Factors Influencing Hepatitis B Virus Reactivation in Lymphoma Patients Treated With Rituximab

Description of factors associated with Hepatitis B virus reactivation:

• Laboratory parameters defining HBV status/activity at time of treatment initiation
• Lymphoma stage at rituximab treatment initiation (Ann Arbor, B-symptoms, bone marrow involvement, IPI, ECOG-score, LDH)
• Immunochemotherapy regimen (treatment line, rituximab dose and cycle)
• Disease status at time of HBV reactivation
• Antiviral prophylaxis (medication, dose, duration at time at time of reactivation)
• Patient demographics (age, gender, residence, ethnic origin, smoking status, alcohol consumption and occupation)

Time to Hepatitis B virus reactivation

• The time from start of rituximab-containing immunochemotherapy until first evidence of HBV reactivation meeting the criteria
• Description of prophylaxis and treatment with antiviral medication HBV vaccination Time of initiation of antiviral therapy of prophylaxis relating to clinical or laboratory signs of possible HBV reactivation Anti-viral medication used in prophylaxis or therapy
• Description of outcomes Outcomes of the HBV reactivation Outcomes of the rituximab-containing immunochemotherapy Demographics and previous infection history: Age, gender, nationality, race, social history, past medical history
• Parameters associated with lymphomas: Ann Arbor stage, number of extranodal involvement, serum LDH, serum β2-microglobulin, ECOG performance status, presence of B symptoms, International Prognostic Index, bone marrow invasion
• Laboratory parameters associated with hepatitis B virus:

hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti- HBs), hepatitis B e antigen (HBeAg), hepatitis B core antibody (anti-HBc), hepatitis B e antibody (anti-HBe), serum HBV DNA

• Lymphoma treatment history:

Line of treatment (first line, second line), rituximab and chemotherapy administration (dose, schedule), start date, last treatment date

• Prophylaxis or treatment against HBV reactivation:

antiviral drug (dose, schedule, duration)

• Hepatitis B virus reactivation:

onset, serologic markers, outcome

Inclusion criteria

• Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) or follicular B-cell lymphoma (FL).
• Patients who had received at least two cycles of rituximab-CHOP or rituximab-CVP as a primary treatment
• Patients with a history of previous exposure to HBV

• HBV surface antigen (HBs Ag) positive Or
• HBV core antibody (IgG anti-HBc antibody) positive
• Patients with documented HBV reactivation (definite or presumptive) occurring during treatment (at least two cycles of R-CHOP or R-CVP) or within 12 months after the last dose of rituximab

• Definitive HBV reactivation

• Elevation of serum HBV DNA level >1 log IU/mL from baseline or absolute increase of HBV DNA by 6 log10 IU/mL in HBsAg positive patients
• Presumptive HBV reactivation - Increase of ALT (≥3x baseline value or absolute value of ≥100 U/L) and positive conversion of HBs Ag in previously HBsAg-negative patients

Exclusion criteria

• Patients who had received chemotherapy other than R-CHOP or R-CVP after diagnosis
• patients diagnosed with HIV, HCV or HDV co-infection
• Patients who had undergone allogenic stem cell transplantation before hepatitis B virus reactivation was documented