Category: Leukemia

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

References

1. NASIM, N. N. N., Malik, K., MOBEEN, N. A. M. S., AWAN, S., & MAZ, N., ‘Investigation on the prevalence of Leukaemia at a tertiary care hospital, Lahore,’ Biomedica, vol. 29(1), pp. 19-22, 2013.
2. World Health Organization, ‘Latest global cancer data: Cancer burden rises to 18.1 million new cases and 9.6 million cancer deaths in 2018.,’ International Agency for Research on Cancer:World Health Organization, Geneva, Switzerland,, 2018.
3. Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A., ‘Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries,’ CA: a cancer journal for clinicians, Vols. 68(6),, p. 3, 2018.
4. Davis, A. S., Viera, A. J., & Mead, M. D. , ‘ Leukemia: An overview for primary care.,’ Am Fam Physician,, pp. 89(9), 731-738., 2014.
5. Sell, S., ”Leukemia: stem cells, maturation arrest and differentiation therapy.’,’ In TUMOR BIOLOGY, pp. 14-14, January,2006.
6. Parkin, D. M., Bray, F., Ferlay, J., & Pisani, P., ‘Global cancer statistics, 2002.,’ CA: a cancer journal for clinicians,, pp. 55(2), 74-108., 2005.
7. CARTWRIGHT, R.A.,, ‘Epidemiology. In: Leukaemia (ed. J.A. Whittaker),,’ Blackwell Scientific Publications, Oxford., pp. pp. 3-33., 1992.
8. D. V. J. PhD, july 2009. [Online]. Available: https://www.akspublication.com/editorial_july2009.html.
9. Ramesh, A. N., Kambhampati, C., Monson, J. R., & Drew, P. J., ‘Artificial intelligence in medicine.,’ Annals of The Royal College of Surgeons of England,, pp. 86(5), 334., 2004.
10. Balakrishnan, S., & Narayanaswamy, R., ‘Feature selection using fcbf in type ii diabetes databases.,’ International Journal of the Computer, the Internet and the Management,, pp. 50-8., 2009.
11. Jatoi, S., Panhwar, M. A., Memon, M. S., Baloch, J. A., & Saddar, S. , ‘Mining complete blood count reports for disease discovery.,’ INTERNATIONAL JOURNAL OF COMPUTER SCIENCE AND NETWORK SECURITY , pp. 121-127., 2018.
12. Abedy, H., Ahmed, F., Bhuiyan, M. N. Q., Islam, M., Ali, M. N., & Shamsujjoha, M. , ‘Leukemia Prediction from Microscopic Images of Human Blood Cell Using HOG Feature Descriptor and Logistic Regression.,’ In 2018 16th International Conference on ICT and Knowledge Engineering (ICT&KE). IEEE., pp. pp. 1-6, 2018, November.
13. Rathee, R., Vashist, M., Kumar, A., & Singh, S. , ‘ Incidence of acute and chronic forms of leukemia in Haryana.,’ Int J Pharm Pharm Sci, , pp. 6, 323-5., 2014.
14. Bhattacharjee, R., & Chakraborty, M. , ‘LPG-PCA algorithm and selective thresholding based automated method: ALL & AML blast cells detection and counting.,’ In 2012 International Conference on Communications, Devices and Intelligent Systems (CODIS). IEEE., pp. pp. 109-112, 2012, December.
15. Ahmad, S., Shah, K. A., Hussain, H., Haq, A. U., Ullah, A., Khan, A., & Rahman, N. U. , ‘Prevalence of Acute and Chronic Forms of Leukemia in Various Regions of Khyber Pakhtunkhwa, Pakistan: Needs Much More to be done!.,’ Bangladesh Journal of Medical Science, , pp. 18(2), 222-227., 2019.
16. Ries, L. A. G., Reichman, M. E., Lewis, D. R., Hankey, B. F., & Edwards, B. K., ‘Cancer survival and incidence from the Surveillance, Epidemiology, and End Results (SEER) program.,’ The oncologist,, pp. 8(6), 541-552., 2003.
17. Semmes, O. J., Feng, Z., Adam, B. L., Banez, L. L., Bigbee, W. L., Campos, D., … & Kagan, J., ‘Evaluation of serum protein profiling by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry for the detection of prostate cancer: I. Assessment of platform reproducibility.,’ Clinical Chemistry,, pp. 51(1), 102-112., 2005.

Definition:

It is a blood cancer that affects white blood cells that affects children, but it may sometimes affect adults and is less complicated than blood cancer, and it is more common in men, This occurs when the rate of white cells resulting from their normal limit increases, As it is the white blood cells that are responsible for immunity in the body.

