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{{Hairy cell leukemia}}
{{Hairy cell leukemia}}
{{CMG}}
{{CMG}}; {{AE}} {{HL}}; {{GRR}} {{Nat}}


==Overview==
==Overview==
There is no curative treatment for [[hairy cell leukemia]]. The mainstay of therapy for [[hairy cell leukemia]] patients is [[chemotherapy]]. Pharmacological agents used for the treatment of [[hairy cell leukemia]] patients include [[cladribine]], [[pentostatin]], [[rituximab]], and [[vemurafenib]].


==Medical Therapy==
==Medical Therapy==
 
* There is no curative treatment for [[hairy cell leukemia]].<ref name="ZinzaniPellegrini2010">{{cite journal|last1=Zinzani|first1=Pier Luigi|last2=Pellegrini|first2=Cinzia|last3=Stefoni|first3=Vittorio|last4=Derenzini|first4=Enrico|last5=Gandolfi|first5=Letizia|last6=Broccoli|first6=Alessandro|last7=Argnani|first7=Lisa|last8=Quirini|first8=Federica|last9=Pileri|first9=Stefano|last10=Baccarani|first10=Michele|title=Hairy cell leukemia|journal=Cancer|volume=116|issue=20|year=2010|pages=4788–4792|issn=0008543X|doi=10.1002/cncr.25243}}</ref>
===First-line therapy: Purine analog chemotherapy===
* The mainstay of therapy for [[hairy cell leukemia]] patients is [[chemotherapy]].
[[Cladribine]] (2CDA) and [[pentostatin]] (DCF) are the two most common first-line therapies.  Cladribine is a kind of mild chemotherapy which can be administered by injection under the skin, by infusion over a couple of hours into a vein, or by a pump worn by the patient that provides a slow drip into a vein, 24 hours a day for 7 days.  Most patients receive cladribine by IV infusion once a day for five to seven days, but more patients are being given the option of taking this drug once a week for six weeks.  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>
* Asymptomatic [[hairy cell leukemia]] patients, with no indications for therapy, may be managed by observation and close follow-up.
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.
* Indications to initiate medical therapy among patients with [[hairy cell leukemia]] include:
 
:* The presence of systemic symptoms such as [[fever]], [[night sweats]], and significant [[weight loss]]
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.
:* The presence of [[subcostal]] [[abdominal]] discomfort due to [[splenomegaly]]
 
:* A positive history of recurrent [[infections]]
(A third related chemical, [[fludarabine]], is not used for hairy cell leukemia, despite being chemically similar.)
:* [[Hemoglobin]] concentration lower than 12 g/dL
 
:* [[Platelets]] count lower than 100,000/μL
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.
:* Absolute [[neutrophils]] count lower than 1000/μL
 
* Pharmacological agents used for the treatment of [[hairy cell leukemia]] patients include:<ref name="pmid19344416">{{cite journal |vauthors=Else M, Dearden CE, Matutes E, Garcia-Talavera J, Rohatiner AZ, Johnson SA, O'Connor NT, Haynes A, Osuji N, Forconi F, Lauria F, Catovsky D |title=Long-term follow-up of 233 patients with hairy cell leukaemia, treated initially with pentostatin or cladribine, at a median of 16 years from diagnosis |journal=Br. J. Haematol. |volume=145 |issue=6 |pages=733–40 |date=June 2009 |pmid=19344416 |doi=10.1111/j.1365-2141.2009.07668.x |url=}}</ref><ref name="pmid10460614">{{cite journal |vauthors=Dearden CE, Matutes E, Hilditch BL, Swansbury GJ, Catovsky D |title=Long-term follow-up of patients with hairy cell leukaemia after treatment with pentostatin or cladribine |journal=Br. J. Haematol. |volume=106 |issue=2 |pages=515–9 |date=August 1999 |pmid=10460614 |doi= |url=}}</ref><ref name="pmid19843881">{{cite journal |vauthors=Grever MR |title=How I treat hairy cell leukemia |journal=Blood |volume=115 |issue=1 |pages=21–8 |date=January 2010 |pmid=19843881 |pmc=2803689 |doi=10.1182/blood-2009-06-195370 |url=}}</ref>
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.
:* [[Cladribine]]  
 
