Clinical and Prognostic Impact of Copy Number Alterations and Associated Risk Profiles in a Cohort of Pediatric B-cell Precursor Acute Lymphoblastic Leukemia Cases Treated Under ICiCLe Protocol
Sanjeev Kumar Gupta,
Minu Singh,
Pragna H. Chandrashekar,
Sameer Bakhshi,
Amita Trehan,
Ritu Gupta,
Rozy Thakur,
Smeeta Gajendra,
Preity Sharma,
Sreejesh Sreedharanunni,
Manupdesh S. Sachdeva,
Deepam Pushpam,
Neelam Varma,
Deepak Bansal,
Richa Jain,
Srinivasan Peyam,
Anthony V. Moorman,
Prateek Bhatia
Affiliations
Sanjeev Kumar Gupta
1 Laboratory Oncology Unit, BRA Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
Minu Singh
2 Hematology Oncology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Pragna H. Chandrashekar
2 Hematology Oncology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Sameer Bakhshi
3 Department of Medical Oncology, BRA Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
Amita Trehan
2 Hematology Oncology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Ritu Gupta
1 Laboratory Oncology Unit, BRA Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
Rozy Thakur
2 Hematology Oncology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Smeeta Gajendra
1 Laboratory Oncology Unit, BRA Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
Preity Sharma
1 Laboratory Oncology Unit, BRA Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
Sreejesh Sreedharanunni
4 Department of Haematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Manupdesh S. Sachdeva
4 Department of Haematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Deepam Pushpam
3 Department of Medical Oncology, BRA Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
Neelam Varma
4 Department of Haematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Deepak Bansal
2 Hematology Oncology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Richa Jain
2 Hematology Oncology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Srinivasan Peyam
2 Hematology Oncology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Anthony V. Moorman
5 Leukaemia Research Cytogenetics Group, Newcastle University Clinical and Translational Research Institute, United Kingdom
Prateek Bhatia
2 Hematology Oncology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Copy number alteration (CNA) status and CNA risk profiles of IKZF1plus, UK-ALL CNA risk groups and MRplus scores, were evaluated for clinical and prognostic impact in a cohort of 493 B-cell acute lymphoblastic leukemia cases diagnosed and treated under the Indian Collaborative Childhood Leukemia group (ICiCLe) protocol trial. Overall CNA frequency was 59% with 60% of cases showing 2-loci deletion. CDKN2A/B deletion was most common CNA (36.3%), while IKZF1 deletion and IKZF1plus profile were noted in 19.5% and 13.4% of cases, respectively. IKZF1 deletions and other CNA risk profiles were significantly associated with poor (PR)/high risk (HR) clinical and genetic profile parameters (P < 0.001). In addition, the 3-year OS, event-free survival (EFS) was significantly poor with high relapse rate (RR) of 38.6%, 46.5%, and 35.2% for IKZF1 deletions, IKZF1plus profiles, and UK-ALL CNA-intermediate risk (IR)+PR risk groups, respectively (P < 0.001). Integrated evaluation of UK-ALL CNA risk profile with ICiCLe trial risk stratification groups revealed a worse overall survival, EFS, and RR of 63.3%, 43.2%, and 35.2% for CNA-IR+PR profile compared to CNA-good risk profile (81.3%, 65.0%, and 21.0%; P < 0.001). Hence, routine CNA testing in our setting is must to identify standard risk and IR cases likely to benefit from HR treatment.
