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Megadose and minitransplantation: What is the biology?
Cytotherapy (2000) Vol. 2, No. 5, 391
Transplantation Biology Workshop
Megadose and minitransplantation: What is the biology? R Handgretinger Scientific Subcommittee on Transplantation Biology report
The workshop of the Scientific Subcommittee Transplantation Biology entitled: ‘Megadose and Minitransplantation: what is the biology?’ was held on June 18, 2000. The session was chaired by Dr R Handgretinger. Dr M Schumm presented data on the transplantation of 39 pediatric patients with megadoses of mobilized purified CD34+ stem cells derived from haploidentical donors. Engraftment could be achieved by using a combination of high stem-cell numbers (median number of transplanted CD34+ stem cells: 20 106/kg) and a short post-transplant rejection prophylaxis with an anti-CD3 antibody. Immunoreconstitution was faster in patients receiving higher stem cell numbers. All except one patient finally engrafted. The concept that megadoses of CD34+ stem cells are necessary for engraftment in partially-mismatched related donors was challenged by Dr J Henslee-Downey. In her experience of both adult and pediatric patients, engraftment was achieved with T-cell depleted BM containing much lower doses of CD34+ stem cells. Grade III–IV GvHD was seen in 23% and 19% of the patients grafted with BM from donors with < 2 Ag and 3 Ag mismatch, respectively. Overall probability of chronic GvHD was 53%. The number of transplanted CD34+
© 2000 ISHAGE
stem cells had no influence on the outcome, and survival was only affected by advanced disease at time of transplantation. Dr Bornhäuser presented data using a reduced nonmyeloablative regimen, followed by the transplantation of mobilized peripheral unseparated or positively selected CD34+ stem cells from matched unrelated donor. Mycofenolate mofetil and cyclosporin were used for GvHD prophylaxis. Although the intital tolerability was good and chemotherapy-related side effects were low, infections, GvHD or both still present a problem after cessation of immunosuppression. A close follow-up of the chimerism in lymphocyte subpopulations showed the dynamic of engraftment and the role of donor lymphocyte infusions in this transplant setting. The advantages and disadvantages of these different transplantion approaches were discussed by the attendees. There was an agreement that non-myeloablative therapies are more in favor for older patients, or for patients who are at high risk of toxicity with a myeloablative therapy. Most discussants agreed that myeloablative therapies still have their place in patients with malignancies, in order to maximize the antileukemic effect of the transplantion.
391
Transplantation Biology Workshop
Megadose and minitransplantation: What is the biology? R Handgretinger Scientific Subcommittee on Transplantation Biology report
The workshop of the Scientific Subcommittee Transplantation Biology entitled: ‘Megadose and Minitransplantation: what is the biology?’ was held on June 18, 2000. The session was chaired by Dr R Handgretinger. Dr M Schumm presented data on the transplantation of 39 pediatric patients with megadoses of mobilized purified CD34+ stem cells derived from haploidentical donors. Engraftment could be achieved by using a combination of high stem-cell numbers (median number of transplanted CD34+ stem cells: 20 106/kg) and a short post-transplant rejection prophylaxis with an anti-CD3 antibody. Immunoreconstitution was faster in patients receiving higher stem cell numbers. All except one patient finally engrafted. The concept that megadoses of CD34+ stem cells are necessary for engraftment in partially-mismatched related donors was challenged by Dr J Henslee-Downey. In her experience of both adult and pediatric patients, engraftment was achieved with T-cell depleted BM containing much lower doses of CD34+ stem cells. Grade III–IV GvHD was seen in 23% and 19% of the patients grafted with BM from donors with < 2 Ag and 3 Ag mismatch, respectively. Overall probability of chronic GvHD was 53%. The number of transplanted CD34+
© 2000 ISHAGE
stem cells had no influence on the outcome, and survival was only affected by advanced disease at time of transplantation. Dr Bornhäuser presented data using a reduced nonmyeloablative regimen, followed by the transplantation of mobilized peripheral unseparated or positively selected CD34+ stem cells from matched unrelated donor. Mycofenolate mofetil and cyclosporin were used for GvHD prophylaxis. Although the intital tolerability was good and chemotherapy-related side effects were low, infections, GvHD or both still present a problem after cessation of immunosuppression. A close follow-up of the chimerism in lymphocyte subpopulations showed the dynamic of engraftment and the role of donor lymphocyte infusions in this transplant setting. The advantages and disadvantages of these different transplantion approaches were discussed by the attendees. There was an agreement that non-myeloablative therapies are more in favor for older patients, or for patients who are at high risk of toxicity with a myeloablative therapy. Most discussants agreed that myeloablative therapies still have their place in patients with malignancies, in order to maximize the antileukemic effect of the transplantion.
391