Central nervous system status is prognostic in T-cell acute lymphoblastic leukemia: a Children’s Oncology Group report.

To determine the prognostic significance of central nervous system (CNS)
leukemic involvement in newly diagnosed T-cell acute lymphoblastic leukemia
(T-ALL), outcomes on consecutive, phase 3 Children’s Oncology Group
clinical trials were examined. AALL0434 and AALL1231 tested efficacy of
novel agents within augmented-Berlin-Frankfurt-Münster (aBFM) therapy. In
addition to testing study-specific chemotherapy through randomization, the
AALL0434 regimen delivered cranial radiation therapy (CRT) to most
participants (90.8%), whereas AALL1231 intensified chemotherapy to
eliminate CRT in 88.2% of participants. In an analysis of 2164 patients
with T-ALL (AALL0434, 1550; AALL1231, 614), 1564 had CNS-1 (72.3%), 441
CNS-2 (20.4%), and 159 CNS-3 (7.3%). The 4-year event-free-survival (EFS)
was similar for CNS-1 (85.1% ± 1.0%) and CNS-2 (83.2% ± 2.0%), but lower
for CNS-3 (71.8% ± 4.0%; P = .0004). Patients with CNS-1 and CNS-2 had
similar 4-year overall survival (OS) (90.1% ± 0.8% and 90.5% ± 1.5%,
respectively), with OS for CNS-3 being 82.7% ± 3.4% (P = .005). Despite
therapeutic differences, outcomes for CNS-1 and CNS-2 were similar
regardless of CRT, intensified corticosteroids, or novel agents. Except for
significantly superior outcomes with nelarabine on AALL0434 (4-year
disease-free survival, 93.1% ± 5.2%), EFS/OS was inferior with CNS-3
status, all of whom received CRT. Combined analyses of >2000 patients with
T-ALL identified that CNS-1 and CNS-2 status at diagnosis had similar
outcomes. Unlike B-ALL, CNS-2 status in T-ALL does not impact outcome with
aBFM therapy, without additional intrathecal therapy, with or without CRT.
Although nelarabine improved outcomes for those with CNS-3 status, novel
approaches are needed. These trials were registered at
www.clinicaltrials.gov as #NCT00408005 (AALL0434) and #NCT02112916 (AALL1231).