Human herpesvirus 6 reactivation before engraftment is strongly predictive of graft failure after double umbilical cord blood allogeneic stem cell transplantation in adults

Bourgeois, Amandine Le; Labopin, Myriam; Guillaume, Thierry; Delaunay, Jacques; Foucher, Yohann; Tessoulin, Benoît; Malard, Florent; Ayari, Sameh; Péterlin, Pierre; Derenne, Sophie; Herry, P.; Cesbron, Anne; Gagne, Katia; Lodé, Laurence; Illiaquer, Marina; Imbert-Marcille, Berthe-Marie; Gouill, Steven Le; Moreau, Philippe; Mohty, Mohamad; Chevallier, Patrice

doi:10.1016/j.exphem.2014.07.264

Cited by 17 publications

(6 citation statements)

References 63 publications

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“…Most often, HHV-6 presented as viremia without end-organ disease and occurred early after UCBT. The clinical significance of asymptomatic HHV-6 viremia remains controversial; however, HHV-6 reactivation has been independently associated with graft failure after UCBT [25]. We did not find a significant relationship between HHV-6 and graft failure in our patients.…”

Section: Discussioncontrasting

confidence: 80%

Infectious Complications After Umbilical Cord Blood Transplantation for Hematological Malignancy

Linder

McDonald

Kauffman

et al. 2019

Open Forum Infectious Diseases

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Background Umbilical cord blood transplant (UCBT) is used for patients who do not have a matched donor, but engraftment often takes longer than with a standard allogeneic transplant, likely increasing the risk for infection. We characterized specific infections and outcomes in adults undergoing UCBT at our 2 centers. Methods All adults who underwent UCBT between January 1, 2006 and December 31, 2015 were included. Infectious episodes from 6 months before to 2 years after UCBT were reviewed. Results Fifty-seven patients underwent UCBT; 47 had neutrophil engraftment. A total of 179 infectious episodes occurred in 55 patients, 73 (41%) within 30 days post-UCBT. Viruses caused 85 (47%) infections. Cytomegalovirus caused 32 infectious episodes and was most common from day 30 to 100. Human herpesvirus 6 occurred in 28 episodes, was most common within 30 days, and caused 1 death. Bacteria were responsible for 82 (46%) infections, most commonly bacteremias due to Staphylococcus spp, Enterococcus spp, and Enterobacteriaceae. Of 11 invasive fungal infections, 9 were aspergillosis, 4 of which were fatal. Overall mortality was 56% in the first year. Thirteen deaths were from infection; 11 occurred in the first 100 days and 7 in the first 30 days post-UCBT. Of 10 patients who never engrafted, 9 died, 6 from infection, within 100 days post-UCBT. Conclusions Infectious complications were common after UCBT, especially in the first 30 days. Deaths from viral infections were fewer than expected. Delayed engraftment and nonengraftment continue to convey increased risk for fatal bacterial and fungal infections post-UCBT.

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Section: Discussioncontrasting

confidence: 80%

Infectious Complications After Umbilical Cord Blood Transplantation for Hematological Malignancy

Linder

McDonald

Kauffman

et al. 2019

Open Forum Infectious Diseases

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“…54 Virus reactivation post-HSCT has been frequently associated with myelosuppression and delayed engraftment, particularly involving platelets 46,55,56 and also allograft failure. 57,58…”

Section: Human Herpesvirus 6b End-organ Disease and Other Outcomes Pomentioning

confidence: 99%

Guidelines from the 2017 European Conference on Infections in Leukaemia for management of HHV-6 infection in patients with hematologic malignancies and after hematopoietic stem cell transplantation

et al. 2019

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Of the two human herpesvirus 6 (HHV-6) species, human herpesvirus 6B (HHV-6B) encephalitis is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplant. Guidelines for the management of HHV-6 infections in patients with hematologic malignancies or post-transplant were prepared a decade ago but there have been no other guidelines since then despite significant advances in the understanding of HHV-6 encephalitis, its therapy, and other aspects of HHV-6 disease in this patient population. Revised guidelines prepared at the 2017 European Conference on Infections in Leukaemia covering diagnosis, preventative strategies and management of HHV-6 disease are now presented.

