Lamivudine for the Prevention of Hepatitis B Virus (HBV) Reactivation in Patients Undergoing Chemotherapy for Acute Lymphoblastic Leukemia (ALL) - PowerPoint PPT Presentation

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Lamivudine for the Prevention of Hepatitis B Virus (HBV) Reactivation in Patients Undergoing Chemotherapy for Acute Lymphoblastic Leukemia (ALL)

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Prevention of Hepatitis B Virus (HBV) Infection Using Passive-Active ... Leukemias: Hyperimmune globulin 0.06 ml/kg. Vaccine (double dose) during maintenance ... – PowerPoint PPT presentation

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Title: Lamivudine for the Prevention of Hepatitis B Virus (HBV) Reactivation in Patients Undergoing Chemotherapy for Acute Lymphoblastic Leukemia (ALL)


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_at_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 a, Lamivudine (nucleoside analog)
  • Adefovir Dipivoxil (nucleotide analog)
  • Entecavir, PEG-IFNa2a

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

4
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5
HBV A major threat in childhood survivors of
Leukemia/Lymphoma
  • India (year) Other
    (year)
  • Wadia (Mumbai) 45 (2003) St Jude lt1 (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 944046
  • Median Follow-Up 20 yrs N89
  • In patients who get HBV infection during Rx of
    cancer, the annual rate of spontaneous clearance
    of HBsAg is lt1 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 13150
  • 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 22193
  • 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 23365
  • 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 26989
  • N60
  • 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

12
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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
  • lt 10 yrs 1 cc (20 mcg) IM gt 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
Passive Prophylaxis Passive Prophylaxis Passive Prophylaxis Active Prophylaxis Active Prophylaxis Anti HBS Assay level
Dose No. Day Date / Dose Day Date / Dose
1 D0
2 D21
3 D42 ?
4 D72
5 D102
6 D132 D0
D30 ?
D60
D180 ?
15
Active-Passive Prophylaxis for Prevention of
Hepatitis B Infection during treatment of Lymphoma
Passive Prophylaxis Passive Prophylaxis Passive Prophylaxis Active Prophylaxis Active Prophylaxis Anti HBS Assay level
Dose No. Day Date / Dose Day Date / Dose
1 D0
2 D21
3 D42 D0
D30 ?
D60
D180 ?
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
    200148298
  • 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 3547
  • 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
undergoing CT 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.
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