Improved Outcomes of Childhood Acute Lymphoblastic Leukemia: A Retrospective Single Center Study in Saudi Arabia

Abstract

Objective: Understanding the clinical and genetic characteristics of pediatric acute lymphoblastic leukemia (ALL)<br /> patients may help assigning the appropriate treatment. This study aims to understand patients' characteristics, "real-world"<br /> treatment practice and outcomes of pediatric ALL.

Methods: A cohort of 213 pediatric ALL patients, treated at (King<br /> Faisal Specialist Hospital and Research Center -Jeddah branch) KFSH and RC-J during the period of January 2002 to<br /> December 2015 were analyzed retrospectively. Statistical analyses were performed on patients' demographic, clinical<br /> and genetics characteristics and outcomes of different treatment protocols. Survival was evaluated using Kaplan-Meier<br /> method, and differences in survival were tested using Log-Rank. Significance was set at 0.05 level.

Results: Median<br /> age of the study cohort was 5 years (range 0.5-15 years) with 55.4% of male population. Majority of the patients had<br /> pre-B-cell ALL (88.7%), WBC count <50, 000/μL at diagnosis (76.1%, median = 13.5/μL with a range of 0.51-553.0/<br /> μL) with involvement of central nervous system (CNS) disease in 8.5%patients.Different common chromosomal<br /> anomalies or abnormalities, including t(12, 21) translocation, MLL genre arrangements, trisomy (4, 10, 17)and others,<br /> were detected. Early response to the risk-directed treatment received by the patients (91.1% achieving <5% blast in<br /> the bone marrow) as well as the end of induction outcome (96.2%) was encouraging.

Conclusion: We found that the<br /> patients' clinical characteristics and distribution of genetic abnormalities were similar to those of the western countries.<br /> Our findings show that the earlier gap between the western countries and KSA in terms of survival has been closed and<br /> that competitive outcomes can be achieved with local infrastructure.

Keywords: Acute Lymphoblastic Leukemia; Central nervous system; Cerebrospinal fluid cytology; Chromosomal abnormalities; Cytogenetics abnormalities.

Figure 1

Frequency of Treatment Protocols Used. (A), Protocols frequently used for treating ALL children (p<0.001); (B), Abundance of protocol use for treating high risk and low risk ALL children (p <0.001)

Figure 2

Kaplan-Meier Curves Illustrating Survival Estimates. (A), OS estimate is 85.4%; (B), EFS estimate is 82.5%

Figure 3

Comparison of OS for Different Risk Factors. (A), Gender: Female patients have survival advantage over male patients (91.6% vs. 80.5%, p=0.013); (B), Immunophenotype: Precursor-B-cell ALL patients have remarkably higher OS than T-cell ALL patients (87.3% vs. 70.8%, p=0.014); (C), CNS status: ALL patients with no leukemic blasts (CNS1) had highest OS followed by with CNS2 (<5 WBC/µl positive blasts) and CNS3 (≥ 5 WBC/µl positive blasts) (88.5% vs. 76.9% vs. 61.1%, p=0.014); (D),WBC count: Patient with WBC <50 had better survival than patient with WBC ≥ 50 (88.3% vs. 76.5%)

Figure 4

Estimation of EFS for Different Risk Factors. (A), Gender: Female patients have higher EFS than male patients (90.4% vs. 76.3%, p=0.006); (B), Immunophenotype: Precursor-B-cell ALL patients have remarkably higher EFS than T-cell ALL patients (85.1% vs. 62.5%, p=0.004); (C), CNS status: ALL patients with no leukemic blasts (CNS1) had highest EFS followed by with CNS2 (<5 WBC/µl positive blasts) and CNS3 (≥5 WBC/µl positive blasts) (85.1% vs. 76.9% vs. 61.1%, p=0.053); (D), WBC count: Patient with WBC <50 had better EFS than patient with WBC ≥ 50 (85.8% vs. 72.0%, p=0.015)

Figure 5

OS in pre-B ALL. (A) Precursor-B-cell ALL patients have comparable OS in HR and LR Groups (87.2% vs. 87.5%, p=0.911); (B) When stratified according to ploidy level, OS in hyperploid Pre-B ALL patients was slightly more than non-hyperploid pre-B ALL (90.1% vs. 86.4%, p=0.557)