Predictors of early death, serious hemorrhage, and differentiation syndrome in Japanese patients with acute promyelocytic leukemia.

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.

• Authors: Hitoshi Minamiguchi, Hiroyuki Fujita, Yoshiko Atsuta, Norio Asou, Toru Sakura, Yasunori Ueda, Masashi Sawa, Nobuaki Dobashi, Yasuhiro Taniguchi, Rikio Suzuki, Yoshihito Uchino, Akihiro Tomita, Shigehisa Tamaki, Maki Hagihara, Katsumichi Fujimaki, Masamitsu Yanada, Yoshinobu Maeda, Masako Iwanaga, Noriko Usui, Yukio Kobayashi, Shigeki Ohtake, Hitoshi Kiyoi, Itaru Matsumura, Yasushi Miyazaki, Tomoki Naoe, Akihiro Takeshita, Japan Adult Leukemia Study Group
• Journal: Annals of hematology (Ann Hematol) Vol. 99 Issue 12 Pg. 2787-2800 (Dec 2020) ISSN: 1432-0584 [Electronic] Germany
• PMID: 32879992 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Anticoagulants

Topics

• Adolescent
• Adult
• Aged
• Anticoagulants (pharmacology, therapeutic use)
• Cell Differentiation (drug effects, physiology)
• Female
• Hemorrhage (diagnosis, drug therapy, mortality)
• Humans
• Japan
• Leukemia, Promyelocytic, Acute (diagnosis, drug therapy, mortality)
• Male
• Middle Aged
• Mortality (trends)
• Predictive Value of Tests
• Prospective Studies
• Remission Induction (methods)
• Severity of Illness Index
• Young Adult