Most patients undergoing allo-transplantation at the NIH are being treated for refractory malignancy. In some cases, especially solid tumors, therapeutic effects of transplant can be monitoring adequately using conventional radiologic and serum-based assays of marker proteins. Patients treated for hematologic malignancies however can achieve complete remissions by conventional clinical criteria, yet retain sufficient residual disease to assure rapid recurrence without further aggressive therapy. Sensitive PCR-based assays are very useful, both in monitoring the anti-tumor efficacy of individual transplants, and in deciding whether additional therapeutic maneuvers, such as donor lymphocyte infusion, are needed. Such assays have been used most extensively in managing CML, a disease characterized by a chromosomal translocation which leads to the production of a unique oncogenic protein product designated BCR-ABL. DLM/hematology has previously adapted an older endpoint assay for detecting BCR-ABL cells. This test is technically difficult and time-consuming. More important, it provides no quantitative data concerning the extent of CML involvement. We have set up and are currently testing newer assays exploiting real time PCR methods. These are much faster to perform, comparable in sensitivity, and capable of providing quantitative data about residual tumor load. These assays will give us a new capability to assess the magnitude of residual BCR-ABL disease and to detect more rapidly changes in disease after therapeutic interventions post transplant. Building on our experience in this disease, we plan to develop comparable quantitative assays for monitoring minimal residual disease in other subsets of transplantation patients, for example using the expression of WT1 to monitor residual disease in patients with acute leukemia. The ability to monitor changes in residual malignant disease will be very useful to clinicians. It also facilitates our efforts to define the impact of donor cell chimerism, and alloreactivity (which are also being monitored using an ELISPOT assay in this laboratory) on the course of malignant disease in transplant patients.
| Rezvani, K; Price, D A; Brenchley, J M et al. (2007) Transfer of PR1-specific T-cell clones from donor to recipient by stem cell transplantation and association with GvL activity. Cytotherapy 9:245-51 |
| Savani, B N; Montero, A; Kurlander, R et al. (2005) Imatinib synergizes with donor lymphocyte infusions to achieve rapid molecular remission of CML relapsing after allogeneic stem cell transplantation. Bone Marrow Transplant 36:1009-15 |
