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

Abstract

Treatment of P190 BCR-ABL+ acute lymphoblastic leukemia (ALL) patients remains problematic: one possibility is to use biologic response modifiers such as ␣-interferon (␣-IFN), which is known to be active in chronic myeloid leukemia (CML). We used ␣-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 Ͻ55 years underwent stem cell harvest followed by autologous transplantation; patients aged у55 years received standard maintenance treatment for 6 months. In the second year, maintenance treatment (all ages) was based on cycles of ␣-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 ␣-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 ␣-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). ␣-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. Leukemia (2000) 14, 22-27.

Long-term molecular complete remission with IFN-α in Ph+ adult acute lymphoid leukemia patients

“…We previously described the ability of interferon-a (IFN-a) plus chemotherapy or autologous SCT (ASCT) to induce molecular complete remission (CR) in Ph þ ALL. 3 We now show that such an approach can lead to sustained molecular remissions, by updating the follow-up of our original report.…”

“…Informed consent had been obtained from all the enrolled patients and the protocol was approved by the local ethical committee. All patients received standard induction chemotherapy (modified L-20) 3,4 consisting of vincristine 2.0 mg m À2 weekly (weeks 1-5); 6-methylprednisolone 60 mg m À2 day À1 (days 1-32); cyclophosphamide 1000 mg m À2 (day 4) and 800 mg m À2 (day 32); and adriamycin 30 mg m À2 (days 15-18 and day 32). Prophylactic central nervous system treatment was performed weekly, introducing the following drugs: dexamethasone 4 mg; cytosine-arabinoside 40 mg; and methotrexate 10 mg.…”

Efficacy of dasatinib in conjunction with α-interferon for the treatment of imatinib-resistant and dasatinib-resistant Ph+ acute lymphoblastic leukemia

“…Notably, in particular, the addition of a-IFN was shown to be effective in patients with sub-optimal response to imatinib, 3,6 or even possibly curative in Ph þ ALL patients receiving CHT and ASCT. 4,8 In conclusion, although new regimens combining different TKIs or TKIs and other agents are under evaluation, we think that the association of dasatinib and a-IFN might be reasonable for patients with sub-optimal response to dasatinib and not suitable for other approaches.…”

“…ASCT was followed by maintenance treatment based on cycles of subcutaneous a-IFN (Roferon-a; Roche, Basel, Switzerland) 3 MU, three times a week for 6 weeks, alternated with metothrexate and 6-mercaptopurine every 6 weeks, continuously administered for 1 year, as described elsewhere. 4 Afterwards, the patient was treated with a-IFN alone with the same schedule (6 weeks on, 6 weeks off) without interruption until morphological CR was maintained. 4 In March 2000, a second hematological relapse was documented.…”

“…4 Afterwards, the patient was treated with a-IFN alone with the same schedule (6 weeks on, 6 weeks off) without interruption until morphological CR was maintained. 4 In March 2000, a second hematological relapse was documented. The patient was then enrolled in an international phase II study and treated with imatinib mesylate (formerly STI571; Novartis Pharma, Basel, Switzerland) at a daily dose of 600 mg, 5 obtaining the third hematological CR (April 2000), with persistence, however, of detectable BCR-ABL1 transcripts on bone marrow sample.…”