hairy cell leukemia

ヘアリー細胞白血病

WordNet

1. small room in which a monk or nun lives (同)cubicle
2. a device that delivers an electric current as the result of a chemical reaction (同)electric cell
3. a room where a prisoner is kept (同)jail cell, prison cell
4. (biology) the basic structural and functional unit of all organisms; they may exist as independent units of life (as in monads) or may form colonies or tissues as in higher plants and animals
5. any small compartment; "the cells of a honeycomb"
6. a small unit serving as part of or as the nucleus of a larger political movement (同)cadre
7. filamentous hairlike growth on a plant; "peach fuzz" (同)fuzz, tomentum
8. a filamentous projection or process on an organism
9. any of the cylindrical filaments characteristically growing from the epidermis of a mammal; "there is a hair in my soup" (同)pilus
10. a covering for the body (or parts of it) consisting of a dense growth of threadlike structures (as on the human head); helps to prevent heat loss; "he combed his hair"; "each hair consists of layers of dead keratinized cells"
11. hazardous and frightening; "hairy moments in the mountains"
12. having or covered with hair; "Jacob was a hairy man"; "a hairy caterpillar" (同)haired, hirsute
13. malignant neoplasm of blood-forming tissues; characterized by abnormal proliferation of leukocytes; one of the four major types of cancer (同)leukaemia, leucaemia, cancer of the blood

PrepTutorEJDIC

1. (刑務所の)『独房』;(修道院の)小さい独居室 / (ミツバチの)みつ房,巣穴 / 小さい部屋 / 『細胞』 / 電池 / 花粉室 / (共産党などの)細胞
2. 〈C〉(人間・動物の1本の)『毛』;(植物・昆虫などの)毛 / 〈U〉《集合的に》『髪の毛』,毛,毛髪;(動物の)体毛 / 《a~》1本の毛ほどの量(距離,程度),ごくわずか
3. 毛深い,毛だらけの・粗い,ざらざらした・《俗》 ぞっとするほど危険な; 困難な，難しい
4. 白血病

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/04/24 18:45:29」(JST)

wiki en

[Wiki en表示]

Hairy cell leukemia
Classification and external resources
Specialty	Hematology and oncology
ICD-10	C91.4
ICD-9-CM	202.4
ICD-O	M9940/3
DiseasesDB	5589
MedlinePlus	000592
eMedicine	med/937
MeSH	D007943

Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. It is usually classified as a sub-type of chronic lymphoid leukemia. Hairy cell leukemia makes up approximately 2% of all leukemias, with fewer than 2,000 new cases diagnosed annually in North America and Western Europe combined.

Hairy cell leukemia was originally described as histiocytic leukemia, malignant reticulosis, or lymphoid myelofibrosis in publications dating back to the 1920s. The disease was formally named leukemic reticuloendotheliosis and its characterization significantly advanced by Bertha Bouroncle and colleagues at The Ohio State University College of Medicine in 1958. Its common name, which was coined in 1966, is derived from the "hairy" appearance of the malignant B cells under a microscope.

Classification

When not further specified, the "classic" form is often implied. However, two variants have been described: Hairy cell leukemia-variant, which usually is diagnosed in men, and a Japanese variant. The non-Japanese variant is more difficult to treat than either 'classic' HCL or the Japanese variant HCL.

Hairy cell leukemia-variant

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 more evenly divided between males and females. While the disease can appear at any age, the median age at diagnosis is over 70.

Similar to B-cell prolymphocytic leukemia ("B-PLL") in Chronic lymphocytic leukemia, HCL-V is a more aggressive disease. It is less likely to be treated successfully than is classic HCL, and remissions tend to be shorter. Many treatment approaches, such as Interferon-alpha, the combination chemotherapy regimen "CHOP", and common alkylating agents like cyclophosphamide provide very little benefit. Pentostatin and cladribine provide some benefit to many HCL-V patients, but typically induce shorter remission periods and lower response rates than when they are used in classic HCL. More than half of victims respond partially to splenectomy.

