FAQs about the treatment of PIDs

Here we answer patients’ questions on aspects of the different treatments available for PIDs.

Immunologlobulin therapy

Q. I have been on 3-weekly immunoglobulin infusions for a long-time. Will this make my veins brittle?

A. Veins can usually recover in the 3-week gap. If your veins do become brittle then your immunology team might recommend changing to another way of giving immunoglobulin such as subcutaneous infusion.

Q. Does immunoglobulin therapy help prevent dementia?

A. There are a number of studies that have looked at IVIG in Alzheimer Disease and there is no evidence of benefit. There are some rarer infections of the central nervous system, associated with loss of higher or cognitive function and good immunoglobulin treatment prevents these infections from taking hold.

Bone marrow transplantation (BMT)

Q. How often can you do a bone marrow transplant (BMT) for a PID?

A. Yes sometimes a BMT doesn’t work because the graft fails and then it may be possible to consider doing another transplant. However this is dependent on finding another suitable donor and the medical condition of the patient considered for subsequent transplant.  There can also be a build up of toxicity in the body from the chemicals used to prepare the body for transplant during chemotherapy that can complicate further attempts at BMT. Second transplants have been done successfully for a number of PID patients but as mentioned above, a number of different factors need to be taken into account.

Q. Is a bone marrow transplant an option for people with CVID?

A. This depends on the type of the CVID, its genetic basis and also the health problems, past and present that the person may have.  We know, at present, that 10 different genes can cause CVID and this is allowing doctors to subgroup CVID patients into those for whom BMT may or may not be a useful treatment option.  One group of people with CVID who have mutations in the enzyme PIP kinase 3 have had BMT with good outcomes but overall there is not much historical information on BMT in CVID.  In some cases the outcomes, where poor, have to be treated with caution because the BMT was sometimes done on patients who were already ill.

Q. Is BMT only possible for children with PID?

A. No over the past few years more adults have started to be treated by BMT but the numbers are still low.  One recent major advance has been the development of what is known as ‘reduced intensity conditioning’; this is a milder form of chemotherapy used to prepare the patient for the donor’s bone marrow. This has been used successfully in BMT for some adults with PID. It is likely that more adults with PID will be treated by BMT in the next few years.

Q. Why is BMT for adults more difficult than that for a child?

A. Usually adults who are being considered for BMT have lots of chronic problems such as lung and gut disease. These chronic problems and chronic infections often make BMT more difficult. Also because of the risks of BMT, the choices of whether a BMT is the right thing to do is more difficult especially since adult PID patients will have jobs, children, etc.

Q.  Can parents be a bone marrow match and so a donor for their child?

A. BMT works best when there is a 10/10 or 9/10 match of important markers on cells between the donor and the person having the BMT.   A parent may only be a 5/10 or 6/10 match so they not ideal as donors.  However, a brother or sister may have a 25% chance of being a match and are often used as donors.

Q. What happens if a BMT match cannot be found within the family?

A. Once doctors have exhausted the possibility of finding a related donor within the family then they will begin the search of a match on national registries such as the Anthony Nolan Registry and cord stem cell banks.  Searches can also be made worldwide through international registries. Umbilical cord blood is increasingly being used and this widens the options available.

Gene therapy

Q. My child has had gene therapy to correct his PID.  Does this mean his PID won’t be passed on to his children?

A. No, gene therapy only corrects the defect in the cells of the bone marrow of the person and not the reproductive cells such as sperm that will still carry the faulty gene causing the PID.  For example a boy who had received gene therapy for an X-linked disorder will have daughters who will carry the condition but will not have affected sons.  It is important to consider family planning issues at the appropriate time and your health team will help with this.

Q. How many people have had gene therapy to treat their PID?

A. Over 100 people have had gene therapy for PID.  The work is taking place all over the world with groups working together sharing gene therapy tools and methods.  There are currently collaborative trials and the major PIDs being targeted are X-SCID, ADA-SCID, WAS, X-CGD, XLP1 and XLA.

Q. Why do some children who have had gene therapy to treat their SCID still need immunoglobulin therapy? 

A. In some cases not all the immune cells are completely corrected by gene therapy. If B cells are not fully corrected (the cells that make immunoglobulin) then the individual may have to continue on immunoglobulin therapy.

Q. Why is gene therapy being developed for some PIDs and not others?

A. Developing gene therapy depends on an in-depth understanding of the genes causing the PID.  For example knowledge is needed on the precise genetic fault (mutation), where it is in the DNA make-up of a cell, what controls the gene involved and in what cells the protein product of the gene is expressed.  Unfortunately, for some PIDs this information is not known at present.

Use of steroids

Q. I’ve been on long-term steroids and worried about osteoporosis, weight gain and cholesterol levels?

A. Doctors when they prescribe steroids carefully weigh up the benefits versus health risks. They will carefully monitor your health and tailor the doses given and will keep them at the lowest level needed to give clinical benefit. Calcium and vitamin D supplements may be recommended to help prevent bone thinning (osteoporosis).

These FAQs were reviewed by Dr Matthew Buckland, Chairman of our Medical Advisory Panel and Dr Bobby Gaspar, Professor of Paediatrics and Immunology, Great Ormond Street Hospital, London. August 2014.