LEEDS TEACHING HOSPITALS TRUST eClinical Guidelines Template Guideline for Adult Patient Immunisation after Haemopoietic Stem Cell Transplant Guideline Detail Ownership: Yorkshire Blood and Bone Marrow Transplant Service Publication date: September 2011 Next Review date: September 2011 Status Summary Background: Patients require re-immunisation following haemopoietic stem cell transplantation (HSCT) as they lose previous immunity to vaccine preventable diseases and are more susceptible to infection. Principles of Immunisation Post-HSCT: Patients are vaccinated according to a schedule that is similar to that followed by a healthy but unimmunised individual of the same age. They may need additional vaccines e.g. seasonal influenza but in many cases live vaccines are contra-indicated. Post-HSCT Schedule: Please see Page 3 Notes: A complete vaccination course will take 5 years to complete. The vaccinations required may differ according to age and gender, guidance on appropriate formulations is given. Aims To improve the delivery of vaccinations post HSCT and care of these patients Objectives To explain the principle of giving vaccinations of patients post HSCT To give clear guidance regarding the timetable of vaccinations for patients who have undergone HSCT Background Haemopoietic Stem Cell Transplantation High doses of cytotoxic therapy, used against several malignancies, severely impair the patient’s haemopoietic and immune system. The purpose of HSCT, often referred to as “bone marrow transplant” is to reconstitute that system, and thus restore immunity, red cell function and clotting functions. The transplant may be a stored stem cell graft from the same patient (“autologous”) or from a tissue matched donor (“allogeneic”). In the case of allogeneic transplantation, the recipient is treated with immunosuppressive therapy to aid acceptance and ongoing tolerance of the graft. As the graft becomes established, the immunosuppressive therapy is tapered and withdrawn. Risk of Infection following HSCT HSCT permits much stronger therapy against malignancy than would otherwise be tolerable, and it also creates a beneficial “graft versus malignancy” effect. However, immune reconstitution takes months to years and is never entirely complete. In addition, especially following allogeneic transplants, the patient may require additional immunosuppressive therapy. This is started in order to treat the common HSCT complication known as “graft versus host disease.” Additional and prolonged immunosuppression renders the patient more susceptible to a variety of infections – to those affecting the population at large and to some that are particular to this situation. This risk of infection can be minimised by: - Universal precautions (e.g. hand washing, catering, toilet hygiene etc) Patient / parent education Rapid access to medical care when illness occurs Immunisation, which is the subject of the present document. European and US consensus guidance on immunisation post-HSCT has been issued and recently updated (Ljungman P et al 2009). The present document translates this into a UK context by: - outlining the general principles of immunisation post-HSCT - suggesting a schedule - explaining the use of specific vaccines Principles of Immunisation Post-HSCT 1. People who have HSCT have in effect had their immune memory wiped out by their preceding cytotoxic therapy. Therefore they need, not just boosters, but complete re-immunisation as appropriate to their age and country of residence. In the UK this will be by adoption of the NHS routine schedule. 2. Immune function recovers slowly and incompletely, which is why most of these vaccines should be offered from about 12 months post HSCT. Once started, the schedule is similar to that followed by a healthy but unimmunised individual of the same age. 3. In addition, because of the immune impairment, some additional vaccines are needed, especially against Streptococcus pneumoniae, Haemophilus influenzae and seasonal influenza. These should generally be started earlier, at 3 months post-treatment, because of the specific vulnerability to these conditions. Conversely, some live vaccines (e.g. BCG) may remain contraindicated long term. 4. It is important for the patient’s surrounding family to be completely immunised themselves, chiefly for the routine vaccines plus occasionally some extras such as chickenpox, where available, to “ring-protect” the individual. 5. Ideally the HSCT donor should have been fully immunised although this is seldom feasible to arrange, particularly if the donor is unrelated. 6. The immunisations recommended here can usually be given routinely in primary care under normal conditions. However, if the patient’s clotting ability is impaired, standard intra-muscular injection may cause serious bruising. Confirm that the platelet count is at least 100 x109/L, or inject subcutaneously when feasible, or refer to the hospital consultant haematologist. 