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

HCL-V differs from classic HCL principally in the following respects:

• Higher white blood cell counts, sometimes exceeding 100,000 cells per microliter;
• A more aggressive course of disease requiring more frequent treatment;
• Hairy cells with an unusually large nucleolus for their size;
• Production of little excess fibronectin produced by classic hairy cells; to interfere with bone marrow biopsies; and
• Low or no cell-surface expression of CD25 (also called the Interleukin-2 [IL-2] receptor alpha chain, or p55).

Low levels of CD25, a part of the receptor for a key immunoregulating hormone, may explain why HCL-V cases are generally much more resistant to treatment by immune system hormones.

HCL-V, which usually features a high proportion of hairy cells without a functional p53 tumor suppressor gene, is somewhat more likely to transform into a higher-grade malignancy. A typical transformation rate of 5%-6% has been postulated in the U.K., similar to the Richter'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

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

Treatment with cladribine has been reported.

Signs and symptoms

In hairy cell leukemia, the "hairy cells" (malignant B lymphocytes) accumulate in the bone marrow, interfering with the production of normal white blood cells, red blood cells, and platelets. Consequently, patients may develop infections related to low white blood cell count, anemia and fatigue due to a lack of red blood cells, or easy bleeding due to a low platelet count. 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 he or she has not eaten much.

Hairy cell leukemia is commonly diagnosed after a routine blood count shows unexpectedly low numbers of one or more kinds of normal blood cells, or after unexplained bruises or recurrent infections 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.

Cause

As with many cancers, the cause of hairy cell leukemia is unknown. Exposure to tobacco smoke, ionizing radiation, or industrial chemicals (with the possible exception of diesel) does not appear to increase the risk of developing HCL. Farming and gardening appear to increase the risk of HCL in some studies.

Recent studies have identified somatic BRAF V600E mutations in all patients with the classic form of hairy cell leukemia thus sequenced, but in no patients with the variant form.

The U.S. Institute of Medicine (IOM) announced "sufficient evidence" of an association between exposure to herbicides and later development of chronic B-cell leukemias and lymphomas in general. The IOM report emphasized that neither animal nor human studies indicate an association of herbicides with HCL specifically. However, the IOM extrapolated data from chronic lymphocytic leukemia and non-Hodgkin lymphoma to conclude that HCL and other rare B-cell neoplasms may share this risk factor. As a result of the IOM report, the U.S. Department of Veterans Affairs considers HCL an illness presumed to be a service-related disability (see Agent Orange).

Human T-lymphotropic virus 2 (HTLV-2) has been isolated in a small number of patients with the variant form of HCL. In the 1980s, HTLV-2 was identified in a patient with a T-cell lymphoproliferative disease; this patient later developed hairy cell leukemia (a B cell disease), but HTLV-2 was not found in the hairy cell clones. There is no evidence that HTLV-II causes any sort of hematological malignancy, including HCL.

Diagnosis

The diagnosis of HCL may be suggested by abnormal results on a complete blood count (CBC), but additional testing is necessary to confirm the diagnosis. A CBC normally shows low counts for white blood cells, red blood cells, and platelets in HCL patients. However, if large numbers of hairy cells are in the blood stream, then normal or even high lymphocyte counts may be found.

On physical exam, 80–90% of patients have an enlarged spleen, which can be massive. This is less likely among patients who are diagnosed at an early stage. Peripheral lymphadenopathy (enlarged lymph nodes) is uncommon (less than 5% of patients), but abdominal lymphadenopathy is a relatively common finding on computed tomography (CT) scans.

Hairy cell leukemia: abnormal B cells look "hairy" under a microscope because of radial projections from their surface.

The most important lab finding is the presence of hairy cells in the bloodstream. Hairy cells are abnormal white blood cells with hair-like projections of cytoplasm; they can be seen by examining a blood smear or bone marrow biopsy specimen. The blood film examination is done by staining the blood cells with Wright's stain and looking at them under a microscope. Hairy cells are visible in this test in about 85% of cases.

