Committee members present: Adriana Zeevi, Frank Christiansen, Joannis Mytilineos.
Chairmen/Coordinators from other components: John Hansen, Eric Mickelson, Effie Peters-dorf, Steve Mack. Committee members absent/unable to attend: Ming-Tseh Lin and other participants from the CGP as well as the Hematopoietic Stem Cell Transplant (HSCT) com-ponent.
In the framework of this year's ASHI meeting we had the opportunity to brainstorm and de-fine more precisely how the phase II studies of the CGP-component of the IHWC will be car-ried out. The following issues were discussed and decisions made:
General issues:
- All laboratories who would like to participate in phase II projects will have to fill in a confirmation form on which they will provide precise and definitive information about the phase II study they want to participate in, the approximate number of samples they want to type, and the reagents they will use.
- On the same form they will be requested to state whether they would be willing to type clinical samples coming from laboratories not participating in the CGP. This seems to be necessary, particularly in the Disease and HSCT component phase II studies.
- In addition, this form will provide the option to order reagents from Heidelberg as well as the quality control DNA panel from the IHW Cell and Gene Bank (Eric Mickelson).
- This form is downloadable from the IHWG Homepage and will be also shipped to all CGP participants from Joannis.
- The Heidelberg set has been shown to provide accurate and reproducible typing since the majority of the participating labs obtained qualitatively satisfactory results with this rea-gent set.
- Other reagents or methods (One Lambda, local sets, RFLP, SnaPShot) provided equally good results, however, in certain instances, the polymorphism detected (gIFN) was a dif-ferent one from that detected by the Heidelberg lab.
- It was decided (also previously discussed in Granada) that for the phase II studies labora-tories could use whatever method they liked provided that they have typed the phase I ref-erence panel (50 DNA samples).
- Since the vast majority of the laboratories have been working with the Heidelberg set, and because it was felt that a computerized analysis of the reaction patterns would make inter-pretation (especially that of haplotypes) easier, Wolfgang Helmberg was asked to help by providing a SCORE platform. Wolfgang promised to have completed that platform by Nov. 15.
- Joannis is currently preparing a manuscript about the phase I evaluation which will be presented to the committee members before submission to a journal (possibly Tissue Antigens or Human Immunology)
- For all phase II studies a selected 15 DNA quality control panel will have to be typed by each laboratory in order to assess quality of the data provided.
- The QC panel will be put together from Joannis based on the phase I panel results. The information will be passed to Eric at the Cell and Gene Bank by October 20 so they can prepare the QC panel sets on time. It is projected that QC sets will be ready to ship by November 26.
- QC samples will be coded and have a different identification from that used in the phase I study. Only the Cell and Gene Bank will be aware of both the old and the new coding.
- Labs who would like to perform cytokine typing for anthropological purposes will need to fill the Anthropology Component data sheet for each sample they want to type.
- This data form is available through the web page, or on request via e-mail from Joannis or Steve Mack. The Anthropology data submission form will provide a wide range of anthropological and demographic information on the samples being typed, while the Cytokine Gene data submission form will be more focused on sample identity and specific cytokine gene polymorphism data.
- If a laboratory has already submitted (or plans to submit) anthropological data on HLA for some or for all of the samples he/she plans to type for cytokine genes, then the Anthropology data sheet does not have to be filled out twice! Please make sure, however, that the same sample ID information has been entered on both the Anthropology and CGP data forms (to permit linking of the data in the database) for each sample tested.
- For the Anthropology Component, not all the cytokine genes need to be typed, however, it is recommended and preferable to include testing for all genes that were included in the phase I study.
- Results should be reported directly to the database via e-mail (data entry file downloadable through the Cytokine Gene web page or available through Joannis upon request).
- Statistical evaluation of the anthropological data will be carried out together with the clas-sical HLA anthropology data.
