NEUTRALIZING ANTI-INTERFERON-ALPHA ANTIBODIES AND RESPONSE TO TREATMENT IN PATIENTS WITH PH(-LEUKEMIA SEQUENTIALLY TREATED WITH RECOMBINANT(ALPHA-2A) AND LYMPHOBLASTOID INTERFERON-ALPHA() CHRONIC MYELOID)

Neutralizing anti-IFN alpha antibodies (nIFN alpha Abs) occur in a sig nificant proportion of patients with hairy cell leukaemia, hepatitis o r solid tumours treated with recombinant IFN alpha (IFN alpha 2a or IF N alpha 2b), but information on their incidence in chronic myeloid leu kaemia (CML) is scanty and their clinical relevance is not yet complet ely defined. By using an IFN alpha antiviral neutralization bioassay, the frequency of nIFN alpha 2a Abs was evaluated in 67 Ph(+) CML patie nts during IFN alpha 2a therapy at doses ranging from 6 to 9MU/d. 15 p atients (22%) developed nIFN alpha 2a Abs (titre ranging from 1:40 to 1:20480) and 11/15 (73%) were haematologically and/or karyotypically u nresponsive to treatment. 52 patients did not develop antibodies and 1 1 of them (21%) were unresponsive. The negative relationship between t he positivity for nIFN alpha 2a Abs and the response to treatment was highly significant (P=00001). In nine nIFN alpha 2a Abs positive patie nts, treatment was changed from recombinant IFN alpha 2a to lymphoblas toid IFN alpha (IFN alpha-ly), at the same dose and schedule. After 9 months of IFN alpha-ly treatment a haematological response was achieve d in 4/7 cases who were non-responsive to prior IFN alpha 2a therapy a nd was maintained in the other two patients previously responsive to I FN alpha 2a. However, no karyotypic response was observed, This data s hows that a significant proportion of Ph(+) CML patients receiving tre atment with IFN alpha 2a can develop neutralizing antibodies and that these antibodies are associated with a loss of IFN alpha 2a efficacy. Changing the patients to treatment with lymphoblastoid IFN alpha may r estore haematological response but it is not likely to induce a karyot ypic response.