INTERFERON MAINTENANCE THERAPY FOR PATIENTS WITH CHRONIC LYMPHOCYTIC-LEUKEMIA IN REMISSION AFTER FLUDARABINE THERAPY

Many patients with chronic lymphocytic leukemia (CLL) achieve remissio n after treatment with fludarabine chemotherapy. Most of these patient s, however, later experience relapse. In addition, immunologic deficit s may persist even in patients in complete remission; lymphopenia, pre dominantly involving the CD4 population, is universal after fludarabin e therapy, We used recombinant alpha interferon (IFN-alpha) maintenanc e therapy in patients with CLL who achieved remission in response to f ludarabine therapy to determine its effect on residual disease, assess ed by either bone marrow biopsy or flow cytometry, and on immune resto ration. Thirty-one patients were treated with IFN-alpha (3 x 10(6) U b y subcutaneous injection three times weekly). Twenty-two patients (71% ) were in complete remission (CR) and nine (29%) were in partial remis sion (PR). Of the 22 patients in CR, 21 (95%) had evidence of residual disease at the start of IFN-alpha therapy. Low CD4 levels were noted in 93% of patients, low IgG levels in 45%, and anergy or hypoergy in 5 2%. Only one patient in PR achieved a CR on IFN-alpha therapy: the onl y patient who had had no prior fludarabine but had been treated with c hlorambucil and prednisone. All patients in OR with minimal residual d isease had persistent disease after IFN-alpha treatment. There were no increases in CD4 counts or IgG levels; three patients with borderline responses to skin testing had an increase in the number of positive t ests while on IFN-alpha. The time to progression was no different in p atients treated with IFN-alpha than in a historical control group of p atients who had received no further therapy after fludarabine. In summ ary, the use of IFN-alpha maintenance did not eradicate residual disea se, restore immune function, or prolong remissions in patients with CL L responsive to fludarabine. (C) 1995 by The American Society of Hemat ology.