Leukemia and its Statistics: Analytical Essay

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Cancer:

Across the world, cancer in all forms causes around 12 percent deaths [1]. This is estimated to have risen to 18.1 million new cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer (9.5 million excluding nonmelanoma skin cancer) patients deaths according to WHO study 2018. Overall measurement shows that one of every 5 men and one in 6 women develop cancer during their lifetime, and one in 8 men and one in 11 women die from the disease [2]. After recent advances and improvement in treatment and avoidance in cardiovascular infections, tumor is a substantial reason for morbidity and mortality [1].

1.1. Risk factors:

Rising cancer rates can be caused by a number of factors, consisting of populace boom and ageing as well as the converting occurrence of positive causes of most cancers related to social and economic development [3]. That is particular authentic in rapidly developing economies, where a move is seen from cancers related to poverty and infections to cancers related to lifestyles more typical of industrialized nations [2].

1.2. Global Cancer Incidence and Mortality Rate:

Statistics show Europe and Americas have a high occurrence rate then mortality yet Asia and Africa has a higher death rate than the occurrence rate, it might be because of restricted access to opportune finding and treatment in numerous nations, and these locales have a higher recurrence of certain cancer growth types related with more unfortunate forecast and higher death rate

Table 1:The incidence and mortality rate of Cancer in different Continents of World [2], [3].

Continents Incidence Rate (in percent) Mortality Rate(in percent)

Europe 23.4% 20.3%

Americas 21.0% 14.4%

Asia 48.4% 57.3%

Africa 5.8% 7.3%

1.3. Globally Major Cancer Types:

Cancers of the lung, woman breast, and colorectum are the top three cancer types in phrases of occurrence and are ranked within the top five in phrases of mortality (first, 5th, and 2nd, respectively). together, those three most cancers sorts are accountable for one third of the cancer occurrence and mortality burden international [3], [2].

Table 2a: Incidence Rate of major types of Cancers [3].

Cancer Type Diagnosed Population Incidence Rate in percent

Lung ~ 2.1 million 11.6%

Female Breast ~2.1 million 11.6%

Colorectal 1.8 million 10.2%

Prostate 1.3 million 7.1%

Stomach 1.0 million 5.7%

Table 2a: Mortality Rate of major types of Cancers [3].

Cancer Type Deaths in Number Mortality Rate in percent

Lung 1.8 million 18.4%.

Colorectal 881 000 9.2%

Stomach 783 000 8.2%

liver 782 000 8.2%

Female Breast 627 000 6.6%

1.4. Cancer Incidence and Mortality Rate in Pakistan:

Certainly one of a major public health danger for Pakistan is cancers, annually about 148,000 new cancer instances are identified and almost one lac could not live to say the narrative [4].

1.5. Leukemia and its Statistics:

Leukemia is one of the fatal diseases and their morbidity and mortality costs increases each day all around the world [1]. It is a type of cancer that originates in the bone marrow and causes abnormal proliferation of white blood cells, red blood cells, and platelets which results in various infections, anemia, and bleeding, etc. [4]. In leukemia, the normal differentiation pathway is blocked and most cells do not go into terminal differentiation [5].

The prevalence of leukemia the world over is 1 per 100,000 annually and contributes to about 25% of childhood cancers contributes to approximately 25% of childhood cancers. Over 300,000 new cases of leukemia (2.8% of all new cancer cases) are diagnosed annually worldwide [6]. Public in Pakistan have also been tormented by leukemia from which approximately fifty eight% are males and forty two% are women [1], [7].

1.6. Diagnoses of Leukemia:

To diagnose leukemia, specialists carry out various tests and exams, which incorporate physical examinations and health history, complete blood counts (CBC), blood chemistry tests, cytochemistry, immunophenotyping, flow cytometry, cytogenetic and molecular studies, lumbar punctures and bone marrow biopsies and many other test also [4].

a) Physical examinations and health history:

Doctor see the patients’ health history like he/she has any genetic syndromes, such as Down syndrome, Fanconi anemia or viral infection or any blood disorders. Beside it they also squared essential signs to see if patient have a fever, shortness of breath and rapid heartbeat or skin for bruising and paleness, etc.

