Aberrant T-Cell Antigen Expression in B-Cell Acute Lymphoblastic Leukemia: An Adverse Prognostic Factor?
SR Hussein, DW Sevilla, A Colovai, VV Murty, G Bhagat, B Alobeid. Columbia University Medical Center, New York, NY
Background: Aberrant T-cell antigen expression is a rare occurrence in B-cell acute lymphoblastic leukemia (T Ag+ B-ALL) and has been documented in the literature mostly as single case reports. In this study, we evaluated cytogenetic abnormalities, T-cell receptor gene rearrangements, and clinical features of all T Ag+ B-ALL occurring at our institution over a 6 year period.
Design: 128 consecutive B-ALL were reviewed (2003-2009) for expression of ≥1 T-cell antigens by flow cytometry (at diagnosis and/or relapse). Expression of other non B-lineage antigens, CD13, CD33, and CD16/56, was also noted. Antigen expression in ≥20% of cells was considered positive. Clinical parameters including age, sex, WBC, and outcomes were assessed. Pathologic studies included flow cytometry, G-band karyotype analysis, and FISH using probes for hyperdiploidy, TEL/AML1, MLL, BCR/ABL,TCF3/PBX1, p53/ATM, and p16/CEP9, and PCR analyses for immunoglobulin heavy chain and T-cell receptor gene rearrangement.
Results: 12 cases of T Ag+ B-ALL were identified representing 9.3% of all B-ALL (age: 8 months to 43 years, median 12.5 years; male:female 5:7). 10/12 were in high-risk age groups, <1 year (2/12) and >10 years (8/12). WBC at diagnosis ranged from 4 to 171 (x10^9/l) and 4/12 had WBC >50. Aberrant T-cell antigens included CD2 (6/12), CD7 (5/12), and CD5 (3/12); 2/12 expressed 2 T-cell antigens (CD2 and CD7). None met criteria for biphenotypic leukemia. In addition, 5/12 expressed CD13 and CD33 and 3/12 expressed CD16/56. 10/12 had cytogenetic abnormalities at diagnosis and/or relapse: 6/12 had complex karyotypes (≥3 abnormalities), 3/12 <3 abnormalities (simple karyotype), and 3/12 normal karyotype. 7/12 had poor prognosis FISH abnormalities (2 MLL rearrangements, 4 p16 deletions and 2 p53 deletions). All 12 cases demonstrated IgH rearrangement, while 5 of 9 cases tested showed TCR rearrangement (3/5 at initial diagnosis, 2/5 at relapse). 9/12 cases achieved initial remission. 9/12 had >1 year follow up, of which 6 relapsed. The remaining 3 had <1 year follow-up and are still in remission.
Conclusions: T Ag+ B-ALL is uncommon. CD2 is the most frequently expressed T-cell antigen, followed by CD7. In our experience, T Ag+ B-ALL is frequently associated with adverse prognostic factors. The majority demonstrated poor prognostic cytogenetic abnormalities and occurred in high-risk age groups. Two thirds of patients with >1 year follow up, relapsed, a rate higher than expected for B-ALL.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 187, Tuesday Afternoon