Are stem cells used in the treatment of sarcoma? |
An ESUN Article
Stem cells are immature cells in the peripheral blood stream and bone marrow which are responsible for the development of the three major components of the hematopoietic system, namely red blood cells, white blood cells and platelets. Stem cell transplantation is an investigational treatment option for patients with sarcoma. There are two major types of transplantation for patients with malignancies, one is allogeneic and the other is autologous. Both forms of treatment rely on stem cells for reconstitution of the bone marrow following high doses of chemotherapy (HDCT) and total body irradiation (TBI). Stem cells may be obtained by bone marrow harvesting or by leukapheresis following mobilization or consolidative therapy.
Mobilization therapy: A treatment that uses growth factors or other treatments that lead to the proliferation and mobilization of stem cells in an inactive bone marrow microenvironment into an environment which promotes their expansion, differentiation and mobilization into the bloodstream. The stem cells are then harvested in order to replace stem cells that have been damaged from aggressive treatments in preparation for a stem cell transplant.
Consolidative therapy: A treatment that follows an initial successful treatment. The goal of the consolidative therapy is to destroy any remaining cancer cells, thus preventing a relapse.
Bone marrow harvesting is generally performed under local or general anesthesia. The sample is obtained from the pelvic bone region where a bone marrow biopsy needle is introduced into the pelvic bone and small portion of bone marrow is aspirated. Multiple samples are obtained, processed and frozen for later infusion.
An alternative method for collecting stem cells is leukapheresis. This is usually the approach for patients undergoing autologous stem cell transplantation (ASCT). In this setting, the patient is given a growth factor support agent such as G-CSF or Gm-CSF to stimulate the peripheral blood cells and stem cells following chemotherapy. This process is referred to as mobilization and the procedure for collecting the sample is known as leukapheresis.
Allogeneic transplants require an HLA compatible donor (usually a sibling or family member). To date, allogeneic transplants have been performed successfully in select patients with hematologic malignancies such as acute and chronic leukemias and lymphomas. In this process, the donor’s transplanted stem cells are infused and reconstitute the bone marrow assisting in the production of normal cells. The patient’s remaining cancer cells are attacked by the donor’s cells in an immune mediated fashion creating a graft versus tumor effect. While this interaction may be essential for cure there are potentially significant side effects known as graft versus host disease (GVHD) whereby the infused donor cells mount an intense immune response against the patient’s cells. Balancing immunologically mediated responses requires additional forms of immunosuppression to temper reactions such as GVHD.
Autologous hematopoietic stem cell transplantation (AHSCT) is the “mobilization “ of one’s own stem cells, removal of the cells by (leukapheresis) and storage for re-infusion following high doses of chemotherapy and TBI. It is unclear whether the cells to be infused need to be completely free of tumor cells. Attempts to “purge” the sample of contaminating tumor cells has not provided improved results. Additional studies are ongoing to evaluate the effect of the presence of tumor cells. In tumors such as Ewing’s, a translocation t(11;22) produces a unique fusion protein EWS-FLI 1 which may be detected in the analysis of bone marrow or peripheral blood.
Patients with unresectable, primary chemorefractory or metastatic sarcoma cannot be cured with standard combination therapy or radiation. Alternative treatment approaches need to be further evaluated in prospective studies. While autologous transplantation relies on high doses of chemotherapy and stem cell rescue to overcome tumor resistance and allogeneic transplantation attempts to utilize immune mediated graft versus tumor effects in addition to chemotherapy to improve prognosis to date, transplantation for the treatment of high risk sarcomas remains experimental. Meyers et al (JCO, Vol 19, No11, June 2001: pp. 2812-2820) reported results of HDCT, TBI and stem cell rescue in Ewing’s sarcoma patients failed to improve probability of event free survival in newly diagnosed metastatic ES patients.
Stem Cell Transplant Resources
*View clinical trials that involve stem cell transplant.
*Information about Understanding Autologous Bone Marrow and Stem Cell Transplantation from the Multiple Myeloma Foundation
*The National Marrow Donor Program: Patient's Frequently Asked Questions
*Stem Cells and Stem Cell Transplantation at Medline Plus
V1N3 ESUN Copyright © 2004 Liddy Shriver Sarcoma Initiative.