ISSN: 2320-5407 Int. J. Adv. Res.

9(05), 1349-1354

Journal Homepage: -www.journalijar.com

Article DOI:10.21474/IJAR01/12979
DOI URL: http://dx.doi.org/10.21474/IJAR01/12979

RESEARCH ARTICLE
INCIDENCE AND PREVALENCE OF ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) IN KASHMIRI
POPULACE (NORTH INDIA)

Fozia Mohammad1, 2, Arshad A. Pandith1, Mithilesh Kumar2, Aabid Koul1, Faisal Guru3, Iqbal Qasim1, Javid
Rasool4, Sajad Geelani4, Saqib Shah3 and Mohammad Rifayi3
1. Advanced Centre for Human Genetics, Sher-I-Kashmir Institute of Medical Sciences (SKIMS), J&K-India.
2. School of Life Sciences, Jaipur National University, Jaipur-302017 Rajasthan, India.
3. Department of Medical Oncology (Paediatric unit)SKIMS, J&K-India.
4. Department of Hematology, SKIMS, J&K-India.
……………………………………………………………………………………………………....
Manuscript Info Abstract
……………………. ………………………………………………………………
Manuscript History Background: The most frequent cancer of the childhood is acute
Received: 31 March 2021 lymphoblastic leukaemia (ALL). It is the blood and bone marrow
Final Accepted: 30 April 2021 cancer affecting white blood cells. It is caused by errors in the DNA in
Published: May 2021 the bone marrow cells. Our goal was to evaluate the prevalence of ALL
in Kashmiri populace.
Key words:-
Acute Lymphoid Leukemia, Methods: The study in the hindsight was initiated for ALL patients
Immunophenotypes, Pre B-cell, T-cell, registered between early 2018up to late 2019 to investigate its
Mixed Phenotype frequency and prevalence.
Results: Overall from 74 ALL patients, based on gender, 44 (59%)
were males and 30 (41%) were females. Based on age, 53 (72%) were
in the age group of ≤18 years while 21 (28%) were in the age group of
>18. Based on immunophenotypes 69 (93%) were of Pre B-cell
phenotype, 3 (4%) belonged to T-cell phenotype while 2 (3%) were of
mixed phenotype. Based on demography, 10 (14%) were from urban
areas while as 64 (86%) were from rural areas of Kashmir region.
Conclusions: Although the prevalence of ALL in this region is very
high, but gender has no significance while age and dwelling has
significance on its overall frequency and significance.

Copy Right, IJAR, 2021,. All rights reserved.

……………………………………………………………………………………………………....
Introduction:-
Acute lymphoblastic leukaemia (ALL) is a blood-line lymphoid progenitor cell cancer that develops significant
amounts of undefined lymphocytes.1 It is the most frequent cancer of the childhood. It is caused by errors in the
DNA of the bone marrow cells, although the origin is unclear in some circumstances. 2 The development of fresh red
blood cells, white blood cells, and platelets has been hindered by excessive production of immature bone marrow
lymphocytes.1 The indications and manifestations of ALL vary3and usually include anemia, bloody nose, bone pain,
breathlessness, bruising, contusions, common infections, drowsiness, enlarged liver and spleen lymph nodes,
fatigue, fever and infection, gum bleeding, headache, joint pain caused by the spread of blast cells, lower
limb and belly swelling, lethargy, loss of weight and appetite, night sweats, rigidity of the neck,4or paralysis of the
cranial nerve5(CNS involvement), paleness, skin rashes/red spots due to low platelet count, shortness of breath,
vomiting, weakness and tiredness. ALL develops quickly as acute leukemia and if untreated may become lethal in a
matter of weeks or months.6During the progression of B and T cell differentiation, any genetic insult that block

Corresponding Author:-Dr. Arshad Ahmad Pandith PhD 1349

Address:-Advanced Centre for Human GeneticsSher-I-Kashmir Institute of Medical Sciences,
Srinagar, Kashmir, India.
ISSN: 2320-5407 Int. J. Adv. Res. 9(05), 1349-1354

precursor B or T cell differentiation and drives their deviant proliferation and survival may cause different health
disorders including ALL. Of all the ALL cases, B-ALL, which is characterized by hard line malignancy of small to
medium size precursor B cells comprises approximately 80-85% as compared to T-ALL.1Like other tumors, ALL
outcome from the amassing of genomic abnormalities that it affects normal control of cellular growth.

