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

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.