Most patients require a bone marrow biopsy for final diagnosis. The bone marrow biopsy is used both to confirm the presence of HCL and also the absence of any additional diseases, such as Splenic marginal zone lymphoma or B-cell prolymphocytic leukemia. The diagnosis can be confirmed by viewing the cells with a special stain known as TRAP (tartrate resistant acid phosphatase).

It is also possible to definitively diagnose hairy cell leukemia through flow cytometry on blood or bone marrow. The hairy cells are larger than normal and positive for CD19, CD20, CD22, CD11c, CD25, CD103, and FMC7. (CD103, CD22, and CD11c are strongly expressed.)

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. The presence of additional lymphoproliferative diseases is easily checked during a flow cytometry test, where they characteristically show different results.

The differential diagnoses include: several kinds of anemia, including myelophthisis and aplastic anemia, and most kinds of blood neoplasms, including hypoplastic myelodysplastic syndrome, atypical chronic lymphocytic leukemia, B-cell prolymphocytic leukemia, or idiopathic myelofibrosis.

Pathophysiology

Pancytopenia in HCL is caused primarily by marrow failure and splenomegaly. Bone marrow failure is caused by the accumulation of hairy cells and reticulin fibrosis in the bone marrow, as well as by the detrimental effects of dysregulated cytokine production. Splenomegaly reduces blood counts through sequestration, marginalization, and destruction of healthy blood cells inside the spleen.

Hairy cells are nearly mature B cells, which are activated clonal cells with signs of VH gene differentiation. They may be related to pre-plasma marginal zone B cells or memory cells.

Cytokine production is disturbed in HCL. Hairy cells produce and thrive on TNF-alpha. This cytokine also suppresses normal production of healthy blood cells in the bone marrow.

Unlike healthy B cells, hairy cells express and secrete an immune system protein called Interleukin-2 receptor (IL-2R). In HCL-V, only part of this receptor is expressed. As a result, disease status can be monitored by measuring changes in the amount of IL-2R in the blood serum. The level increases as hairy cells proliferate, and decreases when they are killed. Although uncommonly used in North America and northern Europe, this test correlates better with disease status and predicts relapse more accurately than any other test.

Hairy cells respond to normal production of some cytokines by T cells with increased growth. Treatment with Interferon-alpha suppresses the production of this pro-growth cytokine from T cells. A low level of T cells, which is commonly seen after treatment with cladribine or pentostatin, and the consequent reduction of these cytokines, is also associated with reduced levels of hairy cells.

In June 2011, E Tiacci et al discovered that 100% of hairy-cell leukaemia samples analysed had the oncogenic BRAF mutation V600E, and proposed that this is the disease's driver mutation. Until this point, only a few genomic imbalances had been found in the hairy cells, such as trisomy 5 had been found. The expression of genes is also 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.

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 the hematologist's office.

Single-drug treatment is typical. 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 used more frequently for refractory cases. Combining rituximab with cladribine or pentostatin may or may not produce any practical benefit to the patient. 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 assumed to be very low. For example, one round of either cladribine or pentostatin gives the median first-time patient a decade-long remission; the addition of rituximab, which gives the median patient only three or four years, might provide no additional value for this easily treated 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.

First-line therapy: purine analog chemotherapy

Cladribine (2CDA) and pentostatin (DCF) are the two most common first-line therapies. They both belong to a class of medications called purine analogs, which have mild side effects compared to traditional chemotherapy regimens.

Cladribine 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. The different dosing schedules used with cladribine are approximately equally effective and equally safe. Relatively few patients have significant side effects other than fatigue and a high fever caused by the cancer cells dying, although complications like infection and acute kidney failure have been seen.

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.

During the weeks following treatment the patient's immune system is severely weakened, but their 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. 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.

It does not seem to matter which drug a patient receives. 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.

Second-line therapy: immunotherapy

If a patient is resistant to either cladribine or pentostatin, then second-line therapy is pursued.

