Hairy cell leukemia (HCL) is a rare type of indolent B-cell leukemia, characterized by symptoms of fatigue and weakness, organomegaly, pancytopenia, and recurrent opportunistic infections. Classic HCL should be considered a distinct clinical entity separate from HCLvariant (HCLv), which is associated with a more aggressive disease course and may not respond to standard HCL therapies. Somatic hypermutation in the IGHV gene is present in most patients with HCL. The BRAF V600E mutation has been reported in most patients with classic HCL but not in those with other B-cell leukemias or lymphomas. Therefore, it is necessary to distinguish HCLv from classic HCL. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of classic HCL.

Abstract

Hairy cell leukemia (HCL) is a rare type of indolent B-cell leukemia, characterized by symptoms of fatigue and weakness, organomegaly, pancytopenia, and recurrent opportunistic infections. Classic HCL should be considered a distinct clinical entity separate from HCLvariant (HCLv), which is associated with a more aggressive disease course and may not respond to standard HCL therapies. Somatic hypermutation in the IGHV gene is present in most patients with HCL. The BRAF V600E mutation has been reported in most patients with classic HCL but not in those with other B-cell leukemias or lymphomas. Therefore, it is necessary to distinguish HCLv from classic HCL. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of classic HCL.

NCCN Categories of Evidence and Consensus

Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.

Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.

All recommendations are category 2A unless otherwise noted.

Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

Overview

Hairy cell leukemia (HCL) is a rare type of indolent B-cell leukemia comprising approximately 2% of all lymphoid leukemias.1 Leukemic cells typically infiltrate the bone marrow and spleen, and may also be found in the liver and lymph nodes. Clinically, HCL is characterized by symptoms of fatigue and weakness, and most patients will present with splenomegaly (symptomatic or asymptomatic) and/or hepatomegaly, pancytopenia, and uncommonly peripheral lymphadenopathy.2 Additionally, patients may also present with recurrent opportunistic infections.3

Diagnosis

Morphological evaluation of peripheral blood smears, bone marrow biopsy with or without aspirate and adequate immunophenotyping by immunohistochemistry (IHC) or flow cytometry are essential to establish a diagnosis of HCL.2 Leukemic cells in HCL are small to medium in size, showing a round, oval, or indented nucleus with a well-defined nuclear border. The presence of a cytoplasm with prominent hair-like projections is characteristic of HCL.4,5 Examination of bone marrow biopsy samples shows hairy cell infiltrates with increased reticulin fibers, which frequently results in a “dry” tap. In some patients with HCL, the bone marrow may show hypocellularity; this is important to recognize to avoid an erroneous diagnosis of aplastic anemia.4,5

Most HCL cases (80%–90%) are characterized by somatic hypermutation in the IGHV gene.6,7 The frequency of unmutated IGHV is much lower in classic HCL than in HCL-variant (HCLv) (17% vs 54%; P<.001).7 Unmutated IGHV may serve as a prognostic factor for poorer outcomes with conventional therapies because it has been associated with primary refractoriness to purine analogue monotherapy and a more rapid disease progression.8 The BRAF V600E mutation has been reported in most patients with classic HCL but not in those with other B-cell leukemias or lymphomas.912 BRAF V600E is also absent in all cases of HCLv and classic HCL expressing IGHV4-34 rearrangement.13,14 Thus, BRAF V600E mutation may potentially serve as a reliable molecular marker to

F1

NCCN Clinical Practice Guidelines in Oncology: Hairy Cell Leukemia, Version 2.2018

Version 2.2018, 09-26-17 ©2017 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 15, 11; 10.6004/jnccn.2017.0165

F2

NCCN Clinical Practice Guidelines in Oncology: Hairy Cell Leukemia, Version 2.2018

Version 2.2018, 09-26-17 ©2017 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 15, 11; 10.6004/jnccn.2017.0165

F3

Hairy Cell Leukemia, Version 2.2018

Clinical trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged. All recommendations are category 2A unless otherwise indicated.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 15, 11; 10.6004/jnccn.2017.0165

distinguish HCL from HCLv and other B-cell leukemias or lymphomas.

