The Decision of Using autologous stem cell transplantation
The relationship between the dose of chemotherapy and/or radiation and the number of tumor cells killed has been extensively studied in vitro and in preclinical animal models, and forms the basis for the decision to pursue autologous stem cell transplantation.
For chemosensitive tumors such as non-Hodgkin lymphoma, Hodgkin lymphoma, and leukemia, a relatively steeply rising dose–response curve is observed, meaning that as the dose of the cytoxic agent is increased the number of tumor cells killed is also increased. The possibility for cure following autologous stem cell transplantation, therefore, is derived from the beneficial effects of the high doses of chemotherapy and/or radiation therapy administered during transplant conditioning that enhance tumor cell kill and overcomes drug resistance. Dose escalation of therapy in autologous stem cell transplantation is possible because the dose-limiting toxicities on hematopoiesis are circumvented by the infusion of the hematopoietic cell graft.
Autologous stem cell transplantation and nonrelapse mortality
Autologous stem cell transplantation is associated with relatively low nonrelapse mortality. The use of mobilized PBPCs has decreased the duration of neutropenia and when combined with improved supportive care the nonrelapse mortality of approximately 8 to 10 percent with marrow in earlier studies has been reduced to 1 to 3 percent with mobilized PBPCs in most centers. In addition, the reduced risks and faster engraftment times have allowed many centers to pursue outpatient transplantation, further easing the difficulty of patients undergoing this procedure, as well as possibly reducing costs.
Tumor Contamination in the autologous stem cell transplantation
A consistent concern in autologous stem cell transplantation is the possibility that residual clonogenic tumor cells may contaminate the hematopoietic stem cell product and contribute to tumor relapse. The relative contributions of tumor cell contamination from the cell product and residual disease in the patient are difficult, if not impossible, to discern. One approach to determine if residual malignant cells do indeed contribute to relapse is to mark the hematopoietic stem cell product at the time of harvest and then assay if the marker gene is present in malignant cells at the time of a subsequent relapse. Studies using this approach have been performed in patients with leukemia, lymphoma, and myeloma.