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 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 (TCRalphabeta+ or TCRgammadelta+), pre-alphabeta T-ALL patients (cTCRbeta+, TCR-), and immature (IM) cTCRbeta-, 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-alphabeta, 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.
Asnafi
Vahid
V
Department of Hematology, Necker-Enfants-Malades, Saint Louis, France.
Buzyn
Agnes
A
Thomas
Xavier
X
Huguet
Francoise
F
Vey
Norbert
N
Boiron
Jean-Michel
JM
Reman
Oumedaly
O
Cayuela
Jean-Michel
JM
Lheritier
Veronique
V
Vernant
Jean-Paul
JP
Fiere
Denis
D
Macintyre
Elizabeth
E
Dombret
Hervé
H
D000293:Adolescent; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003561:Cytarabine / Q000008:administration & dosage; D005838:Genotype; D006801:Humans; D016130:Immunophenotyping; D015994:Incidence; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D011446:Prospective Studies; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D012008:Recurrence; D015996:Survival Rate
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D011948:Receptors, Antigen, T-Cell; D003561:Cytarabine; D008942:Mitoxantrone