Favourable outcome of patients with childhood acute promyelocytic leukaemia after treatment with reduced cumulative anthracycline doses.
Acute promyelocytic leukaemia (APL) treatment often includes high cumulative doses of anthracyclines, which can cause long-term cardiotoxicity. Here, we report the favourable outcome in 81 paediatric APL patients treated according to the consecutive acute myeloid leukaemia-Berlin/Frankfurt/Muenster (AML-BFM) trials -93/-98/-2004 with an anthracycline-cytarabine regimen in combination with all-trans-retinoid acid (ATRA). Outcomes achieved by treatment with a reduced cumulative anthracycline dose (350 mg/m(2)) were comparable to those reported for studies with higher doses. Five-year overall survival of the total cohort was 89 +/- 4% and event-free survival (pEFS) was 73 +/- 6%. Overall survival was similar when comparing AML-BFM trial periods (trial 93: 88 +/- 8%, 98: 85 +/- 7% and 2004: 94 +/- 8%, P((logrank)) = 0.63). Seventy-five (93%) patients achieved complete remission. Most fatal events occurred during the first 6 weeks of treatment. Long-term cardiotoxicity was observed in one patient. Two patients suffered from secondary haematological malignancies. Salvage treatment was effective in 7/9 patients (78%) with relapsed APL, who now are long-term survivors after second line combination treatment with arsenic trioxide (4/7 patients) and stem cell transplantation (5/7 patients). Our results demonstrate that - combined with ATRA - a lower cumulative anthracycline dose can be used safely to maintain high cure rates and promote the reduction of long-term sequelae, such as cardiotoxicity in APL patients.
University Children's Hospital, Department of Paediatric Haematology/Oncology, Muenster, Hannover, Germany. ursula@creutzig.de
Ursula
U
Creutzig
Martin
M
Zimmermann
Michael
M
Dworzak
Christian
C
Urban
Günter
G
Henze
Bernhard
B
Kremens
Max
M
Lakomek
Jean-Pierre
JP
Bourquin
Jan
J
Stary
Dirk
D
Reinhardt
D000293:Adolescent; D018943:Anthracyclines / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D009202:Cardiomyopathies / Q000139:chemically induced; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D016609:Neoplasms, Second Primary / Q000139:chemically induced; D012008:Recurrence; D016019:Survival Analysis; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage
D018943:Anthracyclines; D003561:Cytarabine; D014212:Tretinoin