scholarly journals Letermovir and its role in the prevention of cytomegalovirus infection in seropositive patients receiving an allogeneic hematopoietic cell transplant

2020 ◽  
Vol 11 ◽  
pp. 204062072093715
Author(s):  
Terri Lynn Shigle ◽  
Victoria Wehr Handy ◽  
Roy F. Chemaly
Keyword(s):  
Organ Transplant ◽  
Primary Prophylaxis ◽  
Lessons Learned ◽  
Hematopoietic Cell ◽  
Solid Organ ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Cmv Reactivation

Cytomegalovirus (CMV) reactivation is one of the most common infections affecting allogeneic hematopoietic cell transplant recipients. Although available anti-CMV therapies have been evaluated for the prevention of CMV reactivation, their toxicity profile makes them unfavorable for use as primary prophylaxis; thus, they are routinely reserved for the treatment of CMV viremia or CMV end-organ disease. Pre-emptive CMV monitoring strategies have been widely accepted, and although they have been helpful in early detection, they have not affected the overall morbidity and mortality associated with CMV. Letermovir is a novel agent that was approved for primary prophylaxis in CMV-seropositive adult allogeneic hematopoietic cell transplant recipients. This review focuses on letermovir’s novel mechanism; clinical trials supporting its United States Food and Drug Administration (FDA) approval and subsequent follow-up analyses; clinical considerations, with an emphasis on pharmacology; and lessons learned from solid organ transplant recipients, as well as potential future directions.

scholarly journals Effectiveness of bezlotoxumab for prevention of recurrent Clostridioides difficile infection among transplant recipients

2021 ◽  
Author(s):  
Tanner M Johnson ◽  
Amanda H Howard ◽  
Matthew A Miller ◽  
Lorna L Allen ◽  
Misha Huang ◽  
...  
Keyword(s):  
Organ Transplant ◽  
Standard Of Care ◽  
Hematopoietic Cell ◽  
Solid Organ ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Cell Transplant ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Solid Organ Transplant Recipients

Abstract Background Bezlotoxumab significantly reduces the incidence of recurrent Clostridioides difficile infection; however, limited data is available in solid-organ and hematopoietic-cell transplant recipients. Methods We conducted a single-center retrospective analysis comparing recurrent Clostridioides difficile infection in solid-organ and hematopoietic-cell transplant recipients receiving standard of care alone (oral vancomycin, fidaxomicin, or metronidazole) or bezlotoxumab plus standard of care. The primary outcome was 90-day incidence of recurrent Clostridioides difficile infection, and secondary outcomes included 90-day hospital readmission, mortality, and incidence of heart failure exacerbation. Results Overall, 94 patients received bezlotoxumab plus standard of care (n=38) or standard of care alone (n=56). The mean age was 53 years, patients had a median of 3 prior Clostridioides difficile episodes, and 4 risk factors for recurrent infection. Most patients were solid-organ transplant recipients (76%), with median time to index Clostridioides difficile infection occurring 2.7 years post-transplantation. Ninety-day recurrent Clostridioides difficile infection occurred in 16% (6/38) in the bezlotoxumab cohort compared to 29% (16/56) in the standard of care cohort (p=0.13). Multivariable regression revealed bezlotoxumab was associated with significantly lower odds of 90-day recurrent Clostridioides difficile infection (Odds Ratio [95% CI]: 0.28 [0.08-0.91]). There were no differences in secondary outcomes, and no heart failure exacerbations were observed. Conclusions In a cohort of primarily solid-organ transplant recipients, bezlotoxumab was well tolerated and associated with lower odds of recurrent Clostridioides difficile infection at 90-days. Larger, prospective trials are needed to confirm these findings amongst solid-organ and hematopoietic-cell transplant populations.

scholarly journals Impact of Letermovir Prophylaxis on Voriconazole Exposure in Allogeneic Hematopoietic Cell Transplant Recipients

2021 ◽  
Vol 27 (3) ◽  
pp. S124
Author(s):  
Issam S. Hamadeh ◽  
Michael R. Grunwald ◽  
Allison Martin ◽  
Jai N. Patel ◽  
Alexandra Wolff ◽  
...  
Keyword(s):  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant

scholarly journals Invasive mold infections in allogeneic hematopoietic cell transplant recipients in 2020: have we made enough progress?

2021 ◽  
Author(s):  
Romain Samuel Roth ◽  
Stavroula Masouridi-Levrat ◽  
Yves Chalandon ◽  
Anne-Claire Mamez ◽  
Federica Giannotti ◽  
...  
Keyword(s):  
Risk Factors ◽  
Treatment Strategies ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Incidence Risk ◽  
One Year ◽  
Invasive Mold Infections

Abstract Background Despite progress in diagnostic, prevention and treatment strategies, invasive mold infections (IMI) remain leading cause of mortality in allogeneic hematopoietic cell transplant recipients (allo-HCT-recipients). Methods We describe the incidence, risk factors, and mortality of allo-HCT-recipients with proven/probable IMI in a retrospective single-center 10-year (01.01.2010-01.01.2020) cohort study. Results Among 515 allo-HCT-recipients, 48 (9.3%) patients developed 51 proven/probable IMI: invasive aspergillosis (IA; 34/51, 67%), mucormycosis (9/51, 18%) and other molds (8/51, 15%). Overall 35/51 (68.6%) breakthrough-IMI (bIMI) were identified: 22/35 (62.8%) IA and 13/35 (37.1%) non-IA IMI. One-year IMI cumulative incidence was 7%: 4.9% and 2.1% for IA and non-IA IMI, respectively. Fourteen (29.2 %), 10 (20.8%), and 24 (50.0%) patients were diagnosed during the first 30, 31-180, and >180 days post-HCT, respectively. Risk factors for IMI included: prior allo-HCT (SHR:4.06, p=0.004) and ≥grade-2 acute graft-versus-host disease (aGvHD; SHR: 3.52, p<0.001). All-cause 1-year mortality was 33% (170/515): 48% (23/48) and 31.5% (147/467) for patients with and without IMI (p=0.02). Mortality predictors included: disease relapse (HR:7.47, p<0.001), aGvHD (HR:1.51, p=0.001), CMV-serology-positive recipients (HR:1.47, p=0.03), and IMI (HR:3.94, p<0.001). All-cause 12-week mortality for patients with IMI was 35.4% (17/48): 31.3% (10/32) for IA and 43.8% (7/16) for non-IA IMI (logrank 0.47). At 1-year post-IMI diagnosis, 70.8% (34/48) of patients were dead. Conclusions IA mortality has remained relatively unchanged during the last two decades. More than two thirds of allo-HCT-recipients with IMI die by 1-year post-IMI diagnosis. Dedicated intensified research efforts are required to further improve clinical outcomes.

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