Article Type : Research Article
Authors : Khaled Abu Ali, Japer MO, Al-Bayyouk NA, Shaqra MA, Shab RS and Al-Masri DH
Keywords : Blood cancer; Cancer; Leukemia; Malignancy
Cancer is a major life-threatening disease worldwide. Approximately 9.6 million people died from cancer in 2018 worldwide. The lack of any nationwide leukemia screening program and raising awareness of the Palestinian population also plays a role in underlying late presentation and noncompliance with screening guidelines. Hence it is important for physicians and pathologists to determine the current burden of leukemia in Palestine. This study was a retrospective cross-sectional design started in Jul 2019 and finished in Aug. 2019. The study population was compromised of all participants in Jan 2017 - Jul 2019. Data gathered from governmental specialized hospitals in cancer (Al-Rantisi Hospital for Cancer, Al Europe Hospital) from patients' medical records. The total number of cases was 285. The incidence rate was 15 cases per 100,000 and the annual incidence was 107 case. 28% of the cases with the most cases of Hematological Malignancies were acute lymphocytic leukemia and most of them affect the age groups are children aged 1-18 years. This is followed by Hodgkin disease, which affects males more than females and affects adult and old age groups. The third is multiple myeloma, which is the most common condition that affects old age. Then the non-Hodgkin disease and affects females more than males. The incidence of lymphoid lineage was 85% and myeloid lineage was 12%. There was a considerable difference in the incidence of Hematological malignancies, by age groups.
Cancer is a generic term for a large group of
diseases characterized by the growth of abnormal cells beyond their usual
boundaries that can then invade adjoining parts of the body and/or spread to
other organs. Other common terms used are malignant tumors and neoplasms [1,2].
Cancer can affect almost any part of the body and has many anatomic and
molecular subtypes that each require specific management strategies [3]. Cancer is a major life-threatening disease
worldwide. Approximately 18.1 million patients were newly diagnosed with cancer
and 9.6 million people died from cancer in 2018 worldwide [4]. According to Globocan 2018 statistics computed
using sex-; site- and age-specific incidence to 1-; 3- and 5-year prevalence
ratios from Nordic countries for the period (2000-2009), and scaled using Human
Development Index (HDI) ratios. Reported cases of cancer in Palestine was 4,499
new cases, official statistics of World Health Organization (WHO) revealed that
the rate of cancer in Gaza Strip and West Bank reached 89 new cases per 100,000
population. The Globocan 2018 added that 53.2% of new cancer cases registered
among Palestinians are females, and 46.8% are males, and the rat of death by
cancer was reported 52 death per 100,000 Population [3]. Furthermore, the Ministry of Health of Palestine
(MOHP) in 2015, the total number of reported cases of cancer in Palestine was
3,927 new cases. Moreover, Hematological Malignancy (H. M.) was the most common
type of cancer in children in Palestine and 30.2% of the total cancer recorded
in children. In the past three years, cancer in Palestine has been the second
largest cause of death among Palestinians after cardiovascular disease, after
being the third most important cause of death in Palestine for many years. According
to the Ministry of Health, Palestinian deaths from cancer accounted for 13.8%
of all deaths. In the Gaza strip, the cancer mortality rate was 13.2% of all
deaths, and in the West Bank 14.1% of all deaths [5]. Leukemia is a generic
term for malignant diseases characterized by an uncontrolled proliferation of
immature blood cells. These cells originate from a hematopoietic stem cell
mutation and can lead to bone marrow failure and end up in death [6]. Leukemia is the general term for some
different types of blood cancer. There are four main types of leukemia called: 1.
acute lymphoblastic (lymphocytic) leukemia (ALL), 2. Acute myeloid
(myelogenous) leukemia (AML), 3. Chronic lymphocytic leukemia (CLL), 4. Chronic myeloid
(myelogenous) leukemia (CML) [7]. However, The Global Cancer Observatory from
WHO report H.M. was 15.0% of total malignant neoplasm, the 5.6% of the cancer
was Leukemia, but without any categorization in the report or in the Ministry
of health annual report of Palestine, also Non-Hodgkin lymphoma 5.2%, Hodgkin
lymphoma 2.2%, Multiple myeloma 2.0%
[3-5]. According to illustrate the Incidence and mortality rate are almost
equal (7.7 to 6.7) per 100, 000, the mortality rate of Non-Hodgkin lymphoma is
4.5 less than the incidence rate of 8.2.
