This site is intended for US health care professionals.
01. Foundational / Icons / 32x32px/Menu @1x Open Menu 01. Foundational / Icons / 32x32px/Close @1x Close Menu

Background of CMV infection in hematopoietic stem cell transplantation (HSCT)

Learn about:

CMV R+ hematopoietic stem cell transplant (HSCT) recipients are at increased risk for cytomegalovirus (CMV) infection, disease, and associated mortality1-3

CMV serostatus of the recipient is the strongest predictor of CMV infection post-HSCT. Positive CMV serostatus pre-HSCT is a major risk factor of CMV infection and disease.1,4

  • CMV reactivation has been shown to occur in ~30-65% of CMV-seropositive allogeneic HSCT patients.5,6,a
  • More than 30% of HSCT patients who were CMV-seropositive or had a seropositive donor had CMV infection within 1 month post-transplant.2

(a) Results from two retrospective studies Teira et al and Sousa et al.

Any level of CMV viremia is associated with increased risk of mortality in the first year post-HSCT2,b

CMV viral load as a time-dependent risk factor for overall mortality 1 year after HSCT (n=926)2,b

Overall Risk of Mortality with CMV Post-HSCT

CI, confidence interval; HR, hazard ratio.

(b) Results from a large, retrospective, noninterventional cohort study of previously collected CMV viral load and clinical outcome measures (n=926).2

Early CMV reactivation is associated with increased non-relapse mortality and reduced overall survival following allogeneic HSCT6

Overall Risk Compared to Relative Risk of No CMV Reactivation

AML, ALL, CML, and MDS Disease Groups Experienced Increased Non-Relapse Mortality and Reduced Overall Survival

Adapted from a CIBMTR analysis by Teira et al.

ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CIBMTR, Center for International Blood and Marrow Transplant Research; CML, chronic myeloid leukemia; MDS, myelodysplastic syndrome.

Study design

  • Retrospective, multivariate analysis of 9,469 patients from the Center for International Blood and Marrow Transplant Research (CIBMTR) database who received their first allogeneic HSCT between 2003 and 20106
  • Multivariable analysis of risk factors for outcomes depending on CMV serostatus and reactivation with hematologic disease relapse, non-relapse mortality, and overall survival (AML [n=5,310], ALL [n=1,883], CML [n=1,079], and MDS [n=1,197])6

Study limitations

  • No data was collected on how CMV reactivation was monitored with respect to tests used and values applied for implementing preemptive therapy.6
  • Institutional practices for preemptive and prophylactic therapy vary with respect to initiation and duration of therapy, affecting the ability to assess efficacy of initial therapy and duration of CMV reactivation.6
  • The retrospective nature of the analysis limits generalization of results across transplant settings.6

How could initiation of CMV prophylaxis make a difference for your R+ patients?

References

  1. Hakki M, Aitken SL, Danziger-Isakov L, et al. American Society for Transplantation and Cellular Therapy series: #3— prevention of cytomegalovirus infection and disease after hematopoietic cell transplantation. Transplant Cell Ther. 2021;27(9):707-719. https://doi.org/10.1016/j.jtct.2021.05.001
  2. Green ML, Leisenring W, Xie H, et al. Cytomegalovirus viral load and mortality after haematopoietic stem cell transplantation in the era of pre-emptive therapy: a retrospective cohort study. Lancet Haematol. 2016;3(3):e119–e127.
  3. Camargo JF. Cytomegalovirus in hematopoietic stem cell transplant recipients: prevention, diagnosis, and treatment. In: Morris MI, Kotton CN, Wolfe CR, eds. Emerging Transplant Infections. Cham, Switzerland: Springer; 2021:573-616. doi:10.1007/978-3-030-25869-6_25
  4. Khawaja F, Zamora D, Yong MK, et al. American Society for Transplantation and Cellular Therapy Series #11: updated cytomegalovirus guidelines in hematopoietic cell transplant and cellular therapy recipients. Transplant Cell Ther. Published 2025. doi:10.1016/j.jtct.2025.06.025
  5. Sousa H, Boutolleau D, Ribeiro J, et al. Cytomegalovirus infection in patients who underwent allogeneic hematopoietic stem cell transplantation in Portugal: a five-year retrospective review. Biol Blood Marrow Transplant. 2014;20(12):1958–1967.
  6. Teira P, Battiwalla M, Ramanathan M, et al. Early cytomegalovirus reactivation remains associated with increased transplant-related mortality in the current era: a CIBMTR analysis. Blood. 2016; 127(20)2427-2438. doi:10.1182/blood-2015-11-679639

