scholarly journals A Mortality Analysis of Letermovir Prophylaxis for Cytomegalovirus (CMV) in CMV-seropositive Recipients of Allogeneic Hematopoietic Cell Transplantation

2019 ◽  
Vol 70 (8) ◽  
pp. 1525-1533 ◽  
Author(s):  
Per Ljungman ◽  
Michael Schmitt ◽  
Francisco M Marty ◽  
Johan Maertens ◽  
Roy F Chemaly ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Phase 3 ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
All Cause Mortality ◽  
Clinically Significant ◽  
Status Data

Abstract Background In a phase 3 trial, letermovir reduced clinically significant cytomegalovirus infections (CS-CMVi) and all-cause mortality at week 24 versus placebo in CMV-seropositive allogeneic hematopoietic cell transplantation (HCT) recipients. This post hoc analysis of phase 3 data further investigated the effects of letermovir on all-cause mortality. Methods Kaplan-Meier survival curves were generated by treatment group for all-cause mortality. Observations were censored at trial discontinuation for reasons other than death or at trial completion. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox modeling, adjusting for risk factors associated with mortality. Results Of 495 patients with no detectable CMV DNA at randomization, 437 had vital-status data available through week 48 post-HCT at trial completion (101 deaths, 20.4%). Following letermovir prophylaxis, the HR for all-cause mortality was 0.58 (95% CI, 0.35–0.98; P = .04) at week 24 and 0.74 (95% CI, 0.49–1.11; P = .14) at week 48 post-HCT versus placebo. Incidence of all-cause mortality through week 48 post-HCT in the letermovir group was similar in patients with or without CS-CMVi (15.8 vs 19.4%; P = .71). However, in the placebo group, all-cause mortality at week 48 post-HCT was higher in patients with versus those without CS-CMVi (31.0% vs 18.2%; P = .02). The HR for all-cause mortality in patients with CS-CMVi was 0.45 (95% CI, 0.21–1.00; P = .05) at week 48 for letermovir versus placebo. Conclusions Letermovir may reduce mortality by preventing or delaying CS-CMVi in HCT recipients. Clinical Trials Registration clinicaltrials.gov, NCT02137772.

Number of Prior Chemotherapy Regimens: Important Prognositic Factor of All-Cause Mortality after Allogeneic Hematopoietic Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1104-1104
Author(s):  
Tetsuyuki Kiyokawa ◽  
Shoichi Nagakura ◽  
Michihiro Hidaka ◽  
Naokuni Uike ◽  
Motohiro Hamaguchi ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Prior Chemotherapy ◽  
Allogeneic Hct ◽  
Promising Tool ◽  
Kaplan Meier ◽  
All Cause Mortality ◽  
Cell Transplants

Abstract BACKGROUND: Despite recent advances, mortality rates after allogeneic hematopoietic cell transplantation remain high and cannot accurately predicted. PURPOSE: To determine the value of pretransplant factors in predicting all-cause mortality during first 1 year after allogeneic HCT. PATIENTS AND METHODS: A retrospective review of 303 consecutive allogeneic hematopoietic cell transplants was performed with attention to mortality and pretransplant factors in three hematopoietic cell transplantation centers between 2000 and 2005 in Japan. Patients underwent transplantation from sibling (n=200) or unrelated donors (n=104) with myeloablative (n=188) or nonmyeloablative conditioning (n=116). Pretransplant factors and the hematopoietic cell transplantation-specific comorbidity index (HCT-CI: Sorror et. al.) were assessed with general linear model (GML) analysis. RESULTS: Mortality before 1 year occurred in 145 of 303(48.3%) transplant recipients. The number of prior chemotherapy regimens and the HCT-CI were found to be useful predictors of early mortality. Kaplan-Meier estimates of survival as stratified by the HCT-CI (Fig.1) and the number of prior chemotherapy (Fig.2). The HCT-CI were useful for predicting outcomes. However, the sample size of patients with scores of 1 or more, captured by the HCT-CI did not exceed 15%. Futher, the number of prior chemotherapy regimens showed better suvival prediction. CONCLUSION: The number of prior chemotherapy regimens will be a promising tool to identify patient at risk for all-cause mortality during first 1 year after allogeneic HCT. Figure Figure

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.

scholarly journals Letermovir prophylaxis is effective in preventing cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation: single-center real-world data

2020 ◽  
Author(s):  
Patrick Derigs ◽  
Aleksandar Radujkovic ◽  
Maria-Luisa Schubert ◽  
Paul Schnitzler ◽  
Tilman Schöning ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Real World ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Control Group ◽  
Real World Data ◽  
Cytomegalovirus Reactivation ◽  
Clinically Significant ◽  
Cmv Reactivation

AbstractMorbidity and mortality after allogeneic hematopoietic cell transplantation (alloHCT) are still essentially affected by reactivation of cytomegalovirus (CMV). We evaluated 80 seropositive patients transplanted consecutively between March 2018 and March 2019 who received letermovir (LET) prophylaxis from engraftment until day +100 and retrospectively compared them with 80 patients without LET allografted between January 2017 and March 2018. The primary endpoint of this study was the cumulative incidence (CI) of clinically significant CMV infection (CS-CMVi) defined as CMV reactivation demanding preemptive treatment or CMV disease. With 14% CI of CS-CMVi at day +100 (11 events) was significantly lower in the LET cohort when compared to the control group (33 events, 41%; HR 0.29; p < 0.001). Whereas therapy with foscarnet could be completely avoided in the LET group, 7 out of 80 patients in the control cohort received foscarnet, resulting in 151 extra in-patient days for foscarnet administration (p = 0.002). One-year overall survival was 72% in the control arm vs 84% in the LET arm (HR 0.75 [95%CI 0.43–1.30]; p < 0.306). This study confirms efficacy and safety of LET for prophylaxis of CS-CMVi after alloHCT in a real-world setting, resulting in a significant patient benefit by reducing hospitalization needs and exposure to potentially toxic antiviral drugs for treatment of CMV reactivation.

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.

scholarly journals 2660. Infection Complications Following Mismatched Allogeneic Hematopoietic Cell Transplantation

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S930-S931
Author(s):  
Yosuke Ebisu ◽  
Yoichiro Natori ◽  
Antonio Jimenez ◽  
Maritza C Alencar ◽  
Michele Morris ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Attributable Mortality ◽  
Unrelated Donor ◽  
Significant Difference ◽  
Group 3 ◽  
Clinically Significant ◽  
Group 1

Abstract Background The use of haploidentitical or HLA mismatched unrelated donors permits allogeneic hematopoietic cell transplantation (HCT) in individuals with otherwise no donors available. Post-transplantcyclophosphamide(PTCy) is used for prevention graft-vs.-host disease (GVHD) in recipients of mismatched donors. We hypothesized that type and incidence of infectious complications following allogeneic HCT would vary according to the type of transplant. Methods We systematically assessed viral kinetics and reactivation rates for cytomegalovirus (CMV) in a prospective cohort of mismatched unrelated donor (MMUD) HCT recipients who had PTCy at our center (April 2017–March 2019). In addition, we evaluated the incidence of invasive aspergillosis (IA), invasive candidiasis (IC), bloodstream infection (BSI), pneumonia, Clostridium difficile (CDI), and community-acquired respiratory virus. Haploidentical donor and anti-thymocyte globulin (ATG) treated MMUD recipients were served as historical control groups. Results A total of 81 patients were analyzed in 3 groups (Table 1): PTCy MMUD (group 1; n = 22), ATG MMUD (group 2; n = 40) and haploidentical (group 3; n = 19). Whereas the 1 year incidence of CMV viremia was similar across groups, the rate of clinically significant (requiring preemptive therapy) CMV viremia was lower in group 1, compared with groups 2 and 3 (18 vs 53%; P = 0.02). The 1 year incidence of CDI was 47% in group 3 vs. 18% in groups 1 and 2 (P = 0.01). There was no significant difference in the incidence of IA (5–18%), pneumonia (30–42%), BSI (32–55%) and CARVs (28–53%) between groups. There were no cases of IC in this cohort. 1 year infection attributable mortality was lower in group 1 (figure), compared with groups 2 and 3, (9%, 62% and 39%, respectively; P = 0.005). Conclusion Compared with ATG MMUD and haploidentical donor, PTCy MMUD HCT was associated with lower incidence of clinically significant CMV and lower infection attributable mortality. These findings might be related to the contemporary prophylactic strategies used in this patient population. Larger studies are needed. Disclosures All authors: No reported disclosures.

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