The goal of this laboratory research study is to learn if interrupting a patient's letermovir dosing based on their immune system response can help HSC transplant patients avoid post-treatment CMV infections better than taking letermovir every day without interruption.

Primary Objective

•To compare the proportion of CS-CMVi in allo-HCT recipients who had interrupted letermovir prophylaxis based on CMV CMI or extended duration of letermovir prophylaxis up to 200 days post transplantation.

Secondary Objectives

• To compare the proportion of CS-CMVi in HCT recipients who had interrupted letermovir prophylaxis based on CMV CMI or extended duration of letermovir prophylaxis at 365 days post transplantation.
• To compare the overall use of letermovir in HCT recipients in both arms.
• To compare CMV CMI in HCT recipients in both arms.
• To compare all-cause mortality and nonrelapse mortality between the 2 arms at day +200 and day +365.
• Healthcare expenditures for letermovir use and TCIP for both arms from day +100 to day +200.

Inclusion criteria

1. Allogeneic HCT recipients with positive CMV serostatus

2. On letermovir prophylaxis at day 90 post transplant (+/- 7 days)

3. At high risk for CMV reactivation after day +100:

   1. Prior or active graft versus host disease requiring systemic steroids
   2. Mismatch stem cell donor (includes haploidentical, mismatch unrelated donor (MMUD), match related donor with at least one mismatch at one of the three specified HLA gene loci (HLA-A, HLA-B, or HLA-DR) and cord donor recipients)
   3. Received T cell depletion or anti thymoglobulin during conditioning
   4. CMV reactivation prior to day 100 post transplant
   5. On steroids at any dose within 2 weeks of enrollment

Exclusion criteria

1. Patients under the age of 18
2. Patients are discharged from our institution and unwilling to come back for follow up
3. Patients are actively undergoing treatment for CS-CMVi at time of screening. Prior CS-CMVi is not an exclusion from study.
4. Patients are allergic or intolerant to letermovir or have history of letermovir resistant CMV infection.
5. Not able to procure letermovir for extended prophylaxis beyond day +100.