Table 4.

Summary of adjunctive immunotherapy medications used for cytomegalovirus retinitis treatment post-hematopoietic stem cell transplant

Adjunctive immunotherapy	Route of administration	Mechanism of action	Indication	Advantages	Disadvantages	Side effect
CMV-specific immunoglobulins: Cytogam®[43,78]	IV infusion	Hyperimmune globulin enriched with high titers of antibodies against CMV. Provides passive immunity by supplying CMV-specific antibodies, which neutralize the virus and enhance immune-mediated clearance	Adjunct to antivirals in treatment of active CMV retinitis: To augment the immune response while antivirals control viral replication. Prevention of relapse (prophylaxis). Severe immunosuppression e.g., prolonged neutropenia, T-cell depletion, or GVHD	Enhanced immune response. Potential reduction in antiviral toxicity (may allow for lower doses of antiviral drugs). Broader immunomodulatory effects. Reduced CMV-related mortality	Limited efficacy in isolation: Ineffective as monotherapy; requires combination with antivirals. Cost: Expensive, limiting accessibility. Unclear pediatric-specific data: Limited evidence on efficacy and safety specific to pediatric CMV retinitis cases	Infusion-related reactions: Fever, chills, flushing, nausea, and hypotension. Allergic reactions: Rash, pruritus, and, rarely, anaphylaxis. Headache: Commonly reported during or after infusion. Gastrointestinal symptoms: Nausea, vomiting, and abdominal discomfort. Hypertension or hypotension: Blood pressure fluctuations during infusion. Thrombotic events: Rare but possible in predisposed patients. Renal dysfunction: Risk of acute kidney injury, particularly with rapid infusion or concurrent nephrotoxic drugs
Cytomegalovirus-specific cytotoxic T lymphocyte therapy: Viralym-M[44-46,79,80]	Intravenous infusion	Allogeneic T-cell therapy. Provides adoptive immunity by transferring CMV-specific cytotoxic T lymphocytes, which actively target and eliminate CMV-infected cells	Resistant or refractory CMV retinitis. Restoration of immunity in severe immunosuppression	Targeted immune response: Restores virus-specific immunity directly against CMV. Effective in resistant cases: Addresses CMV infections refractory to antivirals. Reduced toxicity: Avoids the systemic toxicity associated with antivirals	High cost: Expensive therapy, limiting accessibility. Limited availability: Requires specialized facilities for manufacturing and administration. Delayed onset: Time needed for T-cell preparation and expansion. Complex logistics: Requires precise HLA matching and rigorous pre-treatment screening	GVHD: Potential risk in allogeneic T-cell therapy. Infusion reactions: Fever, chills, or allergic reactions. Cytokine release syndrome: Rare but possible with immune cell therapies. Immune rejection: Host immune system may reject infused T cells in some cases
Multivirus-specific T-cell therapy: Posoleucel (ALVR105)[81-83]	Intravenous infusion	It is derived from healthy donors whose T cells are selectively expanded to recognize six viruses commonly affecting immunocompromised patients, including: Cytomegalovirus, Epstein-Barr virus, adenovirus, BK virus, human herpesvirus 6 and JC virus. It contains CD4+ and CD8+ T cells that are pre-sensitized to viral antigens. These T cells can recognize and bind viral peptides presented on infected host cells through HLA molecules. They then trigger apoptosis of the infected cell	Resistant or refractory CMV retinitis. Restoration of immunity in severe immunosuppression. Prophylaxis of viral infections after allo-HCT. Treatment of other concomitant viral infections: Can target other viral infections like adenovirus, BK virus, Epstein-Barr virus, and human herpesvirus-6	Effective in resistant cases: Addresses CMV infections refractory to antivirals. Multivirus efficacy: Can target other opportunistic viral infections. Reduced toxicity: Avoids the systemic toxicity associated with antivirals

CMV: Cytomegalovirus; GVHD: Graft-vs-host disease; allo-HCT: Allogeneic hematopoietic cell transplantation.