Monoclonal antibodies The most common treatment for cladribine-resistant disease is infusing monoclonal antibodies that 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 to eight weeks. A 2003 publication found two partial and ten complete responses out of 15 patients with relapsed disease, for a total of 80% responding. The median patient (including non-responders) did not require further treatment for more than three years. This eight-dose study had a higher response rate than a four-dose study at Scripps, which achieved only 25% response rate. Rituximab has successfully induced a complete response in Hairy Cell-Variant.

Rituximab's 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 Interferon-alpha is an immune system hormone that is very helpful to a relatively small number of patients, and somewhat helpful to most patients. In about 65% of patients, the drug helps stabilize the disease or produce a slow, minor improvement for a partial response.

The typical dosing schedule injects at least 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. About 10% of patients develop a level of depression. It is possible that, by maintaining a steadier level of the hormone in the body, that daily injections might cause fewer side effects in selected patients. Drinking at least two liters of water each day, while avoiding caffeine and alcohol, can reduce many of the side effects.

A drop in blood counts is usually seen during the first one to two months of treatment. Most patients find that their blood counts get worse for a few weeks immediately after starting treatment, although some patients find their blood counts begin to improve within just two weeks.

It typically takes six months to figure out whether this therapy is useful. Common criteria for treatment success include:

• normalization of hemoglobin levels (above 12.0 g/dL),
• a normal or somewhat low platelet count (above 100 K/µL), and
• a normal or somewhat low absolute neutrophil count (above 1.5 K/µL).

If it is well tolerated, patients usually take the hormone for 12 to 18 months. An attempt may be made then to end the treatment, but most patients discover that they 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, although it carries some risks, such as the potential for decreased blood flow to the placenta.

Interferon-alpha works by sensitizing the hairy cells to the killing effect of the immune system hormone TNF-alpha, whose production it promotes. IFN-alpha works best on classic hairy cells that are not protectively adhered to vitronectin or fibronectin, which suggests that patients who encounter less fibrous tissue in their bone marrow biopsies may be more likely to respond to Interferon-alpha therapy. It also explains why non-adhered hairy cells, such as those in the bloodstream, disappear during IFN-alpha treatment well before reductions are seen in adhered hairy cells, such as those in the bone marrow and spleen.

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. "Mini-transplants" are possible.

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. Patients may also receive a hormone to stimulate production of red blood cells. These treatments may be medically necessary, but do not kill the hairy cells.

Patients with low neutrophil counts may be given filgrastim or a similar hormone to stimulate production of white blood cells. However, a 1999 study indicates that routine administration of this expensive injected drug has no practical value for HCL patients after cladribine administration. In this study, patients who received filgrastim were just as likely to experience a high fever and to be admitted to the hospital as those who did not, even though the drug artificially inflated their white blood cell counts. This study leaves open the possibility that filgrastim may still be appropriate for patients who have symptoms of infection, or at times other than shortly after cladribine treatment.

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.

Prognosis

Treatment success

More than 95% of new patients are treated well or at least adequately by cladribine or pentostatin. 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 the average length of remission is somewhat shorter in subsequent treatments.

As with B-cell chronic lymphocytic leukemia, mutations in the IGHV on hairy cells are associated with better responses to initial treatments and with prolonged survival.

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.

Lifespan

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 in the United states with normal blood counts can often qualify for private life insurance with some US companies.

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.

Worldwide, approximately 300 HCL patients per year are expected to die. Some of these patients were diagnosed with HCL due to a serious illness that 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.

Follow-up care

Despite decade-long remissions and years of living very normal lives after treatment, hairy cell leukemia is officially considered an incurable disease. While survivors of solid tumors are commonly declared to be permanently cured after two, three, or five years, people who have hairy cell leukemia are never considered 'cured'. Relapses of HCL 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.

People in remission need 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 about 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.

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

There is also a higher risk of developing an autoimmune disease. Autoimmune diseases may also go into remission after treatment of HCL.

Prevention/Screening

Because the cause is unknown, no effective preventive measures can be taken.

