TY - JOUR
T1 - Therapy reduction in patients with Down syndrome and myeloid leukemia
T2 - the international ML-DS 2006 trial
AU - Uffmann, Madita
AU - Rasche, Mareike
AU - Zimmermann, Martin
AU - Neuhoff, Christine von
AU - Creutzig, Ursula
AU - Dworzak, Michael
AU - Scheffers, Lenie
AU - Hasle, Henrik
AU - Zwaan, C. Michel
AU - Reinhardt, Dirk
AU - Klusmann, Jan Henning
N1 - Publisher Copyright:
© 2017 by The American Society of Hematology
PY - 2017/6/22
Y1 - 2017/6/22
N2 - Children with myeloid leukemia associated with Down syndrome (ML-DS) have superior outcome compared with non-DS patients, but suffer from higher constitutional cytotoxic drug susceptibility. We analyzed the outcome of 170 pediatric patients with ML-DS enrolled in the prospective, multicenter, open-label, nonrandomized ML-DS 2006 trial by Nordic Society for Pediatric Hematology and Oncology (NOPHO), Dutch Childhood Oncology Group (DCOG), and Acute Myeloid Leukemia–Berlin-Frankfurt-Münster (AML-BFM) study group. Compared with the historical control arm (reduced-intensity protocol for ML-DS patients from the AML-BFM 98 trial), treatment intensity was reduced by lowering the cumulative dose of etoposide (950 to 450 mg/m2) and intrathecal central nervous system prophylaxis while omitting maintenance therapy. Still, 5-year overall survival (89% 6 3% vs 90% 6 4%; Plog-rank 5 .64), event-free survival (EFS; 87% 6 3% vs 89% 6 4%; Plog-rank 5 .71), and cumulative incidence of relapse/ nonresponse (CIR/NR; 6% 6 3% vs 6% 6 2%; PGray 5 .03) did not significantly differ between the ML-DS 2006 trial and the historical control arm. Poor early treatment response (5-year EFS, 58% 6 16% vs 88% 6 3%; Plog rank 5 .0008) and gain of chromosome 8 (CIR/NR, 16% 6 7% vs 3% 6 2%, PGray 5 .02; 5-year EFS, 73% 6 8% vs 91% 6 4%, Plog rank 5 .018) were identified as independent prognostic factors predicting a worse EFS. Five of 7 relapsed patients (71%) with cytogenetic data had trisomy 8. Our study reveals prognostic markers for children with ML-DS and illustrates that reducing therapy did not impair excellent outcome. The trial was registered at EudraCT as #2007-006219-2. (Blood.
AB - Children with myeloid leukemia associated with Down syndrome (ML-DS) have superior outcome compared with non-DS patients, but suffer from higher constitutional cytotoxic drug susceptibility. We analyzed the outcome of 170 pediatric patients with ML-DS enrolled in the prospective, multicenter, open-label, nonrandomized ML-DS 2006 trial by Nordic Society for Pediatric Hematology and Oncology (NOPHO), Dutch Childhood Oncology Group (DCOG), and Acute Myeloid Leukemia–Berlin-Frankfurt-Münster (AML-BFM) study group. Compared with the historical control arm (reduced-intensity protocol for ML-DS patients from the AML-BFM 98 trial), treatment intensity was reduced by lowering the cumulative dose of etoposide (950 to 450 mg/m2) and intrathecal central nervous system prophylaxis while omitting maintenance therapy. Still, 5-year overall survival (89% 6 3% vs 90% 6 4%; Plog-rank 5 .64), event-free survival (EFS; 87% 6 3% vs 89% 6 4%; Plog-rank 5 .71), and cumulative incidence of relapse/ nonresponse (CIR/NR; 6% 6 3% vs 6% 6 2%; PGray 5 .03) did not significantly differ between the ML-DS 2006 trial and the historical control arm. Poor early treatment response (5-year EFS, 58% 6 16% vs 88% 6 3%; Plog rank 5 .0008) and gain of chromosome 8 (CIR/NR, 16% 6 7% vs 3% 6 2%, PGray 5 .02; 5-year EFS, 73% 6 8% vs 91% 6 4%, Plog rank 5 .018) were identified as independent prognostic factors predicting a worse EFS. Five of 7 relapsed patients (71%) with cytogenetic data had trisomy 8. Our study reveals prognostic markers for children with ML-DS and illustrates that reducing therapy did not impair excellent outcome. The trial was registered at EudraCT as #2007-006219-2. (Blood.
UR - http://www.scopus.com/inward/record.url?scp=85021381507&partnerID=8YFLogxK
U2 - 10.1182/blood-2017-01-765057
DO - 10.1182/blood-2017-01-765057
M3 - Article
C2 - 28400376
AN - SCOPUS:85021381507
SN - 0006-4971
VL - 129
SP - 3314
EP - 3321
JO - Blood
JF - Blood
IS - 25
ER -