Predictors of early death, serious hemorrhage, and differentiation syndrome in Japanese patients with acute promyelocyti
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ORIGINAL ARTICLE
Predictors of early death, serious hemorrhage, and differentiation syndrome in Japanese patients with acute promyelocytic leukemia Hitoshi Minamiguchi 1 & Hiroyuki Fujita 2 & Yoshiko Atsuta 3,4 & Norio Asou 5 & Toru Sakura 6 & Yasunori Ueda 7 & Masashi Sawa 8 & Nobuaki Dobashi 9 & Yasuhiro Taniguchi 10 & Rikio Suzuki 11 & Yoshihito Uchino 12 & Akihiro Tomita 13 & Shigehisa Tamaki 14 & Maki Hagihara 15 & Katsumichi Fujimaki 16 & Masamitsu Yanada 17 & Yoshinobu Maeda 18 & Masako Iwanaga 19 & Noriko Usui 9 & Yukio Kobayashi 20,21 & Shigeki Ohtake 22 & Hitoshi Kiyoi 23 & Itaru Matsumura 10 & Yasushi Miyazaki 24 & Tomoki Naoe 25 & Akihiro Takeshita 26 & on behalf of the Japan Adult Leukemia Study Group Received: 24 December 2019 / Accepted: 28 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Significant advancements have been achieved with regard to the outcomes of acute promyelocytic leukemia (APL) patients through the introduction of all-trans retinoic acid; however, early hemorrhagic death and differentiation syndrome remain the major causes of remission induction failure in patients with APL. To investigate early death, serious hemorrhage, and differentiation syndrome during remission induction therapy in terms of incidence, risk factors, influence on outcomes, and prophylactic effects of several new anticoagulants, the results of 344 patients enrolled in the Acute Promyelocytic Leukemia 204 study conducted by the Japan Adult Leukemia Study Group were analyzed. Early death was observed in 16 patients (4.7%), of whom 14 had serious hemorrhage and 2 had differentiation syndrome. Serious hemorrhage and differentiation syndrome of grade 2 or higher were observed in 21 and 54 patients, respectively. Patients who achieved complete remission had a 7-year disease-free survival of 84.8% if they did not experience serious hemorrhage and 40.0% if they experienced serious hemorrhage during remission induction therapy (P = 0.001). Risk factor analyses showed that higher white blood cell count was associated with early death, higher white blood cell count and lower platelet count with serious hemorrhage, and leukocytosis during induction therapy and higher body surface area with differentiation syndrome. In conclusion, these results indicate that patients with such high-risk features may benefit from more intensive supportive care. The hemorrhagic risk was not relieved by the introduction of new anticoagulants. Further studies are required to establish the predictive impact of body surface area on differentiation syndrome. This trial is registered with UMIN-CTR as C000000154 on September 13, 2005. Keywords Acute promyelocytic leukemia . Body surface area . Differentiation syndrome . Disseminated intravascular coagulation . Early death . Serious hemorrhage
Introduction Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by a balanced reciprocal chromosomal translocation between chromosomes 15 and 17
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