Single vs double cord blood transplantation: Improved engraftment with comparable efficacy

Abstract Background: For patients with hematologic malignancies, cord blood (CB) is a widely accepted source of hematopoietic stem cells. Due to the limited cell dose in a single CB unit, patients often undergo double-unit cord blood transplantation (CBT) to reduce the risk of graft failure. However, few studies have directly compared outcomes between single- and double-unit CBT. To address this gap, we performed a retrospective analysis of CBT outcomes at our Institution. Methods: Between April of 2006 and February of 2025, 315 patients with malignant disease underwent their first single (sCBT) or double CBT (dCBT) using a myeloablative conditioning regimen with FLU 75 mg/m2, TBI 13.2 Gy, CY 120 mg/kg (n=182) or FLU 150 mg/m2, TBI 4 Gy, CY 50 mg/kg, Thiotepa 10 mg/kg (n=47) or Treo 42 g/m2, FLU 150 mg/m2, TBI 2 Gy (n=86). CB units were 4/6 to 6/6 matched to the recipient at HLA-A, B, and DRB1 antigens. HLA typing was performed at the antigen level for HLA-A and B, and high-resolution for HLA-DRB1 alleles. A sCBT was performed only when the selected unit had a minimum of 2.5 x 107 TNC/kg and 1.7 x 105 CD34/kg. For dCBT, selected units had a minimum of 1.5 x 107 TNC/kg and 1.0 x 105 CD34/kg. Graft-versus-host-disease (GVHD) prophylaxis included Cyclosporine and Mycophenolate Mofetil for all patients. Overall survival (OS) and disease-free survival (DFS) were evaluated with the Kaplan–Meier method and Cox regression. Cumulative incidences (CI) of engraftment, relapse, non-relapse mortality (NRM), and GVHD were compared with Fine–Gray models. Results: Of the 315 patients, 94 (30%) underwent sCBT and 221 (70%) dCBT. Median patient age was 32 years (range 0.6–69). sCBT recipients were significantly younger (median 9 vs 38 years, p<0.001), lighter (median 36 vs 80 kg, p<0.001), and transplanted more recently (median year 2019 vs 2014, p<0.001). Median total TNC/kg was significantly higher for sCBT vs dCBT (6 vs 5 x 107, p=0.004), though median total CD34/kg was not (0.33 vs 0.31 x 106, p=0.157). Most patients had AML (n=132, 42%), ALL (n=108, 34%), or MDS (n=31, 10%), and 115 patients (37%) had a high disease risk index (DRI). Median follow up for survivors was 5 years (range 0.2-17). sCBT engrafted faster than dCBT (neutrophils: median 18 vs 21 days, p<0.001; platelets: 32 vs 36 days, p=0.019) and achieved higher day 100 CI of neutrophil (96 % vs 92 %, p=0.002) and platelet (84 % vs 76 %, p=0.026) recovery. In univariate analyses, 5-year OS favored sCBT (70 % sCBT vs 58 % dCBT, p=0.040); DFS showed a non-significant trend also favoring sCBT (68 % vs 55 %, p=0.065). Relapse risk was similar (18 % vs 16 %, p=0.568), but NRM was lower after sCBT (14 % vs 29 %, p=0.009). Risk of grade II–IV acute GVHD (aGVHD) was more frequent with sCBT (hazard ratio 1.35, CI 1.03-1.77, p=0.029), but no difference was observed for grade III-IV aGVHD (HR 1.36, CI 0.82-2.27, p=0.230). There was a higher risk of extensive chronic GVHD (cGVHD) after dCBT (HR 1.66, CI 1.01-2.74, p=0.046). In multivariate analysis, after adjusting for age and DRI, sCBT was no longer significant for any clinical outcomes, with the exception of neutrophil (p=0.007) and platelet (p=0.004) engraftment, and extensive cGVHD remained significantly higher in the dCBT group (p=0.028). A sub-analysis restricted to adult patients (≥18 years, n=219; sCBT=27, dCBT=192) indicated inferior platelet engraftment with dCBT (HR 0.56, CI 0.35-0.88, p=0.013), with no significant differences in all other clinical outcomes. Conclusion: In our study, sCBT was not inferior to dCBT with outstanding clinical outcomes. In fact, sCBT was associated with significantly faster neutrophil and platelet recovery. These findings encourage the use of sCBT in patients with an adequate cell dose, offering the potential to substantially reduce the cost of CBT without compromising efficacy. Overall, our results support that sCBT should not be deprioritized in favor of dCBT when a suitable single unit is available.