b) Complete blood counts (CBC):

The basic and usual investigation test which may signify this disease is complete blood count (CBC). CBC report measures the quantity of all the different types of cells in the blood.

c) Blood chemistry tests:

Blood chemistry tests measure certain synthetic/chemical compounds in the blood. They show how well certain organs are working and can help discover variations or abnormalities. Levels of the synthetics/chemical might be higher than normal in leukemia like blood urea nitrogen (BUN), creatinine, phosphate, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid.

d) Cytochemistry:

Cytochemistry utilizes stains or dyes, to distinguish tissue structures and segments in blood or bone marrow cells. Some stains are attracted to certain substances found in certain types of leukemia cells or blasts. The stain results can be seen under a microscope. Cytochemistry results can help doctors identify the types of cells that are present.

e) Immunophenotyping:

Immunophenotyping is the study of proteins expressed by cells. It can be used to determine the type or subtype of leukemia. Immunophenotyping uses a very specific antigen-antibody reaction to identify proteins in tissues or cells. It uses monoclonal antibodies identified with a fluorescent label or a specific enzyme label that binds only to specific antigens (proteins). Fluorescent or enzyme labeled allows doctors to see leukemia cells (also known as blasts).

f) Flow cytometry:

Flow cytometry is a technique used to sort and classify cells using fluorescent labels on their surface. Cells undergo a laser, which gives them light. Light is measured and analyzed by a computer. These techniques help define the specific features of leukemia cells or blasts.

g) Cytogenetic and Molecular Studies:

Cytogenetics means the analysis of the cell’s chromosomes, their number, size, shape, and how they are arranged. Cytogenetic karyotyping studies show chromosomal abnormalities. Fluorescence in situ hybridization (FISH) is a molecular genetic test used to detect chromosomal abnormalities and other genetic mutations or explosions in leukemia cells. Polymerase Chain Reaction (PCR) is a method used to make multiple copies of a particular gene segment so that it can be tested in the laboratory.

h) lumbar punctures:

A lumbar puncture, or spinal tap, removes a small amount of cerebrospinal fluid (CSF) from the space around the spine to look at it under a microscope. CSF is a fluid that surrounds the brain and spinal cord. Lumbar punctures are performed to determine if the cancer has spread to the spinal fluid.

i) Bone marrow biopsies :

During bone marrow aspiration and biopsy, cells are removed from the bone marrow so that they can be examined in the laboratory. The report from the lab confirms whether the sample contains leukemia cells and if so, the type of leukemia.

1.7. Background study:

A statistical analysis enables a researcher to draw meaningful conclusions from a study in which data are collected through observation, survey or experimentation. The success of a medical study however depends to a great extent, on the proper statistical analysis of the data originating from such a study [8]. Predictive models help healthcare professionals in making clinical decisions. These techniques are capable of analyzing complex medical data. Their potential to exploit meaningful relationship with in a data set can be used in the diagnosis, treatment, and predicting outcome in many clinical scenarios [9].

Data mining techniques have been widely applied to extract knowledge from medical databases. Feature selection technique is used in Type II Diabetes database [10]. Data mining technique is also applied to discover the core relationship between Anemia and Thalassemia from Complete Blood Count (CBC)test [11].

Leukemia is a type of cancer that originates in the bone marrow and causes abnormal proliferation of white blood cells [4].In leukemias, the normal differentiation pathway is blocked at a stage of differentiation at which the cells continue to proliferate, and most cells do not move on to terminal differentiation [5].

Fig 1: The Figure shows the normal renewal of blood cells that rapidly replaced through proliferation of stem and progenitor cells in the bone marrow whereas in disease it is different for Myeloid and Lymph leukemia [5].

A number of works have put efforts to detect Leukemia from the microscopic images. Hossain et al, 2018 performed the study that show computational methods for Leukemia detection automatically analyze the blood cells and its components from microscopic images. This analysis involved cell classification and blast counting. Generally, healthy or infected blood cell features were extracted from an image dataset based on the morphological analysis, this process was done by Principle Component Analysis (PCA) which reduces the data dimensions without losing any valuable information. Then, the Logistic Regression classifier was employed to predict the condition of a blood cell and classify it accordingly [12].

