Recent clinical trials with JAK or mammalian target of rapamycin (mTOR) inhibitors in primary myelofibrosis (PMF) have identified pruritus as one of the most treatment-responsive disease traits. However, little is known about the prevalence of pruritus in PMF or its clinical and laboratory correlates. Among 566 consecutive patients with PMF seen at our institution, the presence or absence of pruritus was documented in 90 (16%) and 146 (26%) patients, respectively. Patients with pruritus were less likely to express MPLW515 (0% vs. 10%; P = 0.02) or leukopenia (8% vs. 24%; P = 0.002). The latter association was more pronounced in the absence of JAK2 or MPL mutations. Pruritus also clustered with marked leukocytosis (23% vs. 11%; P = 0.01) and JAK2V617F (71% vs. 59%; P = 0.08). Pruritus did not correlate with karyotype (P = 0.33), risk category per the Dynamic International Prognostic Scoring System (DIPSS)-plus (P = 0.37), DIPSS-plus-adjusted survival (P = 0.41), or leukemic transformation (P = 0.13). Plasma levels of 20 cytokines, which are known to be abnormally expressed in PMF, including IL-1b, IL-2R, IL-6, IL-8, and VEGF, were measured in 63 informative cases and showed no correlations with history of pruritus. We conclude that pruritus is relatively frequent in PMF and is prognostically irrelevant. The pathogenesis of PMF-associated pruritus is not necessarily linked to proinflammatory cytokines but may instead involve molecules that are either granulocyte-derived or influence granulopoiesis. The apparently differential effect of MPL vs. JAK2 mutations on pruritus requires further investigation.
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