Within the next 2 years, peripheral blood will replace bone marrow as the medium for autologous transplants, predicted Malcolm A.S. Moore, DPhil, at a press briefing co-sponsored by the Cancer Research Institute and Immunex Corporation.
Although numerous issues remain to be resolved for allogeneic transplants, principally graft-vs-host disease (GVHD), he believes that within the next decade, the technology for mobilizing peripheral blood will be sufficiently advanced to render both autologous and allogeneic bone marrow transplants obsolete.
Once refined, the peripheral blood procedure will be considerably simpler than bone marrow transplant because it can be done repeatedly, without general anesthesia, and because a considerably smaller sample can be expanded for multiple transfusions, said Dr. Moore, Head of the Laboratory of Developmental Hematopoiesis, Memorial Sloan-Kettering Cancer Center.
The key, he said, is to stimulate stem cells to appear in the peripheral blood using colony-stimulating factor treatment. Dr. Moore, who discovered granulocyte colony-stimulating factor (G-CSF), cited three such factors currently available: G-CSF, granulocyte-macrophage CSF(GM-CSF), and stem-cell factor.
None of these, however, accelerate regeneration of platelets. A newly discovered growth factor, thrombopoietin, does seem to do so, and more effectively than the interleukins that have thus far been tried, he said.
Dr. Moore is convinced that many growth factors are needed to produce the desired effect. He is working with various combinations--what he terms a "cocktail"--to direct development of specific cell populations and to expand them, ex vivo, for reinfusion between chemotherapy cycles.
In a randomized trial involving patients with metastatic breast cancer at Memorial Sloan-Kettering, the post-treatment period of hematopoietic recovery was shortened to 10 to 12 days using mobilized peripheral blood (compared to 15 to 20 days with bone marrow transplant). He cautions that the timing of treatment cycles and infusion of "boosted" blood is crucial, and that these aspects of treatment still must be fine-tuned.
Umbilical Cord Blood
An even more abundant source of stem cells than peripheral blood is umbilical cord blood. "It is an intrinsically rich source of stem cells so, unlike peripheral blood, patients do not need to be treated with growth factors," Dr. Moore said. With umbilical cord blood, there is reduced risk of GVHD, and because the cells are younger, they have greater potential for division, he added.
Cord blood withdrawn and frozen can be used at a future time to provide needed cells for either autologous or allogeneic transplant. The New York Blood Center has been awarded an NIH grant to investigate this application, and has already done 20 allogeneic transplants using cord blood, he said.