Epidemiology, risk factors, and outcomes of cytomegalovirus (CMV) reactivation in allogeneic hematopoietic stem cell transplantation: A retrospective observational single-centre study from western India

Abstract

Abstract Background: Cytomegalovirus (CMV) reactivation is a major post-transplant complication, especially in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients from high-seroprevalence regions. While pre-emptive therapy has reduced CMV disease, reactivation remains common, particularly in alternate donor transplants and resource-limited settings where access to newer antivirals like letermovir is limited. Indian data on CMV reactivation patterns, recurrence, and treatment outcomes are scarce. Aims: This study aimed to: 1. Evaluate the incidence, timing, and recurrence of CMV reactivation post-allo-HSCT. 2. Identify associated risk factors, including donor type, conditioning, GVHD prophylaxis, and serotherapy. 3. Assess the toxicity of pre-emptive antiviral therapy. Methods: A retrospective analysis was conducted at Apollo Hospitals International, Gandhinagar, India, involving 58 allo-HSCT recipients treated between 2019–2024, with at least 6 months of follow-up. CMV serostatus was assessed pre-transplant. Conditioning regimens (MAC or RIC), stem cell source, and GVHD prophylaxis (PTCy, PTBEN, or non-PTCy regimens) were selected per clinical protocol. ATG (Grafalon or Thymoglobulin) was used in alternate donor transplants. CMV DNA was monitored via qPCR weekly (until day +100), biweekly (until day +180), and monthly (up to 1 year). Reactivation was defined as >69 IU/mL. Pre-emptive therapy included foscarnet pre-engraftment and ganciclovir/valganciclovir post-engraftment, continued until two negative PCRs. Adverse events were graded per CTCAE v5.0. Results: The median age was 29.4 years (range 3–66); 68.9% received haploidentical transplants and 60.3% underwent MAC. All recipients were CMV IgG positive; 94.7% were D+/R+. CMV reactivation occurred in 89.7% (52/58) patients, with 75.9% reactivating before day +100. Recurrent viremia occurred in 38.4% (20/52). CMV disease (enterocolitis) occurred in one patient (1.7%). Reactivation was more frequent in alternate donor transplants vs. MSD (95.1% vs. 76.5%, p=0.05), and in MAC vs. RIC (94.3% vs. 82.6%, p=0.202). Acute GVHD was significantly associated with reactivation (71.4% vs. 28.6%, p<0.05). PTCy-based GVHD prophylaxis was associated with higher viral load and longer duration of viremia (8335 vs. 2900 copies/mL; 40 vs. 28 days, p<0.05). Pre-engraftment reactivation led to delayed neutrophil recovery (17 vs. 13 days, p=0.034). Serotherapy type did not impact overall reactivation, but early reactivation was significantly higher with Grafalon vs. Thymoglobulin (90% vs. 33.6%, p<0.001). Two patients developed refractory CMV and required second-line antivirals. Adverse effects included neutropenia (ganciclovir/valganciclovir) and nephrotoxicity (foscarnet/cidofovir). CMV reactivation was associated with prolonged hospitalisation but did not affect overall survival. Conclusion: This single-centre study demonstrates a high CMV reactivation rate (89.7%) in a high-seroprevalence Indian cohort, especially in alternate donor and PTCy-treated patients. While CMV disease was rare due to effective surveillance and pre-emptive therapy, recurrence and antiviral toxicity were common. The type of serotherapy influenced early reactivation risk. These findings underscore the need for individualised CMV management and improved access to novel antivirals in resource-limited transplant programs.