What infectious disease considerations are necessary before starting rituximab for Post-Transplant Lymphoproliferative Disease (PTLD)?

Infectious Disease Considerations Before Starting Rituximab for PTLD

Before initiating rituximab for PTLD, you must screen for hepatitis B virus (HBV) infection by measuring both HBsAg and anti-HBc, as HBV reactivation can cause fatal liver failure, and prophylactic antiviral therapy is mandatory for HBV-positive patients. 1, 2

Mandatory Pre-Treatment Screening

Hepatitis B Virus Testing

• Screen all patients for HBV infection before the first rituximab dose by measuring both hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) 1, 2
• Patients with active hepatitis B liver disease should NOT receive rituximab 2
• For patients who are HBsAg positive or anti-HBc positive (regardless of surface antigen status), prophylactic antiviral therapy is strongly recommended over monitoring alone when initiating rituximab 1
• HBV reactivation can occur during and for several months after rituximab therapy, potentially causing serious liver problems including liver failure and death 2

Other Viral Infections to Assess

• Document history of hepatitis C virus (HCV), cytomegalovirus (CMV), herpes simplex virus (HSV), parvovirus B19, varicella zoster virus (chickenpox or shingles), and West Nile virus 2
• Assess for any current active infections or recent severe infections, as rituximab increases infection risk and lowers immune system function 2

Progressive Multifocal Leukoencephalopathy (PML) Risk

• Counsel patients about PML risk, a rare but fatal brain infection caused by JC virus that can occur in immunosuppressed patients receiving rituximab 1, 2
• There is no known treatment, prevention, or cure for PML 2
• Watch for new neurological symptoms: confusion, dizziness, balance problems, difficulty walking/talking, weakness on one side, or vision changes 2

Baseline Laboratory Monitoring

Complete Blood Count

• Obtain complete blood counts (CBC) with differential and platelets before the first rituximab dose 2
• Monitor for baseline cytopenias that may worsen with treatment 2

Immunoglobulin Levels

• Check baseline immunoglobulin levels (IgG, IgM, IgA) before starting rituximab 3, 4
• Rituximab can cause profound and prolonged hypogammaglobulinemia, particularly when combined with antiproliferative agents like mycophenolate mofetil 3
• Fatal sepsis has been reported in transplant patients with rituximab-induced hypogammaglobulinemia 1

Infection Prophylaxis Considerations

Pneumocystis Pneumonia Prophylaxis

• Consider prophylaxis for Pneumocystis pneumonia in all patients receiving rituximab, especially those on concurrent immunosuppression 1

Vaccination Status

• Patients should NOT receive live vaccines before or during rituximab treatment 5, 2
• Live vaccines contraindicated include: MMR, varicella (live), yellow fever, oral polio, BCG, and live attenuated influenza 5
• Administer indicated non-live vaccines (pneumococcal, influenza) BEFORE starting rituximab whenever possible, as response to vaccination is significantly impaired during and up to 6 months after rituximab 5, 2
• Rituximab impairs immune responses for up to 6 months after treatment 5

Immunosuppression Management

Reduction Strategy

• Plan for reduction of immunosuppressive therapy combined with rituximab when clinically feasible 1
• Reduction of immunosuppression alone is rarely successful for PTLD and may increase graft-versus-host disease (GvHD) risk in HSCT recipients 1
• Do NOT reduce immunosuppression in patients with uncontrolled severe acute or chronic GvHD 1

Critical Pitfalls to Avoid

• Never use antiviral drugs (acyclovir, ganciclovir) for EBV-PTLD treatment or prophylaxis, as they are completely ineffective against EBV 1, 6, 7
• Do not overlook HBV screening - this is the single most important infectious disease consideration, as reactivation can be fatal 1, 2
• Recognize that rituximab substantially increases infection risk: studies show 2.2-fold higher infection density and 3.1-fold higher fatal infection incidence compared to no rituximab 4
• Monitor for hypogammaglobulinemia throughout treatment, especially in patients on mycophenolate mofetil or other antiproliferative agents 3
• Be aware that rituximab causes prolonged B-cell depletion (up to 16+ months), creating sustained infection vulnerability 3

Ongoing Monitoring During Treatment

• Monitor for signs of infection continuously: fever, new respiratory symptoms, unusual fatigue 1, 2
• Check CBC with differential at 2-4 month intervals during therapy and continue monitoring after the final dose until resolution of cytopenias 2
• Monitor for HBV reactivation during and for several months after completing rituximab: watch for worsening fatigue or jaundice 2
• Assess immunoglobulin levels at 6 and 12 months post-treatment, as IgM, IgG, and IgA levels remain significantly suppressed 4