Introduction: Sweet syndrome (SS) is well known to be associated with underlying hematologic malignancies. The incidence and qualities of SS among novel targeted therapies for acute myeloid leukemia (AML) have not yet been described. Methods: Through retrospective review of 19,432 patients diagnosed with acute/chronic leukemia or myelodysplastic syndromes/myeloproliferative neoplasms (MDS+/−MPN) over 28 years, we calculated the incidence of SS in the setting of select hematologic malignancies and described the clinicopathologic characteristics of SS in patients with onset of SS after initiation of novel AML-targeted therapies. Results: Overall incidence of SS was 0.36% (95% CI: 0.27–0.45%), which was significantly higher among patients with AML (50/5,248, 0.94%; 95% CI: 0.71–1.25%). Nine AML patients were on 4 classes of novel targeted treatments – IDH1/2 inhibitor alone, FLT3 inhibitor, IDH2 and DOT1L inhibitor, and anti-CD33 therapy. In therapies inducing myeloid blast differentiation, SS occurred at later onset following treatment. Conclusions: In AML patients with fever and unusual skin lesions, physicians may consider SS earlier, which may shorten time to diagnosis. Future assessments of SS among patients treated with novel therapies for AML and molecular studies of biopsies may help further explain this dermatologic adverse event with earlier diagnosis and management of neutrophilic dermatoses in these patients.

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