IN VITRO DETECTION OF RESIDUAL LEUKEMIA

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Current light microscopic techniques are unable to detect small numbers of residual leukemic cells. More sensitive techniques for the detection of residual leukemia are needed in order to allow a more precise definition of remission and a more accurate evaluation of the effectiveness of marrow purging. Recent work has indicated that most lymphoblastic leukemia and lymphomas contain clonal rearrangements of immunoglobulin or T-cell receptor genes. Southern blot analysis can thus detect one malignant cell in 100 normal cells. Avidin-biotin immunoadsorption can be used as a further method for enhancing the ability to detect malignant cells present in the marrow. By combining avidin-biotin immunoadsorption with Southern blot analysis, it is possible to detect clonal rearrangements in as few as one cell in 1,000. Studies outlined in this project will examine the frequency with which clonal gene rearrangements are detectable in marrows obtained from patients with acute lymphoblastic leukemia (ALL) and lymphoma by using Southern blot techniques with and without avidin-biotin immunoadsorption. A prospective study will follow a group of patients with ALL in remission to determine if the presence of clonal gene rearrangements in remission marrows is predictive of relapse. Similar studies will be carried out at the time of marrow storage and at the time of transplant to determine whether the presence of detectable clonal rearrangements is predictive of relapse after AMT for patients with lymphoid malignancies. Once the sensitivity of the assay is determined, these techniques will be used to help monitor the effectiveness of purging myeloma cells from marrow.