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| '''For patient information click [[{{PAGENAME}} (patient information)|here]]'''.
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| {{Infobox_Disease | | | {{Hairy cell leukemia}} |
| Name = {{PAGENAME}} |
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| Image = Hairy_cell_leukemia.jpg |
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| Caption = |
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| DiseasesDB = 5589 |
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| ICD10 = {{ICD10|C|91|4|c|81}} |
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| ICD9 = {{ICD9|202.4}} |
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| ICDO = 9940/3 |
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| OMIM = |
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| MedlinePlus = |
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| MeshID = D007943 |
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| {{Search infobox}}
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| {{CMG}}
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| {{Editor Help}} | | {{CMG}}; {{AE}} {{VKG}}; {{GRR}} {{Nat}} |
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| ==Overview==
| | {{SK}} Leukemic reticuloendotheliosis; Reticuloendotheliosis leukemia; Histiocytic leukemia; Malignant reticulosis; Lymphoid myelofibrosis |
| '''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.
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| 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 [[OSU College of Medicine and Public Health|Ohio State University College of Medicine]] in 1958. Its common name, which was coined in 1966<ref>{{cite web |url=http://bloodjournal.hematologylibrary.org/cgi/content/abstract/27/2/199 |title="Hairy" Cells in Blood in Lymphoreticular Neoplastic Disease and "Flagellated" Cells of Normal Lymph Nodes -- SCHREK and DONNELLY 27 (2): 199 -- Blood |accessdate=2007-09-10 |format= |work=}}</ref>, is derived from the appearance of the cells under a microscope.
| | ==[[Hairy cell leukemia overview|Overview]]== |
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| Two variants have been described: Hairy cell leukemia-variant[http://ajcp.metapress.com/link.asp?id=8qytyq1clqmhq9cl], 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.
| | ==[[Hairy cell leukemia historical perspective|Historical Perspective]]== |
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| ==Pathophysiology of Hairy Cell Leukemia== | | ==[[Hairy cell leukemia classification|Classification]]== |
| Hairy cells are nearly mature, activated clonal cells with signs of VH gene differentiation.<ref>{{cite web |url=http://theoncologist.alphamedpress.org/cgi/content/full/11/7/780 |title=Hairy Cell Leukemia: An Elusive but Treatable Disease -- Wanko and de Castro 11 (7): 780 -- The Oncologist |accessdate=2007-09-10 |format= |work=}}</ref> They may be related to [[memory cells]]. | |
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| While there are few [[Comparative genomic hybridization|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.<ref>{{cite web |url=http://bloodjournal.hematologylibrary.org/cgi/content/abstract/bloodjournal;104/1/250 |title=Comparative expressed sequence hybridization studies of hairy cell leukemia show uniform expression profile and imprint of spleen signature -- Vanhentenrijk et al. 104 (1): 250 -- Blood |accessdate=2007-09-10 |format= |work=}}</ref> It has not yet been demonstrated that any of these changes have any practical significance to the patient.
| | ==[[Hairy cell leukemia pathophysiology|Pathophysiology]]== |
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| ==Risk factors and causes== | | ==[[Hairy cell leukemia causes|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.<ref>{{cite web |url=http://www.pennhealth.com/ency/article/000592.htm |title=Hairy cell leukemia |accessdate=2007-09-07 |format= |work=}}</ref> It does not appear to be hereditary, although occasional familial cases have been reported,<ref>{{cite web |url=http://cat.inist.fr/?aModele=afficheN&cpsidt=4680401 |title=Three cases of familial hairy cell leukemia |accessdate=2007-09-07 |format= |work=}}</ref> usually showing a common HLA type.
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| The cause is unknown, but generally believed not to be caused by tobacco, ionizing radiation, pesticides, or industrial chemicals other than possibly diesel.<ref name="pmid7577624">{{cite journal |author=Clavel J, Mandereau L, Cordier S, ''et al'' |title=Hairy cell leukaemia, occupation, and smoking |journal=Br. J. Haematol. |volume=91 |issue=1 |pages=154-61 |year=1995 |pmid=7577624 |doi=}}</ref> Farming and gardening appear to increase the risk in some studies.<ref name="pmid11083509">{{cite journal |author=Orlandi G, Fanucchi S, Strata G, ''et al'' |title=Transient autonomic nervous system dysfunction during hyperacute stroke |journal=Acta Neurol. Scand. |volume=102 |issue=5 |pages=317-21 |year=2000 |pmid=11083509 |doi=}}</ref> The possibility that HCL is caused by a random accident during routine cell division can not be ruled out.
| | ==[[Hairy cell leukemia differential diagnosis|Differentiating Hairy cell leukemia from other Diseases]]== |
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| ==Symptoms== | | ==[[Hairy cell leukemia epidemiology and demographics|Epidemiology and Demographics]]== |
| 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.<ref>{{cite web |url=http://www.cancer.gov/cancerinfo/pdq/treatment/hairy-cell-leukemia/patient#Keypoint3 |title=Hairy Cell Leukemia Treatment - National Cancer Institute |accessdate=2007-09-07 |format= |work=}}</ref>
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| 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 epidemiology and demographics|Risk Factors]]== |
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| 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. | | ==[[Hairy cell leukemia screening|Screening]]== |
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| Platelet function may be somewhat impaired in HCL patients, although this does not appear to have any significant practical effect.<ref name="pmid512041">{{cite journal |author=Zuzel M, Cawley JC, Paton RC, Burns GF, McNicol GP |title=Platelet function in hairy-cell leukaemia |journal=J. Clin. Pathol. |volume=32 |issue=8 |pages=814-21 |year=1979 |pmid=512041 |doi=}}</ref> 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.
| | ==[[Hairy cell leukemia natural history|Natural History, Complications and Prognosis]]== |
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| Patients with a high tumor burden may also have somewhat reduced levels of cholesterol,<ref>{{cite web |url=http://www3.interscience.wiley.com/cgi-bin/abstract/50446/ABSTRACT?CRETRY=1&SRETRY=0 |title=wiley.com |accessdate=2007-09-07 |format= |work=}}</ref> especially in patients with an enlarged spleen.<ref>{{cite web |url=http://www.bmj.com/cgi/content/full/311/6996/27 |title=Mechanisms behind hypocholesterolaemia in hairy cell leukaemia -- Juliusson et al. 311 (6996): 27 -- BMJ |accessdate=2007-09-07 |format= |work=}}</ref> Cholesterol levels return to more normal values with successful treatment of HCL.
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| ==Diagnosis== | | ==Diagnosis== |
| [[Image:Hairy Cell Leukemia.jpg|thumb|left|Hairy Cell Leukemia <ref>http://picasaweb.google.com/mcmumbi/USMLEIIImages</ref>]] | | [[Hairy cell leukemia diagnotic study of choice|Diagnostic Study of Choice]] | [[Hairy cell leukemia staging|Staging]] | [[Hairy cell leukemia history and symptoms|History and Symptoms]] | [[Hairy cell leukemia physical examination|Physical Examination]] | [[Hairy cell leukemia laboratory tests|Laboratory Findings]] | [[Hairy cell leukemia electrocardiogram|Electrocardiogram]] | [[Hairy cell leukemia chest x ray|Chest X Ray]] | [[Hairy cell leukemia CT|CT]] | [[Hairy cell leukemia MRI|MRI]] | [[Hairy cell leukemia ultrasound|Ultrasound]] | [[Hairy cell leukemia other imaging findings|Other Imaging Findings]] | [[Hairy cell leukemia other diagnostic studies|Other Diagnostic Studies]] |
| The diagnostic path may have begun with a simple test like a [[complete blood count]], but this is not adequate to diagnose HCL. A CBC normally shows low counts for white blood cells, red blood cells, and platelets in HCL patients, but if large numbers of hairy cells are in the blood stream, then normal or even [[lymphocytosis|high lymphocyte counts]] may be found.
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| 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 cell]]s 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]].
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| 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]].<ref>{{cite web |url=http://www.flowcases.org/casebuilder/index.cfm?fuseaction=displayCase2&caseID=54 |title=Clinical Flow Cytometry Case #54 |accessdate=2007-09-07 |format= |work=}}</ref> 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.
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| 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 [[Splenic marginal zone lymphoma|SMZL]] or [[B-cell prolymphocytic leukemia|B-PLL]]. The presence of these diseases is easily checked during a flow cytometry test, where they characteristically show different results.<ref>{{cite web |url=http://theoncologist.alphamedpress.org/content/vol11/issue7/images/large/780tbl4.jpeg |title=theoncologist.alphamedpress.org |accessdate=2007-09-07 |format= |work=}}</ref> Careful review of bone marrow biopsy samples is also reliable for this purpose.