In addition, the highest critical mortality was in Breast cancer, and
the lowest was Thyroid cancer. Due to the lack of any nationwide H.M. screening
program, the majority of the population of Palestine is still unaware of this
blood disorder. Hence, it is important for the physicians and pathologists to
determine how the occurrence and outcome of the disease differ across the whole
Gaza strip (Figure 1).
General objective
In this context, the aim was to Measure Morbidity and Mortality Frequency of Hematological Malignancies and the percentage of their applied Laboratory tests in Gaza strip, Palestine.
Specific objectives
To determine the
incidence and the prevalence of Hematological Malignancies categories.
·
To
verify types of specified applied tests for Hematological Malignancies
patients.
·
To
determine the shortage in required laboratory tests for Hematological
Malignancies.
·
To
calculate the mortality rate for each disease.
·
To
calculate of survival rate in each disease.
Significance
According to incidence of cancer in Gaza Strip and West Bank reached 89 new cases per 100,000 population in Addition to Hematological Malignancy is the most common type of cancer in children in Palestine and 30.2% of total cancer recorded in children, high percentage of deaths among Hematological Malignancy which is 15.9% of the total number of deaths by cancer. Due to the lack of any nationwide Hematological Malignancy screening program especially Leukemia, the majority of the population of Palestine is still unaware of this blood disorder. Lack of awareness also plays a role in underlying late presentation and noncompliance with screening guidelines. Hence, it is important for the physicians and pathologists to determine the current burden of leukemia’s in Gaza strip [8].
Normal hematopoiesis
Blood cells develop through a process called haematopoiesis. This involves bone marrow and part of the lymphatic system. Bone marrow contains unspecialized cells known as haematopoietic stem cells. As they divide and mature, they become more specialized and develop into one of the three types of blood cell, each with a specific function. Blood cells only last for a limited period of time, and so they constantly need to be replaced in the correct numbers to meet the body’s needs. One of the key functions of the spleen is to remove worn out blood cells from circulation. An additional component of blood is plasma (Figures 2 and 3).
What causes blood cancer
To function properly, the body needs to produce exactly the right amount of each type of blood cell. Blood cancers develop when damage occurs to vital genes, disrupting the normal lifecycle of blood cells, and upsetting this balance. Risk factors include as (Figure 4) shown:
What are the symptoms
of blood cancer
Many symptoms of blood cancer are a result of fewer healthy, functioning blood cells, or overproduction of abnormal cells, causing a lack of space where blood cells are produced, i.e. bone marrow and the lymphatic system as presented in (Figure 5).
There are different
types of blood cancer, which can be classified in three main groups as
illustrated in (Figure 6):
Other blood disorders closely related to blood cancers and that may develop into leukemia, include:
WHO classification of myeloid neoplasms
Classification of lymphoid neoplasms
WHO classification of precursor lymphoid neoplasms [2]
Classical hodgkin lymphoma
WHO classification of Mature B-Cell Neoplasms
WHO Classification?of?Mature?T-Cell?and?NK-Cell?Neoplasms
WHO Classification of Histiocytic and Dendritic Cell Neoplasms
Leukemia
Leukemia is a type of cancer
arising from any group of blood cancers that usually begin in the bone marrow
and result in high numbers of abnormal blood cells. Maybe white blood cells
(WBCs) leukemia resulting from malignant transformation of different types of
white blood cell precursors: lymphocytic
leukemia is an overproduction of lymphocytes, and myeloid leukemia is an overproduction
of myelocytes [10-12]. Leukemic
cells grow and divide uncontrollably, displacing healthy blood cells. This can
lead to serious problems such as anemia, bleeding, and infection [10-14].
Leukemia is the fifth leading cause of cancer death in the United States, and
the majority of cases occur in older adults. Leukemia is more common in men
than women and
in 2019, it is estimated that there will be 61,780 new cases of leukemia and an
estimated 22,840 people will die of this disease [15]. Leukemias are also
classified as either acute or chronic, depending on how quickly they
progress [7,10-12].
Acute Leukemias, if left
untreated, progress very rapidly, and without proper care the mortality rate is
extremely high within several months of diagnosis. However, appropriate
treatment can considerably improve prognosis and survival times for acute leukemia patients, and many can be
cured [10].
Chronic Leukemias, on the other
hand, may not cause any significant problems before diagnosis, though sometimes
they cause nonspecific symptoms such as weight loss, fatigue, or abdominal
pain. In many cases, abnormal blood cell counts found during routine blood work
in people without symptoms may prompt a physician to suspect leukemia, which
can be confirmed with further testing [10].
