High-dose chemotherapy (HDCT) with autologous stem cell rescue is an effective treatment modality for a variety of hematologic malignancies and selected solid tumors. This chapter reviews the current role of autologous hematopoietic transplants in the treatment of cancer and outlines promising future directions.
The maximal dose of radiation and cytotoxic chemotherapy a patient can receive is limited by its toxicity to normal tissues. The dose of many effective agents is limited by toxicity to the bone marrow. The dose can be substantially escalated to more effective levels if followed by autologous or allogeneic transplantation of hematopoietic stem cells to restore hematopoiesis. Pluripotent hematopoietic stem cells present in the transplant graft proliferate and differentiate into the mature elements of the blood and immune system, including neutrophils, lymphocytes, platelets, and erythrocytes. Autologous transplantation involves collection and cryopreservation of the patient's own hematopoietic cells. Allogeneic transplantation involves transplantation from another person, a normal donor.
General Procedures for Autologous Transplantation
The following steps are involved in the general procedure for autologous stem cell transplantation (ASCT). The process is summarized in Fig. 13-1.
The procedure for autologous stem cell transplantation (ASCT). Patients with malignancy have normal and malignant cells (M) sensitive to myeloablative chemotherapy and/or radiation. They undergo the collection of bone marrow or peripheral blood containing hematopoietic stem cells (SC), which are then cryopreserved. In some cases, the harvested cells are treated in the laboratory to enrich the stem cell number or deplete contaminating malignant cells. Patients later receive a high-dose preparative regimen of chemotherapy alone or with total-body irradiation designed to eradicate the malignant cells. This treatment also destroys the normal bone marrow, but it can be administered if followed by the infusion of the stored stem cells to restore hematopoiesis.
Transplant physicians evaluate potential candidates to determine their appropriateness for high-dose therapy and their risk for major complications. This consists of a complete history and physical examination, review of past treatment and response, baseline laboratory data, and restaging of the malignancy. If the patient is felt to be an appropriate candidate, additional testing is performed to fully evaluate the function of all organ systems. In general, autologous transplants are generally most effective against chemosensitive malignancies with low-bulk disease. Patients must be in sufficiently good general medical condition in order to tolerate the high-dose myelosuppressive therapy.
Standard chemotherapy is usually given to reduce the tumor burden prior to proceeding to stem cell transplantation. The success of transplantation depends on whether the patient's tumor is chemosensitive; the best outcomes are, in general, in patients who are in remission or with minimal tumor load at time of transplantation.
After patients undergo stem cell collection, the ...