T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993)

David I Marks, Elisabeth M Paietta, Anthony V Moorman, Susan M Richards, Georgina Buck, Gordon DeWald, Adolfo Ferrando, Adele K Fielding, Anthony H Goldstone, Rhett P Ketterling, Mark R Litzow, Selina M Luger, Andrew K McMillan, Marc R Mansour, Jacob M Rowe, Martin S Tallman, Hillard M Lazarus, David I Marks, Elisabeth M Paietta, Anthony V Moorman, Susan M Richards, Georgina Buck, Gordon DeWald, Adolfo Ferrando, Adele K Fielding, Anthony H Goldstone, Rhett P Ketterling, Mark R Litzow, Selina M Luger, Andrew K McMillan, Marc R Mansour, Jacob M Rowe, Martin S Tallman, Hillard M Lazarus

Abstract

The biology and outcome of adult T-cell acute lymphoblastic leukemia are poorly understood. We present here the clinical and biologic features of 356 patients treated uniformly on the prospective trial (UKALL XII/ECOG 2993) with the aim of describing the outcome and identifying prognostic factors. Complete remission was obtained in 94% of patients, and 48% survived 5 years. Positivity of blasts for CD1a and lack of expression of CD13 were associated with better survival (P = .01 and < .001, respectively). NOTCH1 and CDKN2A mutations were seen in 61% and 42% of those tested. Complex cytogenetic abnormalities were associated with poorer survival (19% vs 51% at 5 years, P = .006). Central nervous system involvement at diagnosis did not affect survival (47% vs 48%, P = not significant). For 99 patients randomized between autograft and chemotherapy, 5-year survival was 51% in each arm. Patients with a matched sibling donor had superior 5-year survival to those without donors (61% vs 46%, chi(2), P = .02); this was the result of less relapse (25% vs 51% at 5 years, P < .001). Only 8 of 123 relapsed patients survive. This study provides a baseline for trials of new drugs, such as nelarabine, and may allow risk-adapted therapy in patients with poor-prognosis T-cell ALL.

Figures

Figure 1
Figure 1
Patient flow diagram.
Figure 2
Figure 2
Overall survival from diagnosis of patients with B- versus T- lineage disease.
Figure 3
Figure 3
Overall survival from diagnosis by WBC in patients with T-lineage ALL.
Figure 4
Figure 4
Effect of randomized treatment on overall survival in patients. (A) Survival curve in patients with T lineage. (B) Forest plot within lineage subgroups. Survival was measured from randomization. The forest plot represents the treatment effect (odds ratio) and its 95% CI by a square and horizontal line (within subgroups) and the center and width of a diamond (overall).
Figure 5
Figure 5
Effect of matched sibling donor availability on outcome. (A) Survival curve in patients with T lineage. (B) Forest plot of effects on relapse and on nonrelapse mortality within lineage subgroups. Survival was measured from diagnosis. Forest plot format is as in Figure 4.

Source: PubMed

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