Severe hemorrhagic complications during remission induction therapy for acute promyelocytic leukemia: incidence, risk factors, and influence on outcome.
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.
Yanada
Masamitsu
M
Nagoya University Graduate School of Medicine, Nagoya, Japan. myanada@med.nagoya-u.ac.jp
Matsushita
Tadashi
T
Asou
Norio
N
Kishimoto
Yuji
Y
Tsuzuki
Motohiro
M
Maeda
Yasuhiro
Y
Horikawa
Kentaro
K
Okada
Masaya
M
Ohtake
Shigeki
S
Yagasaki
Fumiharu
F
Matsumoto
Tadashi
T
Kimura
Yukihiko
Y
Shinagawa
Katsuji
K
Iwanaga
Masako
M
Miyazaki
Yasushi
Y
Ohno
Ryuzo
R
Naoe
Tomoki
T
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