Chronic graft-versus-host disease following umbilical cord blood transplantation: retrospective survey involving 1072 patients in Japan

Abstract

We have little information on chronic graftversus-host disease (GVHD) after cord blood transplantation (CBT). We investigated its clinical features in 1072 Japanese patients with hematologic malignancies who received a transplant through the Japan Cord Blood Bank Network. The primary end point was to investigate the incidence of any chronic GVHD. Median age of the patients was 33 years (range, 0-79 years). The cumulative incidence of chronic GVHD 2 years after transplantation was 28%. Chronic GVHD was fatal in 29 patients. Multivariate analysis demonstrated that development of chronic GVHD was favorably associated with both overall survival and event-free survival. Multivariate analysis identified risk factors of chronic GVHD: higher patient body weight, higher number of mismatched antigens for GVHD direction, myeloablative preparative regimen, use of mycophenolate mofetil in GVHD prophylaxis, and development of grades II to IV acute GVHD. Although chronic GVHD is a significant problem after CBT, it is associated with improved survival, perhaps due to graft-versus-malignancy effects. IntroductionChronic graft-versus-host disease (GVHD) is a significant concern in allogeneic hematopoietic stem cell transplantation (HSCT). Many studies have been published on clinical features of chronic GVHD following bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT). In contrast, we have limited information on chronic GVHD following cord blood transplantation (CBT). MethodsInformed consent was obtained in accordance with the Declaration of Helsinki. According to local policy, the study was approved by Japan Cord Blood Bank Network. We had no direct contact with human subjects during our study; data on patients who underwent CBT were obtained from the Japan Cord Blood Bank Network. The primary end point of this study was to investigate the incidence of any chronic GVHD after CBT. Cord blood units are provided with written informed consent. Between June 1997 and August 2006, 2713 cord blood transplant recipients were registered with the Japan Cord Blood Bank Network. All recipients received a single cord blood unit. We included those with hematologic malignancies who underwent CBT without T-cell depletion. We excluded patients with a history of any type of allogeneic HSCT prior to CBT. A total of 2015 patients met the criteria. Of those, we excluded 943 with disease progression, death without progression, and graft failure within 100 days after transplantation. In this study, we retrospectively investigated clinical features of chronic GVHD in the remaining 1072 patients. Cytomegalovirus-seropositive cord blood unit was not provided to transplantation centers. Acute and chronic GVHD were diagnosed and graded according to standard criteria. 1,2 GVHD that developed after day 100 was defined as chronic GVHD. If the mode of presentation for chronic GVHD was progressive, the date of onset was defined as day 100. SAS version 9.1.3 (SAS Institute, Cary, NC) was used for all statistical analyses. Res...

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