|Year : 2018 | Volume
| Issue : 1 | Page : 14-18
Clinical characteristics and outcomes of acute lymphoblastic leukaemia in children treated at a single tertiary hospital in Riyadh, Saudi Arabia
Ali S Al Omari, Talal Alshareef Hussein, Khaled Abdullah Albarrak, Abdulrahman Khalid Habib, Alzubeir Anas Sambas, Nagham Sheblaq, Aamir Omair
Department of Paediatric Oncology, King Abdulaziz Medical City, Riyadh, Saudi Arabia
|Date of Web Publication||8-Jan-2018|
Talal Alshareef Hussein
Department of Paediatric Oncology, King Abdulaziz Medical City, Riyadh
Context: Acute lymphoblastic leukaemia (ALL) is the most common paediatric cancer worldwide, and it accounts for 30% of all cancer cases in children of Saudi Arabia.
Aim: This study aims to describe the clinical characteristics and outcomes of paediatric ALL.
Settings and Design: This case series study was conducted at a single tertiary hospital in Saudi Arabia.
Methods: Clinical data and outcomes of all patients diagnosed between 2000 and 2010 were collected from medical charts using a custom data collection sheet.
Statistical Analysis: Data were analysed using SPSS. Mann–Whitney test was used to compare the median age of diagnosis between different categories as the age was not normally distributed.
Results: This study included 50 patients (median age, 4 years; 58% male). The majority (82%) had pre-B-cell ALL and 18% had T-cell ALL. Thirty-one (62%) patients were in the standard risk category, 18 (36%) in the high-risk category and one (2%) in the very high-risk category. Forty-nine (98%) patients achieved complete remission. The remission status was M1 marrow status in 46 (94%) patients. The overall survival and event-free survival rates were 92% and 74%, respectively, with 4 (8%) deaths due to different complications.
Conclusion: This is the first 10-year case series study in a single tertiary institution in Saudi Arabia. The clinical characteristics of children with ALL were similar to those reported in the literature. The use of well-defined treatment protocols improved the survival rates to levels that are comparable to those of developed countries.
Keywords: Immunophenotype, leukaemia, Middle East, paediatric cancer
|How to cite this article:|
Al Omari AS, Hussein TA, Albarrak KA, Habib AK, Sambas AA, Sheblaq N, Omair A. Clinical characteristics and outcomes of acute lymphoblastic leukaemia in children treated at a single tertiary hospital in Riyadh, Saudi Arabia. J Health Spec 2018;6:14-8
|How to cite this URL:|
Al Omari AS, Hussein TA, Albarrak KA, Habib AK, Sambas AA, Sheblaq N, Omair A. Clinical characteristics and outcomes of acute lymphoblastic leukaemia in children treated at a single tertiary hospital in Riyadh, Saudi Arabia. J Health Spec [serial online] 2018 [cited 2018 Jul 21];6:14-8. Available from: http://www.thejhs.org/text.asp?2018/6/1/14/222463
| Introduction|| |
Acute lymphoblastic leukaemia (ALL) is an aggressive disease that shows malignant transformation in the lymphoid precursors. These cause accumulation of immature early bone marrow (BM) haematopoietic cells known as blast cells. There are three types of ALL which depend on the lymphoid cell lineage affected: B-cell ALL, T-cell ALL and occasionally mixed-lineage ALL. In 2011, ALL was the most common type of cancer and leukaemia affecting children worldwide, accounting for approximately 25% of all childhood cancers and 75% of paediatric leukaemia cases. Furthermore, it affects 4.4 of 100,000 children, with the highest incidence occurring between 3 and 5 years of age. In Saudi Arabia, ALL constitutes almost 70% of paediatric leukaemia cases in boys and 69% in girls.
