Many patients with
chronic lymphocytic leukemia (CLL) achieve remission
after treatment with
fludarabine chemotherapy. Most of these patients, however, later experience relapse. In addition, immunologic deficits may persist even in patients
in complete remission;
lymphopenia, predominantly involving the CD4 population, is universal after
fludarabine therapy. We used recombinant
alpha interferon (IFN-alpha) maintenance
therapy in patients with CLL who achieved remission in response to
fludarabine therapy to determine its effect on residual disease, assessed by either bone marrow biopsy or flow cytometry, and on immune restoration. Thirty-one patients were treated with IFN-alpha (3 x 10(6) U by
subcutaneous injection three times weekly). Twenty-two patients (71%) were
in complete remission (CR) and nine (29%) were in partial remission (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 52%. Only one patient in PR achieved a CR on IFN-alpha
therapy: the only patient who had had no prior
fludarabine but had been treated with
chlorambucil and
prednisone. All patients in CR with
minimal residual disease 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 tests while on IFN-alpha. The time to progression was no different in patients treated with IFN-alpha than in a historical control group of patients who had received no further
therapy after
fludarabine. In summary, the use of IFN-alpha maintenance did not eradicate residual disease, restore immune function, or prolong remissions in patients with CLL responsive to
fludarabine.