Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group.
Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995 to 2004. Non-DS BCP-ALL patients from the Dutch Child Oncology Group and Berlin-Frankfurt-Münster were reference cohorts. DS-ALL patients had a higher 8-year cumulative incidence of relapse (26% ± 2% vs 15% ± 1%, P < .001) and 2-year treatment-related mortality (TRM) (7% ± 1% vs 2.0% ± <1%, P < .0001) than non-DS patients, resulting in lower 8-year event-free survival (EFS) (64% ± 2% vs 81% ± 2%, P < .0001) and overall survival (74% ± 2% vs 89% ± 1%, P < .0001). Independent favorable prognostic factors include age <6 years (hazard ratio [HR] = 0.58, P = .002), white blood cell (WBC) count <10 × 10(9)/L (HR = 0.60, P = .005), and ETV6-RUNX1 (HR = 0.14, P = .006) for EFS and age (HR = 0.48, P < .001), ETV6-RUNX1 (HR = 0.1, P = .016) and high hyperdiploidy (HeH) (HR = 0.29, P = .04) for relapse-free survival. TRM was the major cause of death in ETV6-RUNX1 and HeH DS-ALLs. Thus, while relapse is the main contributor to poorer survival in DS-ALL, infection-associated TRM was increased in all protocol elements, unrelated to treatment phase or regimen. Future strategies to improve outcome in DS-ALL should include improved supportive care throughout therapy and reduction of therapy in newly identified good-prognosis subgroups.
Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands;
Trudy D
TD
Buitenkamp
Shai
S
Izraeli
Martin
M
Zimmermann
Erik
E
Forestier
Nyla A
NA
Heerema
Marry M
MM
van den Heuvel-Eibrink
Rob
R
Pieters
Carin M
CM
Korbijn
Lewis B
LB
Silverman
Kjeld
K
Schmiegelow
Der-Cheng
DC
Liang
Keizo
K
Horibe
Maurizio
M
Arico
Andrea
A
Biondi
Giuseppe
G
Basso
Karin R
KR
Rabin
Martin
M
Schrappe
Gunnar
G
Cario
Georg
G
Mann
Maria
M
Morak
Renate
R
Panzer-Grümayer
Veerle
V
Mondelaers
Tim
T
Lammens
Hélène
H
Cavé
Batia
B
Stark
Ithamar
I
Ganmore
Anthony V
AV
Moorman
Ajay
A
Vora
Stephen P
SP
Hunger
Ching-Hon
CH
Pui
Charles G
CG
Mullighan
Atsushi
A
Manabe
Gabriele
G
Escherich
Jerzy R
JR
Kowalczyk
James A
JA
Whitlock
C Michel
CM
Zwaan
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018572:Disease-Free Survival; D004314:Down Syndrome / Q000150:complications* / Q000401:mortality / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007621:Karyotyping; D008297:Male; D015999:Multivariate Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000401:mortality / Q000628:therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome