title: Severe hemorrhagic complications during remission induction therapy for acute promyelocytic leukemia: incidence, risk factors, and influence on outcome.
abstract: BACKGROUND
  Even after the introduction of all-trans retinoic acid (ATRA), early hemorrhagic death remains a major cause of remission induction failure for acute promyelocytic leukemia (APL).
  
  
  METHODS
  To investigate severe hemorrhagic complications during remission induction therapy with respect to incidence, risk factors, and influence on outcome. Results were analyzed for 279 patients enrolled in the APL97 study conducted by the Japan Adult Leukemia Study Group (JALSG).
  
  
  RESULTS
  Severe hemorrhage occurred in 18 patients (6.5%). Although most of them were receiving frequent transfusions, the targeted levels of platelet counts (30 x 10(9)/L) and plasma fibrinogen (1.5 g/L) for this study were reached at the day of bleeding in only 71% and 40%, respectively. Nine of them succumbed to an early death, while the remaining nine patients eventually achieved complete remission (CR). The 5-yr event-free survival rate was 68.1% for those who did not suffer severe hemorrhage, and 31.1% for those who did (P < 0.0001). For patients who achieved CR, on the other hand, there was no difference in disease-free survival between patients with and without severe hemorrhage (P = 0.6043). Risk factor analysis identified three pretreatment variables associated with severe hemorrhage: initial fibrinogen level, white blood cell count, and performance status. Additionally, patients with severe hemorrhage were more easily prone to develop retinoic acid syndrome or pneumonia than patients without hemorrhage.
  
  
  CONCLUSIONS
  These results indicate that fatal hemorrhage represents a major obstacle in curing APL, and that patients with such high-risk features may benefit from more aggressive supportive care.
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan. myanada@med.nagoya-u.ac.jp
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Yanada
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsushita
authors.forename: Norio
authors.initials: N
authors.lastname: Asou
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kishimoto
authors.forename: Motohiro
authors.initials: M
authors.lastname: Tsuzuki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maeda
authors.forename: Kentaro
authors.initials: K
authors.lastname: Horikawa
authors.forename: Masaya
authors.initials: M
authors.lastname: Okada
authors.forename: Shigeki
authors.initials: S
authors.lastname: Ohtake
authors.forename: Fumiharu
authors.initials: F
authors.lastname: Yagasaki
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Kimura
authors.forename: Katsuji
authors.initials: K
authors.lastname: Shinagawa
authors.forename: Masako
authors.initials: M
authors.lastname: Iwanaga
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ohno
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006470:Hemorrhage / Q000150:complications / Q000209:etiology* / Q000473:pathology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012307:Risk Factors; D016896:Treatment Outcome