Post-allogeneic hematopoietic stem cell transplantation viral reactivations and viremias: a focused review on human herpesvirus-6, BK virus and adenovirus

Abstract

Human cytomegalovirus and Epstein–Barr virus have been recognized as potential drivers of morbidity and mortality of patients undergoing allogeneic stem cell transplantation for years. Specific protocols for monitoring, prophylaxis and pre-emptive therapy are in place in many transplant settings. In this review, we focus on the next three most frequent viruses, human herpesvirus-6, BK virus and adenovirus, causing reactivation and/or viremia after allogeneic transplant, which are increasingly detected in patients in the post-transplant period owing to emerging techniques of molecular biology, recipients’ characteristics, treatment modalities used for conditioning and factors related donors or stem cell source. Given the less frequent detection of an illness related to these viruses, there are often no specific protocols in place for the management of affected patients. While some patients develop significant morbidity (generally older), others may not need therapy at all (generally younger or children). Furthermore, some of the antiviral therapies used are potentially toxic. With the addition of increased risk of secondary infections, risk of graft failure or increased risk of graft- versus-host disease as well as the relationship with other post-transplant complications, the outcomes of patients with these viremias remain unsatisfactory and even long-term survivors experience increased morbidity.

BKV Related Hemorrhagic Cystitis—An Insight into Risk Factors and Later Complications—An Analysis on Behalf of Polish Adult Leukemia Group

“…This value is within the average rates of BKPyV-HC incidences, as reported in ECIL guidelines [10] (8-25% and 7-54% in pediatric and adult patients, respectively). The current literature highlights a variety of risk factors for HC following allo-HCT, including myeloablative (MAC) conditioning, unrelated donors, other than BK-HC associated viremias such as cytomegalovirus (CMV) or human herpesvirus (HHV)-6, and graft-versus-host disease (GVHD) [11][12][13]. However, all these factors were not observed consistently in independent studies.…”

Unique Challenges to Diagnosing Human Herpesvirus-6 (HHV-6) Encephalitis Following Post-Hematopoietic Stem Cell Transplant: A Case and Brief Review

“…Similar to engraftment syndrome and aGVHD, other HHV-6-related sequelae may also have a relationship with HHV-6 encephalitis, which warrants further investigation. While end-organ disease has been reported in relation to HHV-6, the relationship is not well supported 25,27 .…”

“…Engraftment syndrome has also been associated with the development of HHV-6 encephalitis. 7 HHV-6 reactivation is also becoming increasingly associated with delayed T-cell reconstitution, CMV reactivation following HHV-6 reactivation, and idiopathic pneumonia syndrome 25 . Similar to engraftment syndrome and aGVHD, other HHV-6-related sequelae may also have a relationship with HHV-6 encephalitis, which warrants further investigation.…”

“…HHV-6 reactivation following HSCT has been linked with adverse outcomes such as aGVHD [hazard ratio (HR) = 2.65 95% confidence interval (CI): 1.89-3.72; P < 0.001] 24 or engraftment complications 7,25 . A large-scale retrospective study found acute GVHD grades II to IV to be a significant risk factor for HHV-6 post-transplantation acute limbic encephalitis (aHR = 7.5, P < 0.001) 26 .…”

An impact of CMV and HHV-6 reactivation on the course of early period after hematopoietic stem cell transplantation in patients with hematologic malignancies

“…Для клинической практики, бесспорно, име ет значение повышенный риск неприживления трансплантата, развитие РТПХ и других посттран сплантационных осложнений, ассоциированных с реактивацией вирусов у реципиентов гемопоэ тических стволовых клеток [8]. Реактивация ЦМВ и вируса простого герпеса после алло-ТГСК слу ж ит фактором риска развития тяжелых бактери альных осложнений [9], которые значимо влияют на раннюю летальность после ТГСК [10].…”