Not all patients with ALL have the same presenting clinical features, but there are some common features. Most ALL patients complain of high or low fever with unknown causes. The other symptoms are mainly due to a shortage in blood cell production. Furthermore, some features could present in different types of leukaemia, such as central nervous system (CNS) involvement, testicular involvement and lymphadenopathy. Signs and symptoms of ALL are not sufficient to establish the diagnosis, but further investigations are required to confirm it, such as a complete blood count, blood smear examination and bone marrow (BM) examination, which can provide the first evidence of ALL., In addition, CNS evaluation should be performed through a lumbar puncture to look for blast cells in the cerebrospinal fluid.
The treatment options for ALL have improved over the past few years. The current options include chemotherapy, radiotherapy and stem cell transplantation. The survival rate has also improved greatly over the past decades, from 30% in 1970 to >80% in 2000 in paediatric ALL patients. In Saudi Arabia, a study from Jeddah conducted in 2005 on 297 children with ALL: the 5-year survival rate was 74%, and the 10-year survival rate was 64%. ALL is common in Saudi Arabia, but epidemiological data are scarce.
This study was conducted to establish processes for collaborative data collection and to describe the clinical characteristics and outcomes of paediatric ALL in a single tertiary hospital in Riyadh, Saudi Arabia. The specific aims of the study were to identify the subtypes and clinical characteristics of ALL in children from 1- to 14-year olds; and to evaluate the outcome of ALL in terms of mortality, morbidity, remission and relapse according to risk categories.
| Methods|| |
This case series study was conducted at a single tertiary hospital in Riyadh, Saudi Arabia. We included 75 paediatric cases of ALL admitted to the Paediatric Oncology Department from above one until 14 years of age, between 2000 and 2010; most of them Saudi Arabians. We excluded patients diagnosed but not treated at the hospital, those who did not complete chemotherapy and those who were lost to follow-up.
All the patients diagnosed with ALL between 2000 and 2010 were included. Because of the limited sample size of 50 patients, the margin of error was calculated to be ±14%, keeping the confidence level at 95% and the expected percentage of outcome variables at 50%.
The data were collected using a chart review. The outcome variable was patient survival status. The grouping variables were the subtype of ALL (B-cell, T-cell), age (1-5 years, 6-14 years) and risk categories (standard, high risk). Standard (low) risk was defined as children aged one to <10 years with a white blood cell count of <50,000/μL at diagnosis; high-risk children were defined as 10 years or above and/or with a white blood cell count of ≥50,000/μL at diagnosis.
Data management and analysis
All data abstracted on the data collection form were entered into Excel and revised for accuracy and missed information. The period of the disease was calculated by subtracting the date of remission from the date of diagnosis. The disease-free period was calculated by subtracting the date of relapse from the date of remission. The event-free survival was calculated from the age of diagnosis till the date of the event (failure to achieve remission; relapse or death).
Descriptive statistics are presented as mean ± standard deviation for numerical variables and frequencies (percentages) for categorical variables. Interquartile range (IQR) was applied to show the middle 50% range between the 25th and 75th percentiles for data that was not normally distributed. The age at diagnosis was compared between immunophenotype group (precursor B-cell, T-cell), risk categories (standard risk, high risk) and relapse (yes, no). The Mann–Whitney U-test was used for the above comparison because age was not found to be normally distributed. P < 0.05 was considered as showing a statistically significant difference for the statistical tests.
This was a chart review study, and there was no intervention or contact with the study subjects. The approval for the study was obtained from the Institutional Review Board of the King Abdullah International Medical Research Center.
| Results|| |
Clinical data on 75 patients were obtained. A total of 20 patients were excluded because they were infants or >15 years of age; 5 were excluded owing to loss of follow-up and insufficient information. Thus, a total of 50 patients were finally included. Twenty-nine patients were boys and 21 were girls, with a male to female ratio of 1.4:1. The median age at diagnosis was 4 years, and the age range was 1-13 years. Most of the patients (90%) were between the ages of 1 and <10 years, which is the low-risk age category, with better prognosis. There were 5 patients aged 10 years and above. The clinical parameters are given in [Table 1].