In comparison to classic HCL, HCLv tends to be associated with a more aggressive disease course and may not respond to standard HCL therapies.14,15 The 2008 WHO classification determined that classic HCL should be considered as a distinct clinical entity from HCLv.4,5 Therefore, it is necessary to distinguish HCLv from classic HCL, with immunophenotyping being the primary methodology used, although the role of molecular analysis is rapidly expanding. IHC or flow cytometry panel for immunophenotyping should include CD19, CD20, CD5, CD10, CD11c, CD22, CD25, CD103, CD123, cyclin D1, and CD200. The typical immunophenotype for classic HCL shows CD5−, CD10−, CD11c+, CD20+ (bright), CD22+, CD25+, CD103+, CD123+, cyclin D1+, annexin A1+, and CD200+ (bright).14 In contrast, HCLv is characteristically CD25−, CD123−, annexin A1−, and BRAF V600E–negative.14 IHC or molecular studies for BRAF V600E mutation is useful for the distinction of classic HCL from HCLv and other splenic B-cell lymphomas.14,16,17

HCL expressing IGHV4-34 rearrangement has a relatively poorer prognosis and does not respond well to purine analogue therapy.18 Molecular analysis to determine IGHV4-34 rearrangement may be useful to distinguish classic HCL from HCL with IGHV4-34 rearrangement. A high frequency of MAP2K1 mutations was recently reported in HCLv and in classic HCL with IGHV4-34 rearrangement.19 MAPK1 mutation analysis may be useful to distinguish HCLv from classic HCL in BRAF-negative cases.

Workup

The initial workup should include a thorough physical examination with attention to node-bearing areas (although presence of peripheral lymphadenopathy is uncommon), size measurements of the liver and spleen, and performance status evaluation. A bone marrow biopsy with or without aspirate should be obtained. Laboratory assessments should include CBC with differential, serum lactate dehydrogenase levels, and a comprehensive metabolic panel. In particular, close evaluation of renal function is advised considering the renal route of excretion of drugs used in HCL treatment. Hepatitis B virus (HBV) testing is recommended due to the increased risk of viral reactivation associated with the use of immunotherapy and/or chemotherapy. CT scans (with contrast of diagnostic quality) of the chest, abdomen, and/or pelvis may be useful under certain circumstances.

Treatment Options

Initial Treatment

Purine analogues such as pentostatin2026 and cladribine2533 have shown significant monotherapy activity, resulting in durable remissions in patients with previously untreated HCL. Pentostatin and cladribine have not been compared head-to-head, but appear to show comparable clinical activity.

In a phase III Intergroup study that randomized 319 previously untreated patients (1:1 fashion) to pentostatin versus interferon-alfa, pentostatin resulted in significantly higher complete response (CR) rates (76% vs 11%; P<.0001) and longer median relapse-free survival (RFS; not reached vs 20 months; P<.0001) compared with interferon-alfa; the median follow-up was 57 months.21 After a median follow-up of 9.3 years, estimated 5- and 10-year overall survival (OS) rates for patients initially treated with pentostatin were 89% and 80%, respectively22; corresponding RFS rates were 86% and 66%. Survival outcomes were not significantly different between treatment arms, although this analysis was complicated by the crossover design of the study. The most common treatment-related toxicities were neutropenia (grade 3/4; 20%) and infections (any grade; 53%), including those requiring intravenous antibiotics (27%).

In a study of 358 patients with untreated HCL, cladribine resulted in a CR rate of 91% with a median response duration of 52 months and an OS rate of 96% at 48 months.28 Extended follow-up results confirmed the durability of responses with cladribine29: after 7 years of follow-up, of 207 evaluable patients, 95% achieved a CR and 5% achieved a partial response (PR), with median response duration of 98 months for all responders. The most common toxicities were neutropenia (grade 3/4; occurring in ≈65%–85%), febrile neutropenia (40%), thrombocytopenia (grade 3/4; 20%), and infections (10%).