Back to top

INDICATIONS

PREVYMIS® (letermovir) is indicated for prophylaxis of cytomegalovirus (CMV) infection and disease in adult and pediatric patients 6 months of age and older and weighing at least 6 kg who are CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT).

 

PREVYMIS is indicated for prophylaxis of CMV disease in adult and pediatric patients 12 years of age and older and weighing at least 40 kg who are kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]).

SELECTED SAFETY INFORMATION

  • PREVYMIS is contraindicated in patients receiving pimozide or ergot alkaloids.
      • Increased pimozide concentrations may lead to QT prolongation and torsades de pointes.
      • Increased ergot alkaloids concentrations may lead to ergotism.
  • PREVYMIS is contraindicated with pitavastatin and simvastatin when co-administered with cyclosporine. Significantly increased pitavastatin or simvastatin concentrations may lead to myopathy or rhabdomyolysis.
  • The concomitant use of PREVYMIS and certain drugs may result in potentially significant drug interactions, some of which may lead to adverse reactions (PREVYMIS or concomitant drugs) or reduced therapeutic effect of PREVYMIS or the concomitant drug.
  • Intravenous formulation of PREVYMIS contains the excipient hydroxypropyl betadex. PREVYMIS injection should be used only in patients unable to take oral therapy and patients should be switched to oral PREVYMIS as soon as they are able to take oral medications. If possible, intravenous administration should not exceed 4 weeks.
  • In patients with renal impairment, accumulation of hydroxypropyl betadex may occur. In adult patients with CLcr less than 50 mL/min and in pediatric patients with a similar degree of renal impairment (based on age-appropriate assessment of renal function) receiving PREVYMIS injection, closely monitor serum creatinine levels.
  • Animal studies have shown the potential for hydroxypropyl betadex to cause ototoxicity. The active ingredient, letermovir, is not known to be associated with ototoxicity.
  • The rate of adverse events occurring in at least 10% of adult HSCT recipients treated with PREVYMIS and at a frequency at least 2% greater than placebo were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).
  • Hypersensitivity reaction, with associated moderate dyspnea, occurred in one adult HSCT recipient following the first infusion of IV PREVYMIS after switching from oral PREVYMIS, leading to treatment discontinuation.
  • The most common adverse event occurring in at least 10% of adult kidney transplant recipients treated with PREVYMIS and at a frequency greater than valganciclovir was diarrhea (32% vs 29%).
  • The safety profile of PREVYMIS in pediatric subjects was consistent with the safety profile observed in clinical trials of PREVYMIS in adults.
  • If PREVYMIS is co-administered with cyclosporine, the dosage of PREVYMIS should be decreased to 240 mg once daily.
  • If PREVYMIS is co-administered with cyclosporine in pediatric HSCT patients less than 12 years of age, dose adjustment may be required.
  • Co-administration of PREVYMIS may alter the plasma concentrations of other drugs and other drugs may alter the plasma concentrations of PREVYMIS. Consult the full Prescribing Information prior to and during treatment for potential drug interactions.
  • Closely monitor serum creatinine levels in patients with CLcr less than 50 mL/min using PREVYMIS injection.
  • PREVYMIS is not recommended for patients with severe (Child-Pugh Class C) hepatic impairment.
  • The safety and effectiveness of PREVYMIS have not been established for:
      • HSCT recipients less than 6 months of age or weighing less than 6 kg, or
      • Kidney transplant recipients less than 12 years of age or weighing less than 40 kg.
  • For patients with creatinine clearance (CLcr) greater than 10 mL/min (by Cockcroft-Gault equation), no dosage adjustment of PREVYMIS is required based on renal impairment. The safety of PREVYMIS in patients with end-stage renal disease (CLcr less than 10 mL/min), including patients on dialysis, is unknown.

