Impact of TCR status and genotype on outcome in adult T-cell acute lymphoblastic leukemia: a LALA-94 study

被引:45
作者
Asnafi, V
Buzyn, A
Thomas, X
Huguet, F
Vey, N
Boiron, JM
Reman, O
Cayuela, JM
Lheritier, V
Vernant, JP
Fiere, D
Macintyre, E
Dombret, H
机构
[1] Necker Enfants Malades, Dept Hematol, St Louis, MO USA
[2] Hop Edouard Herriot, Assistance Publ Hop Paris, AP HP, Lyon, France
[3] Hop Purpan, Toulouse, France
[4] Inst J Paoli I Calmettes, F-13009 Marseille, France
[5] Hop Haut Leveque, Bordeaux, France
[6] Ctr Hosp Univ, Caen, France
[7] INSERM, EMIU210, F-75654 Paris, France
关键词
D O I
10.1182/blood-2004-09-3666
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Patients with T-cell acute lymphoblastic leukemias (T-ALLs) within the Leucemies Aigues Lymphoblastiques de I'Adulte-94 (LALA-94) prospective trial were treated with a 4-drug per 4-week induction, with intermediate-dose cytarabine and mitoxantrone salvage treatment for patients not achieving complete remission (CR) in 1 course. Only the latter received allografts, if possible, thus providing an informative setting for assessing early response. Representative patients with T-ALL (91 patients) were classified into surface T-cell receptor (TCR)-expressing T-ALL patients (TCR alpha beta(+) or TCR gamma delta(+) ), pre-alpha beta T-ALL patients (cTCR beta(+), TCR-), and immature (IM) cTCR beta(-), TCR- T-ALL patients; 81 patients underwent genotyping for SIL-TAL1, CALM-AF10, HOX11, and HOX11L2. Overall, CR was obtained in 81 (89%) patients; relapse rate was 62% at 4 years and overall survival (OS) rate was 38%. CR rate was significantly lower in IM T-ALL patients after 1 course (45% vs 87%; P <.001) and after salvage (74% vs 97%; P =.002), with the latter inducing a higher rate of CR (9 [64%] of 14) than initial induction. Once CR was obtained, cumulative relapse rates were similar for IM, pre-alpha beta, and TCR+ T-ALL patients (P =.51), but were higher in HOX11L2 (83%) and SIL-TAL1 (82%) T-ALL patients compared with other genetic subgroups (48%; P =.05). This was associated with an inferior OS for HOX11L2 T-ALLs (113% vs 47% in HOX11L2-T-ALLs; P=.009). The majority of patients with HOX11 TALL underwent allografting, predominantly in second CR, but were not associated with a superior OS. Both TCR and genotypic stratification can therefore contribute to risk-adapted management of adult T-ALLs. (c) 2005 by The American Society of Hematology.
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页码:3072 / 3078
页数:7
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