Improved Prevention and Treatment Strategies for Differentiation Syndrome Contribute to Reducing Early Mortality in Patients With Acute Promyelocytic Leukemia

In this report, we present an optimized prevention and treatment strategy for differentiation syndrome (DS). A total of 111 eligible patients with acute promyelocytic leukemia (APL) − 78 classified as low-risk and 33 as high-risk - received induction treatment consisting of all-trans retinoic acid (ATRA) in combination with an arsenic agent. Different doses of dexamethasone were administered based on the dynamics of white blood cell (WBC) counts to prevent DS. Ruxolitinib was used as a second-line therapy for DS. Among the patients, 41 (36.9%) experienced DS, with 16 having a severe form (14.4%) and 25 having a moderate form (22.5%). There was no significant difference in the incidence and severity of DS between the low-risk and high-risk patients (p = 0.057 and p = 0.056, respectively). The efficacy of ruxolitinib in cases of DS resistant to steroids was 67% without interruption of ATRA therapy. After discontinuing ATRA, the remaining DS cases were relieved through treatment with dexamethasone and ruxolitinib. The overall 30-day mortality rate was 1.8% (2/111), with two high-risk patients succumbing to intracranial hemorrhage. Complete remission (CR) was achieved in the remaining 109 patients. Our findings suggest that personalized prophylaxis against DS can mitigate the negative prognostic impact of hyperleukocytosis, and ruxolitinib is effective and well tolerated for refractory DS, ultimately decreasing early mortality in APL patients .(clinical trials.gov NCT04446806).