Background Reduced-intensity conditioning (RIC) used for allogeneic hematopoietic cell transplantation (allo-HCT) is generally associated with lower non-relapse mortality (NRM) but higher risk of relapse compared to myeloablative conditioning (MAC). However, the magnitude of benefits and risks associated with each conditioning intensity may vary depending on patient characteristics. Thus, selection of the optimal regimen intensity for individual patients remains a clinical challenge. We previously proposed the Risk assessment for the Intensity of Conditioning regimen in Elderly patients (RICE) score to identify patients expected to experience reduced NRM with RIC, using a large Japanese registry database (Akahoshi et al. Blood Advances 2023). The score is based on three factors: advanced patient age (≥60 years), a HCT Comorbidity Index (HCT-CI) of ≥2, and use of umbilical cord blood (UCB). The RICE score is calculated as the sum of these factors: scores of 0 or 1 indicate a low RICE score, while 2 or 3 indicate a high RICE score. Comparing RIC and MAC in the Japanese validation cohort, NRM was significantly lower with RIC in patients with a high RICE score but not significantly different in patients with a low RICE score. Although the RICE score was validated in a large Japanese cohort, notable differences in baseline characteristics—such as race and donor source selection—between Japanese and Western populations warrant further validation. This study aimed to evaluate the robustness of the RICE score using a publicly available dataset from the Center for International Blood and Marrow Transplant Research (CIBMTR).

Methods This study used a CIBMTR registry, originally prepared for a previously published study (Bejanyan et al. Transplant Cell Ther. 2021). It included patients aged 40 to 65 years with AML or MDS who underwent first allo-HCT (2009-2015). To reduce heterogeneity related to HCT for active disease, all MDS cases were included regardless of disease status, while AML cases were limited to those in first or second complete remission.

The analysis was further restricted to patients who received conventional GVHD prophylaxis with a calcineurin inhibitor plus either methotrexate or mycophenolate mofetil, and one of four commonly used conditioning regimens: (1) total body irradiation plus cyclophosphamide (CyTBI); (2) busulfan plus cyclophosphamide (BuCy); (3) fludarabine plus busulfan (FluBu); or (4) fludarabine plus melphalan (FluMel). The primary endpoint was NRM, compared between MAC and RIC, stratified by the RICE score.

Results This study identified 1,727 (66.6%) and 868 (33.4%) patients who received MAC and RIC regimens, respectively. A high RICE score was observed in 168 patients (9.8%) in the MAC group and 260 patients (30.0%) in the RIC group. NRM at 4 years among patients with a low RICE score was 22.7% in the RIC group and 23.5% in the MAC group (P=0.403). In patients with a high RICE score, the 4-year NRM was significantly lower in the RIC group compared to MAC group (26.1% vs. 37.3%, P=0.018). In sub analyses limited to patients with a RICE score of 1, RIC was not associated with significant reduction of NRM compared to MAC (23.7% vs. 25.3%, P=0.345). The relapse rate was significantly lower in the MAC group regardless of RICE score (low RICE: 33.2% vs. 42.8%, P<0.001; high RICE: 31.5% vs. 39.6%, P=0.033). As a result, disease-free survival (DFS) at 4 years was significantly lower after RIC in patients with a low RICE score (34.5% vs. 43.3%, P<0.001) but similar between RIC and MAC in those with a high RICE score (34.3% vs. 31.1%, P=0.909). These findings were further confirmed in multivariate analyses. In the high RICE score cohort, RIC compared to MAC was associated with lower NRM (HR 0.69; 95% CI, 0.48–0.99; P=0.048) and higher relapse risk (HR 1.48; 95% CI, 1.06–2.08; P=0.023), but similar DFS (HR 1.01; 95% CI, 0.79–1.29;P=0.944). In contrast, for patients with a low RICE score, MAC conferred benefits by resulting in similar NRM (HR 0.86; 95% CI, 0.70–1.06; P=0.150), lower relapse (HR 1.46; 95% CI, 1.23–1.72; P<0.001), and improved DFS (HR 1.22; 95% CI, 1.08–1.38; P=0.002).

ConclusionThe RICE score successfully identified patients who benefit from lower NRM of RIC in the CIBMTR dataset, validating findings reported using a Japanese cohort. These results support the importance of the RICE score in guiding personalized clinical decision-making of conditioning intensity.

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2025
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