Rathee et al, 2014 performed a study on 650 blood samples of leukemia patients in Haryana state of India. Percentage of blast cell, red blood cell indices, white blood cell indices, number of platelets, and the amount of hemoglobin was determined according to standard laboratory procedures. Diagnosis of leukemia was done by 20% blast criteria and then ‘Sudan Black B’ was used to distinguish between AML & ALL. Analysis of variance (ANOVA) was used for interactions of factors (like age/gender/subtype) affecting leukemia patients. Data on leukemia patients was analyzed and then subjected to ANOVA. The major outcome of the study were 33.8% patients of AML, 39% patients with CML, 17.2% patients with ALL, and 10% with CLL. Acute and chronic leukemia accounts 71.4% and 62.6% male patients while 28.6% and 37.4% female patients respectively. Among four major type of leukemia, ALL was observed in 58% male patients and in 42% female patients, AML in 65% male and 35% female patients, CML in 69% male and 31% female patients, and CLL in 80% male patients and in 20% female patients [13].

R Bhattacharjee et al, 2012, study shows that an automated method was designed to detect Acute Lymphocytic Leukemia (ALL) and Acute Myeloid Leukemia (AML) blast cells from human microscopic blood cell images. In this research the noise reduction was done by Principle Component Analysis (PCA) which uses an orthogonal transformation to completely de-correlate the centralized matrix. Morphological operations and Connected Component Analysis were used to count the number of blast cells present in the images. The performance evaluation was carried out in terms of accuracy based on comparison of number of blast cells detected by manual count and those detected by the selective thresholding-based automated method [14].

Pakistan has also been affected but a limited data regarding the prevalence of different types of acute leukemia’s is there (like AML and ALL). At present, there are no cancer registry programs in Pakistan which can keep a track and notify regarding the prevalence and incidence of various types of cancers including leukemia’s. This is of utmost importance as Pakistan is a developing country and cancer is becoming a serious health issue, being the leading cause of death in Asia Pacific countries [15].

A study was conducted to investigate the prevalence of different types of leukemia at Lahore General Hospital, a tertiary care center catering for a large population of Lahore and nearby areas including Kasur, Hasilpur and Dipalpur. The leukemia’s overall study revealed a male preponderance with a percentage of 58% males and 42% females [1].

Early diagnosis of leukemia generally increases the chances for successful treatment by focusing on detecting symptomatic patients as early as possible. Delays in accessing cancer care are common with late-stage presentation, particularly in lower resource settings and vulnerable populations. The consequences of delayed or inaccessible cancer care are lower likelihood of survival, greater morbidity of treatment, and higher costs of care, resulting in deaths and disability from cancer. Early detection through analysis improves outcomes by providing care at the earliest possible stage and is therefore an important public health strategy in all settings.

1.8. Reason/Justification for the Selection of the Topic:

Cancer is commonly described as a genetic disease. Although many drugs against cancer has been designed but the death rate for the most prevalent cancers have not been reduced. To improve treatment and to reduce the mortality rate from cancer, a key task is to detect the disease as early as possible; however, the majority of patients are diagnosed as having cancer at a late stage like leukemia, liver cancer, lung cancer, colorectal cancer and breast cancer. If these cancers are detected at an early stage, the survival rate can be exceed [16], [17].Therefore, the statistical analysis is required to see the trend and tendencies of different variable of leukemia through CBC reports. For this purpose, time efficient and cost-effective approaches may pave towards early detection of disease.

1.9. Objectives of study:

The main objectives of research are:

To analyze the general trend and tendencies of variables for the examination of Leukemia considered in CBC reports.
Classification of variables for the identification of influential variables of further examination.
Development of predictive model for preliminary identification of suspected patient of leukemia.

1.10. Relevance to National Needs:

Leukemia is a growing disease in Pakistan, affecting both genders and all age groups. Studies show that its early detection is very crucial for human living as Leukemia originates in bone marrow and massively affects the production of appropriate blood cells [12]. So, multiple researches have been performed on image processing of blood samples by using biological techniques. It lacks the advance computational techniques and statistical analysis by CBC reports on Pakistani data. This research will play a key role in statistical analysis of real-life Pakistani dat

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