Interferon Alfa Versus Interferon Alfa Plus Cytarabine Combination Therapy for Chronic Myeloid Leukemia: A Meta-Analysis of Randomized Controlled Trials

Objective

This article compares the effect of interferon alfa plus cytarabine (IFN-alfa + Ara-C) versus IFN-alfa alone on the chronic phase of chronic myelogenous leukemia.

Methods

Electronic searches were performed in the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Chinese Biomedical Database, China Journal Full-text Database, and Chinese Scientific Journals Database. The languages were limited to Chinese and English. Randomized controlled trials were selected by 2 investigators. Analyses were performed using RevMan 5.0 software.

Results

A total of 3139 patients in 4 studies met the inclusion criteria. In those patients, complete hematologic response and cytogenetic responses showed significant improvements in favor of IFN-alfa + Ara-C, with complete hematologic response relative risk (RR) of 1.15 (95% CI, 1.09–1.21), complete cytogenetic response RR of 1.87 (95% CI, 1.47–2.38), partial cytogenetic response RR of 1.48 (95% CI, 1.25–1.75), and major cytogenetic response RR of 1.61 (95% CI, 1.42–1.83), respectively. The overall 3-year survival rate in the IFN-alfa + Ara-C group was 86% compared with 79% in the IFN-alfa group (RR = 1.09; 95% CI, 1.03–1.14). In the other 2 studies, 5-year overall survival was 69% compared with 63%, respectively (RR = 1.08; 95% CI, 1.01–1.15). However, IFN-alfa and Ara-C involved higher risk of hematologic toxicity, gastrointestinal adverse events, and severe mucositis compared with IFN-alfa monotherapy (RR = 2.63 [95% CI, 1.94–3.56); RR = 3.38 [95% CI, 2.28–5.00], and RR = 8.84 [95% CI, 3.82–20.46], respectively). Weight loss and skin rash were also observed more frequently in the combination treatment group (RR = 2.00 [95% CI, 1.47–2.73) and RR = 3.75 [95% CI, 2.13–6.59], respectively).

Conclusions

In patients with chronic myelogenous leukemia in the chronic phase, the combination of IFN-alfa + Ara-C demonstrated improved complete hematologic response, superior cytogenetic responses, and higher rates of 3- and 5-year survival than IFN-alfa alone. However, combination therapy is more likely to cause serious adverse effects. Well-designed studies will be required to determine the outcomes and adverse effects of the 2 drugs as treatment for patients with chronic myelogenous leukemia who cannot afford molecularly targeted drugs.