Different routes of administration (ie, subcutaneous vs intravenous) and dosing schedules (ie, weekly vs daily) of cladribine have also been evaluated. Subcutaneous and intravenous injection has resulted in similar response rates; however, subcutaneous cladribine was associated with a lower rate of viral infections and mucositis despite having a higher rate of neutropenia.3438 In a prospective study, reduced-dose subcutaneous cladribine (total dose, 0.5 mg/kg; given as 0.1 mg/kg/d x 5 days) had a similar efficacy but lower toxicity than standard-dose subcutaneous cladribine (total dose, 0.7 mg/kg; given as 0.1 mg/kg/d x 7 days).37 After a median follow-up of 36 months, CR rates were 63.6% and 73.2%, respectively, for reduced-dose and standard-dose cladribine with no difference in RFS and OS rates. In a retrospective analysis that compared the efficacy and safety of intravenous and subcutaneous injection of cladribine in 49 patients with HCL (18 intravenously, 31 subcutaneously), CR rates were 94% and 97%, respectively.38 After median follow-up of 33.5 months, subcutaneous cladribine was associated with a more favorable 3-year event-free survival rate (96% vs 60%, respectively; P=.104) and a better (although nonsignificant) 3-year OS rate (100% vs 81%, respectively; P=.277) than intravenous cladribine. Neutropenia (grade 3/4; 87% vs 67%), mucositis (grade 1/2; 32% vs 67%), and viral infections (34% vs 78%) were the most frequent complications in the 2 treatment groups, respectively.

Weekly infusion of cladribine was also shown to have similar safety and efficacy to daily continuous infusion.3942 In one study of 100 patients randomized to receive cladribine at standard daily dosing (0.14 mg/kg/d x 5 days) or once-weekly dosing (0.14 mg/kg/d once a week x 5 weeks), the overall response rate (ORR) after 10 weeks was 78% and 68%, respectively.42 There were no significant differences in toxicity profile between the treatment arms after 10 weeks (grade 3/4 neutropenia, 90% vs 80%; acute infection, 44% vs 40%; and erythrocyte support, 22% vs 30%, respectively).

Long-term follow-up data from previous clinical studies suggest that treatment with interferon-alfa (induction and maintenance therapy) results in durable disease control.4345 However, with the advent of purine analogues, the role of interferon-alfa as initial treatment for HCL is very limited. It may, however, be useful for the management of relapsed or refractory (R/R) disease.

Rituximab in combination with purine analogues has also been shown to be effective in previously untreated HCL, but it has not been evaluated extensively in this patient population. In a phase II study that included 59 patients with previously untreated HCL, cladribine followed by rituximab resulted in a CR rate of 100%.46 After a median follow-up of 60 months, 5-year failure-free survival (FFS) and OS rates were 94.8% and 96.8%, respectively.

R/R Therapy

Pentostatin and cladribine are also effective for the treatment of relapsed HCL.22,24,25 In the long-term follow-up of a phase III randomized study that evaluated pentostatin and interferon-alfa, among the 87 patients who crossed over to pentostatin after failure of initial interferon treatment, 5- and 10-year OS rates 93% and 85%, respectively; corresponding RFS rates were 84% and 69%, respectively.22 Retreatment with the same purine analogue may yield a reasonable duration of disease control in patients with relapsed HCL after an initial durable remission to purine analogue therapy.29,32 In the long-term follow-up of a study that evaluated cladribine as initial treatment, relapse occurred in 37% of initial responders, with a median time-to-relapse of 42 months.29 Among those with relapsed disease who received retreatment with cladribine, the CR rate after both first relapse was 75% (median duration of response, 35 months) and after subsequent relapse was 60% (median response duration, 20 months).

Given the observation that retreatment with purine analogues resulted in shorter remission durations with each successive treatment, the use of rituximab in combination with purine analogues has been evaluated in patients with R/R HCL.46,47 In a phase II study that included 14 patients with relapsed HCL, cladribine followed by rituximab resulted in a CR rate of 100%.46 After a median follow-up of 60 months, 5-year FFS and OS rates were 100%. In a retrospective study of 18 patients with pretreated HCL relapsing after purine analogue monotherapy (median of 2 prior therapies), rituximab in combination with pentostatin or cladribine resulted in a CR rate of 89%.47 CR was maintained in all patients after a median follow-up of 36 months, and the estimated 3-year recurrence rate was 7%.