Researchers are making great headway in the battle against leukemia. Innovative
strategies including antibody-based therapies, interventions directed at
leukemia stem cells, and novel targeted agents have shown promise in
preliminary research and early clinical trials [16-20].
Moreover, evidence suggests that some integrative interventions may complement
conventional leukemia therapies. Several medicinal plants are excellent sources
of chemo preventive phytochemicals that have been shown to be active against
various leukemia cell lines, and some may modulate molecular targets known to
be involved in leukemia development and progression [21,22].
Types of leukemia
Leukemia is categorized on the
basis of how long the disease takes to progress and the kinds of blood cells
affected. Acute leukemia usually presents suddenly, and patients often develop
symptoms right away. Chronic leukemia progresses slowly and may not cause
symptoms for years [14,23].
Lymphocytic leukemia affects “T” and “B” white blood cells known as
lymphocytes. Myeloid leukemia affects myeloid cells, which go on to form white
blood cells other than lymphocytes (granulocytes and monocytes), red blood
cells, and platelets. Leukemia is classified into four main types: acute
lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid
leukemia (AML), and chronic myeloid leukemia (CML)
[14,23].
There are several other types of leukemia as well, such as hairy cell
leukemia, chronic neutrophilic leukemia, and acute megakaryocytic leukemia, but
these are relatively rare [24].
Rounded to the nearest 10; the numbers depict estimated new cases of leukemia
in the United States in 2014. Leukemias are further classified into subtypes
depending on the molecular and genetic characteristics of leukemia cells.
Correctly identifying the
properties of each patient’s cancer is critical
for prognosis and treatment [14,17,24,28].
Laboratory Tests of
Hematological Malignancies
Components in the routine clinical evaluation of myeloid diseases current
Related Studied
MOHP demonstrates in the 2018
report on 2011-2016 period there were 8515 cases of malignant neoplasm; the
third-highest percent was Leukemia were 9.1% about 775 cases, Lymphoma 6.2%
about 528 cases, and it was the fourth-highest in female malignancies with 5.3%
of 4705 female cases [29].
In
addition to the incidence of Malignancy in children’s ages, 18 years (yrs) and
less were 608 approximately 7.1% from the total malignant neoplasm; the percentage
of leukemia was 23.8%, and the highest percentage was Lymphoma 17.1% in
children [29]. On the other hand, the second leading cause of death according
to the report of MOHP for deaths was malignancy neoplasm; counted 805 death
about 10.6% of total causes. Furthermore the Mortality rate 36.8/100000 of the
population of in the end 2018; the percentage of deaths according age groups
1-less than 5yrs 5.3%, from 5- less than
20yrs 5.8%, from 20- less than 60yrs 16.7%
and the second-highest percent of total deaths in the age group more
than 60yrs 10.2% from the total 2956 deaths [30]. Finally, according to MOHP
report the shortage in the annual financial needs for laboratory expenses were
26.9% of the essential requirements
[29]. In India, a study by Sharique et al.,2016 evaluated the
frequencies of ALL, AML, CLL and CML, diagnosed in our hospital. Study also
aimed at calculating frequencies as per World Health Organization (WHO)
classified leukemia on the bone marrow studies and found that An upward trend
in incidence of leukemia with age was seen, although the acute leukemia’s were
more common in patients below 20 years of age. The total number of males who
participated in this study were 116[40.6%] while females were 170[59.4%].
Maximum patients were in the age group 21-30 years. The prevalence percentage
of leukemia seen in our study was more in the age group of 51-60 and 71-80
years. Males were seen to be afflicted more than females in all age groups. No
correlation between the gender of the patients and type of leukemia was seen on
applying Fischer Exact test. Acute leukemia show a greater prevalence in second
decade [8]. In Germany, across-sectional study was conducted to evaluate the
oral health of adult patients with newly diagnosed acute leukemia, the study
showed that Thirty-nine patients with leukemia (AML 26, ALL 13) and 38 HCs were
included. Oral mucosal findings were present in 62% of L compared to 0% of HC
patients, whereby gingival hyperplasia was the most detected finding.
