Anti-viral policy (haematology/oncology)

2.1   Pre HSCT Recipient Checklist & Results for Allogeneic Patients (FORM-0003)

2.2   Virological Screening in HSCT Patients (CLIN-0008)

2.3   Diagnosis & Management of Adenovirus (CLIN-0027)

2.4   Diagnosis & Management of EBV (CLIN-0026)

2.5   Diagnosis & Management of CMV (CLIN-0014)

2.6   Administration of Cidofovir by Nursing Staff (NURSE-0004)

2.7   Pulmonary Complications Pre & Post HSCT (CLIN-0016)

2.8   Chicken Pox & Measles in the HSCT Setting (CLIN-0018)

2.9   Prevention & Control of Infection Manual

2.10 Current BNF for Children / BNF

3.1 The diagnosis and management of viral disease will be directed by the HSCT Clinical Team.

3.2 The Medical/nursing team will be responsible for the monitoring & investigation of viruses. Microbiology/Virology staff will inform of recent virology results as they become positive.

4.1 IV/Oral Inpatient Drug Administration Chart

4.2 IV Fluid Prescription Chart

5.1 VIRAL RESPIRATORY TRACT INFECTION:

For further information including clinical features see Pulmonary Complications Pre & Post HSCT SOP (CLIN-0016)

At Risk Group

Patients with respiratory symptoms or signs within any of the listed risk groups should be discussed with the HSCT Clinical Team. The decision to start treatment will be based on the patient’s clinical condition, previous treatment etc:

• Autografts within 30 days of HSCT
• Sibling allograft recipients not in receipt of serotherapy within 100 days of HSCT
• All other allograft recipients within 6 months of HSCT
• Haplo-identical transplants until immune reconstitution
• Patients receiving intensive immunosuppression post allograft
• Patients with chronic GvHD
• Allografts who have known chronic lung disease

This list is not exhaustive and other patients can develop pneumonitis although this is less common. It should be remembered that the presence of a virus may not be the cause of the patient’s symptoms.

5.1.1 Respiratory Syncytial Virus (RSV)

RSV has a 15-20% mortality from pneumonitis in the allograft population. Patients who are RSV positive pre-allogeneic transplant should not begin conditioning until symptoms have settled and viral shedding ceased.

Surveillance

Pre HSCT assessment, which includes nasopharyngeal aspirate (NPA) and throat swab for respiratory viruses.

Investigation

• NPA – Direct Immunofluorescence if showing signs of respiratory symptoms
• Throat swab – PCR if showing signs of respiratory symptoms
• BAL if clinically indicated

Infection Control

• Inpatients should be nursed as a source patient in a closed single doored isolation cubicle without positive pressure.
• Outpatients should be asked to sit away from other patients and to attend clinic/day ward later in the day.
• Following contact, hand washing with soap and water and alcohol is essential.

Refer to Respiratory Syncytial Virus (RSV) NHSGG&C Control of Infection Committee Policy: Infection Prevention and Control - NHSGGC

Contact

If an allograft patient is in the same room as a known case, the patient must be screened.

Treatment

• RSV - Patients with URTI who are <30 days post allograft or <60 days with severe lymphopenia

Ribavirin (Unlicensed medicine)

IV Dosing is not recommended for treatment of infants with RSV - SIGN guidelines 2006

5.1.2 Parainfluenza 3

Parainfluenza 3 has a mortality from pneumonitis of about 5-10% in the allograft

Patients who are positive pre-allogeneic transplant should not begin conditioning until symptoms have settled and viral shedding ceased.

• Symptomatic patients with URTI should receive supportive therapy as required with chest physiotherapy, adequate hydration and oxygen supplementation.
• Intravenous Immunoglobulin may be considered.

LRTI should be discussed with HSCT Clinical Team.  IV Ribavirin is a treatment option which may be used (see above dosing table) for a maximum of 10 days, however there is little evidence to support its efficacy.

• IV IgG 0.5g/kg
• Methylprednisolone (if severe inflammation and no response)

5.1.3 Influenza A + B including H1N1

Flu A has a higher mortality than flu B from pneumonitis.

Prophylaxis

• Vaccinate close household contacts in autumn
• Consider vaccinating donor pre donation
• Patients will receive a letter from the Schiehallion Unit to advise on appropriate action for vaccination for each Flu season.
• Live attenuated influenza vaccines (Fluenz ®) nasal spray are contraindicated for children or adolescents who are severely immunocompromised and for close contacts of severely immunocompromised individuals. Appropriate alternative inactivated influenza vaccines should be considered.

Investigation

• NPA – immunofluorescence, PCR
• Nose /throat swab – PCR
• BAL if clinically indicated
• All patients with positive results should receive treatment even if it is beyond the 48 hour cut off recommended by the NICE guidelines and HPS 2013 – Guidance on the use of antiviral agents for the treatment of and prophylaxis of influenza, 2013-14 or refer to current HPS guideline updated annually

Infection Control

• Inpatients should be nursed as a source patient in a closed single doored isolation cubicle without positive pressure and appropriate signage to control entry.
• Out patients should be asked to sit away from other patients and to attend clinic/ day ward later in the day.
• Following contact with the patient, hand washing with soap and water and alcohol is essential.
• If the patient has H1N1 – the following precautions should be observed:
• Protective Personal Equipment (PPE) must be used as follows - surgical face mask within one metre of patient, clean disposable plastic apron and gloves
• For Aerosol Generating Procedures (AGPs) staff must have passed an FFP3 respirator fit test
• Duration of isolation precautions for hospitalised patients should be continued for 7 days after onset of illness of 24hrs after the resolution of fever and respiratory symptoms, whichever is longer

Contact

If a patient on the HSCT Unit or a patient attending as an outpatient is Flu A/B positive consider giving HSCT patients who have been in prolonged contact prophylactic treatment. Current recommendations are that severely immunocompromised patients should receive Zanamivir as first line therapy, with Oseltamivir as second line therapy where Zanamivir is not a suitable option (see below for details).

