Ganciclovir Inhibits Lymphocyte Proliferation by Impairing DNA Synthesis

Battiwalla, Minoo; Wu, Yongwei; Bajwa, Rajinder; Radovic, Marija; Almyroudis, Nikolaos G.; Segal, Brahm H.; Wallace, Paul K.; Nakamura, Ryotaro; Padmanabhan, Swaminathan; Hahn, Theresa; McCarthy, Philip L.

doi:10.1016/j.bbmt.2007.03.009

Cited by 69 publications

(61 citation statements)

References 24 publications

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“…Unlike acyclovir, ganciclovir inhibits lymphocyte functions in healthy volunteers (32). In healthy volunteers, ganciclovir has been shown to suppress lymphocyte proliferation and activation by inhibiting DNA synthesis (33). Although in an analysis of lymphocyte function in a subgroup of the 2VAL Study, valganciclovir was shown to reduce lymphocyte proliferation and activated T-cell count, this effect was not documented with valacyclovir (34).…”

Section: Discussionmentioning

confidence: 99%

Randomized Trial of Valganciclovir Versus Valacyclovir Prophylaxis for Prevention of Cytomegalovirus in Renal Transplantation

Reischig

Kacer

Jindra

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Both valganciclovir and high-dose valacyclovir are recommended for cytomegalovirus prophylaxis after renal transplantation. A head-to-head comparison of both regimens is lacking. The objective of the study was to compare valacyclovir prophylaxis with valganciclovir, which constituted the control group.Design, settings, participants, & measurements In a randomized, open-label, single-center trial, recipients of renal transplants (recipient or donor cytomegalovirus-seropositive) were randomly allocated (1:1) to 3-month prophylaxis with valacyclovir (2 g four times daily) or valganciclovir (900 mg daily). Enrollment occurred from November of 2007 to April of 2012. The primary end points were cytomegalovirus DNAemia and biopsy-proven acute rejection at 12 months. Analysis was by intention to treat. ResultsIn total, 119 patients were assigned to valacyclovir (n=59) or valganciclovir prophylaxis (n=60). Cytomegalovirus DNAemia developed in 24 (43%) of 59 patients in the valacyclovir group and 18 (31%) of 60 patients in the valganciclovir group (adjusted hazard ratio, 1.35; 95% confidence interval, 0.71 to 2.54; P=0.36). The incidence of cytomegalovirus disease was 2% with valacyclovir and 5% with valganciclovir prophylaxis (adjusted hazard ratio, 0.21; 95% confidence interval, 0.01 to 5.90; P=0.36). Significantly more patients with valacyclovir prophylaxis developed biopsy-proven acute rejection (18 of 59 [31%] versus 10 of 60 [17%]; adjusted hazard ratio, 2.49; 95% confidence interval, 1.09 to 5.65; P=0.03). The incidence of polyomavirus viremia was higher in the valganciclovir group (18% versus 36%; adjusted hazard ratio, 0.43; 95% confidence interval, 0.19 to 0.96; P=0.04).Conclusions Valganciclovir shows no superior efficacy in cytomegalovirus DNAemia prevention compared with valacyclovir prophylaxis. However, the risk of biopsy-proven acute rejection is higher with valacyclovir.

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Section: Discussionmentioning

confidence: 99%

Randomized Trial of Valganciclovir Versus Valacyclovir Prophylaxis for Prevention of Cytomegalovirus in Renal Transplantation

Reischig

Kacer

Jindra

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…On the other hand, the therapy of CMV reactivation (such as ganciclovir) can suppress T-lymphocyte proliferation which may translate into impaired immune reconstitution after HSCT. 26 Thus, CMV reactivation may be associated with PTLD after haplo-HSCT.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Epstein-Barr Virus–Related Post-Transplantation Lymphoproliferative Disorder after Unmanipulated Human Leukocyte Antigen Haploidentical Hematopoietic Stem Cell Transplantation: Incidence, Risk Factors, Treatment, and Clinical Outcomes

Zhang

et al. 2015

Biology of Blood and Marrow Transplantation

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We examined the incidence, risk factors, treatments, and clinical outcomes of post-transplantation lymphoproliferative disorder (PTLD) after unmanipulated haploidentical (haplo) hematopoietic stem cell transplantation (HSCT) in 1184 patients between 2006 and 2012. Age-, transplantation time-, and transplantation duration-matched controls were randomly selected from the same cohort. Forty-five patients experienced PTLD. The median time from HSCT to PTLD occurrence was 61 (range, 33 to 360) days and the 1-year cumulative incidence of total PTLD after haplo-HSCT was 3.0%. In multivariate analysis, a lower absolute count of CD8(+) T lymphocytes at day 30, a lower absolute count of immunoglobulin M at day 30, and cytomegalovirus DNAemia after HSCT were significantly associated with higher risk of PTLD. The 2-year probability of overall survival (OS) after HSCT was 42.8%, which was comparable between the probable PTLD and the proven PTLD patients. Patients who received rituximab-based therapy had significantly better 2-year OS (48.2% versus 13.2%, P = .02). Thus, we were able to identify individuals at a high risk of developing PTLD after unmanipulated haplo-HSCT. Rituximab-based therapy can help to improve the outcomes of PTLD patients.

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“…Furthermore, preemptive treatment of CMV uses costly antiviral agents which incur toxicities such as renal damage and cytopenia, requiring further treatment and hospitalizations (7, 15). The use of ganciclovir enhances immunosuppression in vitro (16) and multiple episodes of CMV reactivation are associated with late relapse and treatment failure (17). Prevention of CMV reactivation rather than its preemptive management may be advantageous by avoiding toxicity from antiviral treatment and reducing the economic burden of post-transplant care.…”

Section: Introductionmentioning

confidence: 99%

The clinical and financial burden of pre-emptive management of cytomegalovirus disease after allogeneic stem cell transplantation—implications for preventative treatment approaches

Jain

Ito

et al. 2014

Cytotherapy

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Background Although CMV infection after allogeneic stem cell transplantation (SCT) is only rarely fatal, the management of CMV by preemptive medication for viral reactivation has toxicity and carries a financial burden. New strategies to prevent CMV reactivation with vaccines and antiviral T cells may represent an advance over preemptive strategies, but have yet to be justified in terms of transplant outcome and cost. Patients and methods We compared outcomes and post-transplant treatment cost in 44 patients who never required preemptive CMV treatment with 90 treated patients undergoing SCT at our institute between 2006–2012. 81 subjects received CD34+ selected myeloablative SCT, 12 umbilical cord blood transplants, and 41 T-replete nonmyeloablative SCT. 119 (89%) patients were at risk for CMV because either the donor or recipient was seropositive. Of these, 90 (75.6%) reactivated CMV at a median of 30 (range 8–105) days post transplant and received antivirals. Results There was no difference in standard transplant risk factors between the two groups. In multivariate modeling, CMV reactivation >250 copies/ml (OR=3, P<0.048), total duration of inpatient IV antiviral therapy (OR = 1.04, P<0.001), type of transplant (T-deplete vs. T-replete) (OR=4.65, P<0.017) were found to be significantly associated with increased non-relapse mortality. The treated group incurred an additional cost of antiviral medication and longer hospitalization within the first 6 months post SCT of $58,000 to $74,000/patient. Discussion Our findings suggest that to prevent CMV reactivation treatment should be given within 1 week of SCT. Preventative treatment may improve outcome and have significant cost savings.

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Ganciclovir Inhibits Lymphocyte Proliferation by Impairing DNA Synthesis

Cited by 69 publications

References 24 publications

Randomized Trial of Valganciclovir Versus Valacyclovir Prophylaxis for Prevention of Cytomegalovirus in Renal Transplantation

Randomized Trial of Valganciclovir Versus Valacyclovir Prophylaxis for Prevention of Cytomegalovirus in Renal Transplantation

Epstein-Barr Virus–Related Post-Transplantation Lymphoproliferative Disorder after Unmanipulated Human Leukocyte Antigen Haploidentical Hematopoietic Stem Cell Transplantation: Incidence, Risk Factors, Treatment, and Clinical Outcomes

The clinical and financial burden of pre-emptive management of cytomegalovirus disease after allogeneic stem cell transplantation—implications for preventative treatment approaches

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