Down syndrome, Li-Fraumeni syndrome or type 1 neurofibromatosis may be some of the genetic risk
factors.1Though chemotherapy or selective medicines that directly destroy cancer cells are used as treatments, but
exposure to radiation or previous chemotherapy may be some of the environmental risk factors.1There is
contradictory evidence about the role of electromagnetic waves or pesticides in the development of ALL. 7, 8Some
theorize that a typical infection may cause an unexpected immune reaction therefore trigger its development. 7While
others speculate that multiple genetic mutations result in rapid cell division thus are the basic underlying
mechanisms.2

Typically, diagnosis is dependent on blood tests and analysis of the bone marrow. 9Initial symptoms, especially in
infants, can be ambiguously defined. More than 50% of children with leukaemia have one or more of
these five traits: hepatomegaly (64%), splenomegaly (61%), pale skin (54%), fever (53%) and bruising
(52%).10 Recurring infections, sluggish feelings, leg or arm pain and swollen lymph nodes may also become
common. Other symptoms are also often present, such as fever, night sweats and weight loss. Symptoms such as
cranial neuropathies attributable to meningeal invasion of the central nervous system (CNS) were detected in 10% of
adults and less than 5% of the infants, in particular mature B-cell ALL (Burkitt leukemia) at the initial diagnosis. 11

ALL is initially treated with chemotherapy to cause remission.This is often usually supplemented over several years
by more chemotherapy.2 Treatment also commonly involves intrathecal chemotherapy, as systemic chemotherapy
may have little access into the central nervous system, a popular site for the regeneration of acute lymphoblastic
leukaemia.12, 13 Radiation therapy can also be used when the disease is spread towards the brain.Transplantation of
stem cells may be used as the condition resurges after conventional therapy. More therapies are being employed and
investigated as of now.2

According to gender, women more likely fare better than men. In general, the African-Americans, Asians and
Hispanics are less likely to develop leukemia than caucasians. ALL in particular happens more frequently in
Caucasians, Hispanics and Latin Americans than in Africans. 14, 15 But they much more likely have positive
prognosis than their non-caucasion counterparts. In the United States, ALL is most prevalent in children of
Caucasian (36 cases/million) and Hispanic (41 cases/million) descent in comparison to children of African descent
(15 cases/million).16 It is more likely that children between the ages of 1 and 10 though develop ALL but in the long
run get healed. The most plausible outcome of chromosome defects (e.g., Philadelphia chromosome) in older
adults that make the treatment management harder with worse prognosis. Older individuals can also have
underlying co-morbidity that make ALL therapy much harder to tolerate. At diagnosis, the number of White Blood
Cells >30,000 (B-ALL) or >100,000 (T-ALL) is concomitant with worse outcomes. Cancer spreads to the CNS
(brain or spinal cord) have worse implications. Person's initial recovery response and longer time needed to achieve
full remission which is >4 weeks. Patients with genetic defects such as Down syndrome and other chromosomal
anomalies may have a different response and remission rate.17