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| 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. [[Lymphadenopathy|Enlarged lymph nodes]] appear in a few patients.
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| <div align="left">
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| <gallery heights="175" widths="175">
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| Image:Hairy cell leukemia 0001.jpg|Hairy cell leukemia
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| Image:Hairy cell leukemia bone marrow 0004.jpg|Hairy cell leukemia bone marrow
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| Image:Hairy cell leukemia TEM 0001.jpg|Hairy cell leukemia TEM
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| </gallery>
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| </div>
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| ==Treatment== | | ==Treatment== |
| Several treatments are available, and successful control of the disease is common.
| | [[Hairy cell leukemia medical therapy|Medical Therapy]] | [[Hairy cell leukemia surgery|Surgery]] | [[Hairy cell leukemia primary prevention|Primary Prevention]] | [[Hairy cell leukemia secondary prevention|Secondary Prevention]] | [[Hairy cell leukemia cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Hairy cell leukemia future or investigational therapies|Future or Investigational Therapies]] |
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| '''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.
| | ==Case Studies== |
| | [[Hairy cell leukemia case study one|Case#1]] |
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| '''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.
| | ==Related chapters== |
| | | * [[Annexin A1]] |
| '''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. It is unclear whether combining rituximab with cladribine or pentostatin will produce any practical benefit to the patient.[http://bloodjournal.hematologylibrary.org/cgi/content/abstract/107/12/4658] 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 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.
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| ===First-line therapy: purine analog chemotherapy===
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| [[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. The different dosing schedules used with cladribine are approximately equally effective and equally safe.<ref>{{cite web |url=http://bloodjournal.hematologylibrary.org/cgi/content/abstract/bloodjournal;109/9/3672 |title=Cladribine in a weekly versus daily schedule for untreated active hairy cell leukemia: final report from the Polish Adult Leukemia Group (PALG) of a prospective, randomized, multicenter trial -- Robak et al. 109 (9): 3672 -- Blood |accessdate=2007-09-10 |format= |work=}}</ref>
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| 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.
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| 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.
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| (A third related chemical, [[fludarabine]], is not used for hairy cell leukemia, despite being chemically similar.)
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| 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.<ref name="pmid16245328">{{cite journal |author=Else M, Ruchlemer R, Osuji N, ''et al'' |title=Long remissions in hairy cell leukemia with purine analogs: a report of 219 patients with a median follow-up of 12.5 years |journal=Cancer |volume=104 |issue=11 |pages=2442-8 |year=2005 |pmid=16245328 |doi=10.1002/cncr.21447}}</ref> 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.
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| 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.
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| ===Second-line therapy: immunotherapy===
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| If a patient is resistant to either cladribine or pentostatin, then second-line therapy is pursued.
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| '''Monoclonal antibodies''' 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 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.<ref>{{cite web |url=http://bloodjournal.hematologylibrary.org/cgi/content/abstract/102/12/3906 |title=Rituximab in relapsed or refractory hairy cell leukemia -- Thomas et al. 102 (12): 3906 -- Blood |accessdate=2007-09-10 |format= |work=}}</ref> 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.<ref>{{cite web |url=http://bloodjournal.hematologylibrary.org/cgi/content/full/102/3/810 |title=Phase 2 study of rituximab in the treatment of cladribine-failed patients with hairy cell leukemia -- Nieva et al. 102 (3): 810 -- Blood |accessdate=2007-09-10 |format= |work=}}</ref> Rituximab has successfully induced a complete response in Hairy Cell-Variant.<ref>{{cite web |url=http://www.informaworld.com/smpp/content?content=10.1080/10428190500083433 |title=Successful treatment of hairy cell leukemia variant with rituximab - Leukemia and Lymphoma |accessdate=2007-09-10 |format= |work=}}</ref>
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| 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 system|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.
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| Other B cell-destroying monoclonal antibodies such as [[Alemtuzumab]], [[Ibritumomab tiuxetan]] and I-131 [[Tositumomab]] may be considered for refractory cases.
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| '''Interferon-alpha''' [[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, in about 65% of patients,<ref>{{cite web |url=http://www.emedicine.com/med/topic937.htm#section~medication |title=eMedicine - Hairy Cell Leukemia : Article by Emmanuel C Besa, MD |accessdate=2007-09-10 |format= |work=}}</ref> the drug helps stabilize the disease or produce a slow, minor improvement for a partial response.<ref>{{cite web |url=http://content.nejm.org/cgi/content/abstract/310/1/15 |title=NEJM -- Alpha interferon for induction of remission in hairy-cell leukemia |accessdate=2007-09-10 |format= |work=}}</ref>
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| 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.
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| Some patients tolerate IFN-alpha very well after the first couple of weeks, while others find that its characteristic flu-like symptoms persist. Perhaps as many as 40% 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.
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| 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.<ref name="pmid3971043">{{cite journal |author=Ratain MJ, Golomb HM, Vardiman JW, Vokes EE, Jacobs RH, Daly K |title=Treatment of hairy cell leukemia with recombinant alpha 2 interferon |journal=Blood |volume=65 |issue=3 |pages=644-8 |year=1985 |pmid=3971043 |doi=}}</ref>
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| It typically takes six months to figure out whether this therapy is useful. Common criteria for treatment success include:
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| * normalization of hemoglobin levels (above 12.0 g/dL),
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| * a normal or somewhat low platelet count (above 100 K/µL), and
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| * a normal or somewhat low absolute neutrophil count (above 1.5 K/µL).<ref name="pmid3971043"> </ref> | |
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| 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.
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| Interferon-alpha works by sensitizing the hairy cells to the killing effect of the immune system hormone TNF-alpha, whose production it promotes.<ref name="pmid12091360">{{cite journal |author=Baker PK, Pettitt AR, Slupsky JR, ''et al'' |title=Response of hairy cells to IFN-alpha involves induction of apoptosis through autocrine TNF-alpha and protection by adhesion |journal=Blood |volume=100 |issue=2 |pages=647-53 |year=2002 |pmid=12091360 |doi=}}</ref> 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.<ref name="pmid12091360"> </ref>
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| ===Experimental therapies===
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| Three immunotoxin drugs are in Phase II trials at the [[NIH]]'s [[National Cancer Institute]] in the U.S.: [[BL22]]<ref>{{ClinicalTrials|NCT00074048}}</ref>, HA22<ref>{{ClinicalTrials|NCT00462189}}</ref> and LMB-2.<ref>{{ClinicalTrials|NCT00337311}}</ref>
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| 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.
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| All three of these 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.
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| ===Other treatment options===
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| '''[[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]].
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| '''[[Bone marrow transplant]]s''' 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.
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| 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.
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| 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.<ref>{{cite web |url=http://bloodjournal.hematologylibrary.org/cgi/content/full/93/8/2471 |title=Filgrastim for Cladribine-Induced Neutropenic Fever in Patients With Hairy Cell Leukemia -- Saven et al. 93 (8): 2471 -- Blood |accessdate=2007-09-10 |format= |work=}}</ref> 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 didn't, 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 immediately after cladribine treatment.
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| 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.
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| ==Prognosis==
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| More than 95% of new patients are treated well or at least adequately by cladribine or pentostatin.[http://www3.interscience.wiley.com/cgi-bin/abstract/112133291/ABSTRACT?CRETRY=1&SRETRY=0] 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.
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| How soon after treatment a patient feels "normal" again depends on several factors, including:
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| *how advanced the disease was at the time of treatment;
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| *the patient's underlying health status;
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| *whether the patient had a "complete response" or only a partial response to the treatment;
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| *whether the patient experienced any of the rare, but serious side effects such as kidney failure;
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| *how aggressive the individual's disease is;
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| *whether the patient is experiencing unusual psychological trauma from the "cancer" diagnosis; and
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| *how the patient perceived his or her pre-treatment energy level and daily functioning.
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| 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.[http://www.euclidmanagers.com/downloads/legrev/rblegrev/RTBaugust.pdf]
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| 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.
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| 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).
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| Worldwide, approximately 300 HCL patients per year are expected to die.[http://www.cambridgeantibody.com/home/glossary] 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.
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| 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.
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| ==Follow-Up Care==
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| 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.
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| 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.<ref>{{cite web |url=http://bloodjournal.hematologylibrary.org/cgi/content/abstract/92/4/1160 |title=Second Malignancies in Patients With Hairy Cell Leukemia in British Columbia: A 20-Year Experience -- Au et al. 92 (4): 1160 -- Blood |accessdate=2007-09-10 |format= |work=}}</ref> 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%.
