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

Objectives: To evaluate the frequency and the course of complete cytogenetic responses in interferon-alpha (IFN-α)-treated patients with chronic myelogenous leukemia. Design: Two prospective trials...

Interferon-Alpha Produces Sustained Cytogenetic Responses in Chronic Myelogenous Leukemia

Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell 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

Treatment of chronic myelogenous leukemia with interferon alfa-2c: response rate and toxicity in a phase II multicenter study. The Austrian Biological Response Modifier (BRM) Study Group.

AIM--To examine lymphocyte subsets in patients with myelodysplastic syndromes (MDS); and to correlate immunohistological variables with prognosis. METHODS--Bone marrow trephine biopsy specimens from 65 patients with MDS were immunophenotyped using a panel of antibodies. A minimum of 1000 cells from representative areas of marrow sections were counted at light microscopy. The association between immunohistological variables and prognosis was assessed. RESULTS--Compared with normal control marrows (n = 23) no major abnormalities of T cells (CD3), T cell subsets (CD4, CD8, CD25, TCR gamma/delta) or natural killer cells (CD56, CD57) were seen in the 65 patients. In high risk MDS (RAEB, RAEB-t) 19% of the cases showed increased numbers of B lymphocytes compared with none in the low risk group (RA, RARS) (p < 0.0090). Only percentages of B cells above 3% significantly correlated with poor survival (p = 0.0121 for CD19, p = 0.046 for CD22). CONCLUSIONS--The deviations in T lymphocyte counts seen in peripheral blood and in bone marrow aspirates could not be verified in bone marrow biopsy specimens.

https://jcp.bmj.com/content/jclinpath/47/6/505.full.pdf

Bone marrow lymphocyte subsets in myelodysplastic syndromes.

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

Treatment of 11 patients with chronic myelogenous leukemia with interferon-alpha-2C and low-dose cytosine arabinoside.

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Treatment of chronic myelogenous leukemia with interferon alfa-2c: response rate and toxicity in a phase II multicenter study. The Austrian Biological Response Modifier (BRM) Study Group.

Bone marrow lymphocyte subsets in myelodysplastic syndromes.

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

Treatment of 11 patients with chronic myelogenous leukemia with interferon-alpha-2C and low-dose cytosine arabinoside.