HaematologyTier 1Disease (DEADMAN)

Complications of immunosuppression

Description

Applies to chemotherapy, HSCT conditioning, immunosuppressants (transplant, autoimmune disease) and targeted/biologic agents
Risk profile depends on which arm of immunity is suppressed - neutrophil, cell-mediated (T-cell), or humoral (B-cell/antibody)

Infection remains a leading cause of morbidity/mortality across haematological malignancy, transplant and autoimmune disease treated with immunosuppression
Risk highest early post-transplant/post-chemo and with combination immunosuppression

By immune defect - determines the infection pattern

Neutropenia (chemo, some biologics) -> bacterial (gram-negative, gram-positive) and fungal (Candida, Aspergillus) infection
Cell-mediated (T-cell) deficiency (steroids, calcineurin inhibitors, purine analogues, alemtuzumab, post-allo-HSCT) -> viral reactivation (CMV, VZV, HSV, EBV/PTLD), PJP, intracellular pathogens (Listeria, mycobacteria, Nocardia), fungal (Cryptococcus)
Humoral (B-cell) deficiency (rituximab, CLL, myeloma, hypogammaglobulinaemia) -> encapsulated bacteria (Strep pneumoniae, H. influenzae, Neisseria), recurrent sinopulmonary infection
Complement/splenic dysfunction (splenectomy, some CTD) -> overwhelming encapsulated bacterial sepsis (OPSI)
Hepatitis B reactivation - specific risk with rituximab and other B-cell depleting therapy

Low threshold for investigation - immunosuppressed patients blunt/mask typical signs of infection (fever may be the only sign)
Baseline screening before starting significant immunosuppression: HBV, HCV, HIV serology, VZV/CMV status, TB risk assessment (esp. before biologics/TNF inhibitors)
Site-directed work-up per presenting syndrome (blood cultures, CT chest for fungal/viral pneumonitis, CMV PCR, PJP PCR/beta-D-glucan)

Prophylaxis (risk-stratified, started pre-emptively)

PJP prophylaxis (co-trimoxazole) - prednisolone >=20mg/day for >=4 weeks, purine analogues, alemtuzumab, post-allo-HSCT
Antiviral prophylaxis (valaciclovir/aciclovir) - HSV/VZV reactivation risk (e.g. bortezomib, HSCT)
HBV antiviral prophylaxis - HBsAg or core-antibody positive patients starting rituximab/B-cell depleting therapy - screen before starting, continue prophylaxis through and after treatment
CMV monitoring (PCR surveillance) - post-allo-HSCT and other high cell-mediated-risk settings, pre-emptive therapy on rising viral load
Vaccination review before immunosuppression where possible (inactivated vaccines; live vaccines contraindicated during significant immunosuppression)
IVIg replacement - for significant secondary hypogammaglobulinaemia with recurrent infection (e.g. post-rituximab, CLL)

Established infection

Treat per organism/syndrome; lower threshold for empirical broad cover while awaiting results in unwell patients
Reduce/hold immunosuppression where feasible, balanced against underlying disease control

Rituximab - HBV reactivation, prolonged hypogammaglobulinaemia, PML (rare, JC virus)
Purine analogues (fludarabine) - profound, prolonged T-cell suppression
Allogeneic HSCT + GVHD therapy - highest combined risk (neutropenia early, then cell-mediated defect for months-years)
Splenectomy/functional asplenia - lifelong OPSI risk, vaccination + sometimes prophylactic penicillin

Infection risk often outlasts the drug - e.g. rituximab B-cell recovery takes 6-12 months, alemtuzumab T-cell recovery even longer
PTLD (post-transplant lymphoproliferative disease, usually EBV-driven) - complication of sustained T-cell suppression
Screening and prophylaxis substantially reduce, but do not eliminate, infection-related mortality

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