HBV infection in Cancer Patients

1. Prevention of Hepatitis B Virus (HBV) Infection Using Passive-Active Prophylaxis (PAP) in Children & Adults on Chemotherapy for Lymphoid Malignancies Banavali SD, Goyal L, Bhagwat R,Arora B, Kolhatkar B, Kelkar R, Pai S, Nair CN, Kurkure PA, Parikh PM. Tata Memorial Hospital, Mumbai; INDIA. banavali_2000@yahoo.com

2. HBV infection in Cancer Patients • HBV infection is a major problem in patients undergoing CT especially in developing countries. • Complications range from an-icteric hepatitis to fulminant hepatic failure. • Interruptions in CT are common. • Once hepatitis develops -- No effective treatment • IFN α, Lamivudine (nucleoside analog) • Adefovir Dipivoxil (nucleotide analog) • Entecavir, PEG-IFNα2a

3. HBV Transmission • Hospitals, esp. general, are regarded as an endemic environment of hepatotrophic viruses. • The difference in seropositivity rates of HBV infection in the transfused and non-transfused groups was not statistically significant. (Data from: Mumbai, Chandigarh, South Africa, Poland, USA) • Therefore suggesting that nosocomial transmission (and not blood transfusion) as an important factor in etiopathogenesis: Horizontal transmission

5. HBV: A major threat in childhood survivors of Leukemia/Lymphoma India % (year)Other % (year) Wadia (Mumbai) 45 (2003) St Jude <1 (2004) PGI (Chandigarh) 48 (2003) Poland 7 (2004) TMH (Mumbai) 56 (2003) Turkey 10 (2004) AIIMS (Delhi) 60 (2003) USA, NCI 21 (1986) Lucknow 76 (1992) S.Africa 23 (2001) Italy 26 (1985) Germany 46 (1985) Turkey 47 (1997) Poland 62 (1995) Turkey 87 (1993)

6. HBV infection in childhood ALL Outcome of Disease • Good prognosis: Masera et al. J Pediatr 1981 (Italy) • Adverse Effect :Ratner et al. Cancer 1986 (NCI) • No effect: Lampert et al. Blut 1987 (Germany)

7. Hepatitis in Childhood Cancer Survivors: LT F/U Utili R et al. Blood 1999; 94:4046 • Median Follow-Up 20 yrs ; N=89 • In patients who get HBV infection during Rx of cancer, the annual rate of spontaneous clearance of HBsAg is <1% and response to mono-therapy with IFN  is also low. • Overall the disease showed a mild histological course with no e/o liver cirrhosis.

8. TMH Data – (1) Hep B Viral infection in ALL Nag S et al. Indian J Hematol Blood Transfusion 1995; 13:150 Data of 1986-93. 45 % of patients were HBsAg positive.

9. TMH Data – (2) Hep B Vaccination in ALL Goyal S et al. Leuk Res 1998; 22:193 162 patients Double dose (20 & 40 mcg) Active immunization (Engerix) at 0,1,2,12 months Vaccination started during Induction Protective AB titers in only 10.5% pts HBsAg positivity in 49% pts Conclusion: Passive-Active Immu. would be better

10. TMH Data -- (3) Hep B Vacination in children with ALL: Results of an intensified Immunization schedule Somjee S et al Leuk Res 1999; 23:365 N= 171 (1996-98) Active, double dose Immunization (Engerix) at months 0,1,2,3,4,12 Protective AB titers in 19% HBV infection in 43%

11. TMH Data – (4) Passive-Acitve Prophylaxis Against HBV in children with ALL. Somjee S et al. Leuk Res 2002; 26:989 N=60 Arm A: 5 double dose Vaccine (Engerix) + Passive Immuniz. (HEPABIG) 40 IU/Kg (Max 800 IU) HBsAg positivity at 6 mo :17.2 ; at 9 mon: 28% Arm B: Active Immuniz. + IFN  5 MIU – same sched. HBsAg positivity at 6 mo : 59 %; at 9 mon: 73%

13. Active-Passive Prophylaxis for Prevention of HBV Infection during treatment of Leukemia/Lymphoma • Passive Prophylaxis:- Inj. HEPABIG (200 IU/ml) 0.06 cc (12 U) /kg IM (Max 3cc; round up to closest 0.5 cc) • Active Prophylaxis:- DD Inj. Engerix; < 10 yrs 1 cc (20 mcg) IM; > 10 yrs 2 cc (40 mcg) IM • To give Injection only intramuscular, on deltoid or antero-lateral thigh muscle • To give HEPABIG and Engerix at separate sites. • Adequate anti – HBs is  10 mIU/ml

14. Active-Passive Prophylaxis for Prevention of Hepatitis B Infection during treatment of Leukemia

15. Active-Passive Prophylaxis for Prevention of Hepatitis B Infection during treatment of Lymphoma

16. Active-Passive Prophylaxis for Prevention of HBV Infection during treatment of Leukemia/Lymphoma • Passive-Active Protocol started in June 2004. • No. of Patients On ALL / NHL Protocols evaluated since June 2004 : 230 (ALL: 205; NHL: 25) • HBsAg positivity at Presentation : 1 • Anti- HBsAssay Positive at Presentation ( h/o prior Immunization) : 77 (33.5%).

17. Active-Passive Prophylaxis for Prevention of HBV Infection during treatment of Leukemia/Lymphoma • Only Active Prophylaxis: 12 Patients. Protective Titers in 11; 1 on Rx. • Passive-Active-Prophylaxis : 141 Patients 28 Pts. On Rx 70 (62%) developed Protective Titer 57 (38%) No Protective Titer 2 (1.3%) became HBsAg Positive.

18. Efficacy of Immunization Against HBV infection in Children with cancer A 9 yr experience of I.P. against HBV infection in children with cancer: Results from a single institution in Poland. Styczynski J et al. J Hosp Infect 2001:48:298 N= 353 Passive + Active along with Induction CT: 95% protection ; 5% Infection rate Pre-vaccinated children: 1 Booster dose At least 1 vaccine dose post completion of CT.

19. Efficacy of Immunization Against HBV infection Children with cancer Meral A, et al (Turkey). Med Ped Onc 2000; 35:47 Solid Tumors / Lymphomas: 4 DD Vaccine 0, 1, 2, 12M Failure rate: 4 % ST, 26% lymphomas Seroconversion after 3rd dose 77 % ST, 48 % Lymph. Leukemias: Hyperimmune globulin 0.06 ml/kg Vaccine (double dose) during maintenance Failure rate 12%. Seroconversion after 3rd dose90% Anti HBs positivity in 78 % No HBsAg conversion in those with protective titer 39% (10/26) HBsAg + in unresponsive group

20. Prevention of HBV Infection in Children undergoingCT for ALL/Lymphoma Recommendations • Best way to tackle the problem of HBV infection during therapy would be to include Hep B vaccine as a part of universal Immunization policy in developing countries. • For those not immunized & taking Rx in centers with high incidence of HBsAg carriers, Passive immunization followed by Active immunization starting at maintenance or after cessation of intensive CT.