Preemptive interferon-α therapy could prevent relapse of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation: A real-world analysis

Abstract

IntroductionMeasurable residual disease (MRD)-directed interferon-a treatment (i.e. preemptive IFN-α treatment) can eliminate the MRD in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, this study aimed to further assess its efficacy in a multicenter retrospective study in a real-world setting.MethodsA total of 247 patientswho received preemptive IFN-α treatment were recruited from 4 hospitals in China. The protocols for MRD monitoring mainly based on quantitative polymerase chain reaction [qPCR] and multiparameter flow cytometry [MFC]. ResultsThe median duration of IFN-α treatment was 56 days (range, 1–1211 days). The cumulative incidences of all grades acute graft-versus-host disease (aGVHD), all grades chronic graft-versus-host disease (cGVHD), and severe cGVHD at 3 years after IFN-α therapy were 2.0% (95% confidence interval [CI], 0.3–3.8%), 53.2% (95% CI, 46.8–59.7%), and 6.2% (95% CI, 3.1–9.2%), respectively. The cumulative incidence of achieving MRD negative state at 2 years after IFN-α treatment was 78.2% (95% CI, 72.6–83.7%). The 3-year cumulative incidences of relapse and non-relapse mortality following IFN-α therapy were 20.9% (95% CI, 15.5–26.3%) and 4.9% (95%CI, 2.0–7.7%), respectively. The probabilities of leukemia-free survival and overall survival at 3 years following IFN-α therapy were 76.9% (95% CI, 71.5–82.7%) and 84.2% (95% CI, 78.7–90.1%), respectively. Multivariable analysis showed that MRD positive state by qPCR and MFC before IFN-α treatment, high-risk disease risk index before allo-HSCT, and receiving identical sibling donor HSCT were associated with a higher risk of relapse and a poorer leukemia-free survival. Severe cGVHD was associated with an increased risk of non-relapse mortality. DiscussionThus, real-world data suggest that preemptive IFN-α is effective for treating patients with AML with MRD after allo-HSCT.

Outcomes of haploidentical haematopoietic stem cell transplantation for adolescent and young adults with acute myeloid leukaemia

“…41 These were also conducted in accordance with the Chinese expert consensus on prevention of the leukaemia relapse after allo-HSCT. 42 Our previous studies suggested that the probability of MRD achieving negative and LFS after IFN-α treatment was 75.0%-76.9% 31,41 and 76.9%-83.1%, 30,31 which was 72.7%-75.0% 29,43 and 49.1%-58.9% 29,43 after DLI. In this study, although AYAs showed a higher incidence of MRD occurrence compared with older adults which may be due to the relatively higher rate of beyond CR2 status before HSCT, the efficacy of pre-emptive immunotherapy (particularly the IFN-α treatment) was satisfactory for AYAs.…”

“…MRD after HID HSCT was detectable by multiparameter flow cytometry (Supplementary Method) 28 . For patient who showed MRD occurrence after HID HSCT, they could receive pre‐emptive immunotherapy including donor lymphocyte infusion (DLI) 29 or interferon‐α treatment (Supplementary Method) 30,31 …”

“…28 For patient who showed MRD occurrence after HID HSCT, they could receive pre-emptive immunotherapy including donor lymphocyte infusion (DLI) 29 or interferon-α treatment (Supplementary Method). 30,31 Definition AML risk category was assessed by the European Leukemia Net (ELN) genetic risk. 32 GVHD was diagnosed according to international criteria.…”

Leukemic transformation during anti-tuberculosis treatment in aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome: A case report and review of literature

“…If patients survive prolonged hematopoietic suppression, they may experience deep remission, a longer remission duration and a lower probability of relapse[ 69 , 70 ]. Recombinant IFN-α[ 71 , 72 ], immune checkpoint inhibitors[ 73 , 74 ] and BCG vaccination[ 75 , 76 ] have been successfully used in the treatment of hematological malignancies, and the major adverse event is hematological toxicity. Much evidence supports the hypothesis that inflammatory stressors, induced either by infectious episodes or administration of immune-activating agents, can strengthen antileukemic activities.…”

Delivery of Interferon β-Encoding Plasmid via Lipid Nanoparticle Restores Interferon β Expression to Enhance Antitumor Immunity in Colon Cancer

“…However, this effect is cellular context-dependent . Emerging clinical and experimental data from both human patients and tumor-bearing mice show that tumor cells, endothelial cells, and tumor resident immune cell intrinsic and extrinsic IFN-I signaling pathway play a critical role in tumor suppression. − IFN-I exerts its tumor suppression function through regulating the expression of genes for the cellular death pathways and immunogenicity in tumor cells. ,− IFN-I also modulates host antitumor immune response through regulating immune cell differentiation, polarization and activation. ,,− Consistent with the critical roles of IFN-I in regulation of tumor response to host immune cell antitumor immune response, loss of function in the IFN signaling pathway has been associated with clinical resistance to immune checkpoint inhibitor (ICI) immunotherapy in human cancer patients. − Tumor cells may use programmed death-ligand 1 (PD-L1) to activate the programmed cell death protein 1 (PD-1)-Src homology domain 2 containing tyrosine phosphatase (SHP2) immune suppressive pathway to repress IFN-I expression to impair cytotoxic T lymphocytes (CTLs) tumor infiltration and function, resulting in tumor immune evasion and progression . Restoring IFN-I expression and production in the tumor microenvironment therefore represents an effective approach in reversing immune suppression and enhancing CTLs tumor infiltration and function to repress tumor progression.…”