Virus reactivations after autologous hematopoietic stem cell transplantation detected by multiplex PCR assay

Inazawa, Natsuko; Hori, Tsukasa; Nojima, Masanori; Saito, Makoto; Igarashi, Keita; Yamamoto, Masaki; Shimizu, Norio; Yoto, Yuko; Tsutsumi, Hiroyuki

doi:10.1002/jmv.24621

Cited by 36 publications

(35 citation statements)

References 12 publications

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“…Several studies have retrospectively described the epidemiology of viral infections post‐auto‐HSCT . Some authors suggest that CMV diagnostic evaluation should be performed only in patients exhibiting suspicious clinical features and antiviral chemotherapy should be administered for persistent and severe signs and symptoms …”

Section: Discussionmentioning

confidence: 99%

Epidemiology of viral infections among children undergoing hematopoietic stem cell transplant: Α prospective single‐center study

Tsoumakas

Giamaiou

Goussetis

et al. 2019

Transplant Infectious Dis

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Background: Viral infections are a significant cause of morbidity and mortality in pediatric transplant populations. We analyzed the epidemiology of viral infections in pediatric hematopoietic stem cell transplant (HSCT) patients, including their incidence, associated risk factors, and outcome. Methods:In a prospective study from September 2011 to September 2015, blood, urine, and stool specimens were monitored weekly from transplantation to day 100 or after if clinically suspected, by use of real-time polymerase chain reaction. Cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK polyomavirus (BKV), Herpes simplex virus-1,2, Varicella zoster virus, Human herpes virus-6,7, and Adenovirus infections were monitored. All children and adolescents who underwent HSCT received long-term follow up in the regular outpatient clinics (range 2-48 months). Results: A total of 192 HSCTs (autologous/allogeneic: 53/139) were performed in 165 subjects (median age: 5.6 years). Viruses most commonly isolated were CMV (46.1%), BKV (25.9%) and EBV (22.6%) and were more frequent in allogeneic versus autologous transplants (P < 0.05). Almost all high-risk allogeneic recipients developed EBV infections post-HSCT. EBV-PTLD was the only cause of death among those who developed viral disease. The factors significantly associated with the development of viral infections were recipient's advanced age, unrelated donor, mismatched graft and use of peripheral blood stem cells grafts. Conclusions: Viral infections were common among our pediatric recipients. Data suggest that monitoring of viral load may be significant to the prevention of viral disease. Particular demographic and transplantation characteristics were associated with the development of viral infections post-HSCT. K E Y W O R D S viral infections, hematopoietic stem cell transplant, risk factors, children

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Section: Discussionmentioning

confidence: 99%

Epidemiology of viral infections among children undergoing hematopoietic stem cell transplant: Α prospective single‐center study

Tsoumakas

Giamaiou

Goussetis

et al. 2019

Transplant Infectious Dis

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“…However, it also favoured the occurrence of new infectious complications, particularly by opportunistic pathogens, including viral infections . Regarding CMV, several studies have been performed aimed at exploring the incidence and clinical impact of CMV infection/reactivation in patients undergoing ASCT in the era of intensive and pleiotropic immunosuppressive therapy . Table summarizes the main reports published during the last 20 years.…”

Section: Cytomegalovirus Infection In Autologous Hematopoietic Stem Cmentioning

confidence: 99%

Cytomegalovirus infection in hematologic malignancy settings other than the allogeneic transplant

Marchesi¹,

Pimpinelli

Ensoli

et al. 2017

Hematological Oncology

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Cytomegalovirus (CMV) infection in clinical settings other than the allogeneic transplant represents a poorly explored issue. Thus, we performed a comprehensive review of the medical literature about CMV infection in patients undergoing autologous hematopoietic stem cell transplant and in other nontransplant-related hematologic patients. In autologous hematopoietic stem cell transplant, a CMV reactivation is reported to occur in up to 41% of CMV seropositive patients, when a prospective monitoring of antigenemia and/or viremia by polymerase chain reaction was adopted. However, more contained frequencies, up to 12%, have been reported when the monitoring criteria were based on a clinically driven diagnostic strategy. The most relevant risk factors appear to be CD34 + selected autografts, total body irradiation, and prior treatment with Alemtuzumab, Fludarabine, or Bortezomib, respectively. Other possible risk factors (ie, prior treatment with Rituximab, T-cell lymphomas, and pretransplant HBcIgG seropositivity) are still debated. In nontransplant settings, the data are very heterogeneous; thus, CMV infection incidence and risk factors are more difficult to establish. Overall, the rate of CMV infection/reactivation ranges between 2 and 67%. High-dose steroids, advanced disease, poor performance status, and treatment with Alemtuzumab, Fludarabine, Bortezomib, and Rituximab appear as the most relevant, though putative, risk factors. Intravenous Ganciclovir represents the gold standard for first-line treatment of CMV infection in these patients. Oral Valganciclovir and Foscarnet are other possible options. Extensive prophylaxis and preemptive therapy are not generally recommended, with the exception of high-risk patients.

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“…The incidence of these infections is lower following autologous relative to allogeneic HSCT (43,44). Nevertheless, viral reactivation following autolo-gous stem cell transplant is a significant problem that is facilitated by the loss of T cell function.…”

Section: Discussionmentioning

confidence: 99%

Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia

Reeves

Peterson

Kiem

et al. 2017

J Virol

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Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts the plasma viral load set point and the rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load but an unchanged viral set point during viral rebound. The addition of an autologous stem cell transplant before cART withdrawal alters viral dynamics: we found a higher rebound set point but similar peak viral loads compared to the primary infection. Mathematical modeling of the data that accounts for fundamental immune parameters achieves excellent fit to heterogeneous viral loads. Analysis of model output suggests that the rapid memory immune response following treatment interruption does not ultimately lead to better viral containment. Transplantation decreases the durability of the adaptive immune response following cART withdrawal and viral rebound. Our model's results highlight the impact of the endogenous adaptive immune response during primary SHIV infection. Moreover, because we capture adaptive immune memory and the impact of transplantation, this model will provide insight into further studies of cure strategies inspired by the Berlin patient. HIV patients who interrupt combination antiretroviral therapy (cART) eventually experience viral rebound, the return of viral loads to pretreatment levels. However, the "Berlin patient" remained free of HIV rebound over a decade after stopping cART. His cure is attributed to leukemia treatment that included an HIV-resistant stem cell transplant. Inspired by this case, we studied the impact of stem cell transplantation in a macaque simian/HIV (SHIV) system. Using a mechanistic mathematical model, we found that while primary infection generates an adaptive immune memory response, stem cell transplantation disrupts this learned immunity. The results have implications for HIV cure regimens based on stem cell transplantation.

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Virus reactivations after autologous hematopoietic stem cell transplantation detected by multiplex PCR assay

Cited by 36 publications

References 12 publications

Epidemiology of viral infections among children undergoing hematopoietic stem cell transplant: Α prospective single‐center study

Epidemiology of viral infections among children undergoing hematopoietic stem cell transplant: Α prospective single‐center study

Cytomegalovirus infection in hematologic malignancy settings other than the allogeneic transplant

Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia

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