Rituximab monotherapy has modest activity in HCL that has relapsed after initial treatment with a purine analogue.4851 In a small cohort of 10 patients with HCL that progressed on prior therapy with cladribine or pentostatin, rituximab monotherapy resulted in an ORR of 50%, with CR in only 10% of patients.48 In another study of 24 patients with relapsed HCL after prior therapy with cladribine, rituximab induced an ORR of only 25%, with a CR in 13% of patients.49 In a smaller study of 15 patients with relapsed or primary refractory HCL after treatment with purine analogues, 8 weekly doses of rituximab (vs standard 4 weekly doses) resulted in ORR and CR rates of 80% and 53%, respectively.50 In another phase II study of 25 patients with less-heavily-pretreated HCL that relapsed after cladribine, the ORR and CR rates with rituximab were 80% and 32%, respectively.51

More recently, tyrosine kinase inhibitors such as vemurafenib (BRAF V600E kinase inhibitor)5254 and ibrutinib (Bruton tyrosine kinase)55 have demonstrated activity in R/R HCL. Vemurafenib, 960 mg twice daily, was evaluated in 2 separate phase II multicenter studies for R/R HCL (28 patients in the Italian trial and 26/36 planned patients in the US trial).52 The ORR was 96% (CR, 35%) after a median of 8 weeks therapy in the Italian trial and 100% (CR, 42%) after a median of 12 weeks therapy in the US trial. In the Italian trial, after a median follow-up of 23 months, the median RFS was longer for patients who achieved CR versus PR (19 vs 6 months, respectively). In the US trial, at 1 year, progression-free survival (PFS) and OS rates were 73% and 91%, respectively. Grade 1/2 rash and arthralgia or arthritis were the most common adverse events leading to dose reductions. In another phase II trial of 22 patients with R/R HCL, vemurafenib in combination with rituximab resulted in a CR rate of 86% after 4 weeks, which is higher than that observed with vemurafenib alone.53 In addition, minimal residual disease (MRD; measured by immunophenotyping and by allelespecific PCR) was undetectable in 73% of patients.

In a phase II study of 28 patients with relapsed HCL (17 patients with classic HCL), ibrutinib resulted in an ORR of 46%.55 At median follow-up of 22 months, the estimated 24-month PFS rate was 79% (median PFS not reached). Lymphopenia (21%), neutropenia (18%), lung infection (18%), thrombocytopenia (14%), hypertension (11%), and hypophosphatemia (11%) were the most common grade ≥3 adverse events. Grade 1/2 atrial fibrillation was observed in 5 patients, but no grade ≥3 atrial fibrillation or bleeding was reported. The benefit and risk of ibrutinib should be evaluated in patients requiring antiplatelet or anticoagulant therapies.

Treatment Guidelines

The current NCCN Guidelines apply to patients with classic HCL. At the present time, there is insufficient data to determine the optimal management of patients with HCLv. Participation in a clinical trial and referral to a medical center with expertise in the management of these patients is recommended.

Initial Treatment

Clinical judgement is required in the decision to initiate therapy, because not all patients with newly diagnosed HCL will require immediate treatment. Indications for treatment initiation may include symptomatic disease with excessive fatigue; physical discomfort due to splenomegaly/hepatomegaly; unexplained weight loss (>10% within prior 6 months); cytopenias (hemoglobin <11g/dL, platelets <100,000/mcL, and/or absolute neutrophil count <1000/mcL); progressive lymphocytosis; or lymphadenopathy.2

Asymptomatic disease is best managed by close observation (ie, “watch and wait” approach) until indications develop. First-line therapy with purine analogues (cladribine or pentostatin) is recommended for patients with indications for treatment. Both agents have shown significant activity, resulting in durable remissions in patients with previously untreated HCL. However, data from randomized controlled trials are not available to compare the efficacy of one purine analogue to the other. Due to the high response rates of purine analogue monotherapy, the role of rituximab in patients with untreated HCL is unclear and is thus generally not recommended as initial treatment.

