For autologous transplantation, the patient must first undergo collection of hematopoietic stem cells and cryopreservation.83,84 Cryopreservation can be reliably performed, and the stored cells remain viable for more than 5 years.
Hematopoietic cell collection should ideally occur at a time when the bone marrow is normally cellular and the blood and marrow do not contain malignant cells. Malignant cells may contaminate autologous stem cell products; the likelihood varies with the diagnosis and disease stage. Mobilized peripheral blood stem cells tend to have a lower frequency of tumor cell contamination than bone marrow harvests.85 Peripheral blood stem cell transplants can be performed in patients in which marrow harvesting is not feasible, such as those with prior pelvic radiotherapy.
Tumor cells can be identified in histologically normal product by a variety of techniques, including cell culture, flow cytometry, immunohistochemistry, and polymerase chain reaction for amplification of clone-specific markers, such as a typical translocation or immunoglobulin gene rearrangement. Gene marking studies using retroviral gene vectors have shown that tumor cells contained in the graft can contribute to relapse in patients with leukemia, neuroblastoma, and presumably other diagnoses.86-88 Numerous clinical studies have shown that tumor cell contamination of the autograft is associated with shortened disease-free survival.89-91 Purging methods have been developed to deplete the autograft of tumor cells in an attempt to improve outcomes.92 Purging methods most often use monoclonal antibodies combined with complement, immunomagnetic beads, or conjugated toxins.89 Positive selection of CD34+ cells is another widely used approach,93,94 and combined methods are investigated as a potentially better purging strategy. Pharmacological purging include ex vivo treatment of the autograft with chemotherapeutic agents such as 4-hydroxycyclophosphamide and are mostly applied to autografts of patients with AML.95,96
The clinical benefit of purging is not well documented. Successful purging of marrow harvests of patients with follicular lymphoma or with breast cancer was associated with superior outcome.89-91 However, the presence of tumor cells in the autograft may correlate with the extent of systemic residual disease, and this is not direct evidence that reinfused tumor cells caused relapse. Most patients relapse in sites of prior disease, and inadequate systemic cytoreduction is believed to be the major cause of relapse post autologous transplantation. An alternative explanation is that tumor cells in the graft home preferentially to sites of prior disease where the microenvironment supports their growth. There are no randomized studies documenting reduced relapse rates using purged versus unpurged autologous transplants, and the role of purging remains controversial.
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