Epstein-Barr virus-associated post-transplant lymphoproliferative disease after bone marrow transplantation mimicking graft-versus-host disease.
In contrast to solid organ transplantation (Tx), the incidence of post-transplant lymphoproliferative disease (PTLD) after hematopoietic stem cell Tx (HSCT) is generally low. This risk, however, is significantly elevated in patients receiving human leukocyte antigen (HLA) mis-matched or T-cell-depleted grafts, or after treatment for severe graft-versus-host disease (GvHD). An 18-yr-old patient with positive Epstein-Barr virus (EBV) serology received a fully matched, unmanipulated bone marrow graft from an unrelated EBV-positive donor for treatment of acute myeloid leukemia (AML) in second complete remission. GvHD prophylaxis was performed with cyclosporin A (CsA) and a short course of methotrexate. Four months after Tx, the patient developed ulcerative tonsillitis that was unresponsive to antibiotic treatment. Diarrhea appearing simultaneously was interpreted as gastrointestinal GvHD and steroids were added to CsA. A few days later the patient was admitted to hospital because of generalized seizure and pneumonia. Despite reduction of immunosuppression, intensification of anti-viral treatment, and subsequent mechanical ventilation, the patient died of acute respiratory distress 6 days later. Autopsy demonstrated disseminated EBV-induced, multi-nodular lymphoma infiltration of the entire colon but no signs of GvHD. Moreover, both lungs, paratracheal lymph nodes, kidneys, thyroid gland, and liver were infiltrated with large B-cell non-Hodgkin's lymphomas. This case underlines the rapid and aggressive course of EBV-induced disseminated PTLD after HSCT, initially mimicking intestinal GvHD because of massive colonic lymphoma infiltration. Tissue biopsies should be performed early for establishing correct diagnosis, thus enabling specific therapy, e.g. infusion of donor leukocytes with cytotoxic T-lymphocytes.
Department of Pediatrics, University of Kiel, Germany. a.claviez@pediatrics.uni-kiel.de
A
A
Claviez
M
M
Tiemann
H J
HJ
Wagner
P
P
Dreger
M
M
Suttorp
D000293:Adolescent; D003937:Diagnosis, Differential; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis*; D017809:Fatal Outcome; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008232:Lymphoproliferative Disorders / Q000175:diagnosis / Q000821:virology*; D008297:Male