Standard-dose purine analogues should not be administered to patients with active, life-threatening, or chronic infection. Active infection should be treated before initiating treatment with standard-dose purine analogues. If it is not possible to control infection, initiating treatment with low-dose pentostatin should be considered to secure a durable response before using standard-dose purine analogues.2

Response Assessment and Additional Therapy

CR is defined as normalization of blood counts (hemoglobin >11 g/dL without transfusion, absolute neutrophil count >1,500/mcL, platelets >100,000/mcL), absence of HCL cells by morphological examination of bone marrow biopsy or peripheral blood samples, regression of splenomegaly by physical examination, and absence of disease symptoms.2 Available evidence suggests that achievement of a CR is associated with a longer duration of RFS.25,33 The clinical relevance of MRD status in patients whose disease responds to therapy remains uncertain at this time. In a phase II study that evaluated cladribine followed by rituximab in patients with previously untreated and relapsed HCL, undetectable MRD status was achieved in 94% of patients at the end of treatment.46 However, MRD-positivity during follow-up did not necessarily result in clinically relevant risk for relapse.

Observation until indications for additional treatment (eg, disease relapse) is recommended for patients who achieve a CR with initial purine analogue therapy. Enrollment on a clinical trial and treatment with an alternate purine analogue ± rituximab, interferon-alfa, or rituximab monotherapy (if unable to receive a purine analogue) are included as options for patients with less than a CR to initial therapy.

Second-Line Therapy for R/R or Progressive Disease

Treatment options for patients with R/R HCL depend on the quality and duration of remission to initial therapy. Patients with disease relapse ≥2 years after achieving CR to initial therapy with a purine analogue may benefit from retreatment with the same purine analogue with or without rituximab. Other options include treatment with an alternative purine analogue with or without rituximab or rituximab monotherapy (if unable to receive a purine analogue). Enrollment on a clinical trial, and treatment with an alternate purine analogue ± rituximab, interferon-alfa, or rituximab monotherapy (if unable to receive purine analogue) are included as options for patients with disease relapse within 2 years after achieving CR to initial therapy.

Clinical trial, ibrutinib, or vemurafenib with or without rituximab are appropriate options for progressive disease after second-line therapy.

Supportive Care

Infections: Patients with HCL are susceptible to infectious complications due to treatment with purine analogues.56 Acyclovir or an equivalent is recommended for herpes virus prophylaxis and sulfamethoxazole trimethoprim or an equivalent is recommended for pneumocystis jiroveci pneumonia prophylaxis.57 Anti-infective prophylaxis for a minimum of 2 months and until CD4 count is ≥200 cells/mm3 is recommended for all patients requiring treatment. Broad-spectrum antibacterial prophylaxis should be considered for patients with neutropenia. Available evidence suggests that the use of use granulocyte-colony stimulating factors (GCSF) shortens the duration of severe neutropenia after treatment with cladribine; however, it has no clinically significant impact on infection-related outcomes.58 The use GCSFs might be considered in patients with severe neutropenic fever after chemotherapy.

HBV Reactivation: HBV reactivation leading to fulminant hepatitis, hepatic failure, and death have been reported in patients receiving chemotherapy and immunosuppressive therapy.59 HBV prophylaxis and monitoring is recommended in high-risk patients receiving rituximab and purine analogues. Hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) testing, and hepatitis B e-antigen (in patients with risk factors or previous history of HBV) is recommended for all patients receiving immunotherapy and/or chemotherapy. In patients who test positive for HBsAg and/or HBcAb, baseline quantitative PCR for HBV DNA should be obtained to determine viral load, and consultation with a gastroenterologist is recommended. A negative baseline PCR, however, does not preclude the possibility of reactivation. Monitoring hepatitis B viral load with PCR monthly during treatment and every 3 months thereafter is recommended. Entecavir is more effective than lamivudine for the prevention of HBV reactivation associated with rituximab-based chemoimmunotherapy.60 Lamivudine prophylaxis should be avoided due to the risks for the development of resistance. Prophylactic antiviral therapy is recommended for patients who are HBsAg+. Prophylactic antiviral therapy is preferred for patients who are HBcAb+. However, if there is a concurrent high-level hepatitis B surface antibody, these patients may be monitored for serial hepatitis B viral load.

