Hairy cell leukemia
From Wikipedia, the free encyclopedia
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| ICD-10 | C91.4 |
| ICD-9 | 202.4 |
| ICD-O: | 9940/3 |
Hairy cell leukemia is a 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 1000 new cases diagnosed each year in the United States. Originally known as leukemic reticuloendotheliosis, hairy cell leukemia was first described by Bertha Bouroncle, M.D. and her colleagues at the Ohio State University College of Medicine in 1958. Its common name is derived from the appearance of the cells under a microscope.
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[1]. It does not appear to be hereditary, although occasional familial cases have been reported[2], 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[3]. Farming and gardening appear to increase the risk[4] in some studies.
Two variants have been described: Hairy cell leukemia-variant[5], 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.
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[edit] 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.[6]
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.
Patients with a high tumor burden may also have somewhat reduced levels of cholesterol[7]
[edit] Diagnosis
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.[8] Hairy cell leukemia-variant (HCL-V), which shares some characteristics with B cell prolymphocytic leukemia (B-PLL), does not show CD25.
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.
[edit] Treatment
Several treatments are available, and successful control of the disease is common.
Not everyone needs treatment. Treatment is usually given when the symptoms of the disease interfere with the patient's everyday life, or when white blood cell or platelet counts decline to dangerously low levels, such as an absolute neutrophil count below one thousand cells per microliter (1.0 K/uL). Not all patients need treatment immediately upon diagnosis, and about 10% of patients will never need treatment.
Treatment delays are less important than in solid tumors. Unlike most cancers, treatment success does not depend on treating the disease at an early stage. Because delays do not affect treatment success, there are no standards for how quickly a patient should receive treatment. However, waiting too long can cause its own problems, such as an infection that might have been avoided by proper treatment to restore immune system function. Also, having a higher number of hairy cells at the time of treatment can make certain side effects somewhat worse, as some side effects are primarily caused by the body's natural response to the dying hairy cells. This can result in the hospitalization of a patient whose treatment would otherwise be carried out entirely at his hematologist's office.
Single-drug treatment is normal. Unlike most cancers, only one drug is normally given to a patient at a time. While monotherapy is normal, combination therapy -- typically using one first-line therapy and one second-line therapy -- is being studied in current clinical trials and is increasingly used for refractory cases. Combination therapy is almost never used with a new patient. Because the success rates with purine analog monotherapy are already so high, the additional benefit from immediate treatment with a second drug in a treatment-naïve patient is very low. For example, one round of either cladribine or pentostatin gives the median first-time patient a ten-year remission; the addition of rituximab, which gives the median patient only three or four years, is reasonably expected to provide no additional value for this patient. In a more difficult case, however, the benefit from the first drug may be substantially reduced and therefore a combination may provide some benefit.
[edit] First-line therapy: purine analog chemotherapy
Cladribine (2CDA) and pentostatin (DCF) are the two most common first-line therapies. Cladribine is a kind of mild chemotherapy which can be administered by injection under the skin, by infusion over a couple of hours into a vein, or by a pump worn by the patient that provides a slow drip into a vein, 24 hours a day for 7 days. Most patients receive cladribine by IV infusion once a day for five to seven days, but more patients are being given the option of taking this drug once a week for six weeks. Relatively few patients have significant side effects other than fatigue and a high fever caused by the cancer cells dying.
Pentostatin is chemically similar to cladribine, and has a similar success rate and side effect profile, but it is always given over a much longer period of time, usually one dose by IV infusion every two weeks for three to six months.
(A third related chemical, fludarabine, is not effective for hairy cell leukemia, despite being chemically similar.)
During the weeks following treatment the patient's immune system is severely weakened, but his bone marrow will begin to produce normal blood cells again. Treatment often results in long-term remission. About 85% of patients achieve a complete response from treatment with either cladribine or pentostatin, and another 10% receive some benefit from these drugs, although there is no permanent cure for this disease. If the cancer cells return, the treatment may be repeated and should again result in remission, although the odds of success decline with repeated treatment.[9] Remission lengths vary significantly, from one year to more than twenty years. The median patient can expect a treatment-free interval of about ten years.
