Incidence and prognostic relevance of genetic variations in T-cell lymphoblastic lymphoma in childhood and adolescence

被引：98

作者：

Bonn, Bettina R. ^{[1
,2
]}

Rohde, Marius ^{[1
,2
]}

Zimmermann, Martin ^{[1
,2
]}

Krieger, David ^{[1
,2
,3
]}

Oschlies, Ilske ^{[4
,5
,6
]}

Niggli, Felix ^{[7
]}

Wrobel, Grazyna ^{[8
]}

Attarbaschi, Andishe ^{[9
]}

Escherich, Gabriele ^{[10
]}

Klapper, Wolfram ^{[4
,5
,6
]}

Reiter, Alfred ^{[1
,2
]}

Burkhardt, Birgit ^{[1
,2
,11
,12
]}

机构：

[1] Univ Giessen, Nonhodgkin Lymphoma Berlin Frankfurt Munster Grp, D-35390 Giessen, Germany

[2] Univ Giessen, Dept Pediat Hematol & Oncol, D-35390 Giessen, Germany

[3] Univ Giessen, Dept Internal Med 5, D-35390 Giessen, Germany

[4] Univ Kiel, Dept Pathol, Hematopathol Sect, Kiel, Germany

[5] Univ Kiel, Lymph Node Registry, Kiel, Germany

[6] Univ Hosp Schleswig Holstein, Kiel, Germany

[7] Childrens Univ Hosp, Dept Pediat Hematol & Oncol, Zurich, Switzerland

[8] Med Univ Wroclaw, Dept Bone Marrow Transplantat & Childhood Oncol &, Wroclaw, Poland

[9] Med Univ Vienna, Dept Pediat Hematol & Oncol, St Anna Childrens Hosp, Vienna, Austria

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

[11] Univ Childrens Hosp Munster, NHL BFM Study Ctr, D-48149 Munster, Germany

[12] Univ Childrens Hosp Munster, Dept Pediat Hematol & Oncol, D-48149 Munster, Germany

来源：

BLOOD | 2013年 / 121卷 / 16期

关键词：

HIGH-DOSE METHOTREXATE; NOTCH1; MUTATIONS; FBXW7; CYTOGENETIC ABNORMALITIES; LEUKEMIA; CHILDREN; IMPACT; PROTOCOL; COMPLEX; HETEROZYGOSITY;

D O I：

10.1182/blood-2012-12-474148

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Probability of event-free survival (pEFS) in pediatric T-cell lymphoblastic lymphoma is about 80%, whereas survival in relapsed patients is very poor. No stratification criteria have been established so far. Recently, activating NOTCH1 mutations were reported to be associated with favorable prognosis, and loss of heterozygosity at chromosome 6q (LOH6q) was reported to be associated with increased relapse risk. The current project was intended to evaluate the prognostic effect of these markers. Mutations in hot spots of NOTCH1 and FBXW7 were analyzed in 116 patients. Concerning LOH6q status, 118 patients were investigated, using microsatellite marker analysis, in addition to an earlier reported cohort of 99 available patients. Ninety-two cases were evaluable for both analyses. All patients were treated with T-cell lymphoblastic lymphoma-Berlin-Frankfurt-Munster group (BFM)-type treatment. LOH6q was observed in 12% of patients (25/217) and associated with unfavorable prognosis (pEFS 27% +/- 9% vs 86% +/- 3%; P < .0001). In 60% (70/116) of the patients, NOTCH1 mutations were detected and associated with favorable prognosis (pEFS 84% +/- 5% vs 66% +/- 7%; P = .021). Interestingly, NOTCH1 mutations were rarely observed in patients with LOH in 6q16. Both prognostic markers will be used as stratification criteria in coming Non-Hodgkin Lymphoma-BFM trials.

引用

页码：3153 / 3160

页数：8

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