Cytomegalovirus infection in autologous stem cell transplant recipients in the era of rituximab

Jain, Tania; John, James; Kotecha, Aditya; Deol, Abhinav; Saliminia, Tanaz; Revankar, Sanjay G.; Chandrasekar, Pranatharthi H.

doi:10.1007/s00277-016-2700-4

Cited by 21 publications

(17 citation statements)

References 16 publications

(22 reference statements)

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“…Moreover, the overall analysis of these data does not clearly indicate a significant increase of CMV reactivation rate during the past 20 years, suggesting that the use of novel and more potent therapeutic agents has had only a modest impact on CMV infection/reactivation and overt disease. In fact, the reported increase of CMV infection/reactivation occurrence in lymphoma patients undergoing ASCT after treatment with Rituximab needs further confirmation . On the contrary, the evidence about the impact of Bortezomib in myeloma patients is more persuasive, and these data need to be confirmed by larger prospective studies.…”

Section: Cytomegalovirus Infection In Autologous Hematopoietic Stem Cmentioning

confidence: 91%

“…Nevertheless, even though CMV reactivation still represents an important complication, most cases are successfully managed with a specific antiviral treatment (often administered within outpatient clinical settings). Still, though rare, CMV end‐organ disease remains a serious life‐threatening event in autografted patients, with an incidence up to 4% as reported throughout the last 20 years, although it is showing a trend toward a significant improvement when considering the more recent studies . Of note, overt CMV disease incidence and mortality appear similar irrespective to the diagnostic strategy adopted, further suggesting the limited usefulness of a prospective monitoring of CMV infection .…”

Section: Cytomegalovirus Infection In Autologous Hematopoietic Stem Cmentioning

confidence: 99%

“…However, the recent large increase of an intensive use of pleiotropic immunosoppressive chemoimmunotherapy, particularly in lymphoproliferative disorders, has led to an increase of viral infections incidence in different hematologic patients. As a consequence, CMV represents an increasingly important pathogen in these patients, also in settings different from the allogeneic transplant and particularly so in specific clinical subsets . Based on these considerations, we performed a comprehensive review of the medical literature about CMV infection/reactivation in hematologic malignancies beyond allogeneic transplant.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Cytomegalovirus Infection In Autologous Hematopoietic Stem Cmentioning

confidence: 91%

Section: Cytomegalovirus Infection In Autologous Hematopoietic Stem Cmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cytomegalovirus infection in hematologic malignancy settings other than the allogeneic transplant

Marchesi¹,

Pimpinelli

Ensoli

et al. 2017

Hematological Oncology

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“…[39] showed that the use of rituximab for stem cell transplantation was not associated with an increased risk of CMV reactivation. However, in a small cohort of AAV patients in the Rituximab versus Cyclophosphamide in ANCA-associated Vasculitis (RITUXIVAS) trial there were two cases of CMV infections [40].…”

Section: Significant Infections Associated With Rituximab Therapymentioning

confidence: 99%

Infectious complications of rituximab therapy in renal disease

Nixon

Ogden²,

Woywodt

et al. 2017

Clinical Kidney Journal

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Rituximab, an anti-CD20 monoclonal antibody, was originally used to treat B-cell malignancies. Its use has significantly increased in recent years, as it is now also used to treat a variety of autoimmune diseases including rheumatoid arthritis and ANCA-associated vasculitis (AAV). Initial studies suggested that the adverse effects of rituximab were minimal. Though the risk of malignancy with rituximab-based immunosuppressive regimens appears similar to that of the general population, there are now concerns regarding the risk of infectious complications. Rituximab has been associated with serious infections, including Pneumocystis jiroveci pneumonia (PJP) and the reactivation of hepatitis B virus (HBV) and tuberculosis (TB). The risk of infection appears to be the result of a variety of mechanisms, including prolonged B-cell depletion, B-cell–T-cell crosstalk, panhypogammaglobulinaemia, late-onset neutropenia and blunting of the immune response after vaccination. Importantly, the risk of infectious complications is also related to individual patient characteristics and the indication for rituximab. Individualization of treatment is, therefore, crucial. Particular attention should be given to strategies to minimize the risk of infectious complications, including vaccinating against bacterial and viral pathogens, monitoring white cell count and immunoglobulin levels, prophylaxis against PJP and screening for HBV and TB.

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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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Cytomegalovirus infection in autologous stem cell transplant recipients in the era of rituximab

Cited by 21 publications

References 16 publications

Cytomegalovirus infection in hematologic malignancy settings other than the allogeneic transplant

Cytomegalovirus infection in hematologic malignancy settings other than the allogeneic transplant

Infectious complications of rituximab therapy in renal disease

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

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