Treatment with all-trans retinoic acid and anthracycline monochemotherapy for children with acute promyelocytic leukemia: a multicenter study by the PETHEMA Group.
OBJECTIVE
To analyze the simultaneous combination of all-trans retinoic acid (ATRA) and anthracycline monochemotherapy for children with acute promyelocytic leukemia (APL).


METHODS
Since November 1996, 66 children (younger than 18 years) with genetically proven APL received induction therapy with ATRA and idarubicin. Consolidation therapy consisted of three courses of anthracycline monochemotherapy. After November 1999, patients with intermediate and high risk of relapse received consolidation therapy with ATRA and slightly reinforced doses of idarubicin. Maintenance therapy consisted of ATRA and low-dose mercaptopurine and methotrexate.


RESULTS
Thirty-nine girls (59%) and 27 boys (41%) were included in this study. The WBC count at presentation was more than 10 x 10(9)/L in 26 patients (39%). Sixty-one children (92%) achieved complete remission (CR). Early deaths from hemorrhage and retinoic acid syndrome occurred in three patients and two patients, respectively. Toxicity was manageable during consolidation and maintenance therapy. No deaths in CR, clinical cardiomyotoxicity, or secondary malignancy occurred. Two patients had molecular persistence at the end of consolidation. Three clinical relapses and two molecular relapses were also observed. Apart from one molecular relapse, all these events occurred among children with hyperleukocytosis. The 5-year cumulative incidence of relapse was 17%, whereas disease-free and overall survival rates were 82% and 87%, respectively.


CONCLUSIONS
A high incidence of hyperleukocytosis in children with APL was confirmed. Besides low toxicity and a high degree of compliance, a risk-adapted therapy combining ATRA and anthracycline monochemotherapy showed an antileukemic efficacy comparable to those previously reported with other chemotherapy combinations in children.
Ortega
Juan J
JJ
Servicio de Hematología, Hospital Universitario La Fe, Avenida Campanar 21, 46009 Valencia, Spain.
Madero
Luis
L
Martín
Guillermo
G
Verdeguer
Amparo
A
García
Purificación
P
Parody
Ricardo
R
Fuster
José
J
Molines
Antonio
A
Novo
Andrés
A
Debén
Guillermo
G
Rodríguez
Antonia
A
Conde
Eulogio
E
de la Serna
Javier
J
Allegue
María J
MJ
Capote
Francisco J
FJ
González
José D
JD
Bolufer
Pascual
P
González
Marcos
M
Sanz
Miguel A
MA
D000293:Adolescent; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D015994:Incidence; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011379:Prognosis; D012074:Remission Induction; D012307:Risk Factors; D015996:Survival Rate; D014212:Tretinoin / Q000008:administration & dosage
D018943:Anthracyclines; D014212:Tretinoin; D015122:Mercaptopurine; D008727:Methotrexate; D015255:Idarubicin