scholarly journals Prophylaxis vs preemptive therapy in prevention of CMV infection: new insight on prophylactic strategy after allogeneic hematopoietic cell transplantation

2020 ◽  
Vol 51 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Jan Styczyński
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Primary Prophylaxis ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Preemptive Therapy ◽  
Solid Organ ◽  
Cell Transplant ◽  
Cmv Infection ◽  
American Society

AbstractCytomegalovirus (CMV), the beta-human herpesvirus type 5 (HHV-5), is a major cause of morbidity in immunocompromised hosts, especially recipients of allogeneic hematopoietic cell transplantation (HCT) or solid organ transplantation. The standard-of-care approach to CMV prevention based on CMV surveillance-guided preemptive therapy is being challenged by the recent approval of letermovir (LMV) for primary prophylaxis. Real-word clinical data show dramatic improvement in the reduction of risk of CMV infection and any CMV viremia in all studies performed so far. LMV is the drug that is breaking the paradigm of preemptive therapy with shift to prophylaxis. A summary of reported data presented in 2019 annual meetings of American Society of Transplantation and Cellular Therapy (ASTCT), European Society for Blood and Marrow Transplantation (EBMT) and American Society of Hematology (ASH), as well as already published results, is presented in this review. A total number of 401 adult high-risk patients on primary prophylaxis after HCT were reported in 11 studies up to January 1, 2020. It was shown that fewer patients in the LMV arms had any CMV reactivation or need for CMV treatment compared with the any other prophylactic or preemptive approaches. In conclusion, LMV is much highly effective than CMV-guided preemptive therapy in preventing CMV infection and CMV disease. The use of LMV in prophylaxis results in an improvement in overall survival during the first 24 and 48 weeks. LMV has a favorable safety profile, as it does not cause myelotoxicity. Current guidelines of European Conference on Infections in Leukemia (ECIL7) recommend LMV for the use in prophylaxis of CMV infection in patients after allogeneic hematopoietic cell transplant.

scholarly journals Cytomegalovirus Infection in Solid Organ and Hematopoietic Cell Transplantation: State of the Evidence

2020 ◽  
Vol 221 (Supplement_1) ◽  
pp. S23-S31 ◽  
Author(s):  
Ghady Haidar ◽  
Michael Boeckh ◽  
Nina Singh
Keyword(s):  
T Cell ◽  
Hematopoietic Cell Transplantation ◽  
Solid Organ Transplantation ◽  
Immune Monitoring ◽  
Hematopoietic Cell ◽  
Preemptive Therapy ◽  
Solid Organ ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Hematopoietic Cell Transplant

Abstract This review focuses on recent advances in the field of cytomegalovirus (CMV). The 2 main strategies for CMV prevention are prophylaxis and preemptive therapy. Prophylaxis effectively prevents CMV infection after solid organ transplantation (SOT) but is associated with high rates of neutropenia and delayed-onset postprophylaxis disease. In contrast, preemptive therapy has the advantage of leading to lower rates of CMV disease and robust humoral and T-cell responses. It is widely used in hematopoietic cell transplant recipients but is infrequently utilized after SOT due to logistical considerations, though these may be overcome by novel methods to monitor CMV viremia using self-testing platforms. We review recent developments in CMV immune monitoring, vaccination, and monoclonal antibodies, all of which have the potential to become part of integrated strategies that rely on viral load monitoring and immune responses. We discuss novel therapeutic options for drug-resistant or refractory CMV infection, including maribavir, letermovir, and adoptive T-cell transfer. We also explore the role of donor factors in transmitting CMV after SOT. Finally, we propose a framework with which to approach CMV prevention in the foreseeable future.

scholarly journals Antiviral prophylaxis for cytomegalovirus infection in allogeneic hematopoietic cell transplantation

2018 ◽  
Vol 2 (16) ◽  
pp. 2159-2175 ◽  
Author(s):  
Kaiwen Chen ◽  
Matthew P. Cheng ◽  
Sarah P. Hammond ◽  
Hermann Einsele ◽  
Francisco M. Marty
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Preemptive Therapy ◽  
Antiviral Prophylaxis ◽  
Cmv Infection ◽  
Allogeneic Hct ◽  
All Cause Mortality ◽  
Cmv Disease

Abstract Patients treated with allogeneic hematopoietic cell transplantation (HCT) are at risk of cytomegalovirus (CMV) reactivation and disease, which results in increased morbidity and mortality. Although universal antiviral prophylaxis against CMV improves outcomes in solid organ transplant recipients, data have been conflicting regarding such prophylaxis in patients undergoing allogeneic HCT. We conducted a systematic review of randomized trials of prophylactic antivirals against CMV after allogeneic HCT to summarize the evolution of the field over the last 35 years and evaluate the prophylactic potential of antiviral agents against CMV after allogeneic HCT. Electronic databases were queried from database inception through 31 December 2017. For included studies, incidence of CMV infection and all-cause mortality were collected as primary outcomes; CMV disease incidence, use of preemptive therapy, and drug toxicities were collected as secondary outcomes. Nineteen clinical trials conducted between 1981 and 2017 involving a total of 4173 patients were included for review. Prophylactic strategies included use of acyclovir, valacyclovir, ganciclovir, maribavir, brincidofovir, and letermovir compared with placebo or a comparator antiviral. Fourteen trials that compared antiviral prophylaxis with placebo demonstrated overall effectiveness in reducing incidence of CMV infection (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.42-0.58), CMV disease (OR, 0.56; 95% CI, 0.40-0.80), and use of preemptive therapy (OR, 0.51; 95% CI, 0.42-0.62; 6 trials); however, none demonstrated reduction in all-cause mortality (OR, 0.96; 95% CI, 0.78-1.18) except the phase 3 trial of letermovir (week-24 OR, 0.59; 95% CI, 0.38-0.98). Additional research is warranted to determine patient groups most likely to benefit from antiviral prophylaxis and its optimal deployment after allogeneic HCT.

