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Benzene and Hairy Cell Leukemia

What Is Hairy Cell Leukemia?

Hairy Cell Leukemia (HCL) is a type of Chronic Lymphocytic Leukemia (CLL). The disease is called “hairy cell” because in this subtype of leukemia the malignant lymphocytes have small projections on their surface that give the appearance of hair when one looks at a blood smear under the microscope.  The abnormal (malignant) cell in Hairy Cell Leukemia is a B-lymphocyte. This cell infiltrates the bone marrow and usually the spleen. Along with fibrosis (scar tissue), it consumes most of the bone marrow space. As a result, the patient often develops pancytopenia (decreased red cells, white cells and platelets).


Symptoms of Hairy Cell Leukemia

Due to decreased blood counts, patients with Hairy Cell Leukemia are highly susceptible to serious infections. They are anemic and can bleed easily because of low platelet counts. They usually experience weakness and fatigue as a result of anemia. They often have splenomegaly (an enlarged spleen) and may also have hepatomegaly (an enlarged liver).  Patients who have Hairy Cell Leukemia often have reduced immunity, and a significant percentage may develop immune diseases.


Incidence of Hairy Cell Leukemia

The incidence of Hairy Cell Leukemia (HCL) is much less than CLL – about 0.4 cases per 100,000 population. Only about 600 new cases of HCL are diagnosed each year in the United States.


Epidemiologic Studies of Benzene and Hairy Cell Leukemia

Although Hairy Cell Leukemia is too rare a subtype of leukemia to fully investigate using epidemiologic methods, a few case-control studies of hairy cell leukemia patients have been performed, and some have shown significant excesses of the disease among benzene-exposed workers.

In 1985, researchers at the University of Chicago reported the results of a case-control study of 45 hairy cell leukemia patients. They found that occupational exposure to organic chemicals was significantly greater among both sexes of the cases than among their respective matched controls (RR = 3.10; 95% CI = 1.51 – 6.36). Oleske, D., et al., “A Case-Control Inquiry into the Etiology of Hairy Cell Leukemia,” Amer. J. Epidemiol. 121(5):675-683 (1985).

In 1988, investigators at the Naval Hospital in San Diego evaluated 86 civilian employees with a history of leukopenia at the Naval Weapons Center in China Lake. Although there was no evidence of myelodysplasia or cellular maturation abnormalities in the subjects, 2 cases of Hairy Cell Leukemia were identified. In reviewing the exposure histories of these 2 subjects, it was determined that both had extensive exposure to a wide variety of solvents, including benzene.  Luiken, G. A., et al., “Hematologic Evaluation of Employees with Leukopenia,” A.J.C.P. 90(6):679-683 (1988).

In 1995, French investigators reported the results of a case-control study of 291 hairy cell leukemia patients. They found a significant association for men with self-reported exposure to petrol (gasoline) or diesel (OR = 1.5; 95% CI 1.0 – 2.1). Clavel, J., et al., “Hairy Cell Leukaemia, Occupation, and Smoking,” Brit. J. Haematol. 91:154-161 (1995). This finding suggests that benzene is a causative factor in Hairy Cell Leukemia because benzene is a gasoline additive, and has typically been found in gasoline at concentrations up to 5%.

In 1998, Swedish investigators reported the results of a case-control study of 121 male hairy cell leukemia patients. They found significantly increased risks of the disease among workers exposed to wood-impregnating agents (OR = 2.4; 95% CI = 1.3 – 4.6), and exhausts (OR = 2.2; 95% CI = 1.3 – 3.9), and non-significantly increased risks of the disease among workers exposed to solvents (OR = 1.5; 95% CI = 0.8 – 2.7). The 2 wood-impregnating agents to which the patients were exposed were pentachlorophenols and creosote. Risks for exposure to both agents was significantly increased: Pentachlorophenols (OR = 2.6; 95% CI = 1.1 – 6.2); Creosote (OR – 3.1; 95% CI = 1.1 – 8.6).  Nordstrom, M., et al., “Occupational Exposures, Animal Exposure and Smoking as Risk Factors for Hairy Cell Leukaemia Evaluated in a Case-Control Study,” Brit. J. Cancer 77(11):2048-2052 (1998).

In 1993, British investigators conducted a case-control study of 50 patients with hairy cell leukemia and 95 controls. They reported nonsignificantly increased risks of hairy cell leukemia for exposure to solvents (OR = 1.45, 95% CI = 0.58 – 3.66) petroleum products, (OR = 2.14, 95% CI = 0.92 – 5.02), and benzene (OR = 2.00, 95% CI = 0.50 – 8.00). Staines, A., et al., “Hairy Cell Leukaemia: Descriptive Epidemiology and a Case-Control Study,” Br. J. Haematol. 85(4):714-717 (1993).


Case Reports

In 1982, Bescol-Liversac and other French investigators reported a case of benzene-induced Hairy Cell Leukemia. Bescol-Liversac, J., et al., “Un cas mixte d’intoxication benzenique professsionnelle et de leucemie a tricholeucocytes,” [“A case of occupational benzene intoxication and associated hairy cell leukemia”], Tox. Eur. Res. 4(6):329-335 (1982). In 1987, Aksoy reported 1 case of benzene-induced Hairy Cell Leukemia along with 2 cases of Chronic Lymphocytic Leukemia. Aksoy, M., “Chronic lymphoid leukaemia and hairy cell leukaemia due to chronic exposure to benzene: report of three cases,” Brit. J. Haematol. 66:209-211 (1987).

In response to Aksoy’s paper, Scottish investigators reported another case of benzene-induced hairy cell leukemia to the British Journal of Haematology. They described a 55-year old patient diagnosed with hairy cell leukemia in 1984. At the time of diagnosis he had been a paint sprayer for more than 25 years who did not wear personal protective equipment. Because spray-painting is an occupation which involves the use of benzene-containing solvents, the investigators considered the case a likely case of benzene-induced hairy cell leukemia. Ng, J-P., et al., “Hairy Cell Leukaemia Due to Chronic Exposure to Benzene,” Brit. J. Haematol. 67:116-121 (1987).

Also in 1987, French investigators reported a series of hairy cell leukemia patients with benzene exposure. They noted that a “striking finding was the frequency of occupations in contact with petroleum-derived substances.” Of 105 Hairy Cell Leukemia patients who were interviewed, 21 worked as garage mechanics or drivers. Flandrin, G., et al., “Is Male Predominance (4/1) in Hairy Cell Leukaemia Related to Occupational Exposure to Ionizing Radiation, Benzene and Other Solvents?” Brit. J. Haematol. 67(1):119-120 (1987).  Because automotive mechanics are typically exposed to benzene from gasoline and solvents, the investigators considered the prevalence of mechanics (20%) among the Hairy Cell Leukemia patients an indication of a benzene-related etiology of their disease.

In 1988, Polish investigators reported another case of benzene-induced hairy cell leukemia and explained the difficulties of making such a causal determination. Byczkowska Z, et al., [“Practical and disputable aspects of the effect of benzene containing organic solvents exemplified by the case of hairy cell leukemia”] [in Polish]; Med. Pr. 39(3):206 211 (1988).



The studies described above provide sufficient data to conclude that exposure to benzene can cause Hairy Cell Leukemia (HCL) and does cause this disease in exposed workers. Indeed, in his recent review of the carcinogenicity of benzene, Professor Myron A. Mehlman, who for many years served as the Director of Toxicology of Mobil Oil Corporation, concluded: “While there is a prevalence of acute myelogenous leukemia, it is certain that all forms of leukemia are caused by benzene exposure.” Table 4 of his review article, titled “Types of leukemias and lymphomas from benzene exposure in humans,” specifically lists Chronic Lymphocytic Leukemia and Hairy Cell Leukemia as types of leukemia that are caused by benzene exposure. Mehlman, M. A., “Benzene: a haematopoietic and multi-organ carcinogen at any level above 0,” Eur. J. Oncol. 9(1):15-36 (2004).