphoma, high disease risk, hematopoietic cell transplant-specific comorbidity index ≥5, and performance status ≥2 as adverse factors. Using the hazard ratio-based scoring system derived from multivariate analysis, patients were stratified into low- (0), intermediate-1- (1), intermediate-2- (2-3), and high-risk (4-5) groups, with 2-year OS rates of 57.1%, 35.0%, 18.3%, and 2.5%, respectively (p < 0.01). We identified prognostic factors and developed a scoring system stratifying survival in patients aged ≥70 years, potentially facilitating the selection of older candidates most likely to benefit from allo-HSCT.

Although allogeneic hematopoietic stem cell transplantation (allo‐HCT) is considered a potentially curative therapy for multiple myeloma, disease progression after allo‐HCT remains a major limitation. Post‐transplant maintenance therapy may help reduce the risk of relapse. Lenalidomide, an immunomodulatory agent, has demonstrated efficacy in multiple myeloma, but its use after allo‐HCT is limited due to concerns regarding graft‐versus‐host disease (GVHD). To evaluate the maximum tolerated dose (MTD) and dose‐limiting toxicity (DLT) of lenalidomide when used as maintenance therapy after allo‐HCT for multiple myeloma. This was a prospective, multicenter, phase I/II clinical trial conducted from 2014 to 2019. Lenalidomide maintenance therapy was initiated 100–365 days post‐allo‐HCT. Eligible patients received lenalidomide on days 1–21 of a 28‐day cycle for at least four cycles, beginning at 5 mg/day. A standard 3 + 3 dose‐escalation design (Fibonacci method) was used to determine DLT and MTD. The study included 10 patients; one was excluded due to early disease progression, leaving nine patients evaluable for toxicity. The phase II portion was not conducted due to expiration of the trial period. The median interval from allo‐HCT to initiation of lenalidomide was 244 days (range, 169–330 days). At the 10 mg/day dose level, one patient experienced moderate chronic GVHD meeting the predefined criteria for DLT. No other DLTs occurred, establishing the MTD at 10 mg/day. No acute GVHD was observed. Two additional patients developed mild chronic GVHD, which resolved spontaneously without treatment. The 2‐year progression‐free survival (PFS) and overall survival (OS) rates from the start of maintenance therapy were 53% and 78%, respectively. Late initiation of lenalidomide maintenance therapy after allo‐HCT for multiple myeloma was feasible at a dose of 10 mg/day and was associated with a low incidence of GVHD‐related complications. However, further studies are required to confirm treatment efficacy.