High dose valacyclovir for cytomegalovirus prophylaxis following allogeneic hematopoietic cell transplantation

2021 ◽  
pp. 107815522110604
Author(s):  
Kelly G Hawks ◽  
Amanda Fegley ◽  
Roy T Sabo ◽  
Catherine H Roberts ◽  
Amir A Toor
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
High Dose ◽  
Cmv Infection ◽  
Allogeneic Hct ◽  
Clinically Significant ◽  
Cmv Disease ◽  
Cmv Prophylaxis

Introduction Cytomegalovirus (CMV) is one of the most common and clinically significant viral infections following allogeneic hematopoietic cell transplantation (HCT). Currently available options for CMV prophylaxis and treatment present challenges related to side effects and cost. Methods In this retrospective medical record review, the incidence of clinically significant CMV infection (CMV disease or reactivation requiring preemptive treatment) following allogeneic HCT was compared in patients receiving valacyclovir 1 g three times daily versus acyclovir 400 mg every 12 h for viral prophylaxis. Results Forty-five patients who received valacyclovir were matched based on propensity scoring to 35 patients who received acyclovir. All patients received reduced-intensity conditioning regimens containing anti-thymocyte globulin. Clinically significant CMV infection by day + 180 was lower in the valacyclovir group compared to the acyclovir group (18% vs. 57%, p = 0.0004). Patients receiving valacyclovir prophylaxis also had less severe infection evidenced by a reduction in CMV disease, lower peak CMV titers, delayed CMV reactivation, and less secondary neutropenia. Conclusion Prospective evaluation of valacyclovir 1 g three times daily for viral prophylaxis following allogeneic HCT is warranted. Due to valacyclovir's favorable toxicity profile and affordable cost, it has the potential to benefit patients on a broad scale as an option for CMV prophylaxis.

Clinical and economic impact of treated CMV infection in adult CMV‐seropositive patients after allogeneic hematopoietic cell transplantation

2020 ◽  
Vol 92 (12) ◽  
pp. 3665-3673
Author(s):  
Régis Peffault De Latour ◽  
Patrice Chevallier ◽  
Didier Blaise ◽  
Sarah Alami ◽  
Laurie Lévy‐Bachelot ◽  
...  
Keyword(s):  
Economic Impact ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Cmv Infection

Impact of geriatric vulnerability on outcomes of older patients in allogeneic hematopoietic cell transplantation.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7017-7017
Author(s):  
Richard Jirui Lin ◽  
Theresa A Elko ◽  
Sean M. Devlin ◽  
Jessica Flynn ◽  
Ann Alice Jakubowski ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Older Patients ◽  
Hematopoietic Cell Transplantation ◽  
Disease Risk ◽  
Risk Index ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Prognostic Impact ◽  
Cell Transplant ◽  
Increased Risk

7017 Background: Older patients are at increased risk for complications and death following allogeneic hematopoietic cell transplantation (allo-HCT). Traditional transplant-specific prognostic indices such as hematopoietic cell transplant comorbidity index (HCT-CI) may not capture all underlying geriatric vulnerabilities, and in-depth evaluation by a geriatrician prior to transplant may not always be available. We hypothesize that routine pre-transplant assessments by interdisciplinary clinical providers may help uncover additional geriatric deficits. Methods: Using an institutional database of 457 adults age 60 years and older (range 60-78.7) who underwent first allo-HCT for hematological malignancies from 2010 to 2017, we retrospectively examined the prevalence and the prognostic impact of pre-transplant geriatric deficits identified by interdisciplinary clinical providers including geriatric domains of functional activity, cognition, medication, nutrition, mobility, and routine laboratory tests. Results: With a median follow-up of 37 months for survivors, the 3-year probability of overall survival (OS) was 50% (95% CI 45-55). The 2-year cumulative incidence of non-relapse mortality (NRM) was 25% (95% CI 22-28). Among pre-transplant geriatric variables, we found that impairment in instrumental activities of daily living (IADL) was associated with increased NRM and inferior PFS and OS. In multivariate analyses, mismatched donor, age-adjusted HCT-CI > 4 (aaHCTCI), and IADL impairment were associated with NRM, while high/very high disease risk index (DRI), IADL impairment, and positive CMV status were associated with OS. The combination of IADL impairment with either aaHCTCI or DRI readily stratifies NRM and OS, respectively. Conclusions: Our findings establish a simple assessment tool to risk stratify older patients prior to allo-HCT using IADL and aaHCTCI and DRI. These results may provide an entry point for prospective, interventional trials to reduce NRM and toxicities for older allo-HCT patients.

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