Alpha-interferon improves survival and remission duration in P-190BCR-ABL positive adult acute lymphoblastic leukemia.
Treatment of P190BCR-ABL+ acute lymphoblastic leukemia (ALL) patients remains problematic: one possibility is to use biologic response modifiers such as alpha-interferon (alpha-IFN), which is known to be active in chronic myeloid leukemia (CML). We used alpha-IFN to treat 10 adult P190BCR-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 alpha-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 alpha-IFN (6 weeks on, 6 off). Eight patients (6/8 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 alpha-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). alpha-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 P190BCR-ABL+ ALL patients (and by extension for Ph+ ALL patients) lacking an HLA-matched donor. Leukemia (2000) 14, 22-27.
Visani
G
G
Institute of Hematology and Medical Oncology 'Seragnoli', University of Bologna, Bologna, Italy.
Martinelli
G
G
Piccaluga
P
P
Tosi
P
P
Amabile
M
M
Pastano
R
R
Cavo
M
M
Isidori
A
A
Tura
S
S
D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome
D016898:Interferon-alpha; D016044:Fusion Proteins, bcr-abl