Clinical Validation of the Definitions of Resistant and Refractory Cytomegalovirus (CMV) Infection and Disease in Hematopoietic Cell Transplant (HCT) Recipients.

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.

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Cytomegalovirus (CMV) Cell-Mediated Immunity and CMV Infection After Allogeneic Hematopoietic Cell Transplantation: The REACT Study

Clinical Infectious Diseases ◽

10.1093/cid/ciz1210 ◽

2020 ◽

Author(s):

Roy F Chemaly ◽

Lynn El Haddad ◽

Drew J Winston ◽

Scott D Rowley ◽

Kathleen M Mulane ◽

...

Keyword(s):

At Risk ◽

Hematopoietic Cell Transplantation ◽

Multivariable Analysis ◽

Hematopoietic Cell ◽

Cell Mediated Immunity ◽

Cell Transplant ◽

Cmv Infection ◽

Hematopoietic Cell Transplant ◽

Allogeneic Hematopoietic Cell Transplant ◽

Patients At Risk

Abstract Background Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients. CMV cell-mediated immunity (CMV-CMI) as determined by a peptide-based enzyme-linked immunospot (ELISPOT) CMV assay may identify patients at risk for clinically significant CMV infection (CS-CMVi). Methods The CS-CMVi was defined as CMV viremia and/or disease necessitating antiviral therapy. CMV-CMI was characterized as high when the intermediate-early 1 (IE-1) antigen spot counts (SPCs) were >100 (cutoff 1) or when the IE-1 and phosphoprotein 65 antigen SPCs were both >100 SPCs per 250 000 cells (cutoff 2), and a low CMV-CMI when SPCs were below these thresholds. In this prospective multicenter study, we evaluated CMV-CMI every 2 weeks from the pretransplant period until 6 months posttransplantation in 241 allo-HCT recipients with positive CMV serostatus. The primary endpoint was CS-CMVi occurring within 2 weeks of the last measurement of CMV-CMI. Results CS-CMVi occurred in 70 allo-HCT recipients (29%). CMV-CMI was low in patients who experienced CS-CMVi (94%), whereas those who had a high CMV-CMI were less likely to have CS-CMVi (P < .0001). Patients with CS-CMVi had higher all-cause mortality (P = .007), especially those with low CMV-CMI (P = .035). On multivariable analysis, CMV-CMI, sex, race, antithymocyte globulin, and steroid use were independent predictors of CS-CMVi, and the time from transplant to engraftment was the only predictor of mortality. Conclusions Measurement of CMV-CMI using a novel ELISPOT assay would be useful clinically to monitor allo-HCT recipients and distinguish between those at risk of developing CS-CMVi and requiring antiviral prophylaxis or therapy and those who are protected.

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Clinical & Economic Burden of Pre-Emptive Therapy (PET) of Cytomegalovirus (CMV) Infection in Hospitalized Allogeneic Hematopoietic Cell Transplant (Allo-HCT) Recipients: The MD Anderson Cancer Center Experience

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2017.12.458 ◽

2018 ◽

Vol 24 (3) ◽

pp. S374-S375

Author(s):

Shashank S. Ghantoji ◽

Jonathan Schelfhout ◽

Lynn El Haddad ◽

Yadira Lobo ◽

Ying Jiang ◽

...

Keyword(s):

Economic Burden ◽

Hematopoietic Cell ◽

Cancer Center ◽

Cell Transplant ◽

Cmv Infection ◽

Hematopoietic Cell Transplant ◽

Allogeneic Hematopoietic Cell Transplant ◽

Md Anderson

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1745. Retrospective Cohort Analysis to Determine the Incidence of CMV Infection and Disease in Allogeneic Hematopoietic Cell Transplant Recipients at an Academic Children’s Hospital

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1608 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S639-S640

Author(s):

Despoina M Galetaki ◽

Molly Hayes ◽

Alexander Newman ◽

Craig L K Boge ◽

Caitlin W Elgarten ◽

...

Keyword(s):

Standard Dose ◽

Cohort Analysis ◽

Hematopoietic Cell ◽

Cell Transplant ◽

Antiviral Prophylaxis ◽

Cmv Infection ◽

Hematopoietic Cell Transplant ◽

Allogeneic Hematopoietic Cell Transplant ◽

Time To Detection ◽

Cmv Prophylaxis

Abstract Background Data on cytomegalovirus (CMV) infection and disease by donor (D)/recipient (R) status or prophylaxis regimen in pediatric hematopoietic cell transplant (HCT) recipients are limited. There is an absence of data on adverse events (AE) attributable to prophylaxis. Methods A single-center cohort (N = 352) of allogeneic HCT episodes between January 2004 and June 2017 was assembled. Exclusion criteria were CMV PCR positivity 30 days before HCT, lack of CMV surveillance (<2 blood PCRs in the 30 days post HCT), or unknown D/R CMV status. CMV prophylaxis was recommended for CMV D+ or R+ patients with ≥1 of the following factors: T-cell depletion, cord blood product, or exposure to distal alemtuzumab. The CMV prophylaxis regimen was standard-dose acyclovir from day −7 to +7, then foscarnet to engraftment, and then valganciclovir to day +100 (acyc → fos → valgan). If a patient did not meet criteria for CMV prophylaxis but was HSV IgG positive then standard-dose acyclovir was given from day −7 to the end of study follow-up (SD-acyc). All remaining patients did not receive antiviral prophylaxis. Outcomes of CMV infection and CMV disease by day +180 were captured. AEs attributable to antiviral prophylaxis were also identified. An AE was attributed to an antiviral prophylaxis medication if the dose was reduced or stopped. AEs were only reported in HCT episodes with complete medical records (n = 221). Results The CMV infection rate was 26.7%, with a median time to detection of 23.5 days (range: 4–146). CMV infection was common in D+/R+ (58.9%) and D−/R+ (34.6%) patients. Just under 11% of CMV infections progressed to disease (Figures 1 and 2). Breakthrough CMV infection occurred in 49.1% of patients despite acyc → fos → valgan (Figure 3) at a median of 11 days from HCT (range: 4–132). The attributable AE rate was 13.4% and 36.8% for SD-acyc and acyc → fos → valgan, respectively (Figure 4). Conclusion CMV infection was common in D+/R+ and D−/R+ patients, and a substantial proportion progressed to disease. Breakthrough infection persisted despite acyc → fos → valgan prophylaxis and AEs attributable to this regimen were common. CMV infection in R+ patients was frequent even in the absence of additional risk factors. Studies of novel prophylaxis approaches are needed and should include R+ patients regardless of other factors. Disclosures All authors: No reported disclosures.

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