:* [[Pentostatin]]
===Second-line therapy: Immunotherapy===
:* [[Rituximab]]
If a patient is resistant to either cladribine or pentostatin, then second-line therapy is pursued. 
:* [[Interferon alpha]]
 
:* [[Vemurafenib]]
=====Monoclonal antibodies=====
===First Line Therapy===
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>
* The preferred pharmacological agent used for the initial management of [[hairy cell leukemia]] could be either [[cladribine]] or [[pentostatin]].<ref name="pmid212205902">{{cite journal |vauthors=Grever MR, Lozanski G |title=Modern strategies for hairy cell leukemia |journal=J. Clin. Oncol. |volume=29 |issue=5 |pages=583–90 |date=February 2011 |pmid=21220590 |doi=10.1200/JCO.2010.31.7016 |url=}}</ref><ref name="pmid77071262">{{cite journal |vauthors=Grever M, Kopecky K, Foucar MK, Head D, Bennett JM, Hutchison RE, Corbett WE, Cassileth PA, Habermann T, Golomb H |title=Randomized comparison of pentostatin versus interferon alfa-2a in previously untreated patients with hairy cell leukemia: an intergroup study |journal=J. Clin. Oncol. |volume=13 |issue=4 |pages=974–82 |date=April 1995 |pmid=7707126 |doi=10.1200/JCO.1995.13.4.974 |url=}}</ref><ref name="pmid104606142">{{cite journal |vauthors=Dearden CE, Matutes E, Hilditch BL, Swansbury GJ, Catovsky D |title=Long-term follow-up of patients with hairy cell leukaemia after treatment with pentostatin or cladribine |journal=Br. J. Haematol. |volume=106 |issue=2 |pages=515–9 |date=August 1999 |pmid=10460614 |doi= |url=}}</ref><ref name="pmid198438812">{{cite journal |vauthors=Grever MR |title=How I treat hairy cell leukemia |journal=Blood |volume=115 |issue=1 |pages=21–8 |date=January 2010 |pmid=19843881 |pmc=2803689 |doi=10.1182/blood-2009-06-195370 |url=}}</ref>
 
* [[Cladribine]] is administered by a single daily IV infusion for a period of 5-7 days.
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.
* [[Pentostatin]] is administered by a single IV infusion every 2 weeks for a period of 3-6 months.
 
* Common side effects of such agents may include:
Other B cell-destroying monoclonal antibodies such as [[Alemtuzumab]], [[Ibritumomab tiuxetan]] and I-131 [[Tositumomab]] may be considered for refractory cases.
:* [[Immune suppression]]
 
:* [[Acute kidney failure]]
=====Interferon-alpha=====
:* [[Fatigue]]
[[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> 
:* High [[fever]]
 
* [[Hairy cell leukemia]] patients who demonstrate a complete response following initial medical therapy should be followed-up with close observation for any signs of relapse.
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. 
* A complete response to medical therapy among patients with [[hairy cell leukemia]] is defined by:
 
:* Resolution of the patient's symptoms
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.
:* The absence of [[splenomegaly]] on physical exam
 
:* Recovery of the patients blood counts to the normal limits
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>
:* The absence of malignant leukemic cells on blood smear or [[bone marrow]] aspiration
 
===Relapsed Therapy===
It typically takes six months to figure out whether this therapy is useful. Common criteria for treatment success include:
* The optimal therapy for patients who relapse after a complete response depends on the duration of disease-free period following the initial medical therapy.
* normalization of [[hemoglobin]] levels (above 12.0 g/dL),
* [[Hairy cell leukemia]] patients who relapse after one year or more are be managed by the same initial [[purine]] analogue {{withorwithout}} [[rituximab]].
* a normal or somewhat low [[platelet count]] (above 100 K/µL), and
* H[[hairy cell leukemia|airy cell leukemia]] patients who relapse before a period of one year are managed by an alternative [[purine]] analogue {{withorwithout}} [[rituximab]].
* a normal or somewhat low [[absolute neutrophil count]] (above 1.5 K/µL).<ref name="pmid3971043"> </ref>
===Refractory Therapy===
 
