A total of 248 patients were included in this study. Their baseline characteristics are summarized in Table 1. Median recipient age was 63 years (range, 20–82), and 63.7% of the patients were male. Karnofsky performance status (KPS) was ≤80% in more than third of patients. Almost half of the patients (47.6%) had a HCT comorbidity index of ≥3. The most common diagnoses among the patients were acute myeloid leukemia (AML) (n = 90), acute lymphoblastic leukemia (ALL) (n = 39), myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN) (n = 58), and lymphoma (n = 40). The median donor age was 32 years (range, 11–65). Donors were MRD/MUD in 32.7%, HID in 47.6% and MMUD in 19.8% of cases.

The median time to neutrophil engraftment was 18 days (range, 18–19), and the median time to platelet engraftment was 32 days (range, 30–34). Multivariate analysis (MVA) revealed no significant difference in neutrophil engraftment by day 28 based on donor type. However, recipients of MRD/MUD showed a higher rate of platelet engraftment by day 35 (P = 0.020) compared to those receiving grafts from HID and MMUD (Supplementary Table 1). There were no significant differences in engraftment rates based on patient age or donor age.

The cumulative incidence of grade II-IV acute GVHD by day 100 was 39.5% (95% CI, 33.4–45.6), and grade III-IV acute GVHD was 14.5% (95% CI, 10.5–19.2). The 1-year cumulative incidence of extensive chronic GVHD was 27.4% (95% CI, 22.0–33.1) for all patients. MVA revealed no significant differences in the incidence of acute or chronic GVHD based on donor type.

With a median follow-up for surviving patients of 24.4 months (range, 3.3–81.2), the 2-year OS, DFS, and GRFS for all patients were 60.4% (95% CI, 53.7–66.5), 55.5% (95% CI, 48.9–61.6), and 49.2% (95% CI, 43.2–56.0), respectively. The adjusted 2-year OS were 58% for HID, 55% for MMUD, and 70% for MRD/MUD (P = 0.13), the adjusted 2-year DFS rates were 52% for HID, 48% for MMUD, and 66% for MRD/MUD (P = 0.084), and the GRFS rates were 48% for HID, 40% for MMUD, and 59% for MRD/MUD (P = 0.088) (Fig. 1a–c).

Adjusted overall survival based on donor type (a), disease-free survival based on donor type (b), graft-vs-host/relapse-free survival based on donor type (c).

Lower HCT comorbidity index, low/intermediate DRI, and HCT during the recent era (2018–2021) were all associated with improved OS on MVA. Additionally, a low/intermediate DRI was linked to improved DFS and GRFS. Importantly, MVA revealed no significant differences in OS, DFS, and GRFS based on donor type, indicating that outcomes were comparable across MRD/MUD, MMUD, and HID when adjusting for other factors.

The 2-year CIR and NRM for all patients were 17.2% (95% CI, 13.0–22.8) and 27.7% (95% CI, 22.5–34.0), respectively. A high or very-high disease risk index (DRI) was significantly associated with a higher CIR (P < 0.001). NRM was notably lower in patients with KPS of ≥90% (P = 0.049). There was no significant difference in NRM based on the HCT comorbidity index. On MVA donor type had no impact on CIR or NRM (Fig. 2a, b). Table 2 summarizes the causes of death across the entire cohort and by donor type group. Overall, 62.7% of patients died from NRM, while 37.3% succumbed to disease relapse.

Adjusted non-relapse mortality based on donor type (a), and cumulative incidence of relapse based on donor type (b).

Figure 3a, b shows improvement in OS and NRM in patients with donors <35 years of age, regardless of whether a HID and MMUD was utilized. Donor age ≥35 years was associated with inferior OS (P = 0.015) and GRFS (P = 0.043) (Supplementary Table 1). While matched donors showed improved OS, DFS, and GRFS on UVA, these differences were not significant on MVA. When comparing baseline characteristics, there were significantly more matched donors in the younger donor cohort (<35 years) (P = 0.021, Supplementary Table 2). There were no differences in incidence or grade of hemorrhagic cystitis between the donor groups (Supplementary Table 3). We observed a higher incidence of fungal and viral infections with HID, while there was no difference in bacterial infections between the two groups. Moreover, there was a higher incidence of BMT CTN grade 3 infections in patients with a mismatch donor (i.e., MMUD or haplo) compared to a matched donor (MRD/MUD), 3.7% vs 11.4% (P = 0.046).

Overall survival based on donor type and age (a). Non-relapse mortality based on donor type and age (b).

Moreover, NRM was lower in patients with donors <35 years on both UVA (P = 0.008) and MVA (P = 0.028) However, there was no significant difference in NRM based on donor type on MVA. Similarly, MVA showed no differences in CIR based on donor type (P = 0.89) or age (P = 0.75). There were also no significant differences in the incidence of grade II-IV and grade III-IV acute GVHD, or in any chronic GVHD and extensive chronic GVHD, based on donor type or donor age.