Alpha-interferon improves survival and remission duration in P-190(BCR-ABL) positive adult acute lymphoblastic leukemia

Treatment of P190(BCR-ABL+) acute lymphoblastic leukemia (ALL) patients remains problematic: one possibility is to use biologic response modifiers such as A-interferon (A-IFN), which is known to be active in chronic myeloid leukemia (CML). We used (A-IFN to treat 10 adult P190(BCR-ABL+) ALL patients (eight newly diagnosed; two in first relapse). All received a remission induction chemotherapy (modified L-20 protocol). Patients achieving morphological, immunological and cytogenetic complete remission (CR) were then submitted to a rotational consolidation regimen lasting 6 months. When no HLA-identical donor was available, patients aged <55 years underwent stem cell harvest followed by autologous transplantation; patients aged ≥ 55 years received standard maintenance treatment for 6 months. In the second year, maintenance treatment (all ages) was based on cycles of A-IFN (3 MU three times a week for 6 weeks) alternated with methotrexate/6-mercaptopurine continuously for up to 2 years from first demonstration of CR. Thereafter, patients maintaining CR had the same schedule of A-IFN (6 weeks on, 6 off). Eight patients (6/6 first diagnosis, 2/2 relapsed) obtained morphological, immunological and cytogenetic CR with persistent molecular positivity. Two with an HLA-identical donor had allogeneic bone marrow transplantation. Six proceeded with chemotherapy: one experienced early relapse, three were autotransplanted, and two received maintenance. Five patients then received A-IFN as scheduled. All five are in continuous morphological and cytogenetic CR, with a longer mean duration of maintained morphological CR (mean 46 months; range: 20-88) than in previous reports of Ph+ ALL patients treated with chemotherapy regimens (excluding allogeneic BMT). A-IFN thus appears effective in this poor-risk subset of patients. This well-tolerated IFN-containing maintenance treatment could be considered to reinforce intensified programs based on autologous stem cell transplantation as an alternative to allogeneic transplantation in P190(BCR-ABL+) ALL patients (and by extension for Ph+ ALL patients) lacking an HLA-matched donor.