Furthermore, a higher caries prevalence in leukemia patients was shown (D value
3.64 ± 3.98 vs. 0.72 ± 1.72, p < 0.01). The periodontal parameters were
poorer in leukemia patients. No substantial differences in microbiological
findings of selected bacteria were detected within L group and between Leukemia
and Healthy Control patients [6]. In
America, a study by Jorge et al .,2012
estimate the increasing prevalence and plateau prevalence of CML in future
years and found that On the basis of these calculations, the mortality ratio of
patients with CML compared with an
age-matched normal population was approximately 1.53. The estimated
prevalence of CML is approximately 70,000
in 2010, 112,000 in 2020, 144,000 in 2030, 167,000 in 2040, and 181,000
in 2050, when it will reach a near plateau
prevalence [31]. In India, Radha et al. 2014 conducted their study to
find out geographic pattern of leukemia and its distribution throughout the
Haryana and he observed that 51%
patients were suffering from acute forms of leukemia while 49% suffered from
chronic type. Leukemia was more frequently observed in adults. Male to female
ratio was 2:1 and majority of the patients (88.92%) belonged to six districts
(i.e. Rohtak, Jind, Bhiwani, Sonipat, Jhajjar, Hissar) [32]. Kyu-Won et al. study
presents the 2014 nationwide cancer statistics in Korea, including cancer
incidence, survival, prevalence, and mortality and he observed that in 2014, 217,057 and 76,611 Koreans were
newly diagnosed and died from cancer respectively. The ASRs for cancer
incidence and mortality in 2014 were 270.7 and 85.1 per 100,000, respectively.
The all-cancer incidence rate has increased significantly by 3.4% annually from
1999 to 2012, and started to decrease after 2012 (2012-2014; annual percent
change, –6.6%). However, overall cancer mortality has decreased 2.7% annually
since 2002. The 5-year relative survival rate for patients diagnosed with
cancer between 2010 and 2014 was 70.3%, an improvement from the 41.2% for
patients diagnosed between 1993 and [33]
(Figures 7-14).
Study
design
The study design was a retrospective
cross-sectional study.
Study
population
The study population was comprised
of any participants Jan 2017- Aug 2019.
Study
period
The study was started in Jul 2019
and finished in Aug. 2019.
Sampling
We was collected data from
governmental specialized hospitals in cancer (Al-Rantisi Hospital for Cancer,
Al Europe Hospital) from medical record.
Inclusion and Exclusion criteria
Inclusion criteria: any Cancer Patient with Hematological
Malignancies, Myeloid or Lymphoid Lineage from Gaza strip included.
Exclusion criteria: other cancer patients, or non-malignant patients.
Ethical Consideration
An authorization to carry out the
study will obtained from the local ethics committee using an agreement
letter.
Tools of the Study
Data
collection
Data gathered from Medical Record in
Governmental Hospitals; Hematological Malignancies Type, all tests used in the
diagnosis and in follow up.
Components in the routine clinical evaluation of myeloid and lymphoid malignances routine tests
Cytogenetic analysis, including
Molecular Genetic analysis for
Potential Future Clinical Studies
In addition to the date of diagnosis, age, where they are from and their gender.
By using IBM SPSS, analysis software 20 to study
the relationships by using Chi-square test and with Microsoft Excel 2016
determined the prevalence, incidence, and Mortality rate of each Malignancy,
and the percentage of the most required tests applied for the patients.
General
incidence of hematological malignancies
The
total Hematological Malignancies (H.M.) were 285 cases, nine of them were
unclassified. However, the diagnosis of the rest, it did not subclassify some
types that needed too, such as AML, ALL and Myeloproliferative Neoplasms.
