Improvement of Early Mortality in Single-Unit Cord Blood Transplantation for Adults During 20 Years: A Retrospective Cohort Study

Abstract

Background: The major limitation of cord blood transplantation (CBT) for adults remains the delayed hematopoietic recovery and higher incidence of graft failure, which result in a higher risk of early mortality in CBT. Methods: We evaluated early overall survival (OS), non-relapse mortality (NRM), neutrophil engraftment, acute graft-versus-host disease, and cause of early death among 9678 adult patients who received single-unit CBT in Japan between 1998 and 2017. Findings: The probability of OS at 100 days was 61.8%, 64.7%, 71.7%, and 78.9% for the periods 1998 to 2002, 2003 to 2007, 2008 to 2012, and 2013 to 2017, respectively (P<0.001). The cumulative incidences of NRM at 100 days during the same period were 33.2%, 27.6%, 20.8%, and 14.6%, respectively (P<0.001). The cumulative incidences of neutrophil engraftment were also improved during the same period (P<0.001). The most common cause of death within 100 days after CBT was bacterial infection in 1998 to 2002 and primary disease in the latter three time periods. Across the four time periods, the proportions of deaths from bacterial and fungal infection, graft failure, hemorrhage, sinusoidal obstructive syndrome, and organ failure decreased in a stepwise fashion. Landmark analysis of OS and NRM after 100 days showed that OS and NRM did not change over time in the multivariate analysis. Interpretation: Our registry-based data demonstrated a significant improvement of early NRM after CBT for adults over the past 20 years. The landmark analysis suggested that improvement of early mortality could lead to an improvement of long-term OS after CBT. Funding Statement: Japan Agency for Medical Research and Development. Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: This retrospective study complied with the Declaration of Helsinki and was approved by the institutional review board at the Institute of Medical Science, The University of Tokyo, where this study was carried out (30-70-B0128).