A Study of the Drug Letermovir (LTV) as Prevention for Recurrent of Cytomegalovirus (CMV) Infection

Inclusion Criteria: * Age \>/= 12 years (any weight) * Have received allogenic HCT * Have received preemptive therapy for clinically significant CMV infection post-HCT and have completed preemptive therapy no longer than 7 days prior to enrollment. Preemptive treatment includes ganciclovir, valganciclovir, foscarnet or cidofovir. Clinically significant CMV infection is defined as CMV viremia requiring preemptive therapy or CMV EOD. Patients who have received LTV prophylaxis prior to onset of clinically significant CMV infection prior to enrollment (see also exclusion criteria below). * Have one or more risk factors for recurrent CMV infection: 1. Human leukocyte antigen (HLA) mismatch * HLA-related (sibling) donor with at least one mismatch at the HLA-A, -B or -DR gene loci * Haploidentical donor * Unrelated donor with at least one mismatch at the HLA-A, -B, -C or -DRC1gene loci, or * Cord blood as stem cell source 2. Acute or chronic GVHD requiring either topical steroids for gastrointestinal GVHD and/or systemic steroid treatment (\>/= 1mg/kg/day of prednisone or equivalent dose of another corticosteroid) within 14 days prior to enrollment 3. T-cell-depleted allograft ex-vivo or in-vivo T-cell depleting agents including but not limited to ATG, alemtuzimab and post HCT cyclophosphamide. * For adult patients, able to provide written consent and complete the informed consent. For patients under 18 years, the patient's parent(s) or legal guardian(s) must provide informed consent and the patient must provide written assent to participation in the study. * Willing and able to comply with trial instructions and requirements * Male and female patients of childbearing potential must be willing to use a highly effective method of contraception for the course of the study. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient. Subject eligibility criteria for the observational cohort: * Age 18 years or older * First allogenic peripheral blood or marrow HCT * LTV prophylaxis starting \<30 days post HCT and given for at least 6 weeks Exclusion Criteria: * Clinically significant CMV infection present at enrollment * Breakthrough CMV infection while on primary LTV prophylaxis (unless patient non-adherent or unable to adequately absorb letermovir or documented resistance to LTV. * Glomerular filtration rate (GFR) \</= mL/min/1.73m\^2(equivalent to creatinine clearance \</=10 mL/min) * Severe hepatic impairment * Routine use of high-dose acyclovir (doses of \> 800 mg twice daily), valacyclovir (doses of \> 500mg twice daily), or famciclovir (doses \> 500mg/day) for varicella zoster virus (VZV)/herpes simplex virus prophylaxis; limited treatment courses at higher doses for VZV infections are permissible if treatment duration dose not exceed 14 days total. Short courses of IV cidofovir for adeno virus (ADV) are permissible * Suspected or known hypersensitivity to active or inactive ingredients of LTV formulations * Patients treated with a medication whose administration with LTV is ontraindicated and whose discontinuation is not possible. Contraindicated medications include pimozide, ergot alkaloids and pitavastatin or simvastatin when co-administered with cyclosporine. * Imminent demise (expected survival \<6 weeks) * Documented positive result for human immunodeficiency virus antibody (HIV-Ab) or for hepatitis C virus antibody (HCV-Ab) with detectable HCV RNA, or hepatitis B surface antigen (HBsAg) at any time prior to HCT * Need for mechanical ventilation and/or vasopressor support at the time of enrollment * Pregnancy or breastfeeding * Plans to conceive or father children within the projected duration of the trial * History of current evidence of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or would place the subject at undue risk as judged by the investigator, such that it is not in the best interest of the subject to participate in this study. * The following antivirals are allowed up to the listed dose limits: * Acyclovir up to 800 mg twice daily * Valacyclovir up to 500 mg twice daily * Famciclovir up to 500 mg/day for VZV/HSV prophylaxis; limited treatment courses at higher doses for VZV infections are permissible if treatment duration does not exceed 14 days total. * Short courses of IV cidofovir for ADV (up to two doses) Exclusion criteria for observational cohort: * Clinically significant CMV infection during the 100 days following HCT. Clinically significant CMV infection defined as either CMV viremia requiring preemptive therapy with CMV antivirals or CMV end organ disease (EOD) * Grade 3-4 GVHD * Cord blood as cell source for HCT * Treatment with systemic steroids (\>0.5mg/kg for 2 weeks or longer) within 3 weeks prior to enrollment