Pre-Emptive Therapy with IFN-α-2b for Acute Leukemia Patients with High Risk of Relapsing Tendency Post Allo-HSCT

Abstract

Objective: To determine the efficacy and safety of IFN-α-2b pre-emptive therapy for acute leukemia(AL) patients with relapsing tendencies after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods: Retrospectively analyzed 986 acute leukemia patients undergoing allo-HSCT from Jan ,2006 to Mar ,2014 in our hospital. After allo-HSCT, 986 AL patients were periodically monitored the minimal residual disease(MRD) including: bone marrow smear, leukemia-associated immunophenotype (LAIP), leukemia specific or related fusion genes, and donor chimerism through multi-parameter detection to evaluate disease status. Patients were given IFN- a -2b 3 million units / day by subcutaneous injection for preemptive treatment once a relapse tendency was detected, such as: increasing proportion of blast in bone marrowbetween 3-5%, or MRD>1.0×10-3, or leukemia specific fusion gene transfrom negative to positive, or dynamic incressing copy number of WT1 more than 200 copies/104 abl, or decreasing of donor chimerism(≤ 90%). There were 98 patients who presented increasing tendency of MRD and were enrolled in this study. Among them, 31 patients received IFN-α-2b pre-emptive therapy, and 67 patients received non-IFN-α-2b therapy such as: withdraw immunosupressant, traditional DLI or DC-CIK immunotherapy.Results: There were no significant differences in disease characteristics between two groups. For the 31 patients who received IFN-α-2b pre-emptive therapy(IFN group), the median time of IFN-αtreatment was 60 days (range: 5-720 days), Twenty five patients had responsed to the treatment without progressing to hematological relapse (response rate 80.6%). 2 patients developed to hematological relapse again after temporary response; 3 patients had no response and eventually progressed to hematological relapse. Regarding 67patients who received non-IFN-α-2b therapy(non IFN group), 22 patients responsed to the treatment (RR 32.8%), 45 patients failed to the treatment and progressed to hematological relapse at a median time of 35 (range: 6-940) days, There was significant difference of RR between two group(P=0.000) . 31 patients of IFN group tolerate well and no patient terminated therapy due to side effects. During the treatment of IFN, 18 patients(58.1%) developed GVHD: 6 patients (19.4%) with aGVHD and 14 (45.2%) with limited cGVHD . The median follow-up time was 21 (4.5-78.5) months. 22 of 31 cases of IFN group maintained disease-free survival. The 5-year overall survival rate (OS) and the leukemia-free survival rate (LFS) of IFN group were 47.0%±13.9% and 38.7%±13.1% respectively. However, the 5-yr OS and LFS of non IFN group were 14.5%±10.7% and12.5%±9.4% respectively.The difference were significantly (P=0.000,P=0.002 respectively). Patients with GVHD had significantly better response than patients without GVHD (88.9% vs 53.8%, P=0.043, P <0.05).Conclusion: IFN-α-2b pre-emptive therapy can effectively prevent high-risk patients with relapsing tendencies for disease progression post allo-HSCT. Further large-scale investigation is warranted. DisclosuresNo relevant conflicts of interest to declare.