Low-Dose Recombinant Alfa-2a-lnterferon: A Feasible Maintenance Therapy in Acute Myeloid Leukaemia in the Older Patient

McSweeney, E.N.; Worman, C. P.; Tsakona, C. P.; Jewel, AP; Av, Hoffbrand; Milligan, DW; Burnett, AK; Lewis, Melissa; Goldstone, A. H.

doi:10.1159/000204473

Cited by 8 publications

(3 citation statements)

References 6 publications

(8 reference statements)

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“…For these patients, further study is necessary on which preemptive interventions might be reasonable alternatives. Some studies observed that IFN-α may be a feasible maintenance therapy for patients with acute myeloid leukemia [4]. In addition, some studies reported that IFN-α exerts a relatively strong immunomodulatory effect and can kill acute myeloid leukemia cells by regulating T cell and natural killer cell functions [5,6].…”

Section: Introductionmentioning

confidence: 99%

IFN-α Is Effective for Treatment of Minimal Residual Disease in Patients with Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: Results of a Registry Study

Zhang

et al. 2017

Biology of Blood and Marrow Transplantation

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The efficacy of minimal residual disease (MRD)-directed IFN-α treatment was investigated in acute leukemia patients who were positive for MRD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n = 107). MRD-positive status was defined as positivity for leukemia-associated aberrant immune phenotypes or positivity for Wilms' tumor gene 1 in a single bone marrow sample. Recombinant human IFN-α-2b injections were administered subcutaneously 2 to 3 times per week for 6 months. The 2-year cumulative incidence of severe acute and chronic graft-versus-host disease after IFN-α treatment was 5.7% and 6.6%, respectively. Eighty-one patients (75.7%) turned MRD-negative after IFN-α treatment 1 month (42; 39.3%), 2 months (6; 5.6%), 3 months (7; 6.5%), and >3 months (26; 24.3%) after MRD-directed IFN-α treatment. Twelve patients showed relapse after IFN-α treatment, and 7 died of relapse. Four patients died of nonrelapse mortality (NRM). The 2-year cumulative incidence of relapse, relapse mortality, and NRM after IFN-α treatment was 11.5%, 6.8%, and 4.3%, respectively. The 2-year probabilities of event-free survival, disease-free survival, and overall survival after IFN-α treatment were 66.5%, 82.4%, and 87.4%, respectively. Persistent MRD after IFN-α treatment was significantly associated with higher relapse risk and poorer survival. Thus, MRD-directed IFN-α treatment is effective for patients who were MRD-positive after allo-HSCT. The study was registered at http://clinicaltrials.gov as NCT02185261.

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Section: Introductionmentioning

confidence: 99%

IFN-α Is Effective for Treatment of Minimal Residual Disease in Patients with Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: Results of a Registry Study

Zhang

et al. 2017

Biology of Blood and Marrow Transplantation

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“…For these patients, further study is necessary on what other preemptive interventions might be reasonable. Some studies observed that interferon‐alpha (IFN‐α) may be a feasible maintenance therapy for AML patients , and could exert a relatively strong immunomodulatory effect . In addition, Singhal et al , Gesundheit et al , and Tang et al reported that IFN‐α could induce a graft‐versus‐leukemia effect in patients with acute leukemia, and that patients who had relapsed after allo‐HSCT achieved complete remission (CR) on this treatment.…”

Section: Introductionmentioning

confidence: 99%

Interferon-α Is Effective for Treatment of Minimal Residual Disease in Patients with t(8;21) Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation: Results of a Prospective Registry Study

Wang

Zhang

et al. 2018

The Oncologist

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In patients with t(8;21) acute myeloid leukemia (AML), the presence of post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) minimal residual disease (MRD), measured by transcript levels, has been established as a powerful marker for predicting relapse. Interferon-alpha (IFN-α) could exert a relatively strong graft-versus-leukemia effect, and MRD-directed IFN-α treatment is effective for patients with t(8;21) AML who were MRD-positive after allo-HSCT.

