Hairy cell leukemia is a mature B cell neoplasm. It is usually classified as a sub-type of chronic lymphoid leukemia for convenience. It is uncommon, representing about 2% of all leukemias, or less than a total of 2000 new cases diagnosed each year in the North America and Western Europe combined.

Originally known as histiocytic leukemia, malignant reticulosis, or lymphoid myelofibrosis in publications dating back to the 1920s, this disease was formally named leukemic reticuloendotheliosis and its characterization significantly advanced by Bertha Bouroncle, M.D., and her colleagues at the Ohio State University College of Medicine in 1958. Its common name, which was coined in 1966, is derived from the appearance of the cells under a microscope.

 Two variants have been described: Hairy cell leukemia-variant, which usually is diagnosed in older men (median age above 70), and a Japanese variant. The non-Japanese variant is more difficult to treat than either 'classic' HCL or the Japanese variant HCL.

 

 Risk Factors and Causes

 Most patients are white males over the age of 50, although it has been diagnosed in at least one teenager. Men are four to five times more likely to develop hairy cell leukemia than women. It does not appear to be hereditary, although occasional familial cases have been reported, usually showing a common HLA type.

 The cause is unknown, but generally believed not to be caused by tobacco, ionizing radiation, pesticides, or industrial chemicals other than possibly diesel. Farming and gardening appear to increase the risk in some studies. The possibility that HCL is caused by a random accident during routine cell division can not be ruled out.

 

Symptoms

 In hairy cell leukemia, the broken "hairy cells" build up in the bone marrow, which means that the bone marrow has difficulty producing enough normal cells: white blood cells to fight infections, red blood cells to carry oxygen, and platelets to stop bleeding. Consequently, patients usually present with infection, anemia-related fatigue, and/or easy bleeding.

 Most symptoms are often vague, such as "persistent fatigue" or "not feeling well." Some of the leukemic cells may gather in the spleen and cause it to swell; this can have the side effect of making the person feel full even when they haven't eaten much.

 Hairy cell leukemia is commonly diagnosed after a routine blood count shows unexpectedly low numbers for one or more kinds of blood cells, or after unexplained bruises or unexplained infections, such as repeated bouts of pneumonia in an otherwise apparently healthy patient. 

Platelet function may be somewhat impaired in HCL patients, although this does not appear to have any significant practical effect. It may result in somewhat more mild bruises than would otherwise be expected for a given platelet count or a mildly increased bleeding time for a minor cut. It is likely the result of producing slightly abnormal platelets in the overstressed bone marrow tissue. 

Patients with a high tumor burden may also have somewhat reduced levels of cholesterol, especially in patients with an enlarged spleen. Cholesterol levels return to more normal values with successful treatment of HCL.

 

Diagnosis

 The diagnostic path may have begun with a simple test like a complete blood count, but this is not adequate to diagnose HCL. Most patients require a bone marrow biopsy for proper diagnosis. The bone marrow biopsy is used to confirm the presence of HCL and also the absence of any secondary disease. Abnormal white blood cells bearing hair-like projections from the cytoplasm are seen on blood film examination or bone marrow biopsy. The diagnosis can be confirmed by viewing the cells with a special stain, known as TRAP, or tartrate resistant acid phosphatase.

 It is also possible to definitively diagnose hairy cell leukemia through a flow cytometry blood test which identifies characteristic proteins on the cell surfaces. These cancerous cells are larger than normal and positive for CD19, CD20, CD22, CD11c, CD25, CD103, and FMC7. Hairy cell leukemia-variant (HCL-V), which shares some characteristics with B cell prolymphocytic leukemia (B-PLL), does not show CD25 (also called the Interleukin-2 receptor, alpha). As this is relatively new and expensive technology, its adoption by physicians is not uniform, despite the advantages of comfort, simplicity, and safety for the patient when compared to a bone marrow biopsy.

 Because a patient could have more than one similar disease, it is also necessary to rule out the presence of leukemias and lymphomas such as SMZL or B-PLL. The presence of these diseases is easily checked during a flow cytometry test, where they characteristically show different results. Careful review of bone marrow biopsy samples is also reliable for this purpose.

 On physical exam, patients may display massive splenomegaly. This is less likely among patients who are diagnosed through routine blood work, when the disease is at an early stage.

 

  Prognosis

More than 95% of new patients are treated well or at least adequately by cladribine or pentostatin.[29] A majority of new patients can expect a disease-free remission time span of about ten years, or sometimes much longer after taking one of these drugs just once. If re-treatment is necessary in the future, the drugs are normally effective again, although, statistically, the length of the remission may be somewhat shorter.

 How soon after treatment a patient feels "normal" again depends on several factors, including:

    * how advanced the disease was at the time of treatment;

    * the patient's underlying health status;

    * whether the patient had a "complete response" or only a partial response to the treatment;

    * whether the patient experienced any of the rare, but serious side effects such as kidney failure;

    * how aggressive the individual's disease is;

    * whether the patient is experiencing unusual psychological trauma from the "cancer" diagnosis; and

    * how the patient perceived his or her pre-treatment energy level and daily functioning.

With appropriate treatment, the overall projected lifespan for patients is normal or near-normal. In all patients, the first two years after diagnosis have the highest risk for fatal outcome; generally, surviving five years predicts good control of the disease. After five years' clinical remission, patients with normal blood counts can often qualify for private life insurance with some companies.

