[1614] Negative TdT Expression Predicts Adverse Treatment Outcome in T-Lymphoblastic Leukemia/Lymphoma in Adults

Yi Zhou, Mark Routbort, Ken H Young, Sa Wang, Daniela Hoehn, Guilin Tang, Carlos Bueso-Ramos, C Cameron Yin, Roberto N Miranda, L Jeffrey Medeiros, Pei Lin. The University of Texas, MD Anderson Cancer Center, Houston, TX

Background: T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) is an aggressive disease that requires intensive chemotherapy regimens such as hyperfractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone (Hyper-CVAD). With this therapy, approximately 90% of the patients initially achieve complete remission. Nevertheless, a significant subset of patients relapses and succumbs to recurrent disease. Unlike patients with B-ALL/LBL, there is currently no risk stratification scheme for T-ALL/LBL patients. To identify the high-risk patients who may benefit from stem cell transplant during the first remission is clinically challenging. A readily accessible prognostic marker for high-risk T-ALL/LBL is essential for risk-adapted therapy and improved outcome.
Design: We reviewed available data of T-ALL/LBL patients treated at our institution between 2003 and 2011 (n=106), and identified TdT negative cases. Negative TdT immunoreactivity was defined as <10% neoplastic cells positive by combined flow cytometric immunophenotyping and immunohistochemical staining. All cases were positive for cytoplasmic CD3. Clinical, morphologic, immunophenotypic and cytogenetic data were reviewed. Relapse-free survival and overall survival were calculated using Kaplan-Meier survival analysis.
Results: We identified 17 (16%) cases of TdT-negative T-ALL/LBL: 8 de novo and 9 relapsed. There were 12 men and 5 women with a median age of 30 years (range, 13 to 62). The median follow-up period was 12 mo (range, 2.9 to 42.3 mo). The immunophenotype was pro-T/pre-T (CD34+) in 8 neoplasms, cortical-T (CD1+) in 5, or other (CD34-/CD1-/CD4-/CD8-) in 4. Of 16 cases with cytogenetic data, 11 had a complex karyotype, 4 were diploid, and 1 had isolated add(3). All patients received intensive chemotherapy, including hyper-CVAD, as frontline or salvage treatment. The estimated relapse-free and overall survival at 2 years was 8 % and 24%, respectively. Among the 8 de novo patients, the estimated relapse-free and overall survival at 1 year was about 24%. Relapse-free and overall survival in this patient group was significantly worse than those of age-matched TdT positive T-ALL/LBL patients treated during the same period (p<0.01).
Conclusions: About 15% of patients with T-ALL/LBL are negative for TdT immunoreactivity, and respond poorly to intensive chemotherapy. Stem cell transplant during first remission may be beneficial for this group of patients.
Category: Hematopathology

Tuesday, March 20, 2012 8:45 AM

Platform Session: Section C, Tuesday Morning

 

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