Clinical Working Party
UPDATED! EBMT/ESID GUIDELINES FOR HAEMATOPOIETIC STEM CELL TRANSPLANTATION FOR PI
Primary immunodeficiencies are rare heterogeneous disorders. Patients present with a variety of clinical symptoms and a wide range of infections and other complications. Treatment by bone marrow transplantation is increasingly successful (reference: Antoine C, et al. The Lancet 2003;361:553-60; Gennery et al., JACI 2010;126:602-610) and the joint EBMT/ESID Working Party has played a pivotal role designing and developing the guidelines which have led to this success.
The clinical heterogeneity of the patients, together with the fact that outcome data are based on observational studies, means that it is not yet possible to recommend tightly defined clinical protocols for transplanting these conditions. Each case needs to be carefully evaluated in a centre which has significant ongoing experience of performing these procedures. The exact transplant protocol will be devised using these guidelines, but sometimes modified according to the particular variant of the primary immunodeficiency and/or the patient’s clinical condition. For all these reasons the Working Party strongly recommends that all patients with primary immunodeficiency are transplanted in a centre that regularly transplants such cases, and also actively participates in the Working Party, as only in this way can optimum results be obtained.
The guidelines are reviewed on an annual basis and sub-groups of Working Party members revise some of the guidelines for specific conditions each year.
B. Conditioning Regimens
Over the years a number of different conditioning regimens have evolved as newer, less toxic conditioning agents have been made available. For these and other reasons, it has been difficult to gather data on the use of a particular conditioning protocol for any one disease such that a strong recommendation can be made. In most cases, groups of primary immunodeficiencies have been transplanted using certain generic protocols often with modifications (e.g Flu/Melph/Campath or ATG). It is also important to note that specific conditioning regimens are not risk factors for survival in the SCETIDE data.
To address these issues and to simplify matters, the IEWP decided that rather than to recommend specific protocols for specific conditions, one approach would be to make a list of protocols available. For disease groups, a recommendation would be made to choose from the protocol list e.g for Wiskott-Aldrich syndrome with a MUD use protocol A, B or D. The aim of this approach is that:
- By limiting the number of protocols available, there will be less variation between centres
- If centres use specific protocols as defined, then we will be able to gather data on the success or otherwise of a specific protocol in treating these conditions
- We also recognise that for smaller or less experienced centres this guidance is important and by making these guidelines available on the EBMT and ESID websites, the information is readily available
We have therefore made a list of four protocols A-D which are outlined and are recommended for the majority of diseases. Specific details/examples of these protocols are made available in the appendix (see PDF below).
Exceptions to these recommendations are SCID, where some transplants can be undertaken without any conditioning and severe immunodeficiencies associated with radiosensitivity which require specialised protocols.
We ask that if protocols are used, then they are adhered to in terms of dosing and schedule as much as possible since only then can meaningful data be accrued over time.