BACKGROUND:
Interferon alfa is a conservative and widely used alternative to bone marrow transplantation in treatment of patients with early chronic myeloid leukemia (CML). A meta-analysis was conducted to develop a reliable prognostic scoring system for estimation of survival of patients with CML treated with interferon alfa.

METHODS:
Patients treated in prospective studies, including major randomized trials, were separated into learning and validation samples. Cox regression analysis and the minimum P-value approach were used to identify prognostic factors for patient survival and to discover groups in the learning sample with the greatest differences in survival. These findings were then validated by applying the new scoring system to patients in the validation sample.

RESULTS:
We collected data on 1573 patients who were participants in 14 studies involving 12 institutions; 1303 patients (learning sample, n = 981; validation sample, n = 322) were eligible for inclusion in this analysis, and their median survival time was 69 months (range, 1-117 months). Because two previously described prognostic scoring systems failed to discriminate risk groups satisfactorily, we developed a new scoring system that utilizes the following covariates: age, spleen size, blast count, platelet count, eosinophil count, and basophil count. Among 908 patients with complete data in the learning sample, three distinct risk groups were identified (median survival times of 98 months [n = 369; 40.6%], 65 months [n = 406; 44.7%], or 42 months [n = 133;14.6%]; two-sided logrank test, P< or =.0001). The ability of the new scoring system to discriminate these risk groups was confirmed by analysis of 285 patients with complete data in the validation sample (two-sided logrank test, P = .0002).

CONCLUSIONS:
A new prognostic scoring system for estimating survival of patients with CML treated with interferon alfa has been developed and validated through use of a large dataset.

A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group.

An evidence-based analysis of the effect of busulfan, hydroxyurea, interferon, and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukemia: Developed for the American Society of Hematology

https://www.gastrojournal.org/article/0016-5085(87)90327-1/pdf

Effects of renal impairment on liver transplantation.

Treatment for chronic myeloid leukemia (CML) has evolved from chemotherapy (busulfan, hydroxyurea) to interferon-α (IFNα), and finally to tyrosine kinase inhibitors such as imatinib. Although imatinib has profoundly improved outcomes for patients with CML, it has limitations. Most significantly, imatinib cannot eradicate CML primitive progenitors, which likely accounts for the high relapse rate when imatinib is discontinued. IFNα, unlike imatinib, preferentially targets CML stem cells. Early studies with IFNα in CML demonstrated its ability to induce cytogenetic remission. Moreover, a small percentage of patients treated with IFNα were able to sustain durable remissions after discontinuing therapy and were probably cured. The mechanisms by which IFNα exerts its antitumor activity in CML are not well understood; however, activation of leukemia-specific immunity may have a role. Some clinical studies have demonstrated that the combination of imatinib and IFNα is superior to either therapy alone, perhaps because of their different mechanisms of action. Nonetheless, the side effects of IFNα often impede its administration, especially in combination therapy. Here, we review the role of IFNα in CML treatment and the recent developments that have renewed interest in this once standard therapy for patients with CML.

/pdf/re-emergence-of-interferon-a-in-the-treatment-of-chronic-2iqc6s9uch.pdf

Re-emergence of interferon-α in the treatment of chronic myeloid leukemia

Type I interferons (IFNs) exhibit antiproliferative activity and apoptotic effects, and regulate an immune response by activating multiple cells types, including dendritic cells, cytotoxic T cells, and natural killer cells. Most recently, a report in the literature identified dysfunctional induction of a type I IFN response in cancer stem cells--specifically, breast cancer-initiating cells, implicating this defect in progression to breast cancer. Indeed, accumulating evidence suggests that cancer stem cells/cancer-initiating cells are prevalent in leukemias and solid tumors, are resistant to chemotherapy and radiation therapy, and therefore likely contribute to tumor recurrence. IFN-β treatment of human glioma xenografts leads to disruption of the vascular niche of glioma stem cells, in further support of a potential therapeutic effect of IFN treatment in limiting cancer stem cells. The implications are that restoring an IFN response, or enhancing an IFN response, may invoke a reduction, or elimination of both cancer stem cells and tumor cells. In this review, the clinical application of type I IFNs, mainly IFN-αs, will be reviewed.

Interferon: current status and future prospects in cancer therapy.

Treatment of chronic myelogenous leukemia with interferon alfa-2c : response rate and toxicity in a phase II multicenter study

Interferon-alpha for idiopathic myelofibrosis

cell activity in various disease states Human large granular lymphocytes and their relationship to natural killer

In den letzten Jahren wurden aus mehreren klinischen Studien Hinweise erhalten, das sowohl α-, wie auch β-Interferon (α-IFN, β-IFN) gewisse antineoplastische Wirkung besitzen (1). Ob Interferone selbst direkt tumor-cytotoxisch wirken, oder ob der Therapieerfolg durch Aktivierung eines zusatzlichen cellularen Effektormechanismus bedingt ist, ist derzeit Ziel zahlreicher Untersuchungen (2). Die potentielle Wichtigkeit cellularer Effektormechanismen fur die Vermittlung IFN-induzierter Tumorcytotoxizitat wird durch die erst jungst erfolgte Entdeckung einer als naturliche Immunitat bezeichneten Aktivitat von bestimmten Blutlymphocyten unterstrichen (3). Diese Aktivitat ist IFN abhangig und gegen embryonale, virustransformierte und maligne Zellen autologer, allogener und xenogener Natur gerichtet. Ziel der vorliegenden Untersuchung war es zu prufen, inwieweit die Instillation von IFN in maligne Pleuraergusse a) zu klinischen Remissionen dieser Tumormanifestationen fuhrt und b) diese erhofften klinischen Effekte mit einer Aktivierung der naturlichen Immunreaktivitat assoziiert werden konnen.

Führt die Instillation von Interferon in malignen Ergüssen zu einer lokalen Steigerung der natürlichen Killer-Zell (NK) Immunität?

Cyclosporin blood levels do correlate with clinical complications.

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