Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study

被引：326

作者：

Balgobind, Brian V. ^{[1
]}

Raimondi, Susana C. ^{[2
,3
]}

Harbott, Jochen ^{[4
]}

Zimmermann, Martin ^{[5
]}

Alonzo, Todd A. ^{[3
]}

Auvrignon, Anne ^{[6
]}

Beverloo, H. Berna ^{[7
,8
]}

Chang, Myron ^{[9
]}

Creutzig, Ursula ^{[10
]}

Dworzak, Michael N. ^{[11
]}

Forestier, Erik ^{[12
]}

Gibson, Brenda ^{[13
]}

Hasle, Henrik ^{[14
]}

Harrison, Christine J. ^{[15
]}

Heerema, Nyla A. ^{[3
,16
]}

Kaspers, Gertjan J. L. ^{[17
,18
]}

Leszl, Anna ^{[19
]}

Litvinko, Nathalia ^{[20
]}

Lo Nigro, Luca ^{[21
]}

Morimoto, Akira ^{[22
,23
]}

Perot, Christine ^{[6
]}

Pieters, Rob

Reinhardt, Dirk ^{[5
]}

Rubnitz, Jeffrey E. ^{[2
]}

Smith, Franklin O. ^{[3
,24
,25
]}

Stary, Jan ^{[26
,27
]}

Stasevich, Irina ^{[20
]}

Strehl, Sabine ^{[11
]}

Taga, Takashi ^{[22
,28
]}

Tomizawa, Daisuke ^{[22
,29
]}

Webb, David ^{[17
,30
]}

Zemanova, Zuzana ^{[31
,32
]}

Zwaan, C. Michel ^{[1
]}

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

机构：

[1] Erasmus MC, Sophia Childrens Hosp, Dept Pediat Oncol Hematol, NL-3000 CB Rotterdam, Netherlands

[2] St Jude Childrens Res Hosp, Memphis, TN 38105 USA

[3] Childrens Oncol Grp, Arcadia, CA USA

[4] Univ Giessen, Acute Myeloid Leukemia Berlin Frankfurt Munster S, Dept Pediat Hematol & Oncol, Giessen, Germany

[5] Hannover Med Sch, Acute Myeloid Leukemia Berlin Frankfurt Munster S, D-3000 Hannover, Germany

[6] Hop Trousseau, F-75571 Paris, France

[7] Dutch Working Grp Hematooncol Genome Diagnost, Dutch Childhood Oncol Grp, The Hague, Netherlands

[8] Erasmus MC, Dept Clin Genet, NL-3000 CB Rotterdam, Netherlands

[9] Ctr Data, Childrens Oncol Grp, Gainesville, FL USA

[10] Univ Hosp, Acute Myeloid Leukemia Berlin Frankfurt Munster S, Munster, Germany

[11] St Anna Childrens Hosp, Childrens Canc Res Inst, A-1090 Vienna, Austria

[12] Umea Univ Hosp, Nord Soc Pediat Hematol & Oncol, Dept Clin Sci, S-90185 Umea, Sweden

[13] Royal Hosp Sick Children, Dept Pediat Oncol Hematol, Glasgow G3 8SJ, Lanark, Scotland

[14] Aarhus Univ, Nord Soc Pediat Hematol & Oncol, Dept Pediat, Hosp Skejby, Aarhus, Denmark

[15] Univ Newcastle, No Inst Canc Res, Newcastle Upon Tyne, Tyne & Wear, England

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

[17] Berlin Frankfurt Munster Study Grp, Acute Myeloid Leukemia Comm 1, Frankfurt, Germany

[18] Vrije Univ Amsterdam, Med Ctr, Dept Pediat Oncol Hematol, Amsterdam, Netherlands

[19] Univ Padua, Pediat Clin, Italian Assoc Pediat Hematol Oncol, Padua, Italy

[20] Res Ctr Pediat Oncol & Hematol, Minsk, BELARUS

[21] Univ Catania, Pediat Clin, Italian Assoc Pediat Hematol Oncol, Catania, Italy

[22] Japanese Pediat Leukemia Lymphoma Study Grp, Tokyo, Japan

[23] Jichi Med Univ, Dept Pediat, Jichi, Tochigi, Japan

[24] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA

[25] Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA

[26] Charles Univ Prague, Univ Hosp Motol, Prague, Czech Republic

[27] Charles Univ Prague, Sch Med 2, Prague, Czech Republic

[28] Shiga Univ Med Sci, Dept Pediat, Shiga, Japan

[29] Tokyo Med & Dent Univ, Dept Pediat & Dev Biol, Tokyo, Japan

[30] Great Ormond St Hosp Sick Children, London WC1N 3JH, England

[31] Charles Univ Prague, Ctr Oncocytogenet, Gen Univ Hosp, Prague, Czech Republic

[32] Charles Univ Prague, Fac Med 1, Prague, Czech Republic

来源：

BLOOD | 2009年 / 114卷 / 12期

关键词：

ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOBLASTIC-LEUKEMIA; PEDIATRIC-ONCOLOGY-GROUP; CHILDRENS-CANCER; AML; TRIALS; MLL; MULTICENTER; ADOLESCENTS; OUTCOMES;

D O I：

10.1182/blood-2009-04-215152

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Translocations involving chromosome 11q23 frequently occur in pediatric acute myeloid leukemia (AML) and are associated with poor prognosis. In most cases, the MLL gene is involved, and more than 50 translocation partners have been described. Clinical outcome data of the 11q23-rearranged subgroups are scarce because most 11q23 series are too small for meaningful analysis of subgroups, although some studies suggest that patients with t(9;11)(p22;q23) have a more favorable prognosis. We retrospectively collected outcome data of 756 children with 11q23- or MLL-rearranged AML from 11 collaborative groups to identify differences in outcome based on translocation partners. All karyotypes were centrally reviewed before assigning patients to subgroups. The event-free survival of 11q23/MLL-rearranged pediatric AML at 5 years from diagnosis was 44%(+/- 5%), with large differences across subgroups (11% +/- 5% to 92% +/- 5%). Multivariate analysis identified the following subgroups as independent prognostic predictors: t(1;11)(q21;q23) (hazard ratio [HR] = 0.1, P = .004); t(6;11)(q27;q23) (HR = 2.2, P < .001); t(10;11)(p12;q23) (HR = 1.5, P = .005); and t(10;11)(p11.2;q23) (HR = 2.5, P = .005). We could not confirm the favorable prognosis of the t( 9; 11)( p22; q23) subgroup. We identified large differences in outcome within 11q23/MLL-rearranged pediatric AML and novel subgroups based on translocation partners that independently predict clinical outcome. Screening for these translocation partners is needed for accurate treatment stratification at diagnosis. (Blood. 2009; 114: 2489-2496)

引用

页码：2489 / 2496

页数：8

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