EBMT

A Report from the Immunobiology Working Party (IWP)

Alejandro Madrigal, Chair of the IWP, presenting at the Toledo Meeting

This has been a successful period for the IWP in which several projects have been undertaken:

1) Long-term genetic and epigenetic effects of granulocyte colony stimulating factor (G-CSF) on the lymphocytes of voluntary unrelated haemopoietic stem cell donors

Nagler et al (2004) at Tel Aviv University, reported finding specific abnormalities in lymphocytes from normal people who had recently received G-CSF that were very similar to those seen in lymphocytes from persons with malignant diseases. Specifically, these abnormalities included loss of synchrony in allelic replication and aneuploidy.  The abnormal timing of allele replication was a transient phenomenon, but the aneuploidy persisted in the longer term.  The authors stated that these changes were characteristic of changes seen in lymphocytes from patients undergoing chemotherapy for malignant disease.   

Following this in December 2006, Bennett et al. reported five cases of haematological malignancy occurring in normal individuals following exposure to haematopoietic growth factors. Three cases described lymphoid malignancies (non-hodgkin lymphoma and chronic lymphocytic leukaemia) occurring months to years after receipt of an investigational agent (pegylated, recombinant megakaryocyte growth and development factor).  The two additional cases, however, were identified among two hundred individuals who had received Filgastrim (rhG-CSF), Neupogen) as a mobilising agent for collection of peripheral blood stem cells (PBSC) for allogeneic transplantation.

Based on these reports, the IWP took action to clarify the potential risk of using G-CSF in unrelated bone marrow donors (UBMD). We held a Working Group Committee in collaboration with the World Marrow Donor Association (WMDA) and the National Marrow Donor Program (NMDP) and undertook an evaluation of the existing data from all worldwide Registers. This gave us the confidence to believe that apparently there is no increase in malignancy in voluntary UBMD who receive G-CSF for mobilisation.

Click here to view the data that was presented at an open session during the Annual EBMT Congress held in Lyon in March this year.

We are currently performing a joint study to perform cytogenetic analysis on UBMD both retrospectively and prospectively.  We will include in this group as a control bone marrow donors and patients with malignancies.

 
This study is being performed under the umbrella of EMBT and in collaboration with members of The Anthony Nolan Research Institute, Royal Free and University College Medical School, British Bone Marrow Registry, NMDP and Chugai Pharma UK.

2) Immunogenetic factors that affect the outcome of stem cell transplantation

Several studies are being performed by members of the IWP to understand the contribution of polymorphic genes, not only within the MHC region, but for instance, within the NOD2/CARD15 gene polymorphism in the outcome of transplantation.  In a multicentric collaborative study, we have observed that Single Nucleotide Polymorphisms (SNPs) of these genes are associated with significant increases in disease relapse and mortality in recipients of haematopoetic stem cell transplantation for acute leukaemia. 

This data was presented during the EBMT Meeting in Lyon and received the van Bekkum Award (enlace a EBMT 2007 Van Bekkum Award).  We are currently extending this study to other haematological diseases in  collaboration with other centres.

3) AlloStem

In collaboration with AlloStem, some members of the IWP have been actively involved in generating antiviral and anti-leukaemic T cells and clinical trials are just beginning.  In addition, last November we held the 2nd AlloStem Training Course in Toledo, Spain and we are in the process of organising a Joint AlloStem-ESH-IWP Training Course on Immunotherapy for Stem Cell Transplantation in La Palma on 17-20 October this year.  For more details please contact Professor Manuel Fernández.

As a result of the increase in IWP activities, we are in the process of creating several subcommittees to focus on important areas. 

The next IWP Board Meeting is planned for Monday, 16th July 2007 in London at The Anthony Nolan Research Institute. 

Professor Alejandro Madrigal
Chair of the IWP