Novel use of low-dose cidofovir (2.5 mg/kg Weekly) as CMV prophylaxis in the pre-engraftment Phase of stem cell transplantation: A viable alternative when ganciclovir is contraindicated and letermovir is not available Free

Background: Cytomegalovirus (CMV) infection in the pre-engraftment phase of hematopoietic stem cell transplantation (HSCT) poses a significant risk of graft failure and mortality. While ganciclovir is the standard therapeutic option, its myelosuppressive effects leading to primary graft failure limit its use during early engraftment. Letermovir, though effective as a prophylaxis agent, remains unavailable and may be financially inaccessible in many regions of the world, including the area where this study was conducted. There is an urgent need for alternative strategies to prevent and treat CMV in this critical phase.

Methods: We evaluated the efficacy and safety of low-dose cidofovir (2.5 mg/kg weekly) as CMV prophylaxis in HSCT recipients during the pre-engraftment period. This was started from Day +3 in most cases, except in haploidentical patients with PTCY, where it was delayed till Day +6. Cases included all those who were deemed to be at high risk of CMV infection as per standard published guidelines. These include CMV-seropositive recipients (R+) with seronegative donors (D-) who are deemed to be at highest risk of CMV infection due to latent virus reactivation, those with previous CMV infections and in haploidentical BMT cases where Post Transplant Cyclophosphamide (PTCy) was used as GVHD prophylaxis. We did not include or start CMV prophylaxis in R+/D+ cases

Patients were monitored for CMV DNAemia with twice weekly CMV viral load, and primary outcome measures of CMV reactivation and disease rates, need for additional therapy, engraftment kinetics, renal toxicity, and survival outcomes were analyzed.

Results: Out of 78 allogeneic transplants done in 2024 till June 2025, 26 patients were deemed to be at high risk of early CMV infection and were started on CMV prophylaxis with Cidofovir at a dose of 2.5 mg/kg weekly. Patients with early CMV viraemia in the pre-engraftment phase were switched to a treatment dose of Cidofovir at 5 mg/kg weekly.

Out of 26 patients, low dose Cidofovir was effective as a prophylaxis agent in 18 patients (70%) requiring no other therapy. 8 (30%) patients had early CMV reactivation necessitating changing the dose of Cidofovir to 5 mg/kg weekly. This is comparable to reported breakthrough rates of 35 to 40% on Letermovir prophylaxis. treatment dose of Cidofovir was effective in 7 cases, with decreasing CMV viral load without needing any other therapy. In 1 case however, there was progressively increasing CMV viral load reaching up to 64,000 copies. White cell engraftment occurred at Day +14, but counts remained low, and platelet engraftment was delayed to Day +36. We continued with Cidofovir weekly, switching to Ganciclovir at Day +28, in the face of increasing CMV viral loads and symptomatic signs of CMV disease with fever and colitis. Though the disease finally came under control after 3 weeks of Ganciclovir therapy, the patient (a case of thalassemia major) had secondary graft failure with autologous reconstitution. There was no mortality or severe renal compromise seen in our cohort,

Our study demonstrated that low-dose cidofovir effectively suppressed CMV reactivation without significant nephrotoxicity or delayed engraftment. The majority of patients who developed breakthrough CMV viremia responded to the same drug without requiring transition to alternative antivirals.

Conclusion: Low-dose weekly cidofovir represents a novel, cost-effective, and practical approach for CMV prophylaxis and treatment in the pre-engraftment phase of HSCT, particularly in settings where letermovir is unavailable. This strategy may reduce CMV-related graft loss while avoiding the myelotoxicity of ganciclovir. Further prospective studies are warranted to validate its role in global transplant protocols.