Quantitation Of Residual Tumor In Patients Undergoing Allo-transplantation

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Abstract

Patients undergoing allogeneic stem cell transplantation for chronic myelogenous leukemia (CML) often enter complete hematologic and cytogenetic remission, but using sensitive RT-PCR techniques to measure the unique translocation product BCR-ABL most patients have residual BCR-ABL tumor cells circulating in their blood for many years. A recent case report describes the clinical course of a patient with CML, treated by Drs. Barrett and Rezvani of NHLBI, whose tumor burden and anti-tumor T cell status were closely monitored after allotransplantation. The study demonstrates a striking inverse relationship between the number of tumor-specific donor-derived T cells (directed against the leukemic antigen PR1) generated as a consequence of allotransplantation, and the level of residual CML measured using quantitative RT-PCR assays. When anti-leukemic T cell levels diminished, disease recurred only to enter remission again when anti-PR1 T cells were regenerated by donor lymphocyte infusion. Using other sophisticated molecular and flow cytometric techniques, Dr. Rezvani could also document anti-tumor T cell clonal persistence over time, and characterize the anti-tumor cells as effector memory T cells. These results provide strong circumstantial evidence that anti-tumor T cells (particularly those with anti-PR1 activity) play a major role in the ongoing leukemic suppression after allotransplantation for CML. The studies reinforce the therapeutic and pathophysiologic potential of using immune monitoring methods in association with sensitive RT-PCR based assays to study patients allotransplanted for the treatment of leukemia.