Individual Disclosures for Hairy Cell Leukemia Panel

T1

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    RobakTJamroziakKGora-TyborJ. 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. Blood2007;109:36723675.

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    • Export Citation
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    ZenhausernRSchmitzSFSolenthalerM. Randomized trial of daily versus weekly administration of 2-chlorodeoxyadenosine in patients with hairy cell leukemia: a multicenter phase III trial (SAKK 32/98). Leuk Lymphoma2009;50:15011511.

    • Search Google Scholar
    • Export Citation
  • 43.

    FedericoMFrassoldatiALamparelliT. Long-term results of alpha interferon as initial therapy and splenectomy as consolidation therapy in patients with hairy cell leukemia. Final report from the Italian Cooperative Group for HCL. Ann Oncol1994;5:725731.

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    • Export Citation
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    DamasioEEClavioMMasoudiB. Alpha-interferon as induction and maintenance therapy in hairy cell leukemia: a long-term follow-up analysis. Eur J Haematol2000;64:4752.

    • Search Google Scholar
    • Export Citation
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    BenzRSicilianoRDStussiGFehrJ. Long-term follow-up of interferon-alpha induction and low-dose maintenance therapy in hairy cell leukemia. Eur J Haematol2009;82:194200.

    • Search Google Scholar
    • Export Citation
  • 46.

    ChiharaDKantarjianHO'BrienS. Long-term durable remission by cladribine followed by rituximab in patients with hairy cell leukaemia: update of a phase II trial. Br J Haematol2016;174:760766.

    • Search Google Scholar
    • Export Citation
  • 47.

    ElseMDeardenCEMatutesE. Rituximab with pentostatin or cladribine: an effective combination treatment for hairy cell leukemia after disease recurrence. Leuk Lymphoma2011;52(Suppl 2):7578.

    • Search Google Scholar
    • Export Citation
  • 48.

    LauriaFLenociMAnninoL. Efficacy of anti-CD20 monoclonal antibodies (Mabthera) in patients with progressed hairy cell leukemia. Haematologica2001;86:10461050.

    • Search Google Scholar
    • Export Citation
  • 49.

    NievaJBethelKSavenA. Phase 2 study of rituximab in the treatment of cladribine-failed patients with hairy cell leukemia. Blood2003;102:810813.

    • Search Google Scholar
    • Export Citation
  • 50.

    ThomasDAO'BrienSBueso-RamosC. Rituximab in relapsed or refractory hairy cell leukemia. Blood2003;102:39063911.

  • 51.

    ZenhausernRSimcockMGratwohlA. Rituximab in patients with hairy cell leukemia relapsing after treatment with 2-chlorodeoxyadenosine (SAKK 31/98). Haematologica2008;93:14261428.

    • Search Google Scholar
    • Export Citation
  • 52.

    TiacciEParkJHDe CarolisL. Targeting mutant BRAF in relapsed or refractory hairy-cell leukemia. N Engl J Med2015;373:17331747.

  • 53.

    TiacciEDe CarolisLZajaF. Vemurafenib plus rituximab in hairy cell leukemia: a promising chemotherapy-free regimen for relapsed or refractory patients [abstract]. Blood2016;128:Abstract 1214.

    • Search Google Scholar
    • Export Citation
  • 54.

    DietrichSPircherAEndrisV. BRAF inhibition in hairy cell leukemia with low-dose vemurafenib. Blood2016;127:28472855.

  • 55.

    JonesJAndritsosLKreitmanRJ. Efficacy and safety of the Bruton tyrosine kinase inhibitor ibrutinib in patients with hairy cell leukemia: stage 1 results of a phase 2 study [abstract]. Blood2016;128:Abstract 1215.

    • Search Google Scholar
    • Export Citation
  • 56.

