Blood Malignancies in Mazandaran Province of Iran

BACKGROUND
Leukemia and lymphoma demonstrate significantly incidence rates throughout the world and particularly in Iran they cause serious mortality and diagnosis and treatment expenditures for both families and the health system. Combined they account for about 11 percent of cancers in Mazandaran province, ranking number 2 in prevalent cancers. The purpose of this study was to provide a first general and specific description of leukemia and lymphoma in Mazandaran province.


MATERIALS AND METHODS
In this descriptive retrospective study, entire patient's data were reviewed which had confirmed diagnosis of leukemia and lymphoma with valid laboratory or pathology reports in the period 2001-2008. The data were collected by Babol health research site related to Tehran University of Medical Science. Incidence rates based on age groups, gender, city of residence and type of malignancy were calculated and analyzed.


RESULTS
In Mazandaran province, 1,146 cases of leukemia and lymphoma were encountered, 5.9 in 100,000 persons on average annually. The highest incidence rates were obtained at age of 70 or above (26.4) and the lowest at age of 0-9 (2.3).The incidence rates in males and females were 7.1 and 4.8 respectively with a ratio of 1.5. The highest incidence rate was in Babol (7.3) and the lowest was calculated in Neka and Tonekabon equally (1.5). According to the type of malignancy, non Hodgkin lymphoma, with 2.5/100,000 have the most incidence rate and myeloid leukemia with 1.8 had the lowest.


CONCLUSIONS
The obtained findings indicate clear differences in incidence rates based on age, gender, residence, and type of malignancy. Therefore it's suggested that in addition to promote data collecting programs, research projects should be programmed to define leukemia and lymphoma risk factors in this province.


Introduction
Neoplastic diseases are one of the most common and most serious illnesses seen in medical science that involves more than a third of the population somehow.Neoplastic diseases have also become the second leading cause of death worldwide after heart diseases and 23% of deaths in the United States and 20% in Iran (Ferlay, 2010;Jemal, 2010).
Blood malignancies have remarkable incidence in the world and Iran, especially in Mazandaran province of Iran.These diseases are seen in all age groups and cause remarkable mortality, so have a lot of diagnosis and treatment costs for families and health care system.These diseases make up about 7% of all cancers in World and 13.6% in Iran (Ferlay, 2010).
Leukemia and lymphoma make up about 11.1% of all

Blood Malignancies in Mazandaran Province of Iran
Bahram Tahmasby 1 , Ahmad Barati Marnani 1 , Mohammadreza Maleki 1 , Mohsen Barouni 2 , Seyyed Hamid Mousavi 3 , Behjat Naseriyan 3 , Mirzaali Nazarnezhad 3 , Ali Alizadeh 4 *, Asma sabermahani 5   cancers in Mazandaran province and in this case are the second most common cancer in the province (Mahmoudy, 1995).Leukemia and lymphoma are neoplastic diseases of the hematopoietic and immune systems with various clinical and pathological presentation and a wide range of factors, including genetic factors, physical and chemical exposures, infectious agents and other environmental factors have mentioned (Robert et al., 2011;Goldman et al., 2012).
Myeloid leukemia is a heterogeneous group of hematopoietic system neoplasm by infiltration of neoplastic cells into the blood, bone marrow and other tissues.This disease is identified and classified into acute and chronic types (Longo et al., 2011;Goldman et al., 2012).Malignant lymphoid cells are variable from very silent to very aggressive types.These cancers are created from the immune cells in different stages of their differentiation.Some of the malignant lymphoid cells almost always are present in the leukemia and can be divided into acute and chronic types.Other malignant lymphoid cells such as solid tumors of immune systems are almost always present lymphoma.
Two important groups of these diseases are Hodgkin's disease (HD) and Non Hodgkin lymphoma (NHL) (2-4).Given that up to now, don ̉t study in description leukemia and lymphoma in Mazandaran province that show general and specific status of these diseases and due to the presence of cancer registration system in the north of the Iran in Babol Research Station(dependent to Tehran University of Medical Sciences), this research is achieved in partnership with station.Because of this study is the first comprehensive and detailed review of the rates of leukemia and lymphoma in accordance to ages groups, sex, incidence of year and city of residence, so the results of this study can be the basis for estimating of blood malignancies (leukemia and lymphoma) in Mazandaran province which is the basis to etiologic studies to ultimately reduce the burden of disease and improve health and reduce the years of life lost.

Materials and Methods
This research is descriptive, cross sectional and retrospective study.In this research, the information of all patients of Mazandaran province for seven years that referred to one of the centers of pathology, cellology, oncology, chemotherapy and radiotherapy of private and public sectors in Mazandaran province and have a valid pathology or laboratory report of leukemia and lymphoma were studied.Repeated cases, double cases (overlapping) and cases with imperfect data were deleted.Data were collected by cancer registries form of Tehran University of Medical Sciences.These data consist of age, residence, race, religious and center or the doctor who was reported.Since Mazandaran province in religious and race have a homogenous population, these two variables were not studied.
In this study, the latest official census in the Mazandaran province and related city has been used.These population were used according to10 years old ages groups (8 ages groups), sex (male and female), and city of residence (15 city).According to ICD-10 classification, the blood malignancies are two general categories: leukemia and lymphoma.In leukemia group, lymphoid leukemia and myeloid leukemia, and, in lymphoma group, Hodgkin's disease (HD) and Non Hodgkin lymphoma (NHL) were studied.To statistical analysis, the incidence of these diseases has been used and to eliminate of the age variable effect, the standardized morbidity ratio (SMR) was calculated and used.

Results
In Mazandaran province, 1,146 cases of leukemia and lymphoma have been realized since 2001-2008, and then incidence rates based on age groups, gender, city of residence and type of malignancy have been calculated and analyzed.
Age groups: trend of increase in incidence of blood malignancies with increase age was seen.So that age groups of 70 years and above, with annual incidence 26.4 per 100000, have shown the highest incidence rate and age group of 0 to 9 years with annual incidence 2.3 per 100000 have shown the lowest incidence rate (Figure 1).
Gender: annual incidence rate of these malignancies in men was7.5 per 100,000 and in woman was 4.8 per 100000.The incidence ratio of male to female was 1.48.In men, Non Hodgkin lymphoma with annual incidence of 3.3 per 100,000 have the highest portion (48.5%) and myeloid leukemia with annual incidence of 1 per 100,000 have the lowest portion (13.2%) of these malignancies.In women Non Hodgkin lymphoma with annual incidence of 1.8 per 100,000 have the highest portion (39.6%) and Hodgkin's disease with annual incidence of 0.8 per 100,000 have the lowest portion (14.8%) of these malignancies (Figure 2).
City of residence: Babol with SMR=7.3 in average have the highest and Tone kabon with SMR=1.4 in average have the lowest incidence rate annually.The highest incidence rate of these malignancies are in center of Mazandaran provinces and the lowest of that are in the west of Mazandaran provinces (Figure 3).

Type of malignancy
Hodgkin's disease (HD): In the average have about 1 in 100,000 incidence annually.The highest incidence rate was seen in the age group of 60-69 years (1.5) and the lowest incidence rate was seen in the age group of 0-9 years (0.2). Incidence rate in the male was calculated 1.2 per 100,000 and in the female 0.8 per 100000.male to female ratio is 1.5.The highest incidence rate was seen in Babol (SMR=2) and the lowest incidence rate equally was seen in the both Neka and Tonekabon equally (SMR=0.2).
Non Hodgkin lymphoma (NHL): In the average have about 2.5 per 100,000 incidence rate annually.The highest incidence rate was seen in the age group of 70 years and above (15.8)and the lowest incidence rate was seen in  the age group of 0 to 9 years (0.3).Incidence rate in the male was calculated 3.3 per 100,000 and in the female 0.8 per 100000.male to female ratio is 1.9.The highest incidence rate was seen in Babol (SMR=1.8)and the lowest incidence rate was seen in Savadkooh (SMR=0.3).
Lymphoid leukemia: In the average have about 1.3 per 100000 incidence rate annually.The highest incidence rate was seen in the age group of 70 years and above (3.6)and the lowest incidence rate was seen in the age group of 40-49 years (0.8).Incidence rate in the male was calculated 1.6 per 100,000 and in the female 1.1 per 100,000.male to female ratio is 1.5.The highest incidence rate was seen in Babol (SMR=1.6)and the lowest incidence rate was seen in Chaloos (SMR=0.2).
Myeloid leukemia: In the average have about 1.1 per 100,000 incidence rate annually.The highest incidence rate was seen in the age group of 70 years and above (6.2) and the lowest incidence rate was seen in the age group of 0 to 9 years (0.1).Incidence rate in the male was calculated 1 per 100,000 and in the female 1.1 per 100,000.Male to female ratio is 0.9.The highest incidence rate was seen in Ghaemshahr (SMR=2.5)and the lowest incidence rate was seen in Mahmoodabad (SMR=0).

Discussion
Since the ages group of under10 years old have the lowest incidence rate (2.3 per 100,000) and the ages group ≥70 years old have the highest incidence rate (26.4 per 100,000), It shows that there are relationship between patient's age and morbidity of leukemia and lymphoma which this point were stated by researchers (Longo et al., 2011;Robert et al., 2011;Goldman et al., 2012).Synchronization of Increased incidence of Non-Hodgkin's lymphoma with increases age is shown higher than the rest of hematological malignancies.Lymphoid leukemia incidence is increased approximately in two periods, that one of it, is under 30 years old and other is above 50 years old and between the ages of 30 and 50 years, the incidence is relatively slow.Hodgkin's disease in the age 10 years and above has steady incidence rate.With increasing of age, the incidence of Myeloid Leukemia increases slowly while in the references were stated that Hodgkin's lymphoma is the most common malignancy among young adults 15-24 years (Arlene et al., 1995) and the incidence of Hodgkin's disease has been relatively stable.Two periods of increased incidence is expressed, first around age 20 years and the other around age 80 years (Wiesenberger, 1994;Arlene et al., 1995;Longo et al., 2011).It also stated that the incidence of Acute Myeloid Leukemia (AML) increases with age, so that 90 percent of this disease is seen around 40 years old and 10 percent in the children (Arlene et al., 1995;Sandler and Ross,1997;Longo et al., 2011;Goldman et al., 2012).Until the middle of the fourth decade of life, the incidence of chronic Myeloid Leukemia (CML) increases with age gradually.The average age of onset of the disease is 53 years, then the incidence is accelerating (Longo et al., 2011;Goldman et al., 2012).Acute lymphoid leukemia (ALL) is often as children and young adult cancer so that 90% of the cases are seen in children and 10 percent of the cases are seen in adults (Sandler, 1992;Longo et al., 2011;Goldman et al., 2012).Chronic lymphoid leukemia (CLL) is the most common form of leukemia in Western countries that more occur in adults and elderly and in the children is rare (Longo et al., 2011;Goldman et al., 2012).

Gender
Overall incidence ratio of hematologic malignancies in the male to female is approximately 1.5 times.The difference in incidence rate between men and women, as stated in previous research, can show the possible impact of gender on the incidence of leukemia and lymphoma (Arlene et al., 1995;Longo and Randolph, 2010;Goldman et al., 2012;Peter et al., 2013).This difference could be due to sex hormones or differences in environmental exposures between the men and women while it has been reported that leukemia tend to involve men more than women (Arlene et al., 1995;Longo and Randolph, 2010;Peter et al., 2013).Another report states that age adjusted incidence rate of Acute Myeloid Leukemia in the men is more than women (2.9 vs. 1.9) as well as age adjusted incidence rate of Chronic Myeloid Leukemia in the men is more than women (1.7 vs. 1) (Longo and Randolph, 2010;Longo et al., 2011;Goldman et al., 2012).It also stated that age adjusted incidence rate of Chronic lymphoid leukemia, Hodgkin's disease and non-Hodgkin's lymphoma in the men is more than women (Arlene et al., 1995;Longo and Randolph, 2010;Longo et al., 2011) and in the last report of Mazandaran province stated that the overall incidence ratio of men to women in all types of leukemia and lymphoma is 1.5 (Mahmoudy et al., 1995;Peter et al., 2013).
Babol city with SMR=7.3 has the highest incidence rate and Tonekaboon with SMR=1.5 has the lowest incidence rate annually.Because the cities of the west province have better situation rather than to east provinces and the center of province have worst situation.As has been stated in various references it seems that residence and the geographical, economical, nutritional features, and environmental exposures influence the difference in incidence rate (Arlene et al., 1995;Sandler and Ross, 1997;Longo et al., 2011;Goldman et al., 2012), that among of them, probably physical and chemical exposures in the center of province are important.
In this study, the total incidence rate of leukemia (Myeloid and Lymphoid) is obtained 2.4 per 100,000 annually and incidence rate of lymphoma (HD and NHL) is obtained 3.5 per 100,000, while the incidence rate of leukemia in the world have estimated 10 per 100,000 (Sant et al., 2010;Goldman et al., 2012).Non-Hodgkin's Lymphoma has the highest annual incidence rate (2.5 per 100,000) and Hodgkin's disease has the lowest annual incidence rate (1 per 100,000) (Ansel and Armitage, 2006;Punnett et al., 2010).The incidence rate of Acute Myeloid Leukemia is 2.3 per 100,000 and the incidence rate of Chronic Myeloid Leukemia is 1-1.3 per 100,000 (Baccaraniet al., 2009;Dohner et al., 2010;Sant et al., 2010) but in this study, the annually incidence rate of Myeloid leukemia (acute and chronic) is obtained 1.1 per 100,000.
In conclusion, given findings indicates clear differences of incidence rate based on age, sex, residence, and type of malignancy.Therefore it's suggested that in addition to promote data collecting program, research projects should be programmed to define leukemia and lymphoma risk factors in this province.By making use of these results, as well as community education, and implementing of some rules and regulations, reduce the risk of hematologic malignancies to reduce the burden of these diseases and years of life lost and ultimately improve the health of the community.

Figure
Figure 1.Incidence Rate of Blood Malignancies Based.A) Age Groups B) Gender