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| ==Variants==
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| '''Hairy cell leukemia-variant''', or HCL-V, is usually described as a prolymphocytic variant of hairy cell leukemia.<ref>{{cite web |url=http://bloodjournal.hematologylibrary.org/cgi/content/abstract/76/1/157 |title=A variant form of hairy cell leukemia resistant to alpha-interferon: clinical and phenotypic characteristics of 17 patients -- Sainati et al. 76 (1): 157 -- Blood |accessdate=2007-09-10 |format= |work=}}</ref> It was first formally described in 1980 by a paper from the University of Cambridge's Hayhoe lab.<ref name="pmid7206776">{{cite journal |author=Cawley JC, Burns GF, Hayhoe FG |title=A chronic lymphoproliferative disorder with distinctive features: a distinct variant of hairy-cell leukaemia |journal=Leuk. Res. |volume=4 |issue=6 |pages=547-59 |year=1980 |pmid=7206776 |doi=}}</ref> 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.<ref name="pmid11243388">{{cite journal |author=Matutes E, Wotherspoon A, Brito-Babapulle V, Catovsky D |title=The natural history and clinico-pathological features of the variant form of hairy cell leukemia |journal=Leukemia |volume=15 |issue=1 |pages=184-6 |year=2001 |pmid=11243388 |doi=}}</ref>
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| 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.<ref name="pmid11243388"> </ref> 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.<ref name="pmid11243388"> </ref>
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| 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.
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| HCL-V differs from classic HCL principally in these respects:
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| * High white blood cell counts, sometimes in excess of 100,000 cells per microliter;
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| * More aggressive course of disease that requires more frequent treatment;
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| * Cells with an unusually large nucleolus for their size;
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| * Little excess fibronectin (which is produced by classic hairy cells<ref>{{cite web |url=http://bloodjournal.hematologylibrary.org/cgi/content/abstract/83/2/497 |title=The bone marrow fibrosis of hairy-cell leukemia is caused by the synthesis and assembly of a fibronectin matrix by the hairy cells -- Burthem and Cawley 83 (2): 497 -- Blood |accessdate=2007-09-10 |format= |work=}}</ref>) to interfere with bone marrow biopsies; and
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| * Low or no expression of CD25 (also called the Interleukin-2 [IL-2] receptor alpha chain or p55) on cell surfaces.<ref>{{cite web |url=http://bloodjournal.hematologylibrary.org/cgi/content/abstract/82/2/528 |title=Phenotypic analysis of hairy cell leukemia: "variant" cases express the interleukin-2 receptor beta chain, but not the alpha chain (CD25) -- de Totero et al. 82 (2): 528 -- Blood |accessdate=2007-09-10 |format= |work=}}</ref>
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| 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.<ref>{{cite web |url=http://bloodjournal.hematologylibrary.org/cgi/content/abstract/76/1/157 |title=A variant form of hairy cell leukemia resistant to alpha-interferon: clinical and phenotypic characteristics of 17 patients -- Sainati et al. 76 (1): 157 -- Blood |accessdate=2007-09-10 |format= |work=}}</ref>
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| 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.<ref name="pmid11243388"> </ref> Among HCL-V patients, the most aggressive cases normally have the least amount of p53 gene activity.<ref name="pmid10576509">{{cite journal |author=Vallianatou K, Brito-Babapulle V, Matutes E, Atkinson S, Catovsky D |title=p53 gene deletion and trisomy 12 in hairy cell leukemia and its variant |journal=Leuk. Res. |volume=23 |issue=11 |pages=1041-5 |year=1999 |pmid=10576509 |doi=}}</ref> Hairy cells without the p53 gene tend, over time, to displace the less aggressive p53+ hairy cells.
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| '''Hairy cell leukemia-Japanese variant''' or HCL-J. There is also a Japanese variant, which is more easily treated.
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| ==References==
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| {{Reflist|2}}
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| ==External links== | | ==External Links== |
| * [http://www.cancer.gov/cancertopics/pdq/treatment/hairy-cell-leukemia National Cancer Institute] | | * [http://www.cancer.gov/cancertopics/pdq/treatment/hairy-cell-leukemia National Cancer Institute] |
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| ==See also==
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| * [[Annexin A1]]
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| {{Hematology}} | | {{Hematology}} |
| {{Hematological malignancy histology}} | | {{Hematological malignancy histology}} |
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