Despite decade-long remissions and years of living very normal lives after treatment, hairy cell leukemia is officially considered an incurable disease. Relapses have happened even after more than twenty years of continuous remission. Patients will require lifelong monitoring and should be aware that the disease can recur even after decades of good health.

 HCL patients are also at a slightly higher than average risk for developing a second kind of cancer at some point during their lives (including before their HCL diagnosis).

 Worldwide, approximately 300 HCL patients per year are expected to die. Some of these patients were diagnosed with HCL due to a serious illness which prevented them from receiving initial treatment in time; many others died after living a normal lifespan and experiencing years of good control of the disease. Perhaps as many as five out of six HCL patients die from some other cause.

 Accurately measuring survival for patients with the variant form of the disease (HCL-V) is complicated by the relatively high median age (70 years old) at diagnosis. However, HCL-V patients routinely survive for more than 10 years, and younger patients can likely expect a long life.

 

  Follow-Up Care

 People who have hairy cell leukemia are never considered 'cured' and should have regular follow-up examinations after their treatment is over. Most physicians insist on seeing patients at least once a year for the rest of the patient's life, and getting blood counts twice a year. Regular follow-up care ensures that patients are carefully monitored, any changes in health are discussed, and new or recurrent cancer can be detected and treated as soon as possible. Between regularly scheduled appointments, people who have hairy cell leukemia should report any health problems, especially viral or bacterial infections, as soon as they appear.

 Patients with HCL are more likely than average to develop another neoplastic disease, such as colon cancer or lung cancer. This appears to relate best to the number of hairy cells, and not to different forms of treatment. On average, patients might reasonably expect to have as much as double the risk of developing another cancer, with a peak about two years after HCL diagnosis and falling steadily after that, assuming that the HCL was successfully treated. Aggressive surveillance and prevention efforts are generally warranted, although the lifetime odds of developing a second cancer after HCL diagnosis are still less than 50%.

 

  Variants

Hairy cell leukemia-variant, or HCL-V, is usually described as a prolymphocytic variant of hairy cell leukemia. It was first formally described in 1980 by a paper from the University of Cambridge's Hayhoe lab. About 10% of HCL patients have this variant form of the disease, representing about 60-75 new HCL-V patients each year in the U.S. While classic HCL primarily affects men, HCL-V is somewhat more evenly divided between males and females.

Similar to B-PLL in Chronic Lymphocytic Leukemia, HCL-V is a more aggressive disease which is harder to treat successfully than classic HCL. Many treatment approaches, such as Interferon-alpha, CHOP and common alkylating agents like cyclophosphamide provide very little benefit. Pentostatin and cladribine provide some benefit to many HCL-V patients, but with shorter remissions and lower response rates compared to classic HCL. More than half of patients respond partially to splenectomy.

 In terms of B cell development, the prolymphocytes are less developed than lymphocyte cells or plasma cells, but are still more developed than their lymphoblastic precursors.

 HCL-V differs from classic HCL principally in these respects:

 

    * High white blood cell counts, sometimes in excess of 100,000 cells per microliter;

    * More aggressive course of disease that requires more frequent treatment;

    * Cells with an unusually large nucleolus for their size;

    * Little excess fibronectin (which is produced by classic hairy cells) to interfere with bone marrow biopsies; and

    * Low or no expression of CD25 (also called the Interleukin-2 [IL-2] receptor alpha chain or p55) on cell surfaces.

 

The lack of CD25, which is part of the receptor for a key immunoregulating hormone, may explain why HCL-V cases are normally resistant to treatment by immune system hormones.

 HCL-V, which has a high proportion of hairy cells without a functional p53 tumor suppressor gene, is somewhat more likely to transform into a higher-grade disease, with Daniel Catovsky suggesting a transformation rate of 5% in the U.K., which is similar to the Ricther's transformation rate for SLVL and CLL. Among HCL-V patients, the most aggressive cases normally have the least amount of p53 gene activity. Hairy cells without the p53 gene tend, over time, to displace the less aggressive p53+ hairy cells.

 Hairy cell leukemia-Japanese variant or HCL-J. There is also a Japanese variant, which is more easily treated.

   Pathology of Hairy Cells

While there are few genomic imbalances in the hairy cells, the expression of genes is dysregulated in a complex and specific pattern. The cells underexpress 3p24, 3p21, 3q13.3-q22, 4p16, 11q23, 14q22-q24, 15q21-q22, 15q24-q25, and 17q22-q24 and overexpress 13q31 and Xq13.3-q21. It has not yet been demonstrated that any of these changes have any practical significance to the patient.

 

 

Cont..
 

 

 

 

 

 

 

 

 

 

 

 

 

Associate Links -  

Computer Animation | 3D Renderings | Health Care | Hair Transplant | Graphic Design | 3D Interior Design | 3D Furniture Design | Ford Quotes | Jewelry Design | Cancer Support | Attorney | Fashion Design | Real Estate | Business Card | Design | Personal Loan | Plastic Surgery | Charity for Children | Mihan | Business Attorney | 3D Animation | Free 3D Models | Graphic Design School | Interior Design | Construction Today |  what is online | Finance India | Design Jewelry | Reiki | Yoga | Nagpur Mihan Chartered Accountant | Nagpur Mihan | Health Forums  | Jewelry Store Catalog | DUI Lawyers |  Latest Jewelry Design |  Ayurveda |  Chikhaldara |   Online Yoga |   Wikipedia |