Prognostic Value of Red Cell Distribution Width at Ruxolitinib Initiation in Myelofibrosis

In a retrospective, observational, single-center study published in Oncology and Therapy in January 2025, Laganà et al. investigated whether red cell distribution width (RDW)—a routine component of the full blood count—could serve as a prognostic marker in patients with myelofibrosis initiating ruxolitinib. The study evaluated whether baseline RDW correlates with adverse disease features, predicts treatment-related anemia, and independently forecasts spleen response and overall survival (OS).

RDW is a measure of anisocytosis and has been recognized as a marker of systemic inflammation in cardiovascular disease, malignancy, and other chronic conditions. Its relevance in myelofibrosis is supported by the disease’s underlying pathophysiology, which includes chronic inflammation, marrow fibrosis, and ineffective erythropoiesis.

In this analysis, 200 patients with either primary or secondary myelofibrosis were assessed at ruxolitinib initiation. Secondary myelofibrosis included post-polycythemia vera (post-PV myelofibrosis) and post-essential thrombocythemia (post-ET myelofibrosis). Median follow-up was approximately 40 months.

The authors identified 20.5 percent as the optimal RDW threshold for risk stratification using receiver operating characteristic (ROC) analysis. Patients with RDW ≥20.5 percent were significantly more likely to exhibit features of aggressive disease: grade 3 marrow fibrosis, transfusion dependence, elevated lactate dehydrogenase, lower hemoglobin, larger spleens, and older age at treatment start.

Clinical outcomes mirrored these biologic differences. Only 33.3 percent of patients with RDW ≥20.5 percent achieved a spleen response, compared with 52.3 percent in the lower RDW group (p = 0.012). Drug-induced anemia was also more common in patients with elevated RDW, 44.4 percent vs. 29.7 percent at three months (p = 0.032), with odds ratios of 1.94 and 2.53 at three and six months, respectively. These associations held even after excluding cases with iron, B12, or folate deficiency.

The survival impact was pronounced. Median OS in the high RDW group was 34.6 months, compared to 84.2 months among those with RDW <20.5 percent. This difference remained significant in multivariate analysis (HR 3.01, p < 0.001), even after adjusting for platelet count and Dynamic International Prognostic Scoring System (DIPSS) risk class.

Importantly, RDW improved the discriminatory power of established prognostic models. Among DIPSS intermediate-2 patients, those with RDW ≥20.5 percent had survival similar to high-risk DIPSS cases. Similar patterns emerged within RR6 categories, where elevated RDW further stratified risk among intermediate- and high-risk groups. The prognostic value of RDW also held among patients with hemoglobin ≥10 g/dL, suggesting that RDW captures disease activity beyond anemia alone.

Thus, in settings where access to genetic evaluation and molecular testing is limited, RDW may serve as an alternative indicator of disease aggressiveness and early treatment risk.

However, the retrospective, single-center design limits generalizability. Prospective studies, including longitudinal assessment and integration with genomic data, are needed before RDW can be adopted as a formal risk tool. Still, a baseline RDW ≥20.5 percent should raise concern for poorer outcomes in patients with myelofibrosis starting ruxolitinib. When used alongside established tools such as DIPSS or RR6, RDW may enhance risk stratification and support more intensive monitoring for anemia or early treatment failure.

Although not yet suitable to guide therapy on its own, RDW shows potential as a simple, inflammation-associated adjunct to current risk frameworks. With further validation, it could help identify high-risk patients who may benefit from earlier intervention or alternative strategies.

Reference

Laganà A, Scalzulli E, Carmosino I, Bisegna ML, Martelli M, Breccia M. Red Blood Cell Distribution Width May Predict Drug-Induced Anemia and Prognosis in Patients Affected by Primary/Secondary Myelofibrosis Treated with Ruxolitinib. Oncol Ther. 2025;13(1):165-183.