1 / how leukemia develops in the body?

It begins with the stage of producing large numbers of white blood cells in excess of the normal rate produced by the body and that go with blood after it comes out of the great bone marrow, where those extra cells do not maintain the body’s immunity as the cells that are similar to it do to nature but rather destroy in the blood and then move to Body parts such as spleen, liver, and others.

2 / how leukemia is diagnosed?

A doctor can diagnose leukemia, know its type, and treat it with several tests:

• A / Physical test on the body where the doctor examines the internal organs of the body and the knowledge of swollen ones such as the liver, sple,en and lymph nodes.
• B / Bone marrow test, through which you can determine the type of cells affected.
• D / A test to find out the amount of white blood cells present in the blood and if the number is greater than normal or not.

How to treat leukemia?

There are many ways in which leukemia is treated, but all of them show a better and faster improvement if the disease is detected earlier because it requires treatment for a long time. One of those methods is chemotherapy by transplanting stem cells from a healthy person because it is the same blood type.

Introduction

White blood cells

White platelets have a basic and significant job in the body. It is to keep up the safe framework and assault all pandemics and sicknesses. Along these lines, that is, regardless of whether enormous or little, it is separated into three sorts:

1 /Granulocytes

It contains protein inside and is divided into three types

a. Basophils b. Eosinophils c. Neutrophils

2 / Lymphocytes

a. B cells b. T cells c. Natural killer cells

3 / Monocytes

Normal ranges

The natural proportions of white blood cells differ from one human to another according to age, where the percentage is very high in children where they need more for them to strengthen their immunity and decrease through days until they decrease until they reach adult age

Normal range

Age

13000:38000 cell

Newborn infant

5000:20000 cell

2-week-old infant

4500:11000 cell

Adult

There are many symptoms that a person may have when a defect occurs in the number of white blood cells, which are divided into the following:

Low white blood cell count

High white blood cell count

1/ bone marrow disorders

2/ vitamin B-12 deficiencies

3/ HIV

4/ leukemia

1/ infections

2/ burns

3/ leukemia

4/ trauma

· White blood cell test

The white blood cell count test is one of the most important tests where in turn one can find many diseases that the body suffers from, including an infection test, an allergy test, and a blood cancer test.

Types of leukemia

There are several types of leukemia as they are classified according to the type of infected white blood cells and the rate of cell growth if it is chronic or temporary.

Chronic

Acute

• (CLL)

It differs from the timer, as it affects adults and rarely appears in children, where stem cells become infected and turn into cells of an abnormal nature. The cure rate in recent years is 83.2% and symptoms do not appear until after years of injury.

• (ALL)

It is an injury in stem cells, where children are often affected and adults may develop. Symptoms appear after a short period of injury, and the cure rate in the last years of it has reached 68.2%.

Lymphocytic leukemia

• (CML)

It develops slowly, with a cure rate of 66.9%, and it affects adults more than most age groups

• (AML)

It develops very quickly from the rest of the species, in addition to that, it happens for all ages, without exception, as the recovery rate resulting from recent years is small, which is 26%.

Myelogenous leukemia

Prevalence

The prevalence of leukemia is much lower than that of the lymph nodes, as it is, as they are both already more male males than women, and the cure rate of lymphoma is higher .

Symptoms of leukemia include:

• Night sweats*
• Fever*
• Loss of appetite*
• Chills *
• Bone pain *
• Red spots on the skin *
• Enlarged lymph nodes*

*easily bruised skin

Blood cancer causes various symptoms, depending on the organ that was affected, as it may affect the lungs, digestive system, kidneys, heart, and nervous system. If the nervous system is affected, it leads to imbalance in the body and not to control it and the muscles.

Risk factors

There are many factors that, in turn, cause leukemia, including hereditary diseases in the family, or exposure to disease by radiation, chemicals, and a weak immune system. All these symptoms increase from the disease, which is often between the ages of 15 to 40 years.

Diagnosing

There are many types to determine and recognize if a person has leukemia through routine checks of the patient, where all the patient’s data are collected from symptoms he experienced and hereditary diseases in the family where the illness may be inherited in the family, then the patient performs several tests that are done Discovering the disease and determining the type of leukemia, including these physical exams and knowing the amount of white blood cells and other tests.