Before prescribing PREVYMIS® (letermovir), please read the accompanying Prescribing Information. The Patient Information and Instructions for Use also are available.

INDICATIONS
SELECTED SAFETY INFORMATION

PREVYMIS® (letermovir) is indicated for prophylaxis of cytomegalovirus (CMV) infection and disease in adult and pediatric patients 6 months of age and older and weighing at least 6 kg who are CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT).

 

PREVYMIS is indicated for prophylaxis of CMV disease in adult and pediatric patients 12 years of age and older and weighing at least 40 kg who are kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]).

SELECTED SAFETY INFORMATION

  • PREVYMIS is contraindicated in patients receiving pimozide or ergot alkaloids.
      • Increased pimozide concentrations may lead to QT prolongation and torsades de pointes.
      • Increased ergot alkaloids concentrations may lead to ergotism.
  • PREVYMIS is contraindicated with pitavastatin and simvastatin when co-administered with cyclosporine. Significantly increased pitavastatin or simvastatin concentrations may lead to myopathy or rhabdomyolysis.
  • The concomitant use of PREVYMIS and certain drugs may result in potentially significant drug interactions, some of which may lead to adverse reactions (PREVYMIS or concomitant drugs) or reduced therapeutic effect of PREVYMIS or the concomitant drug.
  • Intravenous formulation of PREVYMIS contains the excipient hydroxypropyl betadex. PREVYMIS injection should be used only in patients unable to take oral therapy and patients should be switched to oral PREVYMIS as soon as they are able to take oral medications. If possible, intravenous administration should not exceed 4 weeks.
  • In patients with renal impairment, accumulation of hydroxypropyl betadex may occur. In adult patients with CLcr less than 50 mL/min and in pediatric patients with a similar degree of renal impairment (based on age-appropriate assessment of renal function) receiving PREVYMIS injection, closely monitor serum creatinine levels.
  • Animal studies have shown the potential for hydroxypropyl betadex to cause ototoxicity. The active ingredient, letermovir, is not known to be associated with ototoxicity.
  • The rate of adverse events occurring in at least 10% of adult HSCT recipients treated with PREVYMIS and at a frequency at least 2% greater than placebo were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).
  • Hypersensitivity reaction, with associated moderate dyspnea, occurred in one adult HSCT recipient following the first infusion of IV PREVYMIS after switching from oral PREVYMIS, leading to treatment discontinuation.
  • The most common adverse event occurring in at least 10% of adult kidney transplant recipients treated with PREVYMIS and at a frequency greater than valganciclovir was diarrhea (32% vs 29%).
  • The safety profile of PREVYMIS in pediatric subjects was consistent with the safety profile observed in clinical trials of PREVYMIS in adults.
  • If PREVYMIS is co-administered with cyclosporine, the dosage of PREVYMIS should be decreased to 240 mg once daily.
  • If PREVYMIS is co-administered with cyclosporine in pediatric HSCT patients less than 12 years of age, dose adjustment may be required.
  • Co-administration of PREVYMIS may alter the plasma concentrations of other drugs and other drugs may alter the plasma concentrations of PREVYMIS. Consult the full Prescribing Information prior to and during treatment for potential drug interactions.
  • Closely monitor serum creatinine levels in patients with CLcr less than 50 mL/min using PREVYMIS injection.
  • PREVYMIS is not recommended for patients with severe (Child-Pugh Class C) hepatic impairment.
  • The safety and effectiveness of PREVYMIS have not been established for:
      • HSCT recipients less than 6 months of age or weighing less than 6 kg, or
      • Kidney transplant recipients less than 12 years of age or weighing less than 40 kg.
  • For patients with creatinine clearance (CLcr) greater than 10 mL/min (by Cockcroft-Gault equation), no dosage adjustment of PREVYMIS is required based on renal impairment. The safety of PREVYMIS in patients with end-stage renal disease (CLcr less than 10 mL/min), including patients on dialysis, is unknown.

Before prescribing PREVYMIS® (letermovir), please read the accompanying Prescribing Information. The Patient Information and Instructions for Use also are available.