* [[Hairy cell leukemia]] patients who do not demonstrate a complete response to medical therapy could be further managed by any of the following agents:<ref name="pmid21220590">{{cite journal |vauthors=Grever MR, Lozanski G |title=Modern strategies for hairy cell leukemia |journal=J. Clin. Oncol. |volume=29 |issue=5 |pages=583–90 |date=February 2011 |pmid=21220590 |doi=10.1200/JCO.2010.31.7016 |url=}}</ref><ref name="BastieCazals-Hatem2010">{{cite journal|last1=Bastie|first1=J. N.|last2=Cazals-Hatem|first2=D.|last3=Daniel|first3=M. T.|last4=D'agay|first4=M. F.|last5=Rabian|first5=CL.|last6=Glaisner|first6=S.|last7=Noel-Walter|first7=M. P.|last8=Dabout|first8=D.|last9=Flandrin|first9=G.|last10=Dombret|first10=H.|last11=Poisson|first11=D.|last12=Degos|first12=L.|last13=Castaigne|first13=S.|title=Five Years Follow-Up after 2-Chloro Deoxyadenosine Treatment in Thirty Patients with Hairy Cell Leukemia: Evaluation of Minimal Residual Disease and CD4+ Lymphocytopenia after Treatment|journal=Leukemia & Lymphoma|volume=35|issue=5-6|year=2010|pages=555–565|issn=1042-8194|doi=10.1080/10428199909169620}}</ref><ref name="pmid11089434">{{cite journal |vauthors=Gotić M, Rolović Z, Radosević N, Draguljac N, Jovanović V, Bogdanović A, Bosković D |title=[Results of treatment in patients with hairy cell leukemia with splenectomy, alpha-interferon and deoxycoformycin] |journal=Srp Arh Celok Lek |volume=128 |issue=7-8 |pages=262–70 |date=2000 |pmid=11089434 |doi= |url=}}</ref><ref name="pmid7707126">{{cite journal |vauthors=Grever M, Kopecky K, Foucar MK, Head D, Bennett JM, Hutchison RE, Corbett WE, Cassileth PA, Habermann T, Golomb H |title=Randomized comparison of pentostatin versus interferon alfa-2a in previously untreated patients with hairy cell leukemia: an intergroup study |journal=J. Clin. Oncol. |volume=13 |issue=4 |pages=974–82 |date=April 1995 |pmid=7707126 |doi=10.1200/JCO.1995.13.4.974 |url=}}</ref><ref name="pmid27301277">{{cite journal |vauthors=Chihara D, Kantarjian H, O'Brien S, Jorgensen J, Pierce S, Faderl S, Ferrajoli A, Poku R, Jain P, Thompson P, Brandt M, Luthra R, Burger J, Keating M, Ravandi F |title=Long-term durable remission by cladribine followed by rituximab in patients with hairy cell leukaemia: update of a phase II trial |journal=Br. J. Haematol. |volume=174 |issue=5 |pages=760–6 |date=September 2016 |pmid=27301277 |pmc=5396841 |doi=10.1111/bjh.14129 |url=}}</ref><ref name="pmid21821712">{{cite journal |vauthors=Ravandi F, O'Brien S, Jorgensen J, Pierce S, Faderl S, Ferrajoli A, Koller C, Challagundla P, York S, Brandt M, Luthra R, Burger J, Thomas D, Keating M, Kantarjian H |title=Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia |journal=Blood |volume=118 |issue=14 |pages=3818–23 |date=October 2011 |pmid=21821712 |pmc=4081440 |doi=10.1182/blood-2011-04-351502 |url=}}</ref>
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.
:* [[Rituximab]] alone
 
:* [[Interferon alpha]] alone
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>
:* An alternate purine analogue {{withorwithout}} [[rituximab]]
 
* [[Rituximab]] is administered by a single IV infusion every week for a period of 8 weeks.
===Other treatment options===
* [[Interferon alpha]] is administered subcutaneously (3 million units) three times a week for a period of 12-18 months.
=====Blood transfusion=====
* The major side effect of [[rituximab]] treatment is [[serum sickness]], whereas the major side effects of [[interferon]] alpha are flu-like symptoms and [[depression]].
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 progressive [[hairy cell leukemia]], who do not demonstrate a complete response to any of the aforementioned medical therapies, should be managed with a [[BRAF]] kinase inhibitor, such as [[vemurafenib]].<ref name="pub7">{{cite journal |vauthors=Cornet E, Damaj G, Troussard X |title=New insights in the management of patients with hairy cell leukemia |journal=Curr Opin Oncol |volume=27 |issue=5 |pages=371–6 |year=2015 |pmid=26154707 |doi=10.1097/CCO.0000000000000214 |url=}}</ref>
 
<br>'''The algorithm below summarizes the management approach for hairy cell leukemia patients:'''<br>
=====Filgrastim=====
{{familytree/start |summary=PE diagnosis Algorithm.}}
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.
{{familytree | | | | | | A02 | | | | | |A02=<div style="width: 10em; padding:0.2em;">'''Initial patients evaluation'''</div>}}
 
{{familytree|boxstyle= border-top: 0px;| | | | | | A01 | | | | | | |A01=<div style="width: 15em; padding:1em;text-align:center">History<br>Physical examination<br>Complete blood count</div>}}
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.
{{familytree | | | | | | |!| | }}
{{familytree | | | | | | |!| | }}
{{familytree | | | | |,|-|^|-|.| |}}
{{familytree | | | | B02 | |B01| | |B02=<div style="width: 10em; padding:1em;text-align:center">'''Asymptomatic patients with no therapeutic indications'''</div>|B01=<div style="width: 15em; padding:1em;text-align:center">'''Symptomatic patients or evidence of therapeutic indications '''</div>}}
{{familytree | | | | |!| | | |!| | | | }}
{{familytree | | | | |!| | | |!| | | | }}
{{familytree | | | | C02 | | C01| | |C01=<div style="width: 10em; padding:1em;">
'''[[Cladribine]]'''<br>
'''[[Pentostatin]]'''</div>|C02=<div style="width: 15em; padding:1em;text-align:center">'''Patients managed by observation and close follow-up'''</div>}}
{{familytree | | | | | | | | |!| | | | }}
{{familytree | | | | | | |,|-|^|-|.| | }}
{{familytree | | | | | | D02 | | D01 |D01=<div style="width: 15em; padding:1em;text-align:center">'''No evidence of complete response'''</div>|D02=<div style="width: 15em; padding:1em;text-align:center">'''Complete response'''</div>}}
{{familytree | | | | | | |!| | | |!| | }}
{{familytree | | | | | | |!| | | |!| | }}
{{familytree | | | | | | E02 | | E01 | |E01=<div style="width: 17em; padding:1em;text-align:center">
'''[[Retuximab]] alone'''<br>
'''[[Interferon alpha]] alone'''<br>
'''Alternative purine analogue {{withorwithout}} rituximab'''</div>|E02=<div style="width: 13em; padding:1em;text-align:center">'''Follow-up and close observation'''</div>}}
{{familytree | | | | | | |!| | | |!|}}
{{familytree | | | | | | |!| | | |!| | }}
{{familytree | | | | | | E02 | | E01 | |E01=<div style="width: 17em; padding:1em;text-align:center">'''No evidence of complete response'''</div>|E02=<div style="width: 13em; padding:1em;">
'''Relapse after one year: same initial purine analogue ± rituximab'''<br>
'''Relapse before one year: alternative purine analogue ± rituximab'''</div>}}
{{familytree | | | | | | | | | | |!| | | }}
{{familytree | | | | | | | | | | |!| | | }}
{{familytree | | | | | | | | | | E01 |E01=<div style="width: 17em; padding:1em;text-align:lef">'''[[Vemurafenib]]'''</div>}}
{{familytree/end}}
<br>


==References==
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Latest revision as of 17:23, 8 April 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]; Grammar Reviewer: Natalie Harpenau, B.S.[3]

Overview

There is no curative treatment for hairy cell leukemia. The mainstay of therapy for hairy cell leukemia patients is chemotherapy. Pharmacological agents used for the treatment of hairy cell leukemia patients include cladribine, pentostatin, rituximab, and vemurafenib.

Medical Therapy

First Line Therapy

  • The preferred pharmacological agent used for the initial management of hairy cell leukemia could be either cladribine or pentostatin.[5][6][7][8]
  • Cladribine is administered by a single daily IV infusion for a period of 5-7 days.
  • Pentostatin is administered by a single IV infusion every 2 weeks for a period of 3-6 months.
  • Common side effects of such agents may include:
  • Hairy cell leukemia patients who demonstrate a complete response following initial medical therapy should be followed-up with close observation for any signs of relapse.
  • A complete response to medical therapy among patients with hairy cell leukemia is defined by:
  • Resolution of the patient's symptoms
  • The absence of splenomegaly on physical exam
  • Recovery of the patients blood counts to the normal limits
  • The absence of malignant leukemic cells on blood smear or bone marrow aspiration

Relapsed Therapy

  • The optimal therapy for patients who relapse after a complete response depends on the duration of disease-free period following the initial medical therapy.
  • Hairy cell leukemia patients who relapse after one year or more are be managed by the same initial purine analogue ± rituximab.
  • Hairy cell leukemia patients who relapse before a period of one year are managed by an alternative purine analogue ± rituximab.

Refractory Therapy

  • Rituximab is administered by a single IV infusion every week for a period of 8 weeks.
  • Interferon alpha is administered subcutaneously (3 million units) three times a week for a period of 12-18 months.
  • The major side effect of rituximab treatment is serum sickness, whereas the major side effects of interferon alpha are flu-like symptoms and depression.
  • Patients with progressive hairy cell leukemia, who do not demonstrate a complete response to any of the aforementioned medical therapies, should be managed with a BRAF kinase inhibitor, such as vemurafenib.[15]


The algorithm below summarizes the management approach for hairy cell leukemia patients:

 
 
 
 
 
Initial patients evaluation
 
 
 
 
 
 
 
 
 
 
History
Physical examination
Complete blood count
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Asymptomatic patients with no therapeutic indications
 
Symptomatic patients or evidence of therapeutic indications
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patients managed by observation and close follow-up
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete response
 
No evidence of complete response
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Follow-up and close observation
 

Retuximab alone
Interferon alpha alone

Alternative purine analogue ± rituximab
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Relapse after one year: same initial purine analogue ± rituximab

Relapse before one year: alternative purine analogue ± rituximab
 
No evidence of complete response
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


