High Incidence of Posttransplant Lymphoproliferative Disorder after Unrelated Cord Blood Transplantation.

Though posttransplant lymphoproliferative disorder (PTLD) is a well-documented complication arising in recipients of solid organ or hematopoietic stem cell transplantation, data about PTLD following cord blood transplantation (CBT) are limited. Currently less than 20 cases of PTLD have been described after CBT in the literature world-wide. However, we hypothesized that several factors such as relatively lower number and naïve nature of cord blood T-lymphocytes, frequent donor-recipient HLA disparity and in vivo T-cell depletion by ATG might lead unrelated cord blood recipients more susceptible to PTLD. We retrospectively reviewed the medical records of 45 pediatric recipients who received unrelated CBT at our institution from Jan 2002 to Jan 2006. At least 4/6 matched cord blood units were selected for transplant and some patients (n=10) received double cord blood units. ATG was included in the preparative regimen in all but one case. Cyclosporine with either methyl-prednisolone or mycophenolate mofetil were used for GvHD prophylaxis. We assessed the cumulative incidence, clinical features, pathologic findings, and treatment results of PTLD after unrelated CBT. Only pathologically proven cases were included for analysis. Five patients developed PTLD at 3 to 8 mo posttransplant (median, 4 mo). The cumulative incidence of PTLD was 14.1% at 2 year estimated by Kaplan-Meier method. Four of the 5 patients were positive for EBV serology before transplant. The involved sites were variable such as lymph nodes, brain, lung, liver, kidney, parotid gland, and colon. Three patients had multiple sites of PTLD involvement. Biopsied samples of 5 patients revealed diffuse CD20 positivity (n=4), positive for EBV in situ hybridization and/or EBNA/LMP (n=4), monomorphic (n=2), and polymorphic (n=3) histology. One patient had lesions showing diffuse CD3 positivity instead of CD20 suggesting T-PTLD. Two patients with monomorphic disease were cured with rituximab therapy and 2 of 3 with polymorphic PTLD became free of disease after immune withdrawal. The other one with polymorphic B-PTLD underwent progressive course despite immune withdrawal and rituximab therapy. In conclusion, the incidence of PTLD after unrelated CBT in this study was much higher than previously reported. Clinical suspicion and thorough diagnostic work-up followed by early therapeutic intervention should be given not to miss the potentially curable disease.