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“…Interferon (IFN) was used as early as the 1960s for AML treatment and showed some effects in both remission induction and salvage treatment for relapse after HSCT [2][3][4]. Our previous clinical observations found that the combination of thalidomide and IFN had certain effects for the treatment of relapsed or refractory AML [5].…”

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confidence: 99%

Effects of Thalidomide Combined with Interferon on Inhibiting Kasumi-1 Cell Proliferation

Fan

et al. 2016

Adv Clin Exp Med

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with CR will relapse, with a long-term survival of less than 10%. In addition, treatment-related side effects are among the main factors limiting the clinical efficacy for AML treatment. It is of great practical significance to explore safe and effective new treatment options. Steins et al. [1] reported that the effective rate of thalidomide monotherapy in AML was 25% and that this treatment could improve transfusion dependence in patients.With improvements in treatment, the complete remission (CR) rate of young patients with acute myeloid leukemia (AML) can be as high as 70% to 80%, and after subsequent consolidation chemotherapy or hematopoietic stem cell transplantation (HSCT), the 5-year overall survival (OS) rate is approximately 40% to 45%. However, the treatment effect is poor in high-risk and el- Objectives. The aim of this study was to investigate the effects and its mechanism of thalidomide and IFN on inhibiting the proliferation of Kasumi-1 cells. Material and Methods. Thalidomide, IFN and a combination of both drugs were used to treat Kasumi-1 cells. The inhibition of cell proliferation and the apoptosis rate were measured. Vascular endothelial growth factor levels and the expression of apoptosis-related proteins were detected by ELISA and Western blotting, respectively. Results. Thalidomide and IFN could both inhibit Kasumi-1 cell proliferation in a dose-dependent manner. When Kasumi-1 cells were treated with thalidomide 350 μg/mL or IFN1400 U/mL for 48 h, the proliferation inhibition rates were (48.8 ± 4.64)% and (50.19 ± 2.59)% and the rates of apoptosis were (14.68 ± 2.61)% and (21.71 ± 0.71)%, respectively; when treated with a combination, the cell proliferation inhibition rate and apoptotic rate were statistically significantly higher than both the control group and the groups treated with a single drug. The ELISA assay revealed that both 350 μg/mL of thalidomide and 1400 U/mL of IFN could reduce the VEGF levels in cell culture supernatants; the two-drug combination group had a further decreased VEGF concentration. Forty-eighthour treatment of thalidomide 350 μg/mL and IFN 1400 U/mL could significantly decrease Bcl-2 expression and increase the expression levels of phosphor-P38, BAX, cytochrome c, and cleaved caspase-3, -8, and -9 as compared to the control group. The combination group exhibited significantly greater extents of reduction in Bcl-2 protein and increases in p-P38, BAX, and cytochrome c, and cleaved caspase-3, -8, and -9 protein expression as compared to the single drug groups. Conclusions. Thalidomide and IFN can synergistically inhibit Kasumi-1 cell proliferation, which is possibly achieved through the mitochondrial and death receptor pathways and through the activation of the P38 signaling pathway to induce apoptosis and by inhibiting Kasumi-1 cell autocrine VEGF secretion (Adv Clin Exp Med 2016, 25, 3, 403-408).

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Low-Dose Recombinant Alfa-2a-lnterferon: A Feasible Maintenance Therapy in Acute Myeloid Leukaemia in the Older Patient

Cited by 8 publications

References 6 publications

IFN-α Is Effective for Treatment of Minimal Residual Disease in Patients with Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: Results of a Registry Study

IFN-α Is Effective for Treatment of Minimal Residual Disease in Patients with Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: Results of a Registry Study

Interferon-α Is Effective for Treatment of Minimal Residual Disease in Patients with t(8;21) Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation: Results of a Prospective Registry Study

Effects of Thalidomide Combined with Interferon on Inhibiting Kasumi-1 Cell Proliferation

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