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PubMed This is a summary of 18 peer-reviewed journal articles Updated
Hematