Post-transplant lymphoproliferative disorder after autologous peripheral stem cell transplantation in a pediatric patient

Abstract

Summary:Post-transplant lymphoproliferative disorder (PTLD) is a complication of allogeneic bone marrow transplantation (BMT). Rare cases of PTLD after autologous BMT have been reported only in adults. This case report is the first to describe PTLD in a pediatric patient after autologous peripheral stem cell transplantation (PSCT). This 2-year-old male with stage IV neuroblastoma underwent autologous PSCT. The post-PSCT course was complicated by fever with hematochezia and a lung mass. On day 94 post PSCT, colonoscopy revealed an ulcer due to a PTLD, monomorphic type, B cell phenotype, associated with Epstein-Barr virus. Fine needle aspiration identified the lung mass as neuroblastoma. PTLD can occur in pediatric autologous PSCT recipients, and may occur more frequently in autologous grafts manipulated by T cell depletion or CD34 + cell selection. Bone Marrow Transplantation (2000) 26, 1021-1024. Keywords: hematopoietic stem cell transplantation; autologous transplantation; lymphoproliferative disorders; herpesvirus; child Post-transplant lymphoproliferative disorder (PTLD) is a complication in bone marrow transplantation (BMT). 1 PTLD is more frequently associated with allogeneic BMT, particularly with immunosuppressive therapy for graft-versus-host disease or T cell-depleted marrow grafts. Autologous BMT or peripheral stem cell transplantation (PSCT) is less immunosuppressive than allogeneic BMT. There are only rare reports of PTLD following autologous BMT or PSCT, all of which occurred in adults. [2][3][4][5][6][7][8] This case report describes the first pediatric patient with an autologous PSCT to develop a PTLD associated with Epstein-Barr virus (EBV). Materials and methodsClinical information was obtained retrospectively from medical records. Endoscopic biopsy tissues were placed in Bouin's fixative and submitted for routine processing. Paraffin-embedded 4 m thick tissue sections were prepared and stained with hematoxylin-eosin for light microscopic evaluation. Paraffin section immunohistochemistry and EBV encoded RNA (EBER) in situ hybridization studies were performed using previously described methods. 9 Positive controls for EBER in situ hybridization and EBV latent membrane protein (LMP-1) immunohistochemistry stains included sections from a lymph node biopsy containing mixed cellularity Hodgkin's disease prepared with Bouin's fixative which demonstrated appropriate staining of ReedSternberg cells. PTLD was classified using previously described criteria. 10 Case historyA male child presented at age 21 months with stage IV neuroblastoma involving the left adrenal gland, left neck and axillary lymph nodes, and the right orbit. He was treated according to the Memorial Sloan-Kettering Protocol 7 with a total of six cycles of chemotherapy consisting of cyclophosphamide/vincristine/adriamycin alternated with cisplatin/VP-16. Six months after diagnosis, the adrenal mass was completely resected, followed by resection of the residual left neck mass, which demonstrated neuroblastoma. One month later, an autolog...

Successful treatment of post-transplant lymphoproliferative disorder in autologous blood stem cell transplant recipients

“…3 This is not surprising considering the fact that the incidence of PTLD after allogeneic BMT is Ͻ1% and ASCT is less immunosuppressive than allogeneic BMT. 2 Risk factors have not been defined for ASCT, but authors have speculated on the role of T cell depleting the autograft, concurrent CMV infection, and impaired cytolytic T cell response specifically to EBV.…”

“…2 Risk factors have not been defined for ASCT, but authors have speculated on the role of T cell depleting the autograft, concurrent CMV infection, and impaired cytolytic T cell response specifically to EBV. 3,7 In the autologous bone marrow patients with PTLD reported previously, three were in the context of T cell-depleted grafts, and one in a B celldepleted graft. 4,[8][9][10] One patient was also on prednisone as part of his treatment for PCP and CMV pneumonitis.…”

“…There are three previously reported patients treated with gancyclovir in the post-ASCT setting, all of whom died of their disease. 3,11,16 IVIG has not been tried as single agent therapy for PTLD. Because most MM patients are hypogammaglobulinemic, inclusion of this agent would seem reasonable.…”

“…3 These previously reported patients received ASCT for chronic myelogenous leukemia, T cell acute lymphoblastic leukemia, Hodgkin's disease, non-Hodgkin's lymphoma (NHL), multiple myeloma (MM) and neuroblastoma. Outcomes in general were poor, and the only successful treatments for PTLD were seen in two patients who received interferon (IFN).…”

T-cell large granular lymphocytic leukemia occurring after autologous peripheral blood stem cell transplantation

“…In spite of the profound myelosuppression associated with autografting, this procedure is inherently less immunosuppressive than allogeneic bone marrow transplantation and we were able to find less than 20 cases in the English literature describing PTLD following ASCT. [6][7][8] Here, we report the first case of chronic T-LGL leukemia following ASCT for angioimmunoblastic lymphoma.…”