A study of leukemias Profile in central India

Introduction: Leukemia was considered as a rare disease few years back. However, it is increasing in incidence and prevalence slowly and steadily. Leukemias are euplastic proliferations of haematopoietic cells and form a major proportion of haematopoietic neoplasms that are diagnosed worldwide. Objective: To find out the incidence of four major types of leukemias in central India. Methods: Total 73 cases were selected from in and out patient departments of Gandhi Medical College and associated Hamidia Hospital Bhopal over a period from Oct 2013 to Nov 2014. Diagnosis was based on peripheral blood count, peripheral blood smear and bone marrow examination for morphology along with cytochemistry study whenever required. Results: Out of 73 cases on final diagnosis, 23 cases (31.51%) were of Acute Lymphoblastic Leukemias, 11 cases (15.07%) were of Acute Myeloblastic Leukemias, 35 cases (47.97%) were of Chronic Myeloid Leukemias, 1 case (1.37%) is of Chronic Lymphocytic Leukemia and 3 cases (4.11%) were Undiagnosed which were referred to higher centers. Conclusion: The present study revealed that Chronic leukemia was more common than acute leukemia with Chronic Myeloid Leukemias being the most common type, followed by Acute Lymphoblastic Leukemias, Acute Myeloblastic Leukemias and Chronic Lymphocytic Leukemia.


Introduction
Leukemia was considered as a rare disease few years back. However, it is increasing in incidence and prevalence slowly and steadily. Leukemias are the 10th most common cancer in men and 12 th most common in women and constitute 3% of the global cancer burden [1].
Developing countries bear more than half of global cancer burden, because 75% of the world population lives in these countries [2]. The incidence of Leukemia is highest in North America and Australia/New-Zealand and lowest in sub-Saharan Africa [3].
In India,lympho-haematopoietic malignancies constitute 9.5% of all cancers in men and 5.5% in women [4]. As per available information from population-based surveys, the incidence of leukemia in India varies from 0.8/1, 00,000 in Barshi (Rural area of Maharashtra) to 5/1,00,000 in Delhi.
These figures are comparably lower than rest of the world but under diagnosis and under-reporting cannot be ruled out [4]. The cell type distribution of leukemias observed in India is different from that observed in developed world.
Myeloid leukemias predominate in India while lymphoid leukemias dominate in western world mainly because of higher incidence of chronic lymphatic leukemia [5].
Despite being relative uncommon, leukemias have been studied more extensively because of easy accessibility of involved tissue [1].

Original Research Article
Pathology Update: Tropical Journal of Pathology & Microbiology Available online at: www.pathologyreview.in 182 | P a g e The incidence of CML was noted highest (45.3%) and that was lowest of CLL (5.7%) in Capital of India i.e. Delhi during a period of 1970-1979.19 Similar observations were noted in Chandigarh and other metro cities like Mumbai and Calcutta [6,7,8].
There was exception for incidence of ALL (39.2%) which was highest observed in Kerala state during a period of 1980-1983 [9]. The leukemias are defined as diseases in which abnormal proliferation of haematopoetic cells cause progressively increasing infiltration of bone marrow, although in certain forms the lymphatic tissues are particularly affected [10].

Malignant proliferation of haematopoietic cells (leukemia)
constitutes major proportion of haematopoietic neoplasm's worldwide. Leukemias are classified into myeloid and lymphoid subtype [11].
Typing of leukemia is essential for effective therapy because prognosis and survival rate are different for each type and sub-type [12]. Leukemia are of two types; acute and chronic.
Acute leukemias are; acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). In childhood, ALL is most common type than AML. In India, the incidence of ALL and AML are 35% and 15% of all hematological malignancies respectively.
Chronic leukemias are classified into chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL) [13,14]. Due to the lack of any nationwide leukemia screening program, most of the population of India is still unaware of this blood disorder.
Lack of awareness also plays a role in underlying late presentation and noncompliance with screening guidelines [15].
Hence it is important to determine the current incidence of leukemia's in India as well as to understand how the occurrence and outcome of the disease differs across the whole country.

Materials and Methods
Place of study-Department of Pathology, Gandhi Medical College, Bhopal

Sampling methods-Selected from in and out patient departments of Gandhi Medical College and associated Hamidia
Sample collection-Blood, bone marrow smear Inclusion criteriahaving provisional diagnosis of acute leukemia and leucoproliferative disorder.
The study was conducted after approval from institutional ethical committee in the Department of Pathology, Gandhi Medical College, Bhopal from Oct 2013 to Nov 2014.
Total 73 cases were selected from in and out patient departments of Gandhi Medical College and associated Hamidia Hospital Bhopal having provisional diagnosis of acute leukemia and leucoproliferative disorder so on basis of leishman stained smears-Peripheral/bone marrow along with cytochemistry study whenever required.
Thorough case history and clinical examination as per predefined Performa with Hemoglobin estimation, WBC count, Platelet count and various hematological indices were evaluated using automated analyzer.
Peripheral blood/bone marrow smear was made on clean glass slides with fresh blood samples; smears were fixed and stained by leishman stain.
Leishman stain was poured on air dried unfixed smears for a period of 5-7 minutes, then added twice quantity of buffered distilled water for next 10 minutes. Smears prepared on clean glass slides, fixed by methanol and stained for various cytochemical stains (MPO, PAS, NES, and NAP).
For all the special stains, commercially available kits (Leucognost) were used. FAB classification of acute leukemia was applied for sub-typing.

