A classification based on T cell selection-related phenotypes identifies a subgroup of childhood T-ALL with favorable outcome in the COALL studies

Abstract

During T cell selection in the thymic cortex more than 90% of the thymocytes are eliminated by apoptosis. Based on this biology, we propose to define blasts of T cell acute lymphoblastic leukemia (ALL) with the phenotype of cortical thymocytes (CD1 ؉ and/or CD4 ؉ 8 ؉ ) as selection-related (SR) and all other T-ALL immunophenotypes as non-selection-related (NSR). The COALL cooperative treatment studies for childhood ALL offer a tool to study the outcome in T-ALL subgroups as children with T-ALL are allocated uniformly to the high risk arm of the protocol. In the COALL-85, -89 and -92 protocols, 39/83 cases presented as SR and 44/83 cases as NSR. Five-year event-free survival of SR phenotype is significantly better compared to the NSR group (0.87 ± 0.06 vs 0.66 ± 0.07, log rank test, P = 0.01). T-ALL with SR phenotype is a distinct subgroup of leukemia with excellent prognosis under a high risk treatment protocol.

In vitro susceptibility to dexamethasone- and doxorubicin-induced apoptotic cell death in context of maturation stage, responsiveness to interleukin 7, and early cytoreduction in vivo in childhood T-cell acute lymphoblastic leukemia

“…CD1a ϩ T-ALL, previously shown as a prognostically favorable subgroup in 3 representative and independent clinical trials, [3][4][5] disclosed in our study an increased in vitro susceptibility to both dexamethasone-and doxorubicin-induced cell death, compared with pro-/pre-T-ALL as well as mature T-ALL. The observed maturation-dependent difference may reflect a generally higher susceptibility to chemotherapy-induced cell death in cortical T-ALL.…”

“…1,2 However, within T-ALL a heterogeneous therapeutic response has been observed and, in recent years, immunophenotypic studies identified CD markers whose expression patterns distinguish prognostic subgroups in childhood T-ALL. T-ALL patients with a cortical (CD1a ϩ ) immunophenotype were identified as a subgroup with favorable outcome in the acute lymphoblastic leukemia-Berlin-Frankfurt-Mü nster (ALL-BFM) study, 3 in the Cooperative study group for childhood acute lymphoblastic leukemia (COALL) study trial, 4 and the Pediatric Oncology Group study. 5 CD2 ϩ T-ALL had a better 5-year event-free survival compared to CD2 Ϫ T-ALL in the Children's Cancer Study Group (United States) trial.…”

Antigen expression patterns reflecting genotype of acute leukemias

“…147 Patients with T-ALL showing an intermediate stage of differentiation by immunophenotype (defined as CD1a pos alone or combined with CD4 pos CD8 pos phenotype) seem to have a more favorable prognosis. 110,111,149 Although once considered associated with a more favorable outcome, neither CD2 nor CD10 expression have been associated with a different prognosis in a recent trial. 110 A new t(5;14)(q35;q32) translocation has recently been described.…”

True

“…Recently, Niehues et al 14 reported results of the COALL studies in pediatric patients with T-ALL. Their data suggest that T-ALL blasts with the phenotype of cortical thymocytes (CD1 positive and/or CD4 positive, CD8 positive) have a thymic selection-related (SR) phenotype, which may correlate with an increased susceptibility to apoptosis.…”

“…[10][11][12][13][14] Some cooperative groups have placed any patient with the T-ALL immunophenotype in a higher risk group in treatment assignment, regardless of other commonly used prognostic determinants, such as age and WBC. 8,9,[14][15][16][17] Other groups have used the same age and WBC-defined risk categories in designating intensity of treatment for both B-precursor and for T-ALL; 11,18,19 but some of these have assigned any patient with a mediastinal mass and the T immunophenotype to a higher risk category. 11,20,21 Furthermore, many groups have employed the identical risk-1697 Table 1 T3 treatment regimen Reprinted with permission from Amylon et al 12 effective in T cell disease.…”