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Expanding Cytotoxic T Lymphocytes from Umbilical Cord Blood that Target Cytomegalovirus, Epstein-Barr Virus, and Adenovirus
Published on: May 7, 2012
Posttransplant lymphoproliferative disorder after umbilical cord blood transplantation in children
Jerald Z Gong1, Michael G Bayerl, Linda M Sandhaus
1Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. gong0001@mc.duke.edu
Insights
Posttransplant lymphoproliferative disorder (PTLD) is a serious Epstein-Barr virus (EBV)-related complication in children after umbilical cord blood transplantation (UCBT). PTLD can originate from the donor or host and monomorphic histology indicates a poor prognosis.
Area of Science:
- Pediatric Hematology Oncology
- Transplantation Immunology
- Infectious Diseases
Background:
- Umbilical cord blood transplantation (UCBT) is a life-saving procedure for pediatric patients with hematologic malignancies and other conditions.
- Posttransplant lymphoproliferative disorder (PTLD) is a rare but serious complication following solid organ and hematopoietic stem cell transplantation.
- The incidence and characteristics of PTLD specifically after UCBT in children are not well-defined.
Observation:
- This report details 7 pediatric cases of PTLD occurring after UCBT, with a median onset of 4 months post-transplant.
- Patients presented with advanced disease, often involving visceral organs.
- Epstein-Barr virus (EBV) was detected in all PTLD cases, with recipients showing prior EBV infection but donors testing negative for EBV DNA.
Findings:
- PTLD in UCBT recipients can be of host or donor origin, correlating with engraftment status.
- Monomorphic PTLD histology (5 cases) was associated with a poor response to treatment and rapid mortality.
- Polymorphic PTLD histology (2 cases) showed a complete response to therapy, with one long-term survivor.
Implications:
- PTLD following pediatric UCBT is an early, EBV-driven complication requiring prompt recognition and management.
- Histological subtype (monomorphic vs. polymorphic) is a critical prognostic factor in PTLD after UCBT.
- Understanding the origin of PTLD (host vs. donor) may inform therapeutic strategies and improve outcomes in pediatric UCBT recipients.
Abstract:
Reported are 7 cases of posttransplant lymphoproliferative disorder (PTLD) arising in children who received umbilical cord blood transplantation (UCBT). There were 4 females and 3 males with a median age of 3 years (range, 1-16 years). All 7 patients received UCBT, including 1 patient who received multiple units and 1 transplanted under nonmyeloablative condition. The time interval from UCBT to PTLD averaged 4 months (range, 2 weeks to 9 months). Patients typically presented with high-stage disease with visceral organ involvement. Histology of the PTLDs showed monomorphic morphology in 5 cases and polymorphic morphology in the remaining 2 cases. Bone marrow biopsies were performed in 3 cases and were negative for PTLD. Epstein-Barr virus (EBV) was detected in the PTLD in all 7 patients by in situ hybridization. Evidence of past EBV infection was found in the recipients, but the EBV genome was not detected in the donor cord blood samples, suggesting that donor cord blood was not the source of EBV infection. The origin of the PTLD was investigated in 5 cases. PTLD was of host origin in 2 patients who failed engraftment and of donor origin in the remaining 3 patients who had complete engraftment. Four of 5 patients with monomorphic PTLD failed to demonstrate significant responses to rituximab and/or reduction of immunosuppression and died within 1 month after diagnosis. The remaining 2 patients with polymorphic PTLD showed complete response to therapy. One patient was alive 35 months after transplant, and the other patient died of infection 6 months after transplant. It is concluded that PTLD arising after UCBT in children occurs early after transplant and represents a serious EBV-related complication. PTLD may be of donor or recipient origin depending on engraftment status. Both monomorphic and polymorphic histology may be seen, and monomorphic histology appears to predict an unfavorable prognosis.
