Late-Onset Fatal Epstein-Barr Virus-Associated Hemophagocytic Syndrome following Cord Blood Cell Transplantation for Adult Acute Lymphoblastic Leukemia

Abstract

A 43-year-old Japanese woman underwent unrelated cord blood transplantation (CBT) during remission for acute lymphoblastic leukemia with t(4; 11)(q21;q23). Tacrolimus was given for prophylaxis of graft-versus-host disease. The posttransplantation clinical course was mostly uneventful, and the leukemia remained in remission. Fourteen months after CBT, the patient developed pancytopenia and hepatic dysfunction with persistent high-grade fever. The bone marrow was hypocellular with increased numbers of macrophages and hemophagocytes. The numbers of Epstein-Barr virus (EBV) copies in peripheral blood samples were remarkably high. Although the patient showed complete donor-type hematopoiesis, the titer of viral capsid antigen immunoglobulin G was low, and the results of a test for EBV nuclear antigen were negative. There was no clinical response to the reduction of immunosuppressive therapy or to the administration of high-dose methylprednisolone, human immunoglobulin, or acyclovir. The patient died 466 days after CBT of massive gastrointestinal hemorrhage due to bone marrow and hepatic failures. This case demonstrates that fatal EBV-associated hemophagocytic syndrome (HPS) can occur more than 1 year after CBT. This report is the first of a case of late-onset EBV-associated HPS following CBT.

B-Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma

“…Six cases (118,203,235,272,386, and 415) submitted to this session were examples of de novo B-ALL with MLL (11q23) gene rearrangements. More than 75 gene partners for MLL have been identified.…”

“…This is a rare phenomenon, most commonly observed in the pediatric population. The association of HLH and ALL has been well described, [114][115][116][117][118][119][120][121][122][123] but unlike the case submitted to the workshop, in most reported cases, the diagnosis of ALL preceded HLH. In many cases, HLH has been associated with a concurrent infectious etiology, possibly due to immune deficiency following chemotherapy or stem cell transplantation for ALL, and in these patients, the term infection-associated hemophagocytic syndrome may be more appropriate.…”

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Immune Dysregulation and Pathobiology Working Group Report

“…Interestingly, late EBV infection may impact innate immunity inducing hemophagocytic lymphohistiocytosis. 129 Studies of the late recovery of innate immune responses and their interaction with T and B cell populations are warranted.…”

Graft failure

“…Stromal abnormalities occur in myelofi brosis where the normal bone marrow stroma is replaced by a dense fi brotic reaction. Examples include the Epstein-Barr virus (EBV), 33 cytomegalovirus (CMV) 34 and human herpes virus 6 (HHV6). If these are not corrected by transplantation, similar problems may ensue with the donorderived hemopoiesis.…”