*There are several tests that are performed to know the patient. These tests include testing liver function, and whether the effect of leukemia on the rate of its interaction, activity and functions inside the body, as well as a DNA test for the speed of white blood cell growth, through which it may identify the type of leukemia from under the microscope if acute lymphocytic leukemia or was Chronic lymphocytic leukemia, acute myeloid leukemia or chronic myeloid leukemia, examination of the spinal fluid through the lumbar vertebrae, through which it reaches the neurologist. White blood cells are immature and damaged.

How these aid the world ?

In reality, information on the entirety of the above is the place white platelets are and their significance and types and what results from the expansion and diminishing in them and what finishes numerous sorts brought about by those things, including leukemia, which speaks to a major issue while recognizing it in late occasions as it has side effects that recognize it from the remainder of the kinds of malignancy found in the body It additionally has various sorts that contrast from the other in the pace of recuperation from them at the time the manifestations showed up, regardless of whether it was toward the start or end, and the impact is boundless in youngsters, grown-ups, grown-ups, ladies, and men, just as the reasons for leukemia, frequently brought about by radiation, synthetic substances, and hereditary ailments, just as the hazard factors that If he is presented to it, he may make him wiped out and furthermore how the specialist manages the patient and performs tests that thus uncover the sort of leukemia of various sorts.

Methodology of leukemia:

Leukemia methodology, which in turn explains how the disease develops and occurs and is divided into four main phases:

1/Preprocessing. 2/processing. 3/initial diagnosis. 4/advance diagnosis

• Preprocessing the preprocessing: *

Preprocessing the preprocessing From the first stages that are done in order to narrate the slide where it is unclear, the delegate of these images shows the lack of clarity of the images and the noise in them.

1. Poor quality microscopic image for hypergranulated acute promyelocytic leukemia
2. Poor quality microscopic image for acute myeloid leukemia without Maturation

A.fuzzy filter:

It is necessary to use devices to clarify the microscopic image that may be affected and become noise when it is transferred under the microscope from those devices applied fuzzy filter, thus removing the noise to some extent.After applying fuzzy filter

Image Sharpening b.

It is used to increase and clarify image pixels

c. Enhance Contrast

Enhance Contrast it is used to illustrate the image, as you are viewing the images for some.

• Processing Phase

This stage is divided into several steps and they are

1. Convert RGB to HSV
2. Normalize HSV from [ 0 , 360 ] degree to [ 0 , 1] .
3. Separate hue, saturation, and value.
4. Keep saturation and value components, ignore hue.
5. Create binary image using saturation and value threshold.
6. Removing Small objects.
7. Fill holes using Dilation.
8. Replicate the mask in 3D RGB.
9. Initial diagnosis.

Treatment of leukemia

There are numerous approaches to treat leukemia and contrast starting with one individual then onto the next, contingent upon his age and wellbeing condition, and whether this was influenced by his nerves, his Spinal liquid, or not.

Treatment of leukemia is one of the most troublesome ways as not numerous types are analyzed in the first place and are found in its last phases of appearance, because of the side effects of the ailment that show up toward the finish of the sickness stages and this open door must beginning treatment in the prompt and it is hard to have influenced the spinal liquid in light of the fact that along these lines It can’t be controlled and there are numerous strategies for treatment, including chemotherapy, directed treatment, natural treatment, and radiotherapy.

• Targeted therapy *

Targeted therapy is one of the most important therapies that help in the treatment of leukemia. Some of them are pills and injections. They are used to treat some types of leukemia, including ALL and CML. This type may cause cancer cells to stop growing instead of killing them. Also, these drugs have side effects such as bloating, swelling, rashes, and diarrhea.

• Biological therapy. *

Biological therapy is one of the most important treatments. Biomaterials extracted from living organisms are used, as it results in swelling and fever. It also enhances the immune system that identifies foreign cells and destroys them.

• *Chemotherapy:

Chemotherapy is the most difficult type in the side effects, in which the patient’s psyche is destroyed from their occurrence, as hair, pain in the body; bruises, nausea, and loss of appetite are caused. Spaced periods between both doses.

• Outcome:

Toward the finish of this exploration, practically all what identifies with white platelets and their extraordinary job in the insusceptible framework, their common extents and their various kinds and infections coming about because of the inadequacy and the expansion in them are referenced where the defective increment is only blood disease that is a threatening sickness that enters the body in its name and that causes its different indications p The patient’s body, regardless of whether in the beginning of ailment or toward its finish, as per the sort of leukemia, whose manifestations might be fever, tremor, weakness, night sweats and bone agony, and furthermore knew how it spread in the body and the dangers that may make it happen from radiation, concoction and ailment on the off chance that it is acquired in the family previously and furthermore in what way The revelation of the ailment by Dr, it is a higher priority than crafted by assessment, including a blood test and the sort of white platelets and overabundance tests and test Physical Other And among them, the kind of malady is recognized and the treatment explicit to it is resolved, how is the strategy for illness, assessment of various slides, and explanation under the magnifying instrument and the a wide range of sorts of treatment that help in this, including essential and best chemotherapy, yet its troublesome reactions utilized in this and focused on treatment that additionally has an enormous viable job And likewise natural treatment recovered from living beings.