Cross-resistance is common, and a patient who is not successfully treated with one of these two drugs has a reduced chance of being successfully treated with the other. However, there are other options.
[edit] Second-line therapy: immunotherapy
If a patient is resistant to either cladribine or pentostatin, then second-line therapy is pursued. The most common treatment for cladribine-resistant disease is infusing monoclonal antibodies which destroy cancerous B cells. Rituximab is by far the most commonly used. Most patients receive one IV infusion over several hours each week for four weeks. Its major side effect is serum sickness, commonly described as an "allergic reaction", which can be severe, especially on the first infusion. Serum sickness is primarily caused by the antibodies clumping during infusion and triggering the complement cascade. Although most patients find that side effects are adequately controlled by anti-allergy drugs, some severe, and even fatal, reactions have occurred. Consequently, the first dose is always given in a hospital setting, although subsequent infusions may be given in a physician's office. Remissions are usually shorter than with the preferred first-line drugs, but hematologic remissions of several years' duration are not uncommon.
Other B cell-destroying monoclonal antibodies such as Alemtuzumab, Ibritumomab tiuxetan and I-131 Tositumomab may be considered for refractory cases.
Interferon-alpha is an immune system hormone which is very helpful to a relatively small number of patients, and somewhat helpful to most patients. Most commonly, the drug helps stabilize the disease or produce a slow, minor improvement. The typical dosing schedule injects 3 million units of Interferon-alpha (not pegylated versions) three times a week, although the original protocol began with six months of daily injections. Some patients tolerate IFN-alpha very well after the first couple of weeks, while others find that its characteristic flu-like symptoms persist. It is possible that, by maintaining a steadier level of the hormone in the body, that daily injections might cause fewer side effects. It typically takes at least six months to figure out whether this therapy is useful. Most patients then need to continue taking the drug for it to be successful. These patients often continue taking this drug indefinitely, until either the disease becomes resistant to this hormone, or the body produces an immune system response that limits the drug's ability to function. A few patients are able to achieve a sustained clinical remission after taking this drug for six months to one year. This may be more likely when IFN-alpha has been initiated shortly after another therapy. Interferon-alpha is considered the drug of choice for pregnant women with active HCL.
[edit] Experimental therapies
Two immunotoxin drugs are in Phase II trials at the NIH's National Cancer Institute in the U.S.: BL22[10] and LMB-2[11]. Both of these protein-based drugs combine part of an anti-B cell antibody with a bacterial toxin to kill the cells on internalization. BL22 attacks a common protein called CD22, which is present on hairy cells and healthy B cells. LMB-2 attacks a protein called CD25, which is not present in HCL-variant, so LMB-2 is only useful for patients with HCL-classic or the Japanese variant.
Both therapies are available only at the National Cancer Institute in Bethesda, Maryland, USA. While initial results are generally favorable, it is likely to be a number of years before these drugs are available on the market.
[edit] Other treatment options
Splenectomy can produce long-term remissions in patients whose spleens seem to be heavily involved, but its success rate is noticeably lower than cladribine or pentostatin. Splenectomies are also performed for patients whose persistently enlarged spleens cause significant discomfort or in patients whose persistently low platelet counts suggest Idiopathic thrombocytopenic purpura.
Bone marrow transplants are usually shunned in this highly treatable disease because of the inherent risks in the procedure. They may be considered for refractory cases in younger, otherwise healthy individuals.
Patients with anemia or thrombocytopenia may also receive red blood cells and platelets through blood transfusions. Blood transfusions are always irradiated to remove white blood cells and thereby reduce the risk of graft-versus-host disease.
Although hairy cells are technically long-lived, instead of rapidly dividing, some late-stage patients are treated with broad-spectrum chemotherapy agents such as methotrexate that are effective at killing rapidly dividing cells. This is not typically attempted unless all other options have been exhausted and it is typically unsuccessful.
[edit] Prognosis
More than 95% of patients are treated well or at least adequately by cladribine or pentostation.[12] 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.[13]
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).
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.
[edit] 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.
