Acute lymphoblastic leukemia in children with Down syndrome: A retrospective analysis from the Ponte di Legno study group

Trudy D. Buitenkamp, Shai Izraeli, Martin Zimmermann, Erik Forestier, Nyla A. Heerema, Marry M. Van Den Heuvel-Eibrink, Rob Pieters, Carin M. Korbijn, Lewis B. Silverman, Kjeld Schmiegelow, Der Cheng Liang, Keizo Horibe, Maurizio Arico, Andrea Biondi, Giuseppe Basso, Karin R. Rabin, Martin Schrappe, Gunnar Cario, Georg Mann, Maria MorakRenate Panzer-Grümayer, Veerle Mondelaers, Tim Lammens, Hèléne Cav́, Batia Stark, Ithamar Ganmore, Anthony Moorman, Ajay Vora, Stephen P. Hunger, Ching Hon Pui, Charles G. Mullighan, Atsushi Manabe, Gabriele Escherich, Jerzy R. Kowalczyk, James A. Whitlock, C. Michel Zwaan

Research output: Contribution to journalArticle

Abstract

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 3 109/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 DSALLs. 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. (Blood. 2014; 123(1):70-77).

Original languageEnglish (US)
Pages (from-to)70-77
Number of pages8
JournalBlood
Volume123
Issue number1
DOIs
StatePublished - Jan 2 2014
Externally publishedYes

Fingerprint

Down Syndrome
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hazards
B-Lymphoid Precursor Cells
Recurrence
Blood
Disease-Free Survival
Survival
Mortality
Cells
Therapeutics
Oncology
Polyploidy
Berlin
Leukocyte Count
Cause of Death
Incidence
Infection

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Buitenkamp, T. D., Izraeli, S., Zimmermann, M., Forestier, E., Heerema, N. A., Van Den Heuvel-Eibrink, M. M., ... Zwaan, C. M. (2014). Acute lymphoblastic leukemia in children with Down syndrome: A retrospective analysis from the Ponte di Legno study group. Blood, 123(1), 70-77. https://doi.org/10.1182/blood-2013-06-509463

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; Cav́, Hèléne; Stark, Batia; Ganmore, Ithamar; Moorman, Anthony; 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, Vol. 123, No. 1, 02.01.2014, p. 70-77.

Research output: Contribution to journalArticle

Buitenkamp, TD, Izraeli, S, Zimmermann, M, Forestier, E, Heerema, NA, Van Den Heuvel-Eibrink, MM, Pieters, R, Korbijn, CM, Silverman, LB, Schmiegelow, K, Liang, DC, Horibe, K, Arico, M, Biondi, A, Basso, G, Rabin, KR, Schrappe, M, Cario, G, Mann, G, Morak, M, Panzer-Grümayer, R, Mondelaers, V, Lammens, T, Cav́, H, Stark, B, Ganmore, I, Moorman, A, Vora, A, Hunger, SP, Pui, CH, Mullighan, CG, Manabe, A, Escherich, G, Kowalczyk, JR, Whitlock, JA & Zwaan, CM 2014, 'Acute lymphoblastic leukemia in children with Down syndrome: A retrospective analysis from the Ponte di Legno study group', Blood, vol. 123, no. 1, pp. 70-77. https://doi.org/10.1182/blood-2013-06-509463
Buitenkamp TD, Izraeli S, Zimmermann M, Forestier E, Heerema NA, Van Den Heuvel-Eibrink MM et al. Acute lymphoblastic leukemia in children with Down syndrome: A retrospective analysis from the Ponte di Legno study group. Blood. 2014 Jan 2;123(1):70-77. https://doi.org/10.1182/blood-2013-06-509463
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 ; Cav́, Hèléne ; Stark, Batia ; Ganmore, Ithamar ; Moorman, Anthony ; Vora, Ajay ; Hunger, Stephen P. ; Pui, Ching Hon ; Mullighan, Charles G. ; Manabe, Atsushi ; Escherich, Gabriele ; Kowalczyk, Jerzy R. ; Whitlock, James A. ; Zwaan, C. Michel. / Acute lymphoblastic leukemia in children with Down syndrome : A retrospective analysis from the Ponte di Legno study group. In: Blood. 2014 ; Vol. 123, No. 1. pp. 70-77.
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T1 - Acute lymphoblastic leukemia in children with Down syndrome

T2 - 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 - Cav́, Hèléne

AU - Stark, Batia

AU - Ganmore, Ithamar

AU - Moorman, Anthony

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 3 109/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 DSALLs. 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. (Blood. 2014; 123(1):70-77).

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 3 109/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 DSALLs. 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. (Blood. 2014; 123(1):70-77).

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