Reference:

1. Matsuyama, T., Kojima, S., & Kato, K. (1998). Allogeneic bone marrow transplantation for childhood leukemia following a busulfan and melphalan preparative regimen. Bone marrow transplantation, 22(1), 21-26.‏
2. Sawyers, C. L. (1999). Chronic myeloid leukemia. New England Journal of Medicine, 340(17), 1330-1340.
3. Pui, C. H., Relling, M. V., & Downing, J. R. (2004). Acute lymphoblastic leukemia. New England Journal of Medicine, 350(15), 1535-1548.‏
4. Mrozek, K., Heerema, N. A., & Bloomfield, C. D. (2004). Cytogenetics in acute leukemia. Blood reviews, 18(2), 115-136.‏.‏‏
5. Esparza, S. D., & Sakamoto, K. M. (2005). Topics in pediatric leukemia–acute lymphoblastic leukemia. Medscape general medicine, 7(1), 23.‏

Chronic myeloid leukemia (CML) is an indolent neoplasm which is known for its invariable progression from a chronic to blastic phase. However, CML primarily presenting with megakaryocytic blast crisis (MKBC) in a young male without any preceding chronic phase is of extremely rare occurrence. We report an unusual case of a 22-year-old man who presented for the first time with splenomegaly and presence of blasts in the peripheral blood and bone marrow, clinically masquerading as acute leukemia. This case report highlights the uncommon manifestation of MKBC in a previously undiagnosed CML. The case also reveals the importance of a careful bone marrow examination and an appropriate immunophenotyping as well as role of cytogenetics in differentiating this rare entity from other closely mimicking myeloproliferative neoplasms.

CML in transformation carries a dismal prognosis and imposes a major therapeutic challenge. Accumulations of certain mutations and chromosomal aberrations derive a case of CML from a relatively benign chronic phase to blast phase which is characterized by presence of >20% blasts in the peripheral blood or bone marrow or an extramedullary accumulation of blast cells, or large foci or clusters of blasts in the bone marrow biopsy (WHO, 2016). These criteria must be supported by the presence of Philadelphia (Ph) chromosome resulting from reciprocal translocation of chromosomes 9 and 22.1,2 Phenotype most commonly seen in blast crisis is of the myeloid lineage followed by lymphoid and erythroid. MKBC is extremely uncommon, comprising of 90% Ph-positive cells. An overall final diagnosis of CML in MKBC was rendered. Patient was subsequently put on a 7+3 regimen of cytarabine and doxorubicin in combination with Dasatinib 140mg daily. A hemogram repeated after two months showed a striking response to therapy with a WBC count of 2400/µL and a differential count of neutrophil 43%, lymphocyte 55%, eosinophil 1% and monocyte 1%, thereby suggestive of hematological remission. Patient was then advised to continue dasatinib and to remain on clinico-hematological follow-up. Till now there are no features of either residual disease or progression of the disease.

CML in blast crisis may show magakaryoblastic phenotype which poses a diagnostic challenge in differentiating it from de novo Acute Megakaryoblastic Leukemia (AMKL) which is also a rare diagnosis. The two entities are difficult to differentiate morphologically alone especially when no prior history of CML is available. Contrary to the usual occurrence of CML in the fourth decade in the Indian population, our case involved a young patient. Splenomegaly, leukocytosis and basophilia, which are consistent features of CML were also present in our patient. Persistence or increase in any of these signifies disease progression. In contrast, none of the three features are seen in de novo AMKL. The megakaryoblasts are usually medium to large in size (12-18 µm) with a round to indented nucleus, fine reticular chromatin, one to three nucleoli and basophilic cytoplasm which may show distinct blebs or pseudopod formation. Circulating micromegakaryocytes were not seen but megakaryocytic fragments, dysplastic large platelets and hypogranular neutrophils which are a feature of M7 leukemia, were conspicuous in the present case. The dysplastic features seen in the neutrophils as well as the erythroid precursors on BMA in our case can also be seen in AML with myelodysplasia-related changes (AML-MDC), however dysplasia in AML-MDC must be present in minimum 50% of the cells in at least 2 lineages, supplemented by the signature cytogenetic abnormalities. Hence AML-MDC was excluded in this case.

