Acquired hypogammaglobulinaemia secondary to haematological malignancies, or post-haemopoietic stem cell transplantation (HSCT)

Version: 3.3
Published: 20 March 2020
Condition for which Ig has an established therapeutic role.

Serum IgG to be measured on two separate occasions (at least one hour apart and at least one sample taken when the patient does not have an active infection). Baseline serum levels of IgA and IgM should be provided to allow assessment of immune recovery at review.
 

• Significant hypogammaglobulinaemia with serum IgG less than 4g/L (excluding paraprotein) regardless of the frequency and severity of infections
• OR
• Serum IgG (excluding paraprotein) greater than 4g/L but less than the lower limit of the age related reference range with at least one life threatening infection in the last 12 months
   
• OR
• Serum IgG (excluding paraprotein) greater than 4g/L but less than the lower limit of the age related reference range with at least two serious infections in the last six months requiring more than standard courses of antibiotics (e.g. hospitalisation, intravenous or prolonged antibiotic therapy)
   

Initial review is required within six months by any specialist, with ongoing reviews at least annually to assess clinical benefit.

 
In principle, Ig should be continued or renewed only if there is a demonstrated clinical benefit; therefore documentation of clinical effectiveness is necessary for continuation of Ig therapy.
 
Cessation of Ig therapy should be considered at least after each 12 months of treatment. If serum IgM and IgA levels are trending upwards and near normal, this may suggest recovery of the immune system and a trial might be considered if the patient is well. Once the patient has normal IgA and IgM levels, the IgG is also likely to be normal and a trial off therapy may be undertaken. Ig therapy should be extended as required to enable cessation of therapy in September/October, with repeat clinical and/or immunological evaluation before recommencement of therapy.
 
Antibiotic therapy may be indicated in addition to Immunoglobulin therapy.
 

Initial review is required within six months by any specialist with ongoing reviews at least annually to assess clinical benefit.
 
In principle, Ig should be continued or renewed only if there is a demonstrated clinical benefit; therefore documentation of clinical effectiveness is necessary for continuation of Ig therapy.
 
Cessation of Ig therapy should be considered at least after each 12 months of treatment. If serum IgM and IgA levels are trending upwards and near normal, this may suggest recovery of the immune system and a trial might be considered if the patient is well. Once the patient has normal IgA and IgM levels, the IgG is also likely to be normal and a trial off therapy may be undertaken. Ig therapy should be extended as required to enable cessation of therapy in September/October, with repeat clinical and/or immunological evaluation before re-commencement of therapy.
 
Antibiotic therapy may be indicated in addition to Immunoglobulin therapy.
 
Clinical effectiveness of Ig therapy may be assessed by:
 

On review of the initial authorisation period

• Monitoring of serum immunoglobulin levels (IgG, IgA and IgM) and any history of infection

On review of a continuing authorisation period

• Monitoring of serum immunoglobulins (IgG, IgA and IgM) and any history of infection

• There should be regular consideration of a trial period of cessation of IVIg for the purposes of immunological evaluation unless medically contraindicated on safety grounds (such as neutropenia, immunosuppressant medication, active bronchiectasis and/or suppuratives lung disease) or severe hypogammaglobulinaemia persists where no significant improvement has occurred in the underlying condition. Trial cessation is best commenced in September or October.
  
  Criterion
  When IgA and IgM are trending upwards and close to normal and the patient is well, a trial off therapy (in September or October) is considered to allow immunological re-evaluation, or is medically contraindicated

Please note: A diagnosis of bronchiectasis and/or suppurative lung disease must be consistent with the guideline of the Thoracic Society of Australia and New Zealand (Chang AB et al. 2014).
 

• Loading Dose (IVIg) - One loading dose of 0.4 g/kg in the first month of therapy (in addition to the maintenance dose) is permitted if the serum IgG level is <4 g/L.
  This dose is also available as subcutaneous immunoglobulin.
• Disseminated Enterovirus Dose (IVIg) - One dose of 2g/kg at any stage is permitted (in addition to the maintenance dose) in the management of disseminated enterovirus infection.
  This dose is also available as subcutaneous immunoglobulin.
• Maintenance Dose (IVIg) - 0.4–0.6g/kg every four weeks or more frequently, to achieve IgG trough level of at least the lower limit of the age-specific serum IgG reference range. More frequent dosing to achieve IgG trough level of up to 9 g/L is permitted if chronic suppurative lung disease is not adequately controlled at an IgG trough level at the lower limit of the age-specific serum IgG reference range. A total dose of up to 1 g/kg may be given over any four week period.
  Subcutaneous administration of immunoglobulin can be considered as an alternative to IVIg.
• Supplementary Dose (IVIg) - One additional dose of 0.4g/kg is permitted at any stage (in addition to the maintenance dose) if the serum IgG level is <4g/L.
  This dose is also available as subcutaneous immunoglobulin.
• Loading Dose (SCIg) - One loading dose of 0.4 g/kg in the first month of therapy (in addition to the maintenance dose) is permitted if the serum IgG level is <4 g/L.
  This dose is also available as intravenous immunoglobulin.
• Disseminated Enterovirus Dose (SCIg) - One dose of 2g/kg at any stage is permitted (in addition to the maintenance dose) in the management of disseminated enterovirus infection.
  This dose is also available as intravenous immunoglobulin.
• Maintenance Dose (SCIg) - 0.1-0.15g/kg every week or more frequently, to achieve IgG trough level of at least the lower limit of the age-specific serum IgG reference range. More frequent dosing to achieve IgG trough level of up to 9 g/L is permitted if chronic suppurative lung disease is not adequately controlled at an IgG trough level at the lower limit of the age-specific serum IgG reference range. A total dose of up to 1 g/kg may be given over any four week period.
  This dose is also available as intravenous immunoglobulin.
• Supplementary Dose (SCIg) - One additional dose of 0.4 g/kg is permitted at any stage (in addition to the maintenance dose) if the serum IgG level is <4g/L.
  This dose is also available as intravenous immunoglobulin.