Because the disease is rare, routine screening is not cost-effective.

Epidemiology

This disease is rare, with fewer than 1 in 10,000 people being diagnosed with HCL during their lives. Men are four to five times more likely to develop hairy cell leukemia than women. In the United States, the annual incidence is approximately 3 cases per 1,000,000 men each year, and 0.6 cases per 1,000,000 women each year.

Most patients are white males over the age of 50, although it has been diagnosed in at least one teenager. It is less common in people of African and Asian descent compared to people of European descent.

It does not appear to be hereditary, although occasional familial cases that suggest a predisposition have been reported, usually showing a common Human Leukocyte Antigen (HLA) type.

Research directions

The Hairy Cell Leukemia Consortium was founded in 2008 to address researchers' concerns about the long-term future of research on the disease. Partly because existing treatments are so successful, the field has attracted very few new researchers.

In 2013 the Hairy Cell Leukemia Foundation was created when the Hairy Cell Leukemia Consortium and the Hairy Cell Leukemia Research Foundation joined together. The HCLF is dedicated to improving outcomes for patients by advancing research into the causes and treatment of hairy cell leukemia, as well as by providing educational resources and comfort to all those affected by hairy cell leukemia.

Three immunotoxin drugs have been studied in patients at the NIHNational Cancer Institute in the U.S.: BL22, HA22 and LMB-2. All of these protein-based drugs combine part of an anti-B cell antibody with a bacterial toxin to kill the cells on internalization. BL22 and HA22 attack 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. HA-22, now renamed moxetumab pasudotox, is being studied in patients with relapsed hairy cell leukemia at the National Cancer Institute in Bethesda, Maryland, MD Anderson Cancer Center in Houston, Texas, and Ohio State University in Columbus, Ohio. Other sites for the study are expected to start accepting patients in late 2014, including The Royal Marsden Hospital in London, England.

Other clinical trials are studying the effectiveness of cladribine followed by rituximab in eliminating residual hairy cells that remain after treatment by cladribine or pentostatin. It is not currently known if the elimination of such residual cells will result in more durable remissions.

BRAF mutation has been frequently detected in HCL (Tiacci et al. NEJM 2011) and some patients may respond to Vemurafenib

The major remaining research questions are identifying the cause of HCL and determining what prevents hairy cells from maturing normally.

See also

• Annexin A1
• List of cutaneous conditions

References

External links

• About HCL at the US National Cancer Institute
• History of HCL and the Godmother of HCL

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 有毛細胞白血病の治療 treatment of hairy cell leukemia
• 2. 有毛細胞白血病の臨床的特徴および診断 clinical features and diagnosis of hairy cell leukemia
• 3. 成人における抗癌剤の投与 dosing of anticancer agents in adults
• 4. Erythema elevatum diutinum
• 5. 小リンパ球性リンパ腫の臨床症状、病理学的特徴、および診断 clinical manifestations pathologic features and diagnosis of small lymphocytic lymphoma

English Journal

• Uncommon histiocytic disorders: Rosai-Dorfman, juvenile xanthogranuloma, and Erdheim-Chester disease.

• Haroche J1, Abla O2.
• Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program.Hematology Am Soc Hematol Educ Program.2015 Dec 5;2015(1):571-8. doi: 10.1182/asheducation-2015.1.571.
• Rosai-Dorfman disease (RDD), juvenile xanthogranuloma (JXG), and Erdheim-Chester disease (ECD) are non-Langerhans cell (non-LCH) disorders arising from either a dendritic or a macrophage cell. RDD is a benign disorder that presents with massive lymphadenopathy, but can have extranodal involvement. I
• PMID 26637774

• Hairy cell leukemia: Past, present and future.

• Getta BM1, Park JH2, Tallman MS3.
• Best practice & research. Clinical haematology.Best Pract Res Clin Haematol.2015 Dec;28(4):269-72. doi: 10.1016/j.beha.2015.10.015. Epub 2015 Oct 21.
• This brief review highlights the sequence of therapeutic milestones and advances in our understanding of the biology of hairy cell leukemia (HCL) with a focus on recent molecular findings and how these may be applied to improve disease outcomes in the future. Targeted therapy is discussed in the con
• PMID 26614906

• What your hairy cell leukemia patients want you to know.