According to the study period, the population of Gaza strip in the middle of
2018 was 1932843 as mentioned by the Palestinian Central Bureau of Statistics
(PCBS). The incidence rate of H.M. for 100000 People were about 15 cases, on
the other hand, the annual incidence was 107 cases. The lowest age was 1 year
however, the oldest age was 87 years,
ALL was the highest annual incidence reach 28.8 % of the total H.M,
followed by Hodgkin disease, Multiple Myeloma, and Non-Hodgkin disease with the
respect percentage (18.9%, 13%, 9.8%). as mentioned in (Table 2), Also the
lowest percent was for Hairy cell leukemia approximately 0%. These as
illustrated in. We notes from this (Table 3) that children are the most
affected age groups with ALL, especially the category 0-9 years 82 %, in
contrast to its presence in adults (19-27, 28-36, 46-54) and less old age
groups(55-63, 64-72). Hodgkin disease is most prevalent in adults aged 19-27,
37-45 years with 62.1%, 46.7% respectively. Burkitt’s lymphoma appeared in
children aged 18-10 with seven cases. It also appeared in adults aged 53-55
with one case. Follicular lymphoma appeared only in adult categories (37-45,
46-54, 55-63) with total percent of 1.4% of all H.M. Multiple myelomas the
highest incidence in the older age group 82-90 years with 40% and 64-72 with
34.5%. Followed by the older adult group
46-54 with 30.6%. In addition, there was a highly statistically significant
association between types of H.M. and the distribution according to the age groups
as shown in table with P-value 0.000.Furthermore, the and 4.4 illustrate the
disruptions of the H.M. between the classification of Age groups as Children
(1-18) years, Adult (19-54) years and Old Age older than 55 years. There was a
highly statistically significant association between types of H.M. and the
distribution according to the age groups Classes with P-value 0.000. Firstly,
in child group, the highest disease is ALL 68% of all H.M attacks children,
followed by Hodgkin disease 12%, Burkitt’s lymphoma 7% and AML 6%. Meanwhile,
the highest percent 32% of the adult group was Hodgkin disease, followed
Multiple myelomas 16%, Non-Hodgkin disease 15%. The lowest Percent goes for
CLL, AML, Follicular lymphoma and Myeloproliferative Neoplasms. Lastly, among Old Age group, 16% was
Multiple myelomas, it was the highest present, followed by Hodgkin disease,
Non-Hodgkin disease, and CLL, the lowest incidence were Burkitt’s lymphoma,
Follicular lymphoma, and Hairy cell leukemia. Furthermore,
84.6 % of H.M. were myeloid lineage, otherwise 12.3% were lymphoid, and the
unclassified was 3.2% as shown in table 4.3 and. There was no statistically
significant association between H.M. and the Lineage distribution according to
the age groups with P-value 0.269.The relationship between gender Male (M) and Female
(F) with H.M. types was no statistically significant association, the P-value
0.086 as presented in table 4.4.The highest incident of H.M. in both genders
was ALL, Hodgkin disease, multiple myeloma and
Non-Hodgkin disease in descending order, however, the male higher than
female as 45, 37 cases ALL respectively. In the same of ALL the Hodgkin disease
and multiple myeloma but in Non-Hodgkin disease the female cases 18 higher than
male 10 cases as illustrated in. In addition to CML, CLL and Burkitt’s lymphoma
was male higher than Female but lower incidence. Otherwise, the female was higher than in AML
but with low incidence, in some H.M. like Hairy cell leukemia and
Myelodysplastic/Myeloproliferative Neoplasms exclusively attacks female.
Finally, there was not statistically significant relationship between the
gender male and female with H.M. myeloid, lymphoid lineage, the P-value 0.821
as presented demonstrates the lymphoid lineage in female was higher than male
but myeloid lineage approximately equal in both genders. After evaluation,
medical record of Hematological Malignancy Patients for these components in the
routine clinical evaluation of Myeloid and Lymphoid Malignancies applied for
them in Gaza strip hospitals or transferred to other hospitals outside Gaza
strip. We found 28% of routine tests, in general, applied for the patients
outside Gaza strip, but unfortunately, there had not done any test of Potential
Future Clinical Studies in Gaza neither outside Gaza strip. In addition to the
highest percent 50% of applied tests for Hodgkin Lymphoma, However the best
percent for other listed diseases did not exceed 33%. Furthermore, most of the
applied test of a routine test does not applied in Gaza strip Hospitals.
Comparing
the results with related studies
According to results demonstrated leukemia was 43.9%
of hematological Malignancies in Gaza strip, which included ALL, AML, CLL, and
CML, the highest percent of Leukemia in children less than 18yrs was for ALL
and AML. in addition the lymphoma in children was 22% includes Hodgkin disease, Burkitt’s lymphoma,
Non-Hodgkin disease, and lymphoma, that correspond the towering percent of
leukemia 23.8% and lymphoma 17.1% of malignancies neoplasm in children reported
by MOHP, that had been published lastly in July 2019 for the study period 2011-2016 [29].
The demonstrated results were considerably greater
than findings of WHO Globocan 2018 reported for Gaza strip and Westbank, where
Leukemia 37.3% of hematological Malignancies, which was 15% of total
malignancies neoplasm, however, they have coincided with leukemia was the
highest incident in hematological Malignancies.
