https://orcid.org/0000-0001-8329-4179
TO THE EDITOR:
We read with interest the article by Wynn et al1 published in Blood Advances, demonstrating that shared human leukocyte antigen (HLA) mismatches between the patient (PT) and the losing cord blood unit (LU) against the winning unit (WU) during double-unit cord blood transplantation (dCBT), reduced relapse risk without increasing graft-versus-host disease (GVHD). As HLA repertoire diverses across the globe, verification of these findings in other populations is warranted.
Our retrospective analysis of 54 Chinese children in Hong Kong, aged 0.8 to 16.9 years, with high-risk acute leukemia (28 lymphoblastic, 24 myeloid, 2 mixed phenotype; 25 CR1, 22 CR2, 2 CR3, 5 non-remission) revealed significantly superior 5-year overall survival (OS, 92% vs 38.7%; P < .001) and leukemia-free survival (LFS, 83.6% vs 35.5%; P < .001) in dCBT (n = 23) compared to single-unit CBT (sCBT) (n = 31). Notably, within our dCBT cohort, PT-LU sharing the same HLA mismatch with the WU achieved better 5-year OS (100% vs 80%; P = .098) and LFS (100% vs 60%; P = .015) (see figure), independent of cell dose and without increased acute GVHD (23% vs 20%). Relapse incidence was also lower (0% vs 33%, P = .013).
OS (left panel) and LFS (right panel) curves demonstrating superior survival outcomes in dCBT with “HLA vaccine effect” (red, n = 13) over dCBT without “HLA vaccine effect” (green, n = 10) and sCBT (blue line, n = 31).
OS (left panel) and LFS (right panel) curves demonstrating superior survival outcomes in dCBT with “HLA vaccine effect” (red, n = 13) over dCBT without “HLA vaccine effect” (green, n = 10) and sCBT (blue line, n = 31).
Collectively with the Wynn et al study, these observations support the hypothesis that PT-LU shares the mismatched-HLA, which in the LU serves as a “vaccine” for the WU against PT leukemia. Furthermore, the lack of increased GVHD suggests that the “effect” is specific to hematopoietic cell antigens. The survival difference between the sCBT and dCBT group without PT-LU sharing mismatched-HLA suggests that mismatched non-HLA antigen (minor HLA) might also serve as vaccine. Practically, choosing a WU a priori with favorable cell count, viability and infusion order, or selecting 2 units strategically to ensure a "vaccine effect" irrespective of which unit engrafts, may optimize transplant outcomes.
Contribution: All authors were involved in the concept and design of the study, critically reviewed the data, revised the manuscript, and approved the final version of the manuscript; and C.H.W. collected and analyzed the data and drafted the manuscript.
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Correspondence: Chi Hang Wong, Department of Pediatrics, Hong Kong Children’s Hospital, 1 Shing Cheong Rd, Kowloon, Hong Kong; email: wch857@ha.org.hk.
