Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome: a retrospective, international study.
Myeloid leukemia of Down syndrome has a better prognosis than sporadic pediatric acute myeloid leukemia. Most cases of myeloid leukemia of Down syndrome are characterized by additional cytogenetic changes besides the constitutional trisomy 21, but their potential prognostic impact is not known. We, therefore, conducted an international retrospective study of clinical characteristics, cytogenetics, treatment, and outcome of 451 children with myeloid leukemia of Down syndrome. All karyotypes were centrally reviewed before assigning patients to subgroups. The overall 7-year event-free survival for the entire cohort was 78% (± 2%), with the overall survival rate being 79% (± 2%), the cumulative incidence of relapse 12% (± 2%), and the cumulative incidence of toxic death 7% (± 1%). Outcome estimates showed large differences across the different cytogenetic subgroups. Based on the cumulative incidence of relapse, we could risk-stratify patients into two groups: cases with a normal karyotype (n=103) with a higher cumulative incidence of relapse (21%± 4%) than cases with an aberrant karyotype (n=255) with a cumulative incidence of relapse of 9% (± 2%) (P=0.004). Multivariate analyses revealed that white blood cell count ≥ 20 × 10(9)/L and age >3 years were independent predictors for poor event-free survival, while normal karyotype independently predicted inferior overall survival, event-free survival, and relapse-free survival. In conclusion, this study showed large differences in outcome within patients with myeloid leukemia of Down syndrome and identified novel prognostic groups that predicted clinical outcome and hence may be used for stratification in future treatment protocols.
c.m.zwaan@erasmusmc.nl.
Marjolein
M
Blink
Martin
M
Zimmermann
Christine
C
von Neuhoff
Dirk
D
Reinhardt
Valerie
V
de Haas
Henrik
H
Hasle
Maureen M
MM
O'Brien
Batia
B
Stark
Julie
J
Tandonnet
Andrea
A
Pession
Katerina
K
Tousovska
Daniel K L
DK
Cheuk
Kazuko
K
Kudo
Takashi
T
Taga
Jeffrey E
JE
Rubnitz
Iren
I
Haltrich
Walentyna
W
Balwierz
Rob
R
Pieters
Erik
E
Forestier
Bertil
B
Johansson
Marry M
MM
van den Heuvel-Eibrink
C Michel
CM
Zwaan
D059786:Abnormal Karyotype; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D018572:Disease-Free Survival; D004314:Down Syndrome / Q000150:complications / Q000235:genetics / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000150:complications / Q000235:genetics / Q000401:mortality; D008297:Male; D012189:Retrospective Studies; D015996:Survival Rate