Human herpesvirus 6-related pure red cell aplasia, secondary graft failure, and clinical severe immune suppression after allogeneic hematopoietic cell transplantation successfully treated with foscarnet

Abstract

Human herpesvirus 6 (HHV-6) is frequently detected after allogeneic hematopoietic cell transplantation (allo-HCT); however, the clinical interpretation of HHV-6 viremia in a transplant patient is challenging as it may signify asymptomatic reactivation, chromosomal integration of the virus genome in the donor or recipient with no clinical significance, or severe HHV-6 disease. Here we present a case of HHV-6 disease after allo-HCT presenting as pure red cell aplasia, secondary graft failure, and severe immunosuppression causing multiple severe bacterial super-infections. Examination of pre-transplant patient and donor samples as well as serial determination of HHV-6 DNA copy numbers after transplantation were necessary to definitively interpret HHV-6 viremia as active HHV-6 infection with a causative role in pancytopenia and immune suppression. Foscarnet treatment resulted both in viral load decline and disappearance of HHV-6-related bone marrow suppression and predisposition to severe infections. Clinicians should be aware of the wide array of clinical manifestations and the diagnostic pitfalls of post-transplant HHV-6 disease. These issues are extremely challenging, as they may result either in dangerous underestimation of HHV-6 disease or in the institution of unnecessary antiviral therapy. Late bone marrow aplasia and late severe infections after allo-HCT without other obvious causes may be HHV-6 related.

High human herpesvirus 6 viral load in pediatric allogeneic hematopoietic stem cell transplant patients is associated with detection in end organs and high mortality

“…23,29,33,34 Moreover, delayed complications with HHV-6 have also been described including pure red cell aplasia and secondary graft failure. 35 In our examination of the tissue-positive viremic group, there was a wide spectrum of end organs involved. In addition to the central nervous system, lungs, and bone marrow, HHV-6 was found in pericardial fluid, gallbladder, sinuses, and the gastrointestinal tract.…”

Pure red cell aplasia with isolated human herpes virus 6 infection of bone marrow in postcardiac transplant patient

“…15 In the bone marrow transplant literature, HHV-6 has not only been associated with marrow suppression, 16 but with graft failure as well. 3 In these cases, however, the patients experienced severe bicytopenia or pancytopenia, not PRCA.…”

“…Infection in immunocompromised hosts can be more severe, frequently causing end organ damage. 3 Given its pathogenic effects on bone marrow, a causative role of HHV-6 in TEC has been explored with conflicting results. 4,5 We describe a 2-year-old female child status post cardiac transplant on immunosuppression presenting with severe anemia who was subsequently found to have HHV-6 infection isolated to the bone marrow.…”

“…HHV‐6 is a CD4+ T‐lymphotropic virus that causes nearly ubiquitous infection by age 2–3 with symptoms of fever, diarrhea, rash, and cytopenias in immunocompetent hosts. Infection in immunocompromised hosts can be more severe, frequently causing end organ damage . Given its pathogenic effects on bone marrow, a causative role of HHV‐6 in TEC has been explored with conflicting results .…”

Concise Review: Anemia Caused by Viruses

“…First, in one study, when prospective monitoring of HHV‐6 infections was performed following bone marrow transplantation, occurrence of anemia was significantly more frequent in HHV6‐infected transplanted recipients than in uninfected ones [24]. Recently, Lagadinou et al [25] reported a rather convincing case of HHV‐6 infection associated with PRCA also after allogenic hematopoietic cell transplantation. In this case, strikingly high HHV‐6 viremia was detected in the allotransplanted recipient concomitantly with PRCA and, when antiviral therapy was instituted, blood content in hemoglobin returned within normal limits along with eradication of HHV‐6 replication.…”