• Stone EJ1, Margolin M2.
• Best practice & research. Clinical haematology.Best Pract Res Clin Haematol.2015 Dec;28(4):264-8. doi: 10.1016/j.beha.2015.09.001. Epub 2015 Oct 8.
• Hairy cell leukemia is different from most other hematologic malignancies because it is so rare. Patient concerns include finding a knowledgeable physician, confirming the diagnosis at the initial presentation, coping with treatment side effects and monitoring for potential relapse of this chronic d
• PMID 26614905

Japanese Journal

• Tuberculous Meningoencephalitis in a Patient with Hairy Cell Leukemia in Complete Remission

• GIRARDI K,PAVIGLIANITI A,CIRILLO M,BIANCHI A,GHERARDI G,ANNIBALI O,CERCHIARA E,MARCHESI F,TOMARCHIO V,MIGLIO C,TIRINDELLI MC,ONETTI MUDA A,AVVISATI G
• Journal of clinical and experimental hematopathology 52(1), 31-34, 2012-05-01
• NAID 10030615572

• ヘアリー細胞白血病とBRAF変異

• 青木 定夫
• 血液内科 64(5), 603-609, 2012-05
• NAID 40019341887

Related Links

• Hairy cell leukemiaとは - goo Wikipedia (ウィキペディア)

Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. It is usually classified as a sub-type of chronic lymphoid leukemia. Hairy cell leukemia makes up ...

• Hairy Cell Leukemia - Diseases & Conditions - Medscape ...

Hairy Cell Leukemia. Hairy cell leukemia (HCL) is a chronic lymphoid leukemia, originally described in 1958 by Bouroncle and colleagues[1, 2] and named after the hairlike cytoplasmic projections seen on the surface of ...

Related Pictures

---

★リンクテーブル★

国試過去問	「095G033」「107I014」
リンク元	「慢性リンパ性白血病」「ヘアリー細胞白血病」「HCL」「leukemic reticuloendotheliosis」
関連記事	「hairy」「cell」

「095G033」

　　[★]

• 56歳の男性。倦怠感と腹部膨満感とを訴えて来院した。6か月前から左上腹部の重圧態を自覚し、少量の摂食で満腹となるようになった。顔色は不良で、るいそうがある。右肋骨弓下に肝を4cm、左肋骨弓下に脾を5cm触知し、いずれも弾性硬で圧痛はない。血液所見：赤血球320万、Hb 9.5 g/dl、Ht31％、網赤血球13‰、白血球23,000(前骨髄球0.5％、好中性骨髄球3.0％、好中性後骨髄球3.5％、桿状核好中球13.0％、分葉核好中球55.0％、好酸球2.0％、好塩基球3.0％、単球4.0％、リンパ球16.0％、赤芽球5個/100白血球)、血小板57万。好中球アルカリホスファターゼスコア320(基準120～320)。末梢血塗抹May-Giemsa染色標本を以下に示す。

• 最も考えられるのはどれか。

• a. 骨髄異形成症候群
• b. 慢性骨髄性白血病
• c. 本態性血小板血症
• d. 原発性骨髄線維症
• e. hairy cell leukemia

[正答]

D

※国試ナビ4※　［095G032］←［国試_095］→［095G034］

「107I014」

　　[★]

• T細胞の腫瘍はどれか。

• a　濾胞性リンパ腫
• b　Burkittリンパ腫
• c　MALTリンパ腫
• d　hairy cell leukemia(有毛細胞白血病)
• e　菌状息肉症

[正答]

E

※国試ナビ4※　［107I013］←［国試_107］→［107I015］

「慢性リンパ性白血病」

　　[★]

英

chronic lymphocytic leukemia, chronic lymphoid leukemia, CLL

関

白血病

• first aid step1 2006 p.300,302,303,304,309,310,427,430

概念

• the accumulation of nonproliferating mature-appearing lymphocytes in the blood, marrow, lymph nodes, and spleen.
• monoclonal B lymphocytes.
• CD5+ and CD23+CD5, CD23
• derived from memory B cell.

