Outcome Of Standard Risk B-Precursor Acute Lymphoblastic Leukemia Treated Following The Children’s Cancer Group-1991 (CCG-1991) Study: Experience From a Single Center In Saudi Arabia
Authors: Jastaniah Wasil , Elimam Naglla , Abdalla Khalid , Abrar Mohammed Burhan , Khattab Taha , Cittana Iqbal Basheer Ahmed , Felimban Sami 
Published: October 2019

Abstract

Background
Remarkable improvements in the treatment of childhood acute lymphoblastic leukemia (ALL) have been achieved primarily because of the work of cooperative groups such as the Children’s Oncology Group. The objective of the present study was to compare survival outcomes among children with standard-risk (SR) B-precursor acute lymphoblastic leukemia (ALL) treated at Princess Norah Oncology Center, Jeddah, Saudi Arabia, with survival outcomes of the Children’s Cancer Group-1991 (CCG-1991).

Methods
A retrospective study of newly diagnosed SR B-precursor ALL children during the period January 2000 to December 2007 and treated on CCG-1991 protocol following the oral methotrexate/double delayed intensification arm (regimen OD). Medical records of patients were reviewed. Data collected include: age, sex, WBC, date of: diagnosis, remission, induction, relapse, death, last follow-up; cytogenetics, phenotype at diagnosis, CNS status, toxicity, and outcome.

Statistical Analysis
Overall survival (OS) was calculated from the time of diagnosis to the time of death from any cause or until the last follow-up for surviving patients. Event-free survival (EFS) was measured from the date of diagnosis until the occurrence of first event (failure to achieve remission, relapse, death from any cause, or until the last follow-up). Kaplan-Meier method was used to estimate survival rates.

Results
A total of 123 SR B-precursor ALL patients were treated following CCG-1991 (regimen OD). The median duration of follow up was 7 (range: 0.03 – 11.7) years. Median age was 3.9 (range: 1.5 – 9.6) years and the median WBC count was 5.6 (range: 0.9 – 16.7) x 109/L. There were 67 male patients accounting for 54.5% compared to 56 (45.5%) females. The 5-year EFS and OS for SR B-precursor ALL patients were 79.4%±3.7% and 86%±3.2%, respectively. In total, 19 (15.4%) patients had relapse as first event. Death as first event occurred in 6 (4.9%) patients. Of this, 3 (2.4%) occurred during induction, and 3 (2.4%) occurred while in remission.
Comparison of treatment outcomes revealed that our patients had inferior 5-year EFS and OS compared to those reported in the CCG-1991 study (EFS and OS rates of 90.7%±0.9% and 96.2%±0.6%; respectively). The difference is significant and may have been due to treatment regimen, as all our patients were treated with regimen OD. However, when comparison was limited to patients treated with regimen OD in the CCG-1991 study (EFS and OS rates of 88.7%±1.4% and 96%±0.9%; respectively), the difference in survival outcome remained significant.

Conclusion
We postulate that clinical and biological factors may have contributed for the outcome to vary between the present and the CCG-1991 study. The high incidence of death as first event in our patient population may be related to these factors and deserves further exploration. The fact that our patients were not on clinical trial and were treated following a standard protocol may have contributed to this variation. This underscores the need to further refine risk stratification.

Disclosures:
No relevant conflicts of interest to declare.