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

被引：176

作者：

Buitenkamp, Trudy D. ^{[1
]}

Izraeli, Shai ^{[2
,3
]}

Zimmermann, Martin ^{[4
]}

Forestier, Erik ^{[5
]}

Heerema, Nyla A. ^{[6
]}

van den Heuvel-Eibrink, Marry M. ^{[1
]}

Pieters, Rob ^{[1
,7
]}

Korbijn, Carin M. ^{[7
]}

Silverman, Lewis B. ^{[8
]}

Schmiegelow, Kjeld ^{[9
]}

Liang, Der-Cheng ^{[10
]}

Horibe, Keizo ^{[11
]}

Arico, Maurizio ^{[12
]}

Biondi, Andrea ^{[13
]}

Basso, Giuseppe ^{[14
]}

Rabin, Karin R. ^{[15
]}

Schrappe, Martin ^{[16
]}

Cario, Gunnar ^{[16
]}

Mann, Georg ^{[17
]}

Morak, Maria ^{[17
]}

Panzer-Grumayer, Renate ^{[17
]}

Mondelaers, Veerle ^{[18
]}

Lammens, Tim ^{[18
]}

Cave, Helene ^{[19
]}

Stark, Batia ^{[20
,21
]}

Ganmore, Ithamar ^{[2
,3
]}

Moorman, Anthony V. ^{[22
]}

Vora, Ajay ^{[23
]}

Hunger, Stephen P. ^{[24
,25
]}

Pui, Ching-Hon ^{[26
]}

Mullighan, Charles G. ^{[27
]}

Manabe, Atsushi ^{[28
]}

Escherich, Gabriele ^{[29
]}

Kowalczyk, Jerzy R. ^{[30
]}

Whitlock, James A. ^{[31
]}

Zwaan, C. Michel ^{[1
]}

机构：

[1] Erasmus MC Sophia Childrens Hosp, Rotterdam, Netherlands

[2] Edmond & Lily Safra Childrens Hosp, Dept Paediat Haemato Oncol, Sheba Med Ctr, Ramat Gan, Israel

[3] Tel Aviv Univ, Sch Med, IL-69978 Tel Aviv, Israel

[4] Hannover Med Sch, Stat Off, Berlin Frankfurt Munster Study Grp, Hannover, Germany

[5] Umea Univ, Dept Med Biosci, Umea, Sweden

[6] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA

[7] Dutch Childhood Oncol Grp, The Hague, Netherlands

[8] Dana Farber Canc Inst, Boston, MA 02115 USA

[9] Rigshosp, Univ Hosp, Juliane Marie Ctr, DK-2100 Copenhagen, Denmark

[10] Mackay Mem Hosp, Pediat Hematol Oncol Div, Taipei, Taiwan

[11] Nagoya Med Ctr, Natl Hosp Org, Clin Res Ctr, Nagoya, Aichi, Japan

[12] Azienda Osped Univ Meyer Children Hosp, Dept Pediat Hematol Oncol, Florence, Italy

[13] Univ Milano Bicocca, Osped S Gerardo, Dept Pediat, Monza, Italy

[14] Univ Padua, Dept Pediat Salus Pueri, Padua, Italy

[15] Baylor Coll Med, Texas Childrens Canc Ctr, Div Pediat Hematol Oncol, Houston, TX 77030 USA

[16] Univ Med Ctr Schleswig Holstein, Dept Pediat, Kiel, Germany

[17] Univ Med Sch Vienna, St Anna Childrens Hosp, Childrens Canc Res Inst, Vienna, Austria

[18] Ghent Univ Hosp, Dept Pediat Hematooncol, Ghent, Belgium

[19] Univ Paris Denis Diderot, Hop Robert Debre, AP HP, Dept Genet, Paris, France

[20] Schneider Childrens Med Ctr Israel, Ctr Pediat Hematol Oncol, Petah Tiqwa, Israel

[21] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel

[22] Newcastle Univ, Leukaemia Res Cytogenet Grp, Northern Inst Canc Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[23] Sheffield Childrens Hosp, Dept Haematol, Sheffield, S Yorkshire, England

[24] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA

[25] Childrens Hosp, Aurora, CO USA

[26] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA

[27] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA

[28] St Lukes Int Hosp, Dept Pediat, Tokyo, Japan

[29] Univ Med Ctr Hamburg Eppendorf, Clin Pediat Hematol & Oncol, Hamburg, Germany

[30] Med Univ Lublin, Dept Childrens Hematol & Oncol, Lublin, Poland

[31] Univ Toronto, Hosp Sick Children, Div Haematol Oncol, Toronto, ON M5G 1X8, Canada

来源：

BLOOD | 2014年 / 123卷 / 01期

基金：

以色列科学基金会;

关键词：

B-PROGENITOR; CLINICAL CHARACTERISTICS; PEDIATRIC-PATIENTS; CRLF2; BFM; REARRANGEMENT; DISEASE; TRIALS; CELLS; RISK;

D O I：

10.1182/blood-2013-06-509463

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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-Munster 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 x 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.

引用

页码：70 / 77

页数：8

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