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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3072-3078.
Prepublished online as a Blood First Edition Paper on January 6, 2005; DOI 10.1182/blood-2004-09-3666.


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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS

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

Vahid Asnafi, Agnes Buzyn, Xavier Thomas, Francoise Huguet, Norbert Vey, Jean-Michel Boiron, Oumedaly Reman, Jean-Michel Cayuela, Veronique Lheritier, Jean-Paul Vernant, Denis Fiere, Elizabeth Macintyre, and Hervé Dombret

From the Department of Hematology, Necker-Enfants-Malades, Saint Louis, and Pitie-Salpetriere; Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Edouard Herriot, Lyon; Hopital Purpan, Toulouse; Institut Paoli Calmettes, Marseille; Hopital du Haut Leveque, Bordeaux; Centre Hospitalier Universitaire, Caen; and INSERM EMIU210, France.

Patients with T-cell acute lymphoblastic leukemias (T-ALLs) within the Leucémies Aiguës Lymphoblastiques de l'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 (13% vs 47% in HOX11L2-T-ALLs; P = .009). The majority of patients with HOX11 T-ALL 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.


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