Читать книгу Transfusion Medicine - Jeffrey McCullough - Страница 181

For malignancies in which there was suspected marrow involvement, bone marrow aspiration is unsuitable for autologous transplant because of the presence of tumor cells.

However, hematopoietic stem cells are present not only in the marrow but also in the peripheral circulation and can be collected by cytapheresis. Normally the number of circulating PBSCs is much less than in the marrow, but after chemotherapy‐induced marrow suppression, there is a rebound and the number of PBSCs increases substantially. The PBSCs—expected to contain few, if any, malignant cells—can be used for marrow rescue after high‐dose chemotherapy. These autologous transplants of PBSCs made new chemotherapy regimens possible and established that PBSCs could be used successfully for autologous marrow transplantation [97–102].

For several years, the use of PBSCs was limited to autologous transplants. It was feared that the large number of T‐lymphocytes contained in the PBSC concentrates would cause severe graft versus host disease, and that T‐depletion would result in an unacceptably large loss of PBSCs. However, this did not occur [102–107]. PBSCs result in more rapid engraftment [108], give results equivalent to marrow [107, 109], and may provide faster lymphocyte return, resulting in fewer infections [110]. Thus, there has been considerable interest in the methods to obtain PBSCs from both patients and normal donors.

PBSCs can be obtained from the peripheral blood by apheresis, but because of the small number of circulating PBSCs, multiple procedures would be necessary to obtain enough cells for transplantation from unstimulated donors. To further increase the level of circulating PBSCs, donors are given the growth factor G‐CSF. In studies of normal subjects, the administration of G‐CSF causes an increase in the percentage of CD34+ cells from 0.05% before treatment to about 1.5% after 5 days [111–113]. This results in a yield of about 4.5 × 10⁸ CD34+ cells from a single apheresis [112]. The usual dose of CD34+ cells considered suitable for transplantation is about 2.5–5 × 10⁶/kg or about2 × 10⁸ for a 70‐kg person. Thus, one such apheresis concentrate is usually adequate for a transplant.

Another approach to reducing the number of apheresis procedures necessary is large‐volume leukapheresis, in which 15 or more liters of donor blood is processed to increase the number of PBSCs obtained [114] or the use of the agent plerixafor for stem cell mobilization.

As a result of these factors, collection of PBSCs from normal donors now exceeds marrow in many hematopoietic transplant centers [73, 112, 115, 116], thus eliminating marrow collection in the operating suite, along with the attendant risks of anesthesia and the marrow collection process.