In another hand, the incidence of Non-Hodgkin disease in Gaza strip was
9.8% distinguishable from WHO Globocan 2018 reported 34.7%, but Hodgkin disease
18.9% higher than 14.7% for Gaza strip and Westbank. Meanwhile, Multiple
Myeloma has been compatible with the percentage of 13% [3,4]. Table 4.2 has
identified the results and there was a highly statistically significant
association between types of H.M. and the distribution according to the age
groups that were consistent with the study of an estimation new cases of
leukemia in the United States (US) in 2014. however, the highest ALL in
children, it differs in the beak was 83% in the age group 1-9 yrs in contrast
the US ages 3-7yrs [14, 17, 24, 32]. The US study was compatible with the
increasing incidence of CLL in older adult and old age group, CML increased in
Middle-aged adults, rarely children contrary to Gaza strip incidence of CML
increased in old age group, older adults and rarely children [14, 17, 24, 32].
Lastly, AML in the US was mostly in adult and typically over age 40yrs contrary
to Gaza strip study the highest percentage was in the children group [14, 17,
24, 32]. The study was compatible with the Indian Ahmed et.al study in 2016 the
increase of acute leukemia in ages under 20yrs, and there was a statistically
significant association between types of H.M and age groups. Although the
Indian Rathee et.al study compatible with the finding in table 4.5 the highest
incident of H.Ms were in Male, it was distinct in the difference between male
and female [8, 32]. Interestingly the Germany study consistent with illustrated
results in (Figure 8), where was ALL the highest among children [6]. Finally,
according to results presented in (Figure 15)
the percentage of applied routine tests for H.Ms was 28%, most of these
test not included in list of tests available for the patients in Ministry of Health
(MOH) at Gaza strip, particularly Flow cytometry analysis, Protein
Electrophoresis, Immunological Phenotyping, Cytogenetic analysis, including and
Molecular Genetic analysis based on MOHP 2018 report. That explained the
increases of the mortality rate of leukemia in Gaza strip between different age
groups the peak was in older ages over 60yrs as reported by MOH for deaths in
Gaza strip 2018 [29].
Study
limitations
The most important problem in demonstrates prevalence, mortality rate and survival rate for each Hematological Malignancy was the lack of cooperation of the information systems staff in the Ministry of Health (MOH) in Gaza to obtain the necessary data for the research. and Consequently to the rejection of the permeation request from the central public archive for dead patients in MOH, due to lack of an easy system to obtain the necessary data, which lead to substantial work pressure on, the employees, in addition to the research jest for Bachelor degree.
Conclusions and Recommendations
Conclusion
Based on the research data, the conclusion could be:
ALL: Acute Lymphoblastic Leukemia / Lymphocytic;
AML: Acute Myeloid / Myelogenous Leukemia; CLL: Chronic Lymphocytic
Leukemia;ML: Chronic Myeloid / Myelogenous Leukemia; WBC: White Blood Cell;CBC:
Cell Blood Count; EPO: Erythropoietin;BM: Bone Marrow Biopsy; FISH:
Fluorescence In Situ Hybridization; H&E: Hematoxylin And Eosin; WHO: World
Health Organization; PDGFRA: Platelet-Derived Growth Factor Receptor A; DGFRB:
Platelet-Derived Growth Factor Receptor Beta (Pdgfr?); FGFRA: Fibroblast Growth
Factor Receptor A; MD: Myelodysplastic Syndrome; MPN: Myeloproliferative
Neoplasm; BCR: Breakpoint Cluster Region Protein; ABL-1: Abelson Murine
Leukemia Viral Oncogene Homolog 1; EBV: Epstein Barr Virus; DLBCL: Diffuse
Large B-Cell Lymphoma; ALK: Anaplastic Lymphoma Kinase; JAK2: Janus Activated
Kinase; JAK2-V617F: Mutation Analysis Of Granulocytes And Platelets Of Patients
With Chronic Myeloproliferative Disorder; FAB: French – American British; RARS:
Refractory Anemia Ring Sideroblastic; RAEB: Refrectory Anemia Exce Blastic;
CMML: Chronic Myelomonocytic Leukemia; RA: Refractory Anemia; RAEB: Refractory
Anemia With Excess Blastic In Transformation; RCC: Refractory Cytopenia Of
Childhood; PB: Perfiral Blood; Mds-U: Myelodysplastic Syndrome Unclassified;
RUN1-RUNXT1: Runt-Related Transcription Factor / (RUNX1); JMML: Juvenile
Myelomonocytic Leukemia; PML-RARA: Promyelocytic Leukemia/Retinoic Acid
Receptor Alpha; CBFB: Core-Binding Factor Subunit Beta; MLL: Major League
Lacrosse