|Table 1: Characteristics of the patients with acute lymphoblastic leukaemia (n=50)|
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The presenting symptoms of ALL varied among the patients. Fever was the most frequent symptom, presented by 70% of the patients while pallor was present in 54%. The least frequent symptom was nausea and vomiting, which was present in 4% [Figure 1].
|Figure 1: Frequency of symptoms among 50 patients diagnosed with acute lymphoblastic leukaemia. Fever was the most common symptom; nausea and vomiting were the least common symptoms. ‘Others’ comprises a collection of unspecified symptoms|
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Forty-one patients (82%) had pre-B-cell ALL while 9 patients (18%) had T-cell ALL. Only 4 male patients out of 29 males (14%) had testicular involvement: two of them had pre-B-cell ALL while the other 2 had T-cell ALL. The patients were categorised into three risk groups: 31 patients (62%) were in the standard risk group, 18 patients (36%) in the high-risk group and only one patient (2%) in the very high-risk group. The association between median age at diagnosis and different categories is shown in [Table 2]. The median age at diagnosis was significantly greater in patients with T-cell as compared to precursor B-cell (6 vs. 3 years, P = 0.02). There was no significant association found in the mean age of diagnosis for the risk categories (P = 0.18) and occurrence of relapse (P = 0.64).
|Table 2: Median age of diagnosis by immunophenotype, risk category, and relapse|
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Treatment and outcomes
[Figure 2] shows the treatment protocols provided at a single tertiary hospital in Riyadh, Saudi Arabia, from 2000 to 2010. Treatment response was based on a morphological assessment of the BM. A patient was considered to have complete remission if the BM at the end of induction was M1 (blasts <5%). Out of the 50 patients, 49 patients achieved complete remission after the induction phase whereas one patient died before completing the induction phase. The most common sites of relapse were either the BM alone (4 patients) or the BM and testes (4 patients) [Table 3]. The overall survival rate (OS) was 92%, i.e., 46 out of 50 patients (95% confidence interval [CI]: 82%, 97%), 4 patients (8%) died between 2000 and 2010, and all of them were in the high-risk category. In 2010, one patient died due to leukaemia, and one other patient died in 2006 due to infection. The remaining two patients died during 2009–2010 for other reasons [Table 4]. Two of the patients who died had a relapse before their death. There were another 9 patients who relapsed during the study. The event-free survival was 74%, i.e., 37 out of 50 (95% CI: 61%, 85%) patients with no relapse or death. The median duration between the start of treatment and relapse was 3.6 (IQR: 1.3, 6.2) years and the median duration from remission to relapse was 3.4 (IQR: 1, 6.1) years. The overall duration from diagnosis to relapse or death was 3.2 (IQR: 0.6, 4) years [Table 5].
|Figure 2: Frequency of treatment protocols used in 50 patients with acute lymphoblastic leukaemia. The most common protocol used was CCG 1991|
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| Discussion|| |
In this study, most of the results were promising. The survival rate was 92% with 22% relapse rate. Furthermore, majority of the patients were found to be pre-B-cell type and in the standard risk category. It was found that the most common presenting symptom was fever. Regarding the treatment protocols used to treat the patients, the most common protocol used was CCG-1991. The remission rate was found to be 98%.
The characteristics and outcomes differed among patients with ALL considering the differences in race. Some studies conducted in Pakistan and USA have tried to assess the characteristics and outcomes of patients with ALL, but they did not cover some important aspects such as symptoms and treatment protocols., This study included a single tertiary institution in Saudi Arabia to compare the results with those of developed countries.
In this study, the median age at diagnosis was 4 years, which was less than the median age at diagnosis in studies performed in Morocco (7 years) and Egypt (5 years)., The mean age in this study was 4.7 ± 3.0 years, while in the Egyptian study, the mean age was 6.6 ± 4.3 years. Considering the male-to-female ratio, the results were almost the same as those in developed nations, which showed a similar incidence of ALL., The male-to-female ratio in this study was 1.4:1 while the ratio in other developing countries such as Pakistan was even higher for boys. In the USA, the pre-B-cell type is more common than the T-cell type, which is similar to the results of our study; however, this is different from the results of studies conducted in other developing countries such as Pakistan and Egypt, which showed almost the same incidence for both types.
Children with ALL presented with diverse signs and symptoms. In this study, the most common presenting symptom in children with ALL was fever, similar to that documented in a study conducted in the USA, but unlike that documented in a study done in Pakistan, in which pallor was the most common symptom.
A study at a tertiary care centre in Asia documented a relapse rate of 24%, whereas in this study, the relapse rate was lower (22%). However, a study in the USA revealed a relapse rate of 16%. Thus, although the relapse rate obtained in this study was better than that observed in other Asian studies, it was still inferior to that observed in developed countries. Therefore, further research and re-evaluation are required to identify the reason, to ensure better patient outcomes. Furthermore, in studies carried out in the USA and Asia,, BM was the most common site of relapse, which is similar to the results of this study.
In Asia, over two-thirds of ALL cases could be categorised as high-risk. In contrast, high-risk disease accounts for only 10% - 15% of the ALL cases in developed countries.,, In this study, high-risk disease was observed in 36% of the cases. The higher percentage of high-risk disease in this study compared with that observed in developed countries might be due to late referrals, but the inherent difference in the biology of leukaemia cells needs to be investigated.
In this study, the survival rate was 92%, while the survival rate in a study done in Pakistan was 83% (n = 121). However, the survival rate in a study done in the USA was 78% (n = 14192). The comparison between our study and the USA study showed unexpected results which might be due to the big difference in the sample sizes of both studies. The difference in the survival rate between developed and developing countries is mainly owing to the response to therapy that varied between patients, probably because of genetic variations, disease complications, racial differences, and improved supportive care.,,,,
Common causes of death in ALL patients included infection, leukaemia, haemorrhage, and chemotherapy toxicity. In this study, causes of death were due to multiple causes such as infection, leukaemia or other causes. This result is different from those of studies conducted in developing countries such as Pakistan where infection was the most common cause of death, while in developed countries such as the USA, the pre-B ALL type was the leading cause of death in children as well as in adults., The main reasons for these variations are differences in treatment, hospital resources, quality of infection control and socioeconomic status between developing and developed countries.
A multi-institutional retrospective national collaborative study was conducted in Riyadh, Saudi Arabia, and documented similar results. While their study covered only 4 years (2004–2008), we expanded the duration of our study to 10 years (2000–2010) to be more thorough. Their study focused more on the genetic aspects of the disease while our study focused more on the clinical characteristics of the patients. Although there were differences in the sample size, most of the results were similar such as median age, male-to-female ratio and the most common subtype of ALL. However, the most common treatment protocol used in their study was CCG-1882 while in our study was CCG-1992. Moreover, the survival rate in their study was 97% while in our study it was 92%. Because of the differences in sample size, study period and study methods between the two studies, comparisons are difficult to be made.
Our study suffered from several limitations. Firstly, undocumented information in the files, loss of files and unclear handwriting made the extraction of information difficult and time-consuming. Moreover, some results were difficult to interpret due to our lack of experience as medical students, so we needed assistance from haematology specialists to overcome this difficulty. Secondly, the relatively small number of patients made our study inadequately equipped to assess the actual prevalence, characteristics and outcomes of ALL subtypes. Therefore, a larger sample size and more institutions were needed to conduct the study in order to have a better understanding about the results and how to apply them on our population.
| Conclusion|| |
This is the first 10-year case series study in a single tertiary institution in Saudi Arabia. The clinical characteristics of children with ALL were similar to those reported in the literature. After comparing the results with those obtained in studies performed in developed and developing countries, it was found that the protocols used for treatment were effective in improving the survival rate, comparable to that in developed countries. Thus, children with ALL should be treated at tertiary hospitals with specialised paediatric oncology services, using well-defined protocols, to improve the survival rate, comparable to that obtained in developed countries.
Financial support and sponsorship
This study was supported by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]