Favorable Outcomes of Single-Unit Cord Blood Transplantation As Salvaged Treatment for Advanced Hematologic Malignancies

Treatments of advanced hematologic malignancies are limited, and the effects are very poor even after allogeneic hematopoietic stem cell transplantation. Recent study showed that cord blood transplantation was benefit for patients with pretransplantation minimal residual disease compared to both HLA-matched and HLA-mismatched unrelated donor transplantation. The relapse rate was lowest in cord blood transplantation group. But the effect of cord blood transplantation in advanced hematologic malignancies as salvaged treatment still remains unknown. We retrospectively analyzed 55 consecutive patients with advanced hematologic malignancies who received single-unit unrelated cord transplantation at our centre between December 2013 and December 2016. Among the patients, 42with acute leukemia, 8 with myelodysplastic syndrome (MDS with refractory anemia with excess blasts [RAEB]), 4 with CML-BC and 1 with plasma cell leukemia. All of them were in non-remission before transplantation. The median age was 10 years (range, 2-43 years), and the median weight was 31 kg (range, 9-82kg).All the patients received intensified conditioning regimen and a combination of CsA and MMF as GVHD prophylaxis. The infused total nucleated cell (TNC) dose was 4.99 (range 2.17-13.9) × 10⁷/kg and CD34⁺ cell dose was 2.53 (range 0.64-7.45) × 10⁵/kg. Neutrophil and platelet engraftment occurred in 49 (89.1%) and 42 (76.4%) patients, respectively. The median times to neutrophil recovery and platelet recovery were 16 days (range, 12-32 days) and 37.5 days (range, 18-83 days), respectively. Forty patients (72.7%) experienced pre-engraftment syndrome (PES). The cumulative incidence rates of II-IV acute GVHD and chronic GVHD were 25.5% (95% CI, 14.8-37.6%) and 18.8% (95% CI, 8.6-32.1%), respectively. The median follow-up period for the surviving patients was 654 days (range, 208 to 720 days). The probability of 2- year OS and LFS were 53.9% and 46.8%, respectively, whereas the cumulative incidence of 2-year NRM and relapse rate were 34.5% (95% CI, 21.6-47.8%) and 20.7% (95% CI, 10.9-32.7%), respectively. To further define the importance of matching at the HLA C locus on our special patient cohort outcomes, we analyzed the effect of HLA C disparity on patient outcomes. Results showed that although OS, LFS and NRM were not significantly different between the two groups, the relapse rate was significantly higher after transplantations with matched at HLA C(n=12) than mismatched at HLA C(n=42)(58.5% VS 27.9%,P=0.0426).Since the favorable outcomes, our results showed that single-unit cord blood transplantation might be a feasible choice as salvaged treatment for advanced hematologic malignancies, even in patients with a high leukemia burden. Choosing the cord blood with mismatch at HLA C locus might reduce the relapse rate without increasing the NRM in our special patient cohort, but this metric still requires further evaluation with a larger cohort.