Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin.
An understanding of the prognostic factors associated with the various forms of induction mortality in patients with acute promyelocytic leukemia (APL) has remained remarkably limited. This study reports the incidence, time of occurrence, and prognostic factors of the major categories of induction failure in a series of 732 patients of all ages (range, 2-83 years) with newly diagnosed APL who received all-trans retinoic acid (ATRA) plus idarubicin as induction therapy in 2 consecutive studies of the Programa de Estudio y Tratamiento de las Hemopatias Malignas (PETHEMA) Group. Complete remission was attained in 666 patients (91%). All the 66 induction failures were due to induction death. Hemorrhage was the most common cause of induction death (5%), followed by infection (2.3%) and differentiation syndrome (1.4%). Multivariate analysis identified specific and distinct pretreatment characteristics to correlate with an increased risk of death caused by hemorrhage (abnormal creatinine level, increased peripheral blast counts, and presence of coagulopathy), infection (age>60 years, male sex, and fever at presentation), and differentiation syndrome (Eastern Cooperative Oncology Group [ECOG] score>1 and low albumin levels), respectively. These data furnish clinically relevant information that might be useful for designing more appropriately risk-adapted treatment protocols aimed at reducing the considerable problem of induction mortality in APL.
de la Serna
Javier
J
Hospital 12 de Octubre, Madrid, Spain.
Montesinos
Pau
P
Vellenga
Edo
E
Rayón
Chelo
C
Parody
Ricardo
R
León
Angel
A
Esteve
Jordi
J
Bergua
Juan M
JM
Milone
Gustavo
G
Debén
Guillermo
G
Rivas
Concha
C
González
Marcos
M
Tormo
Mar
M
Díaz-Mediavilla
Joaquín
J
González
Jose D
JD
Negri
Silvia
S
Amutio
Elena
E
Brunet
Salut
S
Lowenberg
Bob
B
Sanz
Miguel A
MA
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001752:Blast Crisis / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced / Q000401:mortality*; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects; D007239:Infections / Q000097:blood / Q000209:etiology / Q000401:mortality*; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000188:drug therapy / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012307:Risk Factors; D012737:Sex Factors; D015996:Survival Rate; D013577:Syndrome; D017211:Treatment Failure; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects
D014212:Tretinoin; D003404:Creatinine; D015255:Idarubicin