Publication Date:
2016-12-02
Description:
Background:Ph-like acute lymphoblastic leukemia (ALL) is a high-risk subtype of ALL in children. There are limited and conflicted data on the incidence and prognosis of Ph-like ALL in adults. Methods:Patients with newly-diagnosed B-ALL who received frontline chemotherapy at MD Anderson Cancer Center underwent gene expression profiling of leukemic cells to identify Ph-like ALL. Gene expression profiling was performed on 148 RNA samples using either U133 Plus 2.0 microarrays, or a customized Taqman low density array (LDA) card to identify patients with the Ph-like ALL gene signature (Roberts et al. NEJM 2014). An additional 7 previously untreated patients were found to have CRLF2 overexpression by multicolor flow-cytometry (MFC), and received induction chemotherapy at MDACC were included in the outcome analysis (but not for subtype frequency calculation). We performed targeted sequencing of 303 recurrently mutated genes (L300 panel, MDACC) in 40 patients with CRFL2 rearrangements (15 with matched germline control). Minimal residual disease (MRD) was assessed by MFC, with a sensitivity of 0.01%. Results:Of 148 patients, 49 (33.1%) were Ph-like, 46 patients (31.1%) were Ph+, and 53 patients (35.8%) were of other B-ALL subtypes (B-other). The median age of Ph-like cohort was 33.5 years (range, 15-71), Ph+ cohort was 49 years (range, 22-84), and B-other was 38 years (range, 15-79). Within the Ph-like ALL cohort, 61% had overexpression of CRLF2. Patients received hyper-CVAD (80%) or an augmented-BFM regimen (20%). The rate of CR/CRp was similar in the 3 disease subgroups (Ph-like ALL 89%, Ph+ ALL 93%, B-other 94%, p = 0.57). However, patients with Ph-like ALL were significantly less likely to achieve MRD-negative remission (30% vs. 56% for Ph+ ALL vs. 87% for B-other, p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine