Outcome of childhood acute promyelocytic leukemia with all-trans-retinoic acid and chemotherapy.
OBJECTIVE
To determine the results of treatment combining all-trans-retinoic acid (ATRA) and chemotherapy (CT) in childhood acute promyelocytic leukemia (APL).


METHODS
Children (< 18 years) with newly diagnosed APL were included in the APL93 trial, treated by ATRA followed or combined with daunorubicin-cytarabine, and then randomly assigned between no maintenance, intermittent ATRA, continuous CT, or both.


RESULTS
Of the 576 patients included in APL93 trial, 31 (5%) were children, including 22 girls (71%) and nine boys (29%). Thirty of the children (97%) obtained complete remission (CR). ATRA syndrome occurred in four children (13%), who all achieved CR, and headaches occurred in 12 children (39%), with signs of pseudotumor cerebri in five children (16%). Seven patients (23%) relapsed. None of the eight patients who received both ATRA and CT for maintenance relapsed. All relapsing patients achieved a second CR. Twenty-two patients remained in first CR after 43+ to 96+ months, six remained in second CR after 17+ to 66+ months, and three patients had died. The 5-year event-free survival (EFS), relapse, and overall survival rates were 71%, 27%, and 90%, respectively. No difference between adults and children included in the APL93 trial was seen for CR rate, 5-year relapse rate, EFS, and overall survival, but significantly better survival was seen in children after adjustment on WBC counts (P =.02) and incidence of microgranular M3 variant (P =.04).


CONCLUSIONS
ATRA combined with CT for induction and also probably for maintenance provides as favorable results in children with APL as in adults and currently constitutes the reference first-line treatment in both age groups.
de Botton
S
S
Programme Hospitalier de Recherche Clinique (Centre Hospitalier Universitaire Lille), Lille, France.
Coiteux
V
V
Chevret
S
S
Rayon
C
C
Vilmer
E
E
Sanz
M
M
de La Serna
J
J
Philippe
N
N
Baruchel
A
A
Leverger
G
G
Robert
A
A
San Miguel
J
J
Conde
E
E
Sotto
J J
JJ
Bordessoule
D
D
Fegueux
N
N
Fey
M
M
Parry
A
A
Chomienne
C
C
Degos
L
L
Fenaux
P
P
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000627:therapeutic use; D003630:Daunorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007223:Infant; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014212:Tretinoin / Q000627:therapeutic use*
D003561:Cytarabine; D014212:Tretinoin; D003630:Daunorubicin