Fred Hutchinson Cancer Research Center, Seattle Seattle transplanters developed the original mini transplant regimen based on years of dog experiments. They deleted up-front chemotherapy, relying instead on low doses of total body irradiation to immunosuppress the patient. Later, they began adding the anti-leukemia and immune-suppressing drug fludarabine (which is now standard with virtually all low-dose protocols). With this regimen, they have achieved high engraftment rates. A paper from the group, which, according to Rainer Storb, M.D., is awaiting publication at a major journal, describes the outcomes of the first 45 patients treated on the Seattle protocol. Storb says that the results for some diseases, particularly chronic myelogenous leukemia, are "spectacular."
Hadassah University Hospital, Jerusalem Another pacesetter in low-dose transplants, Shimon Slavin, M.D., published one of the first papers on the subject, which has been cited a whopping 86 times. A report in the May 2000 Bone Marrow Transplantation from Hadassah details the treatment of 23 refractory lymphoma patients. All received intermediate doses of pre-transplant chemotherapy. Disease-free survival at 3 years post-transplant is an encouraging 40%. However, seven patients (30%) died from transplant-related complications, about the same proportion found in conventional transplants.
University of Texas M. D. Anderson Cancer Center, Houston The Houston protocol is similar to Hadassahs, using low doses of various chemotherapy drugs, including cisplatin and cyclophosphamide. In presentations to the American Society of Clinical Oncology annual meeting this spring, Sergio Giralt, M.D., and colleagues reported encouraging results in advanced lymphoma patients. Out of 15 transplant recipients, 10 had complete or partial responses, and four died from transplant-related complications.
National Cancer Institute, Bethesda, Md. Besides striving for quick engraftments, NCI researchers are testing various ways of combining low-dose transplants with manipulated T cells, to increase the graft-versus-tumor effect while reducing graft-versus-host disease. In particular, the NCI group has begun culturing donor marrow to produce subpopulations of T cells called type 2 helper cells. Mouse evidence shows that these cells, which secrete a particular anti-inflammatory cocktail of immune cytokines, can reduce graft-versus-host disease. A phase I study is under way to gauge the safety of infusing patients with large numbers of these cells.
Massachusetts General Hospital/Harvard University, Boston Boston is one of a few sites attempting mismatched low-dose transplants. While expanding the pool of potential donors, mismatched marrow usually means higher rates of complications and graft rejection. But Megan Sykes, M.D., said that depleting both the donors and recipients T cells with a targeted antibody lessens these problems. An early report in The Lancet from 1999 showed that four out of five lymphoma patients achieved engraftment with mismatched donors. All patients suffered some graft-versus-host disease, but two of the patients survived. One was alive 16 months post-transplant.
![]() |
||||
|
Oxford University Press Privacy Policy and Legal Statement |