Improved outcome of acute promyelocytic leukemia with high WBC counts over the last 15 years: the European APL Group experience.
OBJECTIVE
Acute promyelocytic leukemia (APL) with pretreatment WBC counts greater than 10,000/microL is still considered to carry a poorer prognosis than APL with WBC lower than 10,000/mL. We evaluated outcome improvement in such patients in recent years.


METHODS
Nine hundred two patients with APL, including 204 patients and 68 patients with WBC counts more than 10,000/microL and more than 50,000/microL, respectively, were enrolled between 1993 and 2005 in two successive randomized trials of the European APL group (APL 93 and APL 2000) that tested, in particular, the modalities of combination of all-trans retinoic acid (ATRA) and chemotherapy, maintenance treatment, escalating doses of cytarabine, early administration of dexamethasone, and CNS prophylaxis.


RESULTS
Between the APL 93 and 2000 trials, the complete response (CR) rate increased from 89.6% to 93%, and the 5-year cumulative incidence of relapse (CIR) decreased from 40% to 9.5% in patients with WBC counts of 10,000 to 50,000/microL. In patients with WBC counts more than 50,000/microL, the CR rate increased from 82% to 91%, and 5-year CIR decreased from 59% to 24%. Whereas in the APL 93 trial, increased WBC counts were significantly associated with higher CIR and shorter survival, this was not the case in the APL 2000 trial. In patients with increased WBC counts, enrollment onto the APL 2000 trial (v APL 93) and combined maintenance with ATRA and chemotherapy were associated with significantly lower CIR and better survival.


CONCLUSIONS
Outcome of APL with high WBC count has markedly improved over the years as a result of fewer early deaths and fewer relapses. Better initial supportive care and combined maintenance treatment have contributed to this improvement.
European APL Group, L'Institut National de la Santé et de la Recherche Médicale U848, Villejuif, France.
Charikleia
C
Kelaidi
Sylvie
S
Chevret
Stéphane
S
De Botton
Emmanuel
E
Raffoux
Agnès
A
Guerci
Xavier
X
Thomas
Arnaud
A
Pigneux
Thierry
T
Lamy
Françoise
F
Rigal-Huguet
Sandrine
S
Meyer-Monard
Patrice
P
Chevallier
Frédéric
F
Maloisel
Erick
E
Deconinck
Augustin
A
Ferrant
Nathalie
N
Fegueux
Norbert
N
Ifrah
Miguel
M
Sanz
Hervé
H
Dombret
Pierre
P
Fenaux
Lionel
L
Adès
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010043:Outcome and Process Assessment, Health Care; D016016:Proportional Hazards Models; D011787:Quality of Health Care / Q000639:trends; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult