Eric Kraut, MD

The Ohio State University

Hairy cell leukemia (HCL) is a slow growing cancer of the lymphocyte cell line. In the majority of patients, the cell affected is a mature B lymphocyte. The disease begins in the bone marrow but often involves the liver, spleen and sometimes lymph nodes. The symptoms seen in patients with HCL are varied and reflect both direct involvement in organs, secondary effects on the immune system, and release of cytokines or proteins from the malignant cell itself.

Autoimmune Disease

The development of immunologic disorders in association with hairy cell leukemia has been documented in individual case presentations as well as a retrospective review of patients. Patients may present with polyarthritis or diffuse joint pain, erythema nodosum or skin rash, or pulmonary infiltrates. In some cases a diagnosis of lupus or rheumatoid arthritis was entertained before the diagnosis of hairy cell leukemia. Patients can present with systemic symptoms with fever, weight loss, and organ involvement including the liver and kidney. Patients can be treated as necessary with anti-inflammatory drugs including steroids with clinical improvement. Improvement in autoimmune disease does not necessarily respond to effective treatment for the HCL.

Hematologic Complications

The most common complications seen involve the blood and the spleen. The effects on the blood are as follows: The majority of patients will have some degree of reduced blood count with about 40% of patients having depression of all blood cell lines or pancytopenia. In looking at the individual cell lines in large retrospective series anemia as defined by a hemoglobin less than 12 grams/dl is seen in up to 80% of patients with severe anemia with hemoglobin less than 8.5 grams/dl in about one third of patients. This significant anemia may lead to fatigue and reduced exercise tolerance and is often the first symptoms of this disease. The cause of the anemia may be multifactorial including iron deficiency from blood loss and occasionally autoimmune hemolytic anemia. However, the common reason for the anemia is removal of red blood cells in the spleen and marrow infiltration with hairy cells leading to reduced red cell production. Thrombocytopenia is a frequent complication of this disease with platelets less than 100,000/ul in up to 80% of patients. Severe thrombocytopenia of less than 50,000/ul occurs in about one third of patients with about 10% having counts under 20,000/ul.Significant bleeding is usually only seen in severely depressed platelet counts.

The spleen appears to play a significant role, since platelets return to normal after splenectomy in 70% of patients and is especially important in patients with large spleens. However, post splenectomy patients do develop thrombocytopenia due to hairy cell involvement in the marrow and occasionally immune thrombocytopenia is seen.

Leucopenia and neutropenia is one common reason to suspect HCL and leads to one the most severe complications that of significant infections. Life threatening neutropenia with neutrophils of under 500/ul occurs in almost 40 % of patients. This depressed white count will often be improved by the use of granulocyte growth factors. An additional diagnostic finding is the presence of marked monocytopenia with resultant susceptibility to unusual organisms.

Hepatomegaly (Liver)

Hepatomegaly is much less frequent in hairy cell patients with enlargement noted about one third of the time and marked hepatomegaly or greater than 10 cm below the costal margin only 2% of the time. Pain from this hepatomegaly is not common but can occur. The liver is almost always infiltrated with hairy cells without significantly altering hepatic function or elevating liver enzymes.(21. The development of marked hyperbilirubinemia and elevated liver enzyme elevations does occur, but its rarity should make one consider an infectious etiology. In addition, one can see portal hypertension due to involvement with subsequent ascites.

Splenomegaly (Spleen)

Splenomegaly is one the classic findings found at presentation in patients with hairy cell leukemia.On physical examination up to 90% of patients will have an enlarged spleen and marked splenomegaly of greater than 10 cm below the costal margin seen in 20% of patients. The enlarged spleen may cause early satiety with subsequent weight loss and can be associated with painful splenic infarction or splenic rupture.

Infectious Complications

One of the most recognized and important clinical problems in patients with hairy cell leukemia is the development of severe life threatening and unusual infections. These may involve the common sites of lung and urinary tract as well as less common involvement of the liver and central nervous system. Patients may develop a wide range of infections including those usually seen in the neutropenic host such as staphylococcus aureus. Pseudomonas aeruginosa Herpes zoster with painful skin lesions is usually only seen after patients have been treated with chemotherapy. Patients with fever of unknown origin should always be treated as if they have a significant infection and a careful search for bacterial, fungal, or viral infection be initiated.

Other Complications

Several other unusual complications can be seen. 1) Neurologic complications including symptoms and signs of meningitis and nerve compression has been reported but one should always look for infection as a cause. 2) Lymphadenopathy is infrequent and when it is present usually involves the chest or abdominal nodes. These can be bulky and cause symptoms of compression. 3) Destructive bone lesions with severe pain can be seen usually in long bones or vertebrae. 4) Finally, involvement of the lining of the lung cavity or pleura or that of the abdominal cavity or peritoneal surface can lead to accumulation of fluid in these areas with symptoms of abdominal pain and or shortness of breath.