Patients with Early T-Cell Precursor (ETP) Acute Lymphoblastic Leukemia (ALL) Have High Levels of Minimal Residual Disease (MRD) at the End of induction—A Children's Oncology Group (COG) Study.

Abstract 9

Current risk stratification algorithms in children with B-lineage ALL have facilitated the identification of subgroups with adverse outcomes that benefit from intensified therapy. However, many of the features that are highly prognostic of outcome in B-precursor ALL, such as the combination of age and white blood cell count (WBC) at diagnosis, have limited ability to predict outcome in T-ALL. In contrast, early response to induction therapy, as measured by bone marrow (BM) morphology at days 8, 15 or 29, and day 29 (end induction) BM MRD are highly predictive of outcome in both B-precursor and T-ALL. Coustan-Smith and colleagues (Lancet Oncology 10:147-156 2009) have recently identified a subset of children with ETP ALL that have an extremely high risk of induction failure or relapse. The ETP ALL blasts exhibit stem cell-like features as defined by the presence of antigens seen on early progenitors including CD117, CD34, HLA-DR and/or CD13/33, the absence of antigens seen on later stage immature T cells including CD1a and CD8, and decreased to absent expression of the early T cell antigen CD5.

We analyzed patients enrolled in current generation COG ALL trials, including patients with B-precursor ALL treated on AALL0232 (high risk, n=2129) or AALL0331 (standard risk, n=3747), and 416 patients with T-ALL enrolled on AALL03B1. Clinical features including age, WBC, gender, and CNS status were compared between ETP-positive (n=25) and –negative (n=391) T-ALL patients. We also compared response to four weeks of induction therapy (prednisone, vincristine, PEG-asparaginase, and daunorubicin) as measured by day 15 and 29 BM morphology and day 29 BM MRD determined by flow cytometry. Twenty-five of 416 (6%) T-ALL patients had an ETP phenotype. The ETP-positive patients were older and presented with a lower white blood cell count than the ETP-negative patients (see Table). There was no difference in the gender distribution or the presence of CNS disease at diagnosis between the two groups. Strikingly, the ETP-positive patients had a dramatically inferior early response to therapy with 100% having ≥ 0.01% day 29 MRD (vs. 46% of ETP-negative T-ALL and 23.4% of precursor B-ALL) and 74% having ≥ 1% day 29 MRD (vs. 21% of ETP-negative T-ALL and 5% of precursor B-ALL). These results confirm the poor response of ETP T-ALL and suggest that novel treatment strategies are warranted in this patient subgroup.