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“…In the setting of transplantation several authors have reported that HHV-6 infection may cause skin rash [10], interstitial pneumonia [13,14], and bone marrow suppression [15] in the early postengraftment phase and trigger acute graft-versus-host disease (GVHD) or determine graft failure [15,16]. Moreover, studies in children have correlated blood HHV-6 DNAemia levels > 1000 viral copies/mL with an increased nonrelapse mortality [17,18], and resolution of viremia correlated with better absolute lymphocyte count recovery [19]. Nevertheless, the 7th European Conference on Infections in Leukemia (ECIL-7) do not recommended the routine surveillance of HHV-6 blood viral load by PCR [20]because encephalitis is the only organ disease in which a causative role of HHV-6 has been documented.…”

Section: Introductionmentioning

confidence: 99%

High Incidence of Early Human Herpesvirus-6 Infection in Children Undergoing Haploidentical Manipulated Stem Cell Transplantation for Hematologic Malignancies

Perruccio¹,

Sisinni

Pérez‐Martínez

et al. 2018

Biology of Blood and Marrow Transplantation

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Human herpesvirus-6 (HHV-6) infection is increasingly recognized among allogeneic hematopoietic stem cell transplantation (HSCT) recipients, with 30% at risk of reactivation in the haploidentical setting. It has been associated with encephalitis, acute graft-versus-host disease, and graft failure. Here we report 2 cohorts of pediatric haploidentical manipulated HSCT in which, despite many differences, HHV-6 reactivation and disease occurred with very high incidence compared with data reported in the literature and represented the main early post-transplant infectious complication compared with other viral, bacterial, or fungal infections. The 2 cohorts were recruited at the pediatric transplant centers of Perugia (n = 13), Barcelona (n = 10), and Madrid (n = 15). All patients received myeloablative conditioning regimens and 2 different types of ex vivo graft manipulation: CD34 selection and regulatory T cell/conventional T cell infusion in 13 patients and CD45RA T cell depletion in 25 patients. Antiviral prophylaxis was acyclovir in 33 and foscarnet in 5 patients. HHV-6 DNAemia was checked by quantitative or qualitative PCR. In vitro experiments demonstrated that donor CD4 T cells are the reservoir of HHV-6 and suggested a role of the graft composition in both transplant settings (rich in CD4 T cells) in the high rate of HHV-6 infections. All patients presented very early HHV-6 DNAemia after transplantation, and although viremic, 9 patients (24%) developed symptomatic limbic encephalitis. All patients responded to antiviral treatment, and none died of infection, although 2 experienced long-term neurologic sequelae (22%). Moreover, 6 patients presented organ involvement in absence of other causes: 1 hepatitis, 1 pneumonia, 2 gastroenteritis, and 2 multiorgan involvement(1 encephalitis, pneumonia, and gastritis; 1 pneumonia and enteritis). Incidences of other viral, bacterial, and fungal diseases were lower in both cohorts. In vitro, HHV-6 was found to infect only CD4 fraction of the graft. Co-culturing CD4 T cells with CD56 natural killer (NK) cells eliminated the virus, demonstrating the main role of NK cells in the antiviral immune response. All 38 pediatric patients undergoing these manipulated haploidentical HSCTs showed HHV-6 reactivation, and 14 of 38 developed HHV-6 disease with similar features in terms of timing, morbidity, response to treatment, and outcome. The graft composition in both transplant platforms, rich in CD4 T cells and poor in NK cells, seems to play a key role. HHV-6 DNAemia surveillance was useful to diagnose and treat preemptively HHV-6 infection.

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Human herpesvirus 6 reactivation before engraftment is strongly predictive of graft failure after double umbilical cord blood allogeneic stem cell transplantation in adults

Cited by 17 publications

References 63 publications

Infectious Complications After Umbilical Cord Blood Transplantation for Hematological Malignancy

Infectious Complications After Umbilical Cord Blood Transplantation for Hematological Malignancy

Guidelines from the 2017 European Conference on Infections in Leukaemia for management of HHV-6 infection in patients with hematologic malignancies and after hematopoietic stem cell transplantation

High Incidence of Early Human Herpesvirus-6 Infection in Children Undergoing Haploidentical Manipulated Stem Cell Transplantation for Hematologic Malignancies

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