References

  1. ↑ Zinzani, Pier Luigi; Pellegrini, Cinzia; Stefoni, Vittorio; Derenzini, Enrico; Gandolfi, Letizia; Broccoli, Alessandro; Argnani, Lisa; Quirini, Federica; Pileri, Stefano; Baccarani, Michele (2010). "Hairy cell leukemia". Cancer. 116 (20): 4788–4792. doi:10.1002/cncr.25243. ISSN 0008-543X.
  2. ↑ Else M, Dearden CE, Matutes E, Garcia-Talavera J, Rohatiner AZ, Johnson SA, O'Connor NT, Haynes A, Osuji N, Forconi F, Lauria F, Catovsky D (June 2009). "Long-term follow-up of 233 patients with hairy cell leukaemia, treated initially with pentostatin or cladribine, at a median of 16 years from diagnosis". Br. J. Haematol. 145 (6): 733–40. doi:10.1111/j.1365-2141.2009.07668.x. PMID 19344416.
  3. ↑ Dearden CE, Matutes E, Hilditch BL, Swansbury GJ, Catovsky D (August 1999). "Long-term follow-up of patients with hairy cell leukaemia after treatment with pentostatin or cladribine". Br. J. Haematol. 106 (2): 515–9. PMID 10460614.
  4. ↑ Grever MR (January 2010). "How I treat hairy cell leukemia". Blood. 115 (1): 21–8. doi:10.1182/blood-2009-06-195370. PMC 2803689. PMID 19843881.
  5. ↑ Grever MR, Lozanski G (February 2011). "Modern strategies for hairy cell leukemia". J. Clin. Oncol. 29 (5): 583–90. doi:10.1200/JCO.2010.31.7016. PMID 21220590.
  6. ↑ Grever M, Kopecky K, Foucar MK, Head D, Bennett JM, Hutchison RE, Corbett WE, Cassileth PA, Habermann T, Golomb H (April 1995). "Randomized comparison of pentostatin versus interferon alfa-2a in previously untreated patients with hairy cell leukemia: an intergroup study". J. Clin. Oncol. 13 (4): 974–82. doi:10.1200/JCO.1995.13.4.974. PMID 7707126.
  7. ↑ Dearden CE, Matutes E, Hilditch BL, Swansbury GJ, Catovsky D (August 1999). "Long-term follow-up of patients with hairy cell leukaemia after treatment with pentostatin or cladribine". Br. J. Haematol. 106 (2): 515–9. PMID 10460614.
  8. ↑ Grever MR (January 2010). "How I treat hairy cell leukemia". Blood. 115 (1): 21–8. doi:10.1182/blood-2009-06-195370. PMC 2803689. PMID 19843881.
  9. ↑ Grever MR, Lozanski G (February 2011). "Modern strategies for hairy cell leukemia". J. Clin. Oncol. 29 (5): 583–90. doi:10.1200/JCO.2010.31.7016. PMID 21220590.
  10. ↑ Bastie, J. N.; Cazals-Hatem, D.; Daniel, M. T.; D'agay, M. F.; Rabian, CL.; Glaisner, S.; Noel-Walter, M. P.; Dabout, D.; Flandrin, G.; Dombret, H.; Poisson, D.; Degos, L.; Castaigne, S. (2010). "Five Years Follow-Up after 2-Chloro Deoxyadenosine Treatment in Thirty Patients with Hairy Cell Leukemia: Evaluation of Minimal Residual Disease and CD4+ Lymphocytopenia after Treatment". Leukemia & Lymphoma. 35 (5–6): 555–565. doi:10.1080/10428199909169620. ISSN 1042-8194.
  11. ↑ Gotić M, Rolović Z, Radosević N, Draguljac N, Jovanović V, Bogdanović A, Bosković D (2000). "[Results of treatment in patients with hairy cell leukemia with splenectomy, alpha-interferon and deoxycoformycin]". Srp Arh Celok Lek. 128 (7–8): 262–70. PMID 11089434.
  12. ↑ Grever M, Kopecky K, Foucar MK, Head D, Bennett JM, Hutchison RE, Corbett WE, Cassileth PA, Habermann T, Golomb H (April 1995). "Randomized comparison of pentostatin versus interferon alfa-2a in previously untreated patients with hairy cell leukemia: an intergroup study". J. Clin. Oncol. 13 (4): 974–82. doi:10.1200/JCO.1995.13.4.974. PMID 7707126.
  13. ↑ Chihara D, Kantarjian H, O'Brien S, Jorgensen J, Pierce S, Faderl S, Ferrajoli A, Poku R, Jain P, Thompson P, Brandt M, Luthra R, Burger J, Keating M, Ravandi F (September 2016). "Long-term durable remission by cladribine followed by rituximab in patients with hairy cell leukaemia: update of a phase II trial". Br. J. Haematol. 174 (5): 760–6. doi:10.1111/bjh.14129. PMC 5396841. PMID 27301277.
  14. ↑ Ravandi F, O'Brien S, Jorgensen J, Pierce S, Faderl S, Ferrajoli A, Koller C, Challagundla P, York S, Brandt M, Luthra R, Burger J, Thomas D, Keating M, Kantarjian H (October 2011). "Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia". Blood. 118 (14): 3818–23. doi:10.1182/blood-2011-04-351502. PMC 4081440. PMID 21821712.
  15. ↑ Cornet E, Damaj G, Troussard X (2015). "New insights in the management of patients with hairy cell leukemia". Curr Opin Oncol. 27 (5): 371–6. doi:10.1097/CCO.0000000000000214. PMID 26154707.


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