An unexpectedly high incidence of Epstein-Barr virus lymphoproliferative disease after CD34+ selected autologous peripheral blood stem cell transplant in neuroblastoma

• Published in: Bone marrow transplantation (Basingstoke) Vol. 33; no. 6; pp. 651 - 657
• Main Authors: POWELL, J. L, BUNIN, N. J, CALLAHAN, C, APLENC, R, GRIFFIN, G, GRUPP, S. A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.03.2004; Nature Publishing Group UK
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antigens, CD - blood; Antigens, CD34 - immunology; Autografts; Biological and medical sciences; Blood; Bone marrow, stem cells transplantation. Graft versus host reaction; Case reports; CD34 antigen; Chemotherapy; Child, Preschool; Clinical trials; Epstein-Barr virus; Epstein-Barr Virus Infections - epidemiology; Female; Hematologic and hematopoietic diseases; Hematopoietic stem cells; Humans; Immunoglobulins; Immunoproliferative diseases; Immunosuppression; Immunosuppressive agents; Incidence; Induction therapy; Intravenous administration; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocytes; Lymphocytes T; Lymphoproliferative Disorders - epidemiology; Lymphoproliferative Disorders - virology; Male; Medical sciences; Neuroblastoma; Neuroblastoma - therapy; Patients; Pediatrics; Peripheral blood; Risk analysis; Risk factors; Rituximab; Stem cell transplantation; Stem Cell Transplantation - adverse effects; Stem Cell Transplantation - methods; Stem cells; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation, Autologous - adverse effects; Transplants; Transplants & implants; Viruses; Gammaherpesvirinae; Human; Nervous system diseases; lymphoproliferative disease; Herpesviridae; Stem cell; Hematopoietic cell; Malignant hemopathy; Epstein Barr virus; Malignant tumor; Neuroblastoma; Epidemiology; Incidence; Virus; Blood cell; Treatment; Lymphoproliferative syndrome; CD34 selection; EBV; Complication; Graft; Autonomic neuropathy; autologous peripheral blood stem cell transplant
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1704402

The risk of Epstein-Barr virus lymphoproliferative disease (EBV-LPD) increases with the use of highly immunosuppressive therapies. Allogeneic BMT, especially supported by T-cell-depleted stem cell products, is a risk factor for EBV-LPD. Although the risk of EBV-LPD after autologous transplantation is low, case reports of this complication in the autologous setting exist. We report a higher incidence than previously described of EBV-LPD in children undergoing sequential high-dose chemotherapy supported with CD34 selected peripheral blood stem cells (CD34+ PBSC). The median time to LPD after tandem transplant was 3 months (range 1-5 months). Five patients out of 156 (3.5%) developed EBV-LPD while enrolled on two trials of tandem autologous SCT in high-risk pediatric malignancies. Both studies employed five cycles of induction therapy, followed by tandem autologous PBSC transplants. In all, 108 out of 156 patients received CD34+ PBSC; 48 received unselected PBSC. All patients contracting LPD were from the CD34 selected group. Treatment of EBV-LPD included rituximab in four out of five patients, i.v.Ig in two out of five patients, and gancyclovir in two out of five patients. EBV-LPD resolved in four out of five patients. We conclude that the combination of tandem SCT and CD34 selection may have increased immunosuppression in these patients to a point where there is an elevated risk of EBV-LPD.