- Since there was a whole batch of different diseases for which single CGP participants in-dicated their interest to perform cytokine typing, it was decided that it wouldn't make sense to study all of them in the framework of the workshop. Individual studies can of course been carried out by each participant separately.
- The CGP committee and Erik Thorsby (communicated through John Hansen) suggested that we should concentrate on the two diseases for which the majority of the labs ex-pressed their interest, i.e. IDDM and RA.
- Since there is already a large number of samples included in the HLA typing disease com-ponent procedure, it was proposed, that some or all of these samples might also be typed for the cytokine genes. Part of these samples have also been typed for microsatellites within the MHC region, and this work is still been carried out. For those samples there would be no need to fill the additional data sheets (similarly to the anthropology compo-nent) since that work will already have been done before.
- For samples which have not yet been registered within the disease component, a Disease Component data form will have to be completed (soon downloadable through the IHWG web site).
- It was also decided that the laboratories that wanted to do some cytokine work on IDDM and RA would be identified and the information passed to Erik Thorsby. Erik would then contact all IDDM and RA laboratories in the Disease Component and ask if they would be interested in participate in the CGP or would be willing to provide some material for CGP typing by another laboratory.
- Labs who would be willing to perform Cytokine typing for another lab will have to be identified.
- Because of the control groups, this work will have to be very well coordinated. This will be a real challenge. Ideally, anthropological CGP data could be used for this purpose.
- Also for the Disease Component, not all the cytokine genes will need to be typed, how-ever, it would be recommendable and mostly preferable to include testing for all genes, which were included in the phase I study.
- Results will have to be reported directly to the database via e-mail (data entry file downloadable through the web or available through Joannis upon request).
- Statistical evaluation of the disease data will be carried out together with the chairmen of the respective disease component.
- For the time being, the source of already (or almost surely) existing samples for this com-ponent is restricted to those coming from the NMDP, Seattle, France, Canada, and Aus-tralia. Samples from Germany might also become available. Other countries might also provide samples and data in the near future.
- The efforts of the CGP should therefore concentrate on the already existing samples.
- There was concern about policies for shipping DNA material of transplant patients in foreign countries. Thus it was felt that samples for Cytokine typing should be performed in the individual countries, i.e.: French patients should be typed in France, NMDP patients in the US, Ca-nadian patients in Canada, etc.
- Therefore it will be imperative to identify laboratories who have gone through the phase I evaluation (or still want to do this soon) and are willing to share this very interesting and challenging task of examining the role of cytokine gene polymorphisms in hematopoietic stem cell transplantation.
- Joannis is going to write to all participants and ask them to check their laboratory capacities in this context.
- New laboratories from the US have expressed their interest to participate in the CGP. Adriana is trying to coordinate their cooperation in the Stem cell project (Nancy Reinsmoen, Andrea Zachary). Carolyn Hurley has contacted Joannis and Dan Cook also presented data in a poster.
- It appears that it would be sufficient to ask each laboratory to type at least 200 samples. Concerning the laboratory situation in countries other than US:
- Frank would be obviously willing to type the Australian samples
- The laboratory in France (Marseille) will have to type the French samples (Dr. Raffoux will contact him to coordinate sample shipment)
- Deborah Nickerson could possibly work on the Canadian samples and finally
- Joannis will type the German samples if they eventually will become available to the study. (Need feedback on this from Effie and Gary Schoch. Will you tell me if and when any data from Germany start to come in? - If no German samples come in, Joannis would be able to type samples from the NMDP or from anywhere else).
- In this component, it will be important that everyone will have to type for the whole set of cytokines included in the phase I study.
- Results will have to be reported directly to the database via e-mail (data entry file down-loadable through the web or available through Joannis upon request).
- Statistical evaluation of the transplant data will be coordinated and carried out from Effie, Adriana, Frank and Joannis.
San Francisco, October 16, 2001 (revised on October 31, 2001)
Joannis Mytilineos, MD