Clinical bottom line
Patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT) face a high risk of infectious complications due to profound immunosuppression, mucosal barrier injury, and prolonged neutropenia. Current evidence supports a multifaceted infection prevention and management approach including risk-adapted antimicrobial prophylaxis, vigilant surveillance for viral reactivations, and prompt treatment of bacterial, fungal, and viral infections. Emerging data emphasize individualized strategies based on transplant type, conditioning regimen, and immune reconstitution status. Despite advances, infection remains a leading cause of morbidity and mortality post-HSCT, underscoring the need for ongoing refinement of prophylactic protocols and early diagnostic tools.
What the evidence shows
1. **Bacterial infections and prophylaxis:** Neutropenic fever remains a common early post-transplant complication. Guidelines recommend fluoroquinolone prophylaxis during neutropenia in high-risk patients to reduce bacteremia incidence, although concerns about resistance necessitate local epidemiology consideration [1]. Empiric broad-spectrum antibiotics remain standard for febrile neutropenia, with de-escalation guided by cultures and clinical response [2].
2. **Fungal infections:** Invasive fungal infections (IFIs), particularly due to Candida and Aspergillus species, are significant causes of mortality post-HSCT. Antifungal prophylaxis with agents such as posaconazole or voriconazole is recommended in high-risk patients, especially those with graft-versus-host disease (GVHD) or prolonged neutropenia [3]. Recent meta-analyses confirm posaconazole’s superiority in preventing IFIs compared to fluconazole or itraconazole [4].
3. **Viral infections:** Reactivation of latent viruses, notably cytomegalovirus (CMV), Epstein-Barr virus (EBV), and herpes simplex virus (HSV), is common. Preemptive monitoring using quantitative PCR assays enables early detection and initiation of antiviral therapy, reducing progression to overt disease [5]. Letermovir prophylaxis has emerged as an effective strategy to prevent CMV reactivation in CMV-seropositive HSCT recipients, with randomized trials demonstrating reduced CMV infection rates and improved survival [6].
4. **Vaccination:** Post-transplant immunization schedules are critical but often delayed due to immune recovery variability. Current guidelines recommend initiating inactivated vaccines approximately 3–6 months post-HSCT, with live vaccines deferred until at least 24 months and only in patients without GVHD or ongoing immunosuppression [7].
5. **Diagnostic advances:** Non-culture-based diagnostics, including galactomannan and β-D-glucan assays for fungal infections and multiplex PCR panels for respiratory viruses, have improved early detection, although sensitivity and specificity vary by clinical context [8].
Caveats and uncertainty
- Most prophylactic recommendations derive from heterogeneous patient populations and transplant modalities; extrapolation to specific subgroups (e.g., cord blood or haploidentical transplants) requires caution.
- Antimicrobial resistance patterns vary geographically and temporally, potentially limiting the generalizability of fluoroquinolone and antifungal prophylaxis efficacy.
- The optimal duration and timing of prophylaxis and preemptive therapy remain areas of active investigation.
- Immune reconstitution kinetics differ widely, complicating standardized vaccination timing.
- Many studies are limited by small sample sizes or observational design, warranting further randomized controlled trials.
How this may change practice
Clinicians managing HSCT recipients should integrate individualized infection risk assessments incorporating transplant type, conditioning intensity, and GVHD status to tailor prophylaxis and monitoring strategies. Adoption of letermovir for CMV prophylaxis in seropositive patients can reduce CMV-related morbidity. Utilization of rapid molecular diagnostics can facilitate earlier targeted therapy, potentially improving outcomes. Awareness of local antimicrobial resistance trends is essential to optimize prophylactic regimens. Finally, structured vaccination protocols aligned with immune recovery milestones can enhance long-term protection against vaccine-preventable infections.