Treatment for Influenza A and B and H1N1

Influenza A and B

NB: This MUST be initiated by the HSCT Clinical Team.

Severely immunocompromised patients should receive inhaled Zanamivir as first line therapy.

Zanamivir Dosing:

Inhalation of powder

Zanamivir is not licensed for children under 5 years old. For these children, and for any child unable to use the diskhaler, prescribe Oseltamivir. However, severely immunocompromised patients are at increased risk of developing oseltamivir-resistant influenza, therefore need close monitoring.

Oseltamivir may also be appropriate for any HSCT patients no longer considered to be severely immunocompromised.

Oseltamivir (Tamiflu) Dosing: (give once daily for 10 days for prophylaxis and twice daily for 5 days for treatment):

*Follow up testing may also be indicated in outbreak situations. During an epidemic prophylaxis may be used up to 6 weeks.

NB: For severely immunocompromised patients who are unable to receive Zanamivir via diskhaler and/or in cases of suspected or confirmed oseltamivir resistance, an aqueous solution of Zanamivir is available for nebulisation or IV administration. This is an unlicensed preparation which is only available on a named patient basis direct from GSK.  Contact details are available in HPS Guidance document (2013)

5.1.4H1N1

Severely immunocompromised patients should receive inhaled Zanamivir as first line therapy (see 5.1.3).

If the patient is not considered severely immunocompromised treat initially with Oseltamivir (see 5.1.3). If no response to treatment with Oseltamivir consider the possibility of drug resistance. Zamanivir is an alternative viral neuraminidase inhibitor, which may be used following discussion with the virologist.

Post exposure PROPHYLAXIS: as per dosing guidelines in 5.1.3 at using prophylactic regimen.

5.1.5 Human Metapneumovirus

This is a recognised cause of idiopathic pneumonia in immunocompromised children, putting them at risk of severe disease and hospitalisation. Patients develop rapidly spreading infiltrates and hypoxia. There are no large published studies to guide treatment. IVIgG has been used and Ribavirin demonstrates some in vitro activity.

5.2 OTHER VIRAL INFECTION

5.2.1 HHV6

HHV6 is a ß herpes virus with similarities to CMV and HHV7. It is widespread in the human population, and persists in the lymphocytes and salivary glands. It can be reactivated during times of immunosuppression.

Clinical Features

• Rash
• Encephalitis
• Convulsions
• Short term memory loss
• Graft failure

Investigation

• Blood – HHV6 PCR
• CSF – HHV6 PCR
• MRI
• EEG

Treatment

• 1st line agent GANCICLOVIR- dose depends on renal function
• 2nd line agent CIDOFOVIR

NB: This MUST be initiated by the HSCT Clinical Team

Duration: Until patient improves

5.2.2HSV

Clinical Features

• Cold sores
• Mouth ulcers
• Genital lesions
• Encephalitis
• Meningitis Hepatitis
• Oesophagitis
• Generalised infection
• Pneumonitis

Prophylaxis

Aciclovir Dosing:

At Risk Group

• Autografts to D30
• Allografts to D100
• Alemtuzumab (Campath) recipients CD4<0.4
• Acute Leukaemia Neutrophil <1.0 x 10⁹/L
• Chemotherapy recipients with high incidence of previous coldsores/genital herpes

Surveillance

Pre HSCT assessment, which includes serological testing

Investigation

• Viral Swab (in VTM) – PCR (please indicate patient symptoms on form)
• If encephalitis – MRI, EEG, CSF for PCR, Hepatitis – biopsy sample to virology
• Disseminated – EDTA blood for HSV PCR

Treatment

1st line :ACICLOVIR IV

NB: Commence IV maintenance fluids during IV aciclovir administration. In renal impairment see dose adjustment table (Section 5.3).

If aciclovir resistance is suspected, a swab in viral transport medium should be sent to virology.

2nd line GANCICLOVIR see dosing and administration in Diagnosis & Management of CMV SOP (CLIN-0014)

3rd line: FOSCARNET IV infusion 40mg/kg three times a day for 2 - 3weeks or until lesions heal (see dosing & administration).

5.2.3 VSV

NB: VZV titres should be assessed for of all at risk patients prior to commencement of immunosuppressive treatment.  See Chickenpox & Measles in the HSCT Setting SOP (CLIN-0018)

5.2.4 COVID

All patients and household contacts should be vaccinated if eligible .The field of antiviral / antibody therapies is changing fast and all patients should be discussed with Infectious Diseases to assess eligibility for treatment.

5.3 DRUG DOSE REDUCTION IN RENAL IMPAIRMENT

This SOP will be reviewed every two years.

Identify how the procedure/process within the SOP will be audited

For further information contact:

Haemopoietic Stem Cell Transplant Team On-Call Consultant (via switchboard)