Acute lymphoblastic leukemia in children with Down Syndrome: a retrospective analysis from the Ponte di Legno study group
Standard
Acute lymphoblastic leukemia in children with Down Syndrome: a retrospective analysis from the Ponte di Legno study group. / Buitenkamp, Trudy D; Izraeli, Shai; Zimmermann, Martin; Forestier, Erik; Heerema, Nyla A; van den Heuvel-Eibrink, Marry M; Pieters, Rob; Korbijn, Carin M; Silverman, Lewis B; Schmiegelow, Kjeld; Liang, Der-Cheng; Horibe, Keizo; Arico, Maurizio; Biondi, Andrea; Basso, Giuseppe; Rabin, Karin R; Schrappe, Martin; Cario, Gunnar; Mann, Georg; Morak, Maria; Panzer-Grümayer, Renate; Mondelaers, Veerle; Lammens, Tim; Cavé, Hélène; Stark, Batia; Ganmore, Ithamar; Moorman, Anthony V; Vora, Ajay; Hunger, Stephen P; Pui, Ching-Hon; Mullighan, Charles G; Manabe, Atsushi; Escherich, Gabriele; Kowalczyk, Jerzy R; Whitlock, James A; Zwaan, C Michel.
in: BLOOD, Jahrgang 123, Nr. 1, 02.01.2014, S. 70-77.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Acute lymphoblastic leukemia in children with Down Syndrome: a retrospective analysis from the Ponte di Legno study group
AU - Buitenkamp, Trudy D
AU - Izraeli, Shai
AU - Zimmermann, Martin
AU - Forestier, Erik
AU - Heerema, Nyla A
AU - van den Heuvel-Eibrink, Marry M
AU - Pieters, Rob
AU - Korbijn, Carin M
AU - Silverman, Lewis B
AU - Schmiegelow, Kjeld
AU - Liang, Der-Cheng
AU - Horibe, Keizo
AU - Arico, Maurizio
AU - Biondi, Andrea
AU - Basso, Giuseppe
AU - Rabin, Karin R
AU - Schrappe, Martin
AU - Cario, Gunnar
AU - Mann, Georg
AU - Morak, Maria
AU - Panzer-Grümayer, Renate
AU - Mondelaers, Veerle
AU - Lammens, Tim
AU - Cavé, Hélène
AU - Stark, Batia
AU - Ganmore, Ithamar
AU - Moorman, Anthony V
AU - Vora, Ajay
AU - Hunger, Stephen P
AU - Pui, Ching-Hon
AU - Mullighan, Charles G
AU - Manabe, Atsushi
AU - Escherich, Gabriele
AU - Kowalczyk, Jerzy R
AU - Whitlock, James A
AU - Zwaan, C Michel
PY - 2014/1/2
Y1 - 2014/1/2
N2 - 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.
AB - 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.
KW - Adolescent
KW - Child
KW - Child, Preschool
KW - Cohort Studies
KW - Disease-Free Survival
KW - Down Syndrome
KW - Female
KW - Follow-Up Studies
KW - Humans
KW - Infant
KW - Karyotyping
KW - Male
KW - Multivariate Analysis
KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma
KW - Prognosis
KW - Proportional Hazards Models
KW - Recurrence
KW - Retrospective Studies
KW - Treatment Outcome
U2 - 10.1182/blood-2013-06-509463
DO - 10.1182/blood-2013-06-509463
M3 - SCORING: Journal article
C2 - 24222333
VL - 123
SP - 70
EP - 77
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 1
ER -