7. Local Patient Group Directions (PGDs) may not cover all of the immunisations recommended here. If not, nurses could administer them under Patient Specific Directions (PSD) or individual prescription instead. These guidelines do not describe contractual or remuneration aspects of such immunisations. But in general, where they are not covered by existing local immunisation service agreements, they should be encompassed by the agreements for primary care prescribing of a hospital specialist’s individual recommendation. These guidelines do not cover immunisations required for foreign travel and specific advice, to supplement routine advice, should be sought from the haematology service. Management-Post HSCT Immunisation Schedule The following schedule is suggested; but because individual treatment and remission patterns are so variable, the hospital consultant will always confirm IF there are any changes, otherwise please follow the suggested plan. Although the schedule refers to trade names of some vaccines, it should be understood to apply to any generic or trade equivalent licensed for UK use. Note that available formulations not infrequently change. Immunisation Schedule & timing post HSCT 6 months: Haemophilus influenzae with Neisseria meningitis group C (e.g. Mentorix ) Streptococcus pneumoniae PCV i.e Prevenar -13 (see Note 2) Seasonal influenza vaccine (may require two doses) and annually thereafter (see Note 3) 8 months: Meningococcal A, C, W135, and Y conjugate vaccine (“Quad conjugate”) (e.g. Menveo - see Note 4) Seasonal influenza vaccine Streptococcus pneumoniae PPV i.e Pneumovax II (see Note 2) 12 months: Diphtheria-tetanus-pertussis-poliomyelitis (Dip-tet-pert-polio) (see Note 5) Human Papilloma Virus (HPV) (eg Cervarix) for women born post 1985 (Note 6) 13 months: Dip-tet-pert-polio HPV (see note 6) 15 months: Dip-tet-pert-polio 18 months: HPV ( see note 6) 24 months: MMR (live vaccine, see Note 7) 27 months: MMR (live vaccine, see Note 7) 2½ years: Dip-tet-polio 5½ years: Dip-tet-polio Notes 1. A full re-immunisation course will take five years to complete for an adult. Advise the patient that over that period, evolution of individual condition or expert guidance (on HSCT, or on immunisation in general) may well supersede the initial recommendation. In particular, the duration of response and hence the need for boosters is not yet fully established. 2. Streptococcus Pneumoniae Two vaccines are in common use: PCV: Pneumococcal polysaccharide from 13 capsular types of pneumococci conjugate vaccine (adsorbed) (e.g. Prevenar-13). This vaccine is conjugated to protein. PPV: Pneumococcal polysaccharide from 23 capsular types of pneumococci vaccine (e.g. Pneumovax II) Schedule: PCV followed, after two months, by one dose of PPV. 3. Influenza: if the 3 month post-HSCT mark is reached between March and August, defer until the new season’s vaccine arrives. Give two doses for the first winter season. 4. Quad (ACW135Y) conjugate vaccine: can be given one month after a previous vaccination against Meningococcus C. It may be practical to wait two months so as to coincide with any second dose of pneumococcal vaccination. 5. Dip-tet-polio: Schedule: The first three doses should be of Repevax, with boosters of Revaxis. 6. HPV: women born 1985 or later are usually eligible for HPV until they pass the age of 18; but post-HSCT it may be offered beyond that age. However women born before 1985, and men, are not eligible. Three doses are needed, ideally with a one month interval between first and second, and a five month interval between second and third (e.g. Cervarix). 7. MMR: This is a live vaccine, so extra care is needed. Defer if the patient is immunosuppressed or suffering from graft-versus-host disease. If in any doubt, contact the transplant consultant haematologist. Vaccines contra-indicated post-HSCT: Yellow Fever, BCG, Heaf / Mantoux, Smallpox, Chickenpox, oral polio If an indication for these appears to exist, discuss with the hospital consultant how the patient’s risk might be otherwise reduced. For instance it may help to “ring-immunise” the household contacts. No particular need: Hepatitis A & Hepatitis B Patients post-HSCT in general are not at heightened risk of those conditions, and do not need immunising. But individuals who happen to fall into a risk category can be immunised on the standard schedule from 12 months postHSCT. Travel vaccinations are not covered by this document – patients should discuss travel plans with the transplant consultant haematologist. Audit and Monitoring Compliance Patients should ideally have a hand held record from the GP so that each vaccination they have is recorded. Vaccination status will be reviewed at the haematology clinic. An audit will be performed to see if patients are being vaccinated according to these guidelines. Provenance: Author name (s)/ Post and addresses 1. Dr. Maria Gilleece, Consultant Clinical Haematologist, Yorkshire Blood and Bone Marrow Transplant Centre, Bexley Wing, St. James University Hospital 2. Dr. Graham Sutton, Consultant in Communicable Disease Control, Health Protection Agency, Seacroft Hospital. 3. Elizabeth O’Dowd, Medical Student, University of Leeds 4. Suzanne Liebersbach, Kay Kendall Leukaemia Fund “Long Term Followup” Clinical Nurse Specialist, Yorkshire Blood and Bone Marrow Transplant Centre, Bexley Wing, St. James University Hospital Clinical condition: Post-HSCT Target patient group: Patients who have undergone HSCT Target professional group: GP’s and other healthcare professionals Adapted From: Ljungman P et al 2009. Guidelines: vaccination of hematopoietic cell transplant recipients. Bone Marrow Transplantation 44: 521-526 Evidence Base: References and Evidence levels: Guidelines: C- Expert Consensus A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs B. Robust experimental or observational studies C. Expert consensus. D.Leeds consensus. (where no national guidance exists or there is wide disagreement with a level C recommendation or where national guidance documents contradict each other) 1. Ljungman P et al 2009. Guidelines: vaccination of hematopoetic cell transplant recipients. Bone Marrow Transplantation 44: 521-526 2. Tomblyn M, Chiller T et al 2009. Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective. Biology of Blood and Marrow Transplantation 15(10): 1143-1238. 3. Ljungman P and Small TN (2010). Vaccination of SCT recipients. Bone Marrow Transplantation doi 10 1038/bmt 2010.274 4. Dept of Health 2007. Immunisation against infectious disease Online at www.dh.gov.uk > public health > Green Book