細胞表面マーカー WCH.2438

condition

smIg

CD5

CD10

CD11c

CD19

CD20

CD22

CD23

CD25

CD43

CD79b

CD103

FMC7

chronic lymphocytic leukemia

Dim

＋＋

－

－/＋

＋＋

Dim

－/＋

＋＋

＋/－

＋

－

－

－/＋

Waldenstrom macroglobulinemia

＋＋

－

－

－/＋

＋＋

＋＋

＋

－

－/＋

＋/－

＋

－

＋

prolymphocytic leukemia

＋＋＋

－/＋

－/＋

－/＋

＋＋

＋＋＋

＋＋

＋＋

－/＋

＋

＋＋

－

＋

hairy cell leukemia

＋＋＋

－

－

＋＋

＋＋＋

＋＋＋

＋＋＋

－

＋＋＋

＋

＋

＋＋＋

＋＋＋

hairy cell leukemia variant

＋＋＋

－

－

＋＋

＋＋＋

＋＋＋

＋＋＋

－

－

＋

＋

＋＋＋

＋＋＋

splenic lymphoma with villous lymphocytes

＋＋

－/＋

－/＋

＋/－

＋＋

＋＋

＋＋

＋/－

－/＋

＋

＋＋

－/＋

＋＋

marginal zone B-cell lymphoma

＋＋

－

－

＋/－

＋＋

＋＋

＋/－

＋/－

－

－/＋

＋＋

－

＋

mantle cell lymphoma

＋＋

＋＋

－/＋

－

＋＋

＋＋

＋＋

－

－

＋

＋＋

－

＋＋

follicular lymphoma

＋＋

－/＋

＋＋

－

＋＋

＋＋

＋＋

－/＋

－

－

＋＋

－

＋＋

臨床像

HIM.693

	年齢	子供における頻度	男性(%)	ステージI,II vs III,IV(%)	B症状(%)	骨髄浸潤(%)	消化管浸潤(%)	5年生存率(%)
B細胞CLL/小リンパ球性リンパ腫	65	まれ	53	9 vs 91	33	72	3	51

疫学

YN.G-49

• 全白血病の2-3%
• 60歳以上に多い。
• 男女比=2:1

病態

YN.G-49

• 正常な免疫グロブリンの産生が抑制されるばかりでなく、異常な自己抗体を産生　→　続発性免疫不全症、自己免疫性溶血性貧血

USMLE

• Q book p.246 42

参考

• 1. [charged] Epidemiology and clinical manifestations of chronic lymphocytic leukemia - uptodate [1]
• 2. [charged] Pathologic features, diagnosis, and differential diagnosis of chronic lymphocytic leukemia - uptodate [2]
• 3. [charged] Pathophysiology and cytogenetics of chronic lymphocytic leukemia - uptodate [3]

[show details]

慢性リンパ性白血病 : 約 28,600 件
慢性リンパ球性白血病 : 約 47,100 件

「ヘアリー細胞白血病」

　　[★]

英

hairy cell leukemia HCL

同

ヘアリーセル白血病、毛髪細胞白血病、有毛細胞白血病、毛様細胞白血病、有毛細胞性白血病

関

2-クロロデオキシアデノシン

• first aid step1 2006 p.295

「HCL」

　　[★]

• ヘアリー細胞白血病 hairy cell leukemia
• 出血性黄体嚢胞 hemorrhagic corpus luteum

「leukemic reticuloendotheliosis」

　　[★]

白血病性細網内皮症、白血病性細網組織増殖症

関

hairy cell leukemia

「hairy」

　　[★]

• 毛髪状の、毛様

　 　 　

「cell」

　　[★] 細胞