Factors influencing reconstitution by bone marrow transplantation

Reconstitution of levels of pheripheral blood cells following bone marrow transplantation is dependent on the engraftment of the pluripotent hemopoietic stem cells of the transplant. In the case of allogeneic transplants, a successful engraftment carries a high risk of the development of GvHD, which is a serious and often life-threatening complication. T cell depletion of the allogeneic bone marrow graft can completely prevent GvHD provided a sufficient degree of depletion is achieved. Experiments with laboratory animals and clinical experience have shown that the higher rate of graft failure that occurs with T cell depleted marrow grafts can be avoided by increasing the conditioning dose of TBI with approximately 2 Gy. Experiments with T cell depleted autologous bone marrow grafts and with grafts of autologous purified stem cells in monkeys demonstrate that the decreased engraftment of T cell depleted bone marrow cannot be ascribed to a trophic function of T lymphocytes, e.g. via production of hemopoietic growth factors. Using sublethally irradiated Rhesus monkeys, the effect of post-irradiation treatment with GM-CSF or with Rhesus monkey r IL-3 was studied. Enhancement of blood cell regeneration was only recorded within a relatively small TBI dose range. When the dose of TBI induces more than approximately a 3-log stem cell kill, treatment with growth factors becomes ineffective. Comparable results are obtained when supralethally irradiated monkeys given relatively small grafts of T cell depleted autologous bone marrow were treated with the hemopoietic growth factors.