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| {{CMG}} | | {{CMG}} |
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| ==Overview==
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| ==Medical Therapy==
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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=====
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| 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=====
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| [[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 count]]s 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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| ===Other treatment options===
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| =====Blood transfusion=====
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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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| =====Filgrastim=====
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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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| ==References== | | ==References== |