    TadmorT. Purine analog toxicity in patients with hairy cell leukemia. Leuk Lymphoma2011;52(Suppl 2):3842.

  • 57.

    CooleyLDendleCWolfJ. Consensus guidelines for diagnosis, prophylaxis and management of Pneumocystis jirovecii pneumonia in patients with haematological and solid malignancies, 2014. Intern Med J2014;44:13501363.

    • Search Google Scholar
    • Export Citation
  • 58.

    SavenABurianCAdusumalliJKoziolJA. Filgrastim for cladribine-induced neutropenic fever in patients with hairy cell leukemia. Blood1999;93:24712477.

    • Search Google Scholar
    • Export Citation
  • 59.

    Di BisceglieAMLokASMartinP. Recent US Food and Drug Administration warnings on hepatitis B reactivation with immune-suppressing and anticancer drugs: just the tip of the iceberg?Hepatology2015;61:703711.

    • Search Google Scholar
    • Export Citation
  • 60.

    HuangHLiXZhuJ. Entecavir vs lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial. JAMA2014;312:25212530.

    • Search Google Scholar
    • Export Citation

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    Version 2.2018, 09-26-17 ©2017 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

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    Hairy Cell Leukemia, Version 2.2018

    Clinical trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged. All recommendations are category 2A unless otherwise indicated.

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    DamasioEEClavioMMasoudiB. Alpha-interferon as induction and maintenance therapy in hairy cell leukemia: a long-term follow-up analysis. Eur J Haematol2000;64:4752.

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    ElseMDeardenCEMatutesE. Rituximab with pentostatin or cladribine: an effective combination treatment for hairy cell leukemia after disease recurrence. Leuk Lymphoma2011;52(Suppl 2):7578.

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    • Export Citation
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    LauriaFLenociMAnninoL. Efficacy of anti-CD20 monoclonal antibodies (Mabthera) in patients with progressed hairy cell leukemia. Haematologica2001;86:10461050.

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    NievaJBethelKSavenA. Phase 2 study of rituximab in the treatment of cladribine-failed patients with hairy cell leukemia. Blood2003;102:810813.

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    ThomasDAO'BrienSBueso-RamosC. Rituximab in relapsed or refractory hairy cell leukemia. Blood2003;102:39063911.

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    TiacciEParkJHDe CarolisL. Targeting mutant BRAF in relapsed or refractory hairy-cell leukemia. N Engl J Med2015;373:17331747.

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    TiacciEDe CarolisLZajaF. Vemurafenib plus rituximab in hairy cell leukemia: a promising chemotherapy-free regimen for relapsed or refractory patients [abstract]. Blood2016;128:Abstract 1214.

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    • Export Citation
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    DietrichSPircherAEndrisV. BRAF inhibition in hairy cell leukemia with low-dose vemurafenib. Blood2016;127:28472855.

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    JonesJAndritsosLKreitmanRJ. Efficacy and safety of the Bruton tyrosine kinase inhibitor ibrutinib in patients with hairy cell leukemia: stage 1 results of a phase 2 study [abstract]. Blood2016;128:Abstract 1215.

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    • Export Citation
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    TadmorT. Purine analog toxicity in patients with hairy cell leukemia. Leuk Lymphoma2011;52(Suppl 2):3842.

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    CooleyLDendleCWolfJ. Consensus guidelines for diagnosis, prophylaxis and management of Pneumocystis jirovecii pneumonia in patients with haematological and solid malignancies, 2014. Intern Med J2014;44:13501363.

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    • Export Citation
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    SavenABurianCAdusumalliJKoziolJA. Filgrastim for cladribine-induced neutropenic fever in patients with hairy cell leukemia. Blood1999;93:24712477.

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    Di BisceglieAMLokASMartinP. Recent US Food and Drug Administration warnings on hepatitis B reactivation with immune-suppressing and anticancer drugs: just the tip of the iceberg?Hepatology2015;61:703711.

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    HuangHLiXZhuJ. Entecavir vs lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial. JAMA2014;312:25212530.

    • Search Google Scholar
    • Export Citation

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