Preemptive Interferon-α Therapy Could Protect Against Relapse and Improve Survival of Acute Myeloid Leukemia Patients After Allogeneic Hematopoietic Stem Cell Transplantation: Long-Term Results of Two Registry Studies

Abstract

For allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, preemptive interferon-α (IFN-α) therapy is considered as a useful method to eliminate the minimal residual disease (MRD). Our purpose is to assess the long-term efficacy of preemptive IFN-α therapy in acute myeloid leukemia (AML) patients following allo-HSCT based on two registry studies (#NCT02185261 and #NCT02027064). We would present the final data and unpublished results of long-term clinical outcomes with extended follow-up. We adopted polymerase chain reaction (PCR) and multiparameter flow cytometry (MFC) to monitor MRD, and a positive result of bone marrow specimen examined by either of them would be identified as the MRD-positive status. Subcutaneous injections of recombinant human IFN-α-2b were performed for 6 cycles, and prolonged IFN-α therapy could be permitted at the request of patients. The median cycles were 3.5 (range, 0.5-30.5) cycles. A total of 9 patients suffered from grade ≥3 toxicities (i.e., infectious: n = 6; hematologic: n = 3). The 6-year cumulative incidences of relapse and non-relapse mortality following IFN-α therapy were 13.0% (95% confidence interval [CI], 5.4-20.6%) and 3.9% (95%CI, 0.0-17.6%), respectively. The probability of disease-free survival at 6 years following IFN-α therapy was 83.1% (95%CI, 75.2-91.9%). The probability of overall survival at 6 years following IFN-α therapy was 88.3% (95%CI, 81.4-95.8%). The cumulative incidences of total chronic graft-versus-host disease (cGVHD) and severe cGVHD at 6 years following IFN-α therapy were 66.2% (95%CI, 55.5-77.0%) and 10.4% (95%CI, 3.6-17.2%), respectively. Multivariable analysis showed that an alternative donor was associated with a lower risk of relapse and the better disease-free survival. Thus, preemptive IFN-α therapy could clear MRD persistently, prevent relapse truly, and improve long-term survival in AML patients following allo-HSCT.

Keywords: acute myeloid leukemia; hematopoietic stem cell transplantation; interferon-α; minimal residual disease; preemptive.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Shen, Zhang, Xu, Wang, Yan, Chen, Chen, Han, Wang, Wang, Zhao, Qin, Chang, Liu, Huang and Mo.

Figures

Figure 1

Diagram of enrolled patients. Among the 53 patients with MRDsin+ who did not agree to receive any interventions, 22 of them reduced immunosuppression after the MRDsin+ diagnosis, but only 2 of them showed MRD clearings when the tests were repeated 2 weeks after the first positive results were obtained. Four patients showed MRD negative without any interventions. (MRDsin+ group, n=46; MRDco+ group: IFN-α n = 31, Chemo-DLI n = 31).

Figure 2

Using cyclosporine A in MRD-positive patients who received preemptive IFN-α therapy after allo-HSCT.

Figure 3

Response. Swimmer plot displaying all patients who received preemptive IFN-α therapy after allo-HSCT.

Figure 4

Cumulative incidence of (A) relapse, (B) non-relapse mortality, (C) disease-free survival, and (D) overall survival at 6 years after preemptive IFN-α therapy in the low- and high-level MRD groups.