In 2015, ALL affected approximately 876,000 people in the world and led to approximately 111,000 deaths. 18, 19
This is the most prevalent cause of cancer and death in children in the United States. 2 It is observed in both adults
and children, but in children especially between the ages of 3 and 7 highest frequencies of ALL is observed. 4, 20 It is
believed to affect 1 in 1500 children.21 Around 75% of cases appear before 6 and a secondary spike after 40 years of
age.22 Children survived for a median period of 3 months, primarily due to either infection or bleedings, before
chemotherapy regimen and hematopoietic stem cell transplant were introduced. ALL has been the first cancer to be
cured.23 The prognosis of childhood leukaemia after chemotherapy has been significantly improved and the
likelihood of complete recovery of children with ALL after 4 weeks is projected at 95% after initial therapy. In
developing nations, paediatric ALL patients have a 5-year survival rate of more than 80%. 60-80% of people
receiving induced chemotherapy are expected to have full remission after 4 weeks and those over 70 years are
estimated to have a cure rate of 5%. 22 Infant survival rose to 90% in 2015 from less than 10% in the 1960s.2 For
babies survival still remains less (50%)24 and adults, the survival rate is even lesser (35%). 25 The National Cancer
Intelligence Network (NCIN) reports that after initial diagnosis 70% people with ALL typically live for 5 years or
longer.

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ALL presently occurs in ~1.7/106 /year with the broad age profiles of those affected. ALL is the most prevalent
childhood disease, represented about 20% of adults and 80% of childhood leukaemias. 26 Although a long-term,
comprehensive response towards treatment is seen in 80% to 90% of children,27 it still remains the leading cause of
childhood deaths.28 85% of the cases among both males and females are of B cell passages having the same number
of cases. The remaining 15% are male predominant T-cell lineage. Here in this region (J&K, India), ALL ranks 5th
among common cancers occurring at a frequency of 9.9% with male: female ratio of 1:1. The average incidence of
leukemia in our valley is 5.8/105/year with highest incidence in Acute Lymphoblastic Leukemia.

Methods:-
The presentstudy was carried out in Advanced Centre for Human Genetics atSheri-I-Kashmir Institute of Medical
Sciences (SKIMS) Srinagar, India from the beginning of 2018 till the end of 2019.For frequency and prevalence
studies, 74cases diagnosed with ALL were enrolledfrom Department of Pediatric Oncology and Clinical
Hematology.The records were screened retrospectively for patients with ALL. Patients from outside the valley of
Kashmir were excluded from the study. Emphasis was laid to determine the various factors responsible for ALL
which primarily included age, smoking status, use of pesticides, family history and immunological parameters.The
research was approved by the local Institutional Ethical Committeeof Sher-i-KashmirInstitute of Medical Sciences.
The patient’s history was evaluated thoroughly and written informed consents were obtained from either the patients
themselves or their guardians. The admission records available were scrutinised and reviewed for detailed history.
An in-house proforma was used to collect information on demographic data and risk factors.Every parameter such as
blast percentage, hemoglobin, WBC and platelet count was taken into consideration.

Results:-
In our study we included a total of 74 cases of ALL patients from Kashmir region who had been diagnosed for the
said disease in the Department of Paediatric Oncology and Department of Clinical Haematology at Sher-i-Kashmir
Institute of Medical Sciences (SKIMS). Various parameters were taken into study like age, smoking status, and use
of pesticides, family history and immunological parameters which can be the risk factors for the development of
ALL.

Among the 74 ALL patients, 53 were children (72%) whereas 21 were adult (28%). According to the gender, ALL
was common among males 44 (59%) than in females 30 (42%). As far as age is concerned, regardless of the gender,
53 (72%) were in the age group of ≤18 years while 21 (28%) were in the age group of >18 signifying that lower age
groups have a higher chance of developing ALL. Based on demography, 10 (14%) were from urban areas while as
64 (86%) were from rural areas of Kashmir region indicating that there may be some environmental risks which can
be one of the links leading to the development of ALL (Table 1).

Based on clinical parameters, 56 (76%) of the ALL patients had WBC count of <10 × 10 3/µL while 18 (24%) of the
ALL patients had WBC count of >10 × 103/µL suggesting that most of the ALL patients are presented with high
WBC counts. Based on platelet count, 57 (77%) of the ALL patients had platelet count of >150 mm3/µL while 17
(23%) of the ALL patients had platelet count of <150 mm3/µL suggesting that the high platelets as WBCs is also
observed in most of the ALL patients (Table 1).. Based on immunophenotypes 69 (93%) were of Pre B-cell
phenotype, 3 (4%) belonged to T-cell phenotype while 2 (3%) were of mixed phenotype which depicts that in
Kashmiri population there is a predominance of Pre B-cell ALL phenotype (Graph 1)

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Characteristics ALL Cases, n= 74 (%)

Gender
Male 44 (59%)
Female 30 (41%)
Age
≤18 years 53 (72%)
>18years 21 (28%)
WBC counts (103/µl)
<10 56 (76%)
≥10 18 (24%)
Platelet count at base line - cells/mm3
<150
≥150 17 (23%)
57 (77%)
Immunophenotypes
T-ALL 03 (04%)
precursor-B ALL 69 (93%)
Mixed phenotype 02 (03%)
Average % Blast
T-ALL 03 57%
precursor-B ALL 69 81%
Mixed phenotype 02 90%
Dwelling
Urban 10 (14%)
Rural 64 (86%)
Table 1:- Clinico-pathological parameters of Acute lymphoblastic leukemia Patients.

100 Immunophenotype

90 Average Blast %age

80

70

60

50

40

30

20

10

0
T-cell ALL Pre B-cell ALL Mixed Phenotype
Graph 1:- Pattern of Average Blast percentage among different ALL Immunophenotypes.

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Discussion:-
ALL is mainly the most common pediatric cancer that has comparably better survival rate if treated and managed
properly with the background knowledge of clinical parameters and genetic molecular profile. Prospects of
successful treatment is associated numerous factors like age, gender, WBC count, French-American-British (FAB)
classification, and a lot of other factors as well. As per a detailed study by Arshad et al (2011) 29 in valley of
Kashmir, leukemia ranks 5th among common cancers occurring at a frequency of 9.9% with male: female ratio of
1:1. The average incidence of leukemia in our valley is 5.8/105/year with highest incidence in Acute Lymphoblastic
Leukemia. The common age group found to be affected is 2 to 10 years of age. In this study we have discussed
multiple features and risk factors of ALL and compared characteristics of ALL patients from Kashmir region. The
data covered most aspects of ALL, its incidence and prevalence in addition to factors which are correlated with
overall diagnosis and prognosis such as gender, ALL immunophenotypes, and WBC as well as platelet counts.

Leukemia has been seen to be one of the most significant causes of infant deaths, however over the past decades
significant progress has been made in the treatment of infant cancers.30 Just 10% of children's tumours were
clinically and epidemiologically differentiated and in 90% of the cases no clear aetiology has been established.
Infant leukaemia and other cancers seem to be multifactorial diseases, in which environmental and genetic
causes play significant role.31 Tiredness, fever, bleeding, chest pain and splenomegaly is often associated with
leukaemia. Leukemia is also one of the common causes of deaths in children. Finding beneficial factors can
contribute to early diagnosis and effective treatment of patients and to the improvement of screening procedures for
that patients.32

The most prevalent findings in many patients compared to many experiments were systemic complications, typically
severe anaemia, erratic platelet counts, lymphadenopathy and hepato-splenomagaly. ALL has several unfavourable
prognostic variables, such as high WBC counts, high platelet counts and lymphadenopathy.33 In the present study, 56
(76%) of the ALL patients had WBC count of <10 × 10 3/µL while 18 (24%) of the ALL patients had WBC count of
>10 × 103/µL suggesting that most of the ALL patients are presented with high WBC counts. In our study, 57 (77%)
of the ALL patients had platelet count of >150 mm3/µL while 17 (23%) of the ALL patients had platelet count of
<150 mm3/µL suggesting that the high platelets like WBCs is also observed in most of the ALL patients. In most
studies, only few patients were diagnosed with normal levels of these variables but almost all patients were having
abnormal levels of these variables.34

Acknowledgment:-
The current study was funded by SERB DST Govt. of India (EMR/2014/001089 dated 24/05/2018) and we thank
them for their financial support. We thank all the subjects for their active participation in the study. We also show
our gratitude to the Department of Hematology and Medical oncology, SKIMS for their assistance and cooperation
in procurement of samples.

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