CHRONIC LYMPHOCYTIC-LEUKEMIA - CORRELATION OF RESPONSE AND SURVIVAL

Chronic lymphocytic leukemia (CLL) is considered to be an incurable he matologic malignancy using conventional therapy. Complete remissions ( CR) were unusual with conventional approaches such as chlorambucil wit h or without prednisone or cyclophosphamide, vincristine, and predniso ne (CVP). Pathologic complete remissions including negative bone marro w biopsies were seldom mentioned in the literature. Two parameter flow cytometry has demonstrated that CLL cells co-express CD5 and pan-B ce ll antigens such as CD19 and CD20. In addition, immunoglobulin gene re arrangement occurs predictably in B-cell CLL and can be used as a furt her marker of completeness of remission. The National Cancer Institute (NCI) has published criteria for complete remission which allow persi stent lymphoid nodules to be present on the bone marrow biopsy and the patient can be considered in complete remission. Our group has consid ered these patients to have a nodular CR (Nod CR) to separate them fro m having a true remission on bone marrow biopsy (CR-bx). Thus bone mar row biopsy criteria, two parameter flow cytometry, and immunoglobulin gene rearrangement are now available for routine clinical application to re-define completeness of remission in CLL. With the use of fludara bine monophosphate (Fludara), complete and partial responses are obtai ned in 50-55% of previously treated patients with CLL and 75-80% of pa tients with previously untreated CLL. There was a strong correlation o f probability of response with degree of previous therapy, stage of di sease, age, hemoglobin level, platelet count, serum albumin and beta 2 -microglobulin, and bone marrow infiltration with lymphocytes. Patient s can be identified as being at high/low risk of achieving a complete or partial response. Analysis of previously untreated patients with CL L demonstrates that patients who achieve a true CR/CR-bx have a 90% ch ance of five-year survival versus 75% for those with a CR-Nod. Relativ ely few partial responders were available for comparison. There is a s ignificantly longer survival for CR-bx and Nod-CRs than in the previou sly treated group. However, in previously treated patients with CLL th ere is no difference in survival according to whether the patient had a CR-bx, Nod-CR, or PR using NCI criteria. Studies of two parameter fl ow cytometry demonstrate that there is a much longer time-to-progressi on for patients who have <5% CD5+, CD19+ co-expressing cells in their bone marrow aspirate. Patients with persistent nodules have a longer t ime-to-progression than those with interstitial aggregates. Those who have true pathologic bone marrow biopsy CRs have a longer time-to-prog ression. However, this does not translate into a survival advantage. N ew methods are available to quantitate the degree of cytoreduction whi ch is achieved in CLL with therapy. These measures of minimal residual disease will be useful in planning an analysis of clinical trials for autologous bone marrow transplantation and maintenance programs in CL L.