BMA of our patient yielded a diluted marrow probably due to myelofibrosis which is a frequent finding in both AML-M7 and MKBC. Besides fibrosis, bone marrow biopsy in both conditions shows varying proportions of blasts and maturing dysplastic megakaryocytes. Confirmation of megakaryocytes and megakaryoblasts requires expression of platelet-specific antigens such as CD41, CD42, CD61 or Factor VIII on IHC or FCM. Megakaryoblasts are often negative for CD34 and MPO, however markers like CD13 or CD33 may be positive, as in our case. A leukoerythroblastic blood picture along with presence of >20% blasts, myelofibrosis and presence of clusters of abnormal megakaryocytes in the BMB implicate consideration of AML-M7, acute panmyelosis with myelofibrosis, and primary myelofibrosis in blast transformation as the possible differentials besides a diagnosis of CML with blast crisis. Features such as leukocyte count, splenomegaly, basophilia and CD34 positive blasts in the marrow provide a valuable clue in differentiating between these close mimicking entities. However, demonstration of BCR-ABL fusion protein or Ph chromosome proves pivotal in arriving at a diagnosis as in our case. Here, another neoplasm namely, Ph-positive AML (WHO, 2016) needs to be addressed. Literature states that presence of left shifted myeloid maturation, splenomegaly and basophilia in the peripheral blood favour a diagnosis of CML in blast crisis rather than Ph-positive AML9.

CML-MKBC carries a poor prognosis with usually low expected survival rate. Combination of chemotherapy and tyrosine kinase inhibitors (TKI) has proven beneficial in improving the disease outcome to the extent of achieving a haematological remission as in our patient.

Conclusion

Megakaryocytic blast crisis has a characteristically low incidence and may prove to be a diagnostic challenge for the clinicians and the pathologists especially in previously undetected CML cases. The case report highlights the importance of differentiating blast transformation of CML from other close differentials with the use of an appropriate IHC panel and cytogenetic studies, as there are therapeutic implications.

References

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There are numerous approaches to treat leukemia and contrast starting with one individual then onto the next, contingent upon his age and wellbeing condition, and whether this was influenced by his nerves, his spinal liquid, or not. Treatment of leukemia is one of the most trouble some ways as not numerous types are analyzed in the first place and are found in its last phases of appearance, because of the side effects of the ailment that show up toward the finish of the sickness stages. This open door must beginning treatment in the prompt and it is hard to have influenced the spinal liquid in light of the fact that along these lines. It can’t be controlled and there are numerous strategies for treatment, including chemotherapy, directed treatment, natural treatment, and radiotherapy.

Targeted therapy

Targeted therapy is one of the most important therapies that help in the treatment of leukemia. Some of them are pills and injections. They are used to treat some types of leukemia, including ALL and CML. This type may cause cancer cells to stop growing instead of killing them. Also, these drugs have side effects such as bloating, swelling, rashes, and diarrhea.

Biological therapy

Biological therapy is one of the most important treatments. Biomaterials extracted from living organisms are used, as it results in swelling and fever. It also enhances the immune system that identifies foreign cells and destroys them.

Chemotherapy

Chemotherapy is the most difficult type in the side effects, in which the patient’s psyche is destroyed from their occurrence, as hair, pain in the body; bruises, nausea, and loss of appetite are caused. Spaced periods between both doses.

Toward the finish of this exploration, practically all what identifies with white platelets and their extraordinary job in the insusceptible framework, their common extents and their various kinds and infections coming about because of the inadequacy and the expansion in them are referenced where the defective increment is only blood disease that is a threatening sickness that enters the body in its name and that causes its different indications. The patient’s body, regardless of whether in the beginning of ailment or toward its finish, as per the sort of leukemia, whose manifestations might be fever, tremor, weakness, night sweats and bone agony, and furthermore knew how it spread in the body and the dangers that may make it happen from radiation, concoction and ailment on the off chance that it is acquired in the family previously and furthermore in what way.

The revelation of the ailment by Dr, it is a higher priority than crafted by assessment, including a blood test and the sort of white platelets and overabundance tests and others tests. The kind of malady is recognized and the treatment explicit to it is resolved, how is the strategy for illness, assessment of various slides, and explanation under the magnifying instrument and the a wide range of sorts of treatment that help in this, including essential and best chemotherapy, yet its troublesome reactions utilized in this and focused on treatment that additionally has an enormous viable job. And likewise natural treatment recovered from living beings.