Results
The present study comprises 73 cases of Leukemia. The observations made in this study are as follows.

Original Research Article
Pathology Update: Tropical Journal of Pathology & Microbiology Available online at: www.pathologyreview.in 183 | P a g e

Discussion
The incidence of leukemia has increased considerably and this rise is noticeable because of improved statistics, better case findings with novel technologies which lead to better diagnosis and treatment methods.
This incidence varies in different geographical regions according to varying life styles, economic conditions, and poverty rate [16].
In India the incidence of various hematological cancers is different as compared to western countries. This can be attributable to less health awareness and poor availability of health care delivery system in India [17,18]. In present study 73 cases of leukemias were studied 34 cases (46.58%) and 36 cases (49.32%) were of acute and chronic leukemias respectively and 3 cases (4.11%) were undiagnosed. Most of the cases (82.61% and 100%) of acute lymphoblastic leukemia (ALL) acute myeloid leukemia (AML) had moderate to severe thrombocytopenia. Whereas in chronic myeloid leukemia (CML) and chronic lypmphocytic leukemia (CLL) most of cases had platelet above 1lakh/cu mm.
In present study four special staining procedures were done after making a provisional diagnosis of leukemias by leishman stain (Stain used Myeloperoxidase, Periodic acid Schiff, Non-specific Esterase and alkaline phosphates). On special staining we found Myeloblasts of AML and CML showed positive (coarse brown black granules) staining with MPO in more than 3% of blasts in all cases except one in which NSE stain was positive.
Whereas ALL and CLL were negative for MPO stain. The lymphoblasts of ALL and CLL showed positive (block positive) PAS staining. Among all leukemias the incidence and prevalence of chronic myeloid leukemia (CML) remains higher due to chronicity, earlier diagnosis because of accurate and cheaper diagnostic tool and greater physician awareness.
Our study revealed chronic myeloid leukemia (CML) (47.95%) as the most common type of leukemia ( Table  1). The varying findings of Menzes and Malik [24] and Verghese et al [9] can be attributable to geographical variation and population bias.
The incidence of acute lymphoblastic leukemia was higher in studies by Prakash et al [25] and Verghese et al [9]. In our study the cases of acute lymphoblastic leukemia were the second predominant (31.51%) which correlates with study of Advani et al [26], Dicosta et al [7], Modak H et al [27], Chen et al [28] and Shome et al [6] ( Table 1).
The incidence of Acute myeloid leukemia (AML) in our study was the third most common. Similar findings are reported by Advani et al [26] and D'Costa GG et al [7]. Incidence of higher percentage than ours was reported by Chatterjee et al [8], Prakash et al [25], Rani et al [21], Kushwaha et al [20], Shome et al [6], and Rathee et al [23] (Table 8).
Our study shows the incidence of chronic lypmphocytic leukemia (CLL) to be lowest (1.37%) among all the four major types of leukemia which correlates well with the findings of Kushwaha et al [20], Verghese et al [9] and D'Costa GG et al [7] (Table 2).
It has been seen that the spectrum of cancer epidemiology seen in India is different than that seen in any developed country. It should be stressed that there are not many cancer registry data's in India despite a large population, so better development of regional and national registries is the need of the hour.

Conclusion
Present study concluded that the incidence of different types of leukaemia in central India doesn't differ markedly from rest of the Indian populations. Chronic leukemia was more common than acute leukemia with chronic myeloid leukemia being the most common type, followed by Acute Lymphoblastic Leukemias, Acute Myeloblastic Leukemias and Chronic Lymphocytic Leukemia.
Chronic myeloid leukemia which came out to be more common in our study, is mainly a leukemia of adults affecting the myeloid series while AML occurring in younger age group is characterized by presence of >20% blasts in marrow, as per the WHO criteria.
This incidence varies in different geographical regions according to varying life styles, economic conditions, and poverty rate. It should be stressed that there are not many cancer registry data's in India despite a large population, so better development of regional and national registries is the need of the time.
Addition to existing knowledge: Though numerous studies of leukemia have been done in various regions of India but this study is exclusively the first one which details the leukemia profile in central part of India.
Funding: Nil, Conflict of interest: None initiated Permission from IRB: Yes