Background
Hematological malignancies mainly include leukemia, lymphoma, and plasma cell neoplasm. There were about 172,910 new cases of hematological malignancies and 58,300 deaths due to hematological malignancies projected to occur in 2017 in USA [
1]. Great advances have recently been achieved in the therapy for patients with hematologic malignances. However, the overall survival for patients has not been obviously improved. Identification of prognostic factors for hematologic malignancies is very helpful for clinicians to choose therapeutic strategies and for patients to improve their prognosis.
A number of prognostic molecular markers for hematologic malignances have been identified, however, many of these prognostic means are costly, difficult to perform, or not easily interpreted. Therefore, other prognostic models that are inexpensive, widely available, and easily interpreted are urgently needed for clinicians.
Red blood cell distribution width (RDW) is a parameter measured in blood routine test, and is widely used to distinguish between different types of anemia [
2]. As an easy-to-measure marker of the systemic inflammatory response, the RDW has been established as a novel prognostic factor in many pathophysiological conditions, including cardiovascular disease [
3,
4] and inflammation [
5,
6]. Recently, RDW grows to be recognized as an independent prognosis factor in numerous types of cancer, including lung cancer [
7], gastrocolorectal cancer [
8], breast cancer [
9], prostate cancer [
10], as well as in several types of hematologic malignances.
However, due to the variance in the study design and sample size, direct impact of RDW level on hematologic malignances patients’ survival remains inconclusive. In this study, we searched PubMed (Medline), OVID (Embase), and ISI Web of Science databases for relevant studies and performed a meta-analysis in order to assess the correlation between RDW and the survival outcomes in patients with hematologic malignances.
Discussion
Cancer associated inflammation is recognized as a hallmark feature of tumor development and progression. Previous studies have reported the association between RDW and the clinical outcome of solid tumor. Recently, numerous studies have provided evidence on the correlation between elevated RDW and poor prognosis in hematologic malignances, including chronic lymphocytic leukemia (CLL) [
15], chronic myeloid leukemia (CML) [
16], DLBCL [
17,
18], NK/T lymphoma [
19], as well as multiple myeloma [
20‐
22].
However, these results are not comparable, because of the heterogeneous designs and patient population, and the diversity in cut-off value defining “elevated RDW”. Our study is the first meta-analysis covering a total of 7 published studies with 1031 patients to clarify the prognostic value of RDW in the pretreatment patients with hematologic malignances. The combined results indicated that elevated RDW significantly predicted poor OS, poor EFS and poor PFS of patients with hematologic malignances. Furthermore, the similar results were observed in subgroup analysis stratified by cancer type, such as MM, DLBCL, etc.
The prognostic value of RDW was investigated in a variety of cancer patients and gathering evidences suggested that RDW was an independent factor for prognosis [
23,
24]. The exact mechanism underlying the associations of RDW with these cancers has not been clearly elucidated. Recently, numerous studies have reported the positive correlation between RDW and a variety of inflammatory markers, including the erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), C-reactive protein (CRP), soluble tumor necrosis factor (TNF) receptors I and II, and soluble transferrin receptor [
25]. One possible explanation for this finding is that inflammation impairs erythropoiesis and causes changes in red blood cell maturation, which contributed to the increase in RDW [
26]. In addition, RDW was found to be associated with malnutrition (i.e., deficiencies in nutrients such as vitamin B12 and folate), which has been shown to be correlated to lower response to treatment, and poorer prognosis in cancer patients [
18]. Moreover, in the terminal stage of malignancy, digestive system dysfunction may lead to inadequate resorption of the iron, resulting in the disturbed iron metabolism and the inhibition of iron transport in the blood, which might contribute to increased RDW levels. This mechanism has been found in most of the cancers [
27]. Therefore, elevated RDW might bridge the relationship between inflammation and tumorigenesis, thereby correlating to poor prognosis of cancer patients.
This meta-analysis had some limitations that call for cautious interpretation of the results. First, only 7 studies were included in this meta-analysis, and tumor types of this study were also limited, which could decrease the accuracy of the results. Second, the cut-off value defining elevated RDW varied among studies (Table
1). Third, differences of paper quality and sample size across the studies might cause bias in the meta-analysis. Forth, most of the included studies reported positive results, therefore our results might overestimate the prognostic significance of RDW to some degree.
Despite the above limitations, our meta-analysis supports the values of RDW for predicting survival outcome in patients of hematologic malignances. RDW can be easily obtained from routine blood tests, thus intermediate assessments about changes in RDW during therapy were simply available. That is, RDW can help personalize the treatment intensity, as well as aftercare schedule, in order to increase the likelihood of early detection.
Conclusion
Here, we searched electronic databases for relevant studies, and enrolled 7 studies with a total of 1031 patients for meta-analysis, drawing a conclusion that patients with higher RDW are more likely to have poorer prognosis than those with lower RDW. Taken together, the results from our meta-analysis suggest that RDW gains a prognostic value for patients with hematologic malignances. More multi-center prospective cohorts should be conducted to further validate the role of the RDW in hematologic malignances.
Authors’ contributions
SM and LA collected and analyzed the data, wrote the paper; LA and YH conceived and designed this study, analyzed the data, wrote the paper; and all authors reviewed the paper. All authors read and approved the final manuscript.