Clinical lymphoma, myeloma & leukemia · 2022
Clinico-hematological and Outcome Profile of Pediatric B-other-ALL and BCR::ABL1-like pre-B-ALL: An Integrated Genomic Study From North India.
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Peyam Srinivasan, Bhatia Prateek, Singh Minu, Sharma Pankaj, Sreedharanunni Sreejesh, Sachdeva Manupdesh S, Naseem Shano, Bansal Deepak, Varma Neelam, Thakur Rozy, Trehan Amita
Аннотация
PURPOSE: BCR::ABL1-like pre-B-ALL comprises a myriad of genetic lesions making molecular diagnosis challenging and expensive. Its frequency and outcome are less studied in resource-constraint settings.
METHODS: 154 pre-B-ALL cases (0-12 years) were enrolled as group 1 (37 cases of B-other-ALL) and group 2 (117 patients with recurrent translocations/ hyperdiploidy). Group 1 was evaluated for BCR::ABL1-like genetic lesions and copy-number abnormalities (CNAs) as per our published PACE approach supplemented with targeted RNA sequencing.
RESULTS: BCR::ABL1-like frequency was 5.2% (8 of 154) and 22% (8 of 37) with the PACE approach alone in the whole and B-other-ALL cohort, respectively. The addition of targeted RNA-sequencing had led to the frequency increasing to 9% (14 of 154) and 38% (14 of 37) in the whole and B-other-ALL cohort, respectively. P2RY8::CRLF2, IGH::CRLF2, and RCSD1::ABL1 were noted in 8 (57.1%), 4 (28.6%), and 2 (14.3%) patients, respectively. CNAs were noted in 56.7% (21 of 37) of patients. The BCR::ABL1-like group had a significantly higher initial WBC count of ≥ 50,000/mm3 (71.4%; P < .001) than group 2. The 4-year OS, EFS, RFS of group 1 was not statistically different from group 2, though RFS was borderline poor (84.2%, 51.7%, 56.9% Vs. 82.6%, 62.9%, 78% [P - .42, P - .53, P - .059]). The 4-year EFS and RFS for BCR::ABL1-like cases was 70.7% and 76.6%, respectively.
CONCLUSIONS: The sensitivity of detecting BCR::ABL1-like lesions had increased significantly from 22% using the PACE approach alone to 38% in B-other-ALLs with the integrated approach. Although outcomes were not statistically different, a higher percentage of relapses were noted in the B-other-ALL group.
METHODS: 154 pre-B-ALL cases (0-12 years) were enrolled as group 1 (37 cases of B-other-ALL) and group 2 (117 patients with recurrent translocations/ hyperdiploidy). Group 1 was evaluated for BCR::ABL1-like genetic lesions and copy-number abnormalities (CNAs) as per our published PACE approach supplemented with targeted RNA sequencing.
RESULTS: BCR::ABL1-like frequency was 5.2% (8 of 154) and 22% (8 of 37) with the PACE approach alone in the whole and B-other-ALL cohort, respectively. The addition of targeted RNA-sequencing had led to the frequency increasing to 9% (14 of 154) and 38% (14 of 37) in the whole and B-other-ALL cohort, respectively. P2RY8::CRLF2, IGH::CRLF2, and RCSD1::ABL1 were noted in 8 (57.1%), 4 (28.6%), and 2 (14.3%) patients, respectively. CNAs were noted in 56.7% (21 of 37) of patients. The BCR::ABL1-like group had a significantly higher initial WBC count of ≥ 50,000/mm3 (71.4%; P < .001) than group 2. The 4-year OS, EFS, RFS of group 1 was not statistically different from group 2, though RFS was borderline poor (84.2%, 51.7%, 56.9% Vs. 82.6%, 62.9%, 78% [P - .42, P - .53, P - .059]). The 4-year EFS and RFS for BCR::ABL1-like cases was 70.7% and 76.6%, respectively.
CONCLUSIONS: The sensitivity of detecting BCR::ABL1-like lesions had increased significantly from 22% using the PACE approach alone to 38% in B-other-ALLs with the integrated approach. Although outcomes were not statistically different, a higher percentage of relapses were noted in the B-other-ALL group.