Abstract 564: Favorable prognostic features at diagnosis along with young age, early remission, high relapse rate and poor survival of TCF3-PBX1 positive adult ALL necessitates the need for differential genetic diagnosis and treatment using pediatric ALL protocols

Abstract

Abstract Introduction: ALL involves many genetic abnormalities, many of which lead to formation of fusion oncogenes (FGs) causing leukemogenesis1. Role of FGs in prognosis and drug selection is established in pediatric ALL but is unclear in adult AL 2 except BCR-ABL and MLL-AF4. Therefore, objective our was to find out the association of common FGs with clinical pattern. Methods: We studied 5most common FGs by RT-PCR3 and interphase FISH at diagnosis and their association with clinical features and treatment outcome in 208 adult ALL patients (2002-2012) treated with MRC UKALL XII protocol. Results: FGs were detected in 78.8% patients. Overall survival (OS) was 26.17 months (mo) and relapse free survival (RFS) was 11.147 mo. SIL-TAL1+ ALL (35.36%) manifested lymphadenopathy, frequent organomegaly, low platelets count and poor survival. BCR-ABL+ (20.3%) ALL manifested high TLC, prominent spleenomegaly, low platelets count, poor survival (OS & RFS 9.3 & 6.3 mo, respectively) and 10% less chances of 4-6 week remission as compared to BCR-ABL negative. MLL-AF4 (12.19%) was associated with elevated TLC, organomegaly, frequent CNS involvement and poor clinical outcome (OS 8.8 mo). ETV6-RUNX1 (t 12;21) (4.8%), was associated with low TLC, uncommon organomegaly, high CR rates and with higher OS (30.2 mo). Long term survival of ETV6-RUNX1 was negatively affected by frequent late relapses. Unexpectedly, TCF3-PBX1 (16.3%) was significantly higher than globally reported (3%). It was associated with younger age (59% with 15-29 years), lower TLC (82%), platelet count higher than 50×109/l (71%), less common hepatomegaly (12%), less common spleenomegaly (18%), early CR (65%), all indicative of good prognosis. Despite that, very surprisingly, high relapse rate (76.1%) and shorter OS (11.6 months) were observed in TCF3-PBX1+ patients. Discussion / Conclusions: Favorable prognosis, younger age, high 4-week CR (65%), higher relapse rates and shorter OS highlight in TCF3-PBX1+ ALL necessitate differential genetic diagnosis and intensified and treatment with pediatric protocols in this subgroup4,5. Lymphadenopathy in SIL-TAL1 can help in differential diagnosis of this subgroup (t-cell ALL) ALL in poor countries. These findings along with lower ETV6-RUNX1 frequency and higher MLL-AF4 reflect ethnic differences in disease biology and treatment outcome of adult ALL5. Overall high percentage of poor prognostic FGs may be the strongest reasons of overall poor outcome of adult ALL in our country. Therefore, routine molecular testing for ALL FGs at diagnosis and its implication in prognostic stratification and drug selection during various phases of treatment are recommended.