Interferon Alpha Alone Is Able to Cure Chronic Myeloid Leukemia In a Small Subset of Patients Despite the Persistence of Leukemic Cells: Experience of Long Follow up After Treatment Discontinuation

Abstract 2299

Before the imatinib era and besides allogeneic hematopoietic stem cell transplantation (HSCT), interferon alpha (IFN) was an alternative therapeutic option to treat chronic myeloid leukemia (CML). In very rare situations, some patients achieved a complete molecular remission (CMR) defined as the absence of detectable BCR-ABL transcript using qualitative PCR available at that time.We previously reported the outcome of patients with CML in complete cytogenetic remission after cessation of IFN (J Clin Oncol., 2002, 20:214-220.). Here, we update this experience with a long outcome after discontinuation of IFN. The main criteria for IFN discontinuation was the achievement of a sustained CMR lasting for at least two years. Twenty-one patients (9 males, 12 females; median age 39 years) were eligible for this study. One, 2 and 18 pts belonged to respectively high, intermediate and low risk group according to the Sokal score.All patients were treated with IFN (median dose 56ui/week) during a median time of 7.5 years (2.4-14) and 4 of them received an autologous HSCT. The median time to achieve CMR was 54 month (5-140). The median follow up after discontinuation of IFN treatment was 8 years (mean 9, range 5–18). Quantitative PCR was used to quantify BCR-ABL and evaluate residual disease. We distinguished two groups of patient according to the molecular pattern: group 1 (n=12) regards patients with sustained CMR confirmed by quantitative PCR. One patient belonging to this group relapsed and progressed suddenly after 5 years of IFN discontinuation and was treated with allogeneic HSCT. Group 2 (n=9) regards patients who are not in CMR with leukemic cells detectable by RQ-PCR. Six of them exhibit a fluctuation of BCR-ABL detection assessed by RQ-PCR. For the 3 other patients with a median follow up of 6 years after discontinuation, RQ-PCR became clearly positive after a median time of 2 years with a level of residual disease that corresponds to the definition of major molecular response (3 log reduction of BCR-ABL). No progression was observed in this group.

So we conclude that the persistence of leukemic cells at low level after discontinuation of IFN treatment does not automatically lead to CML relapse. This long term follow up after IFN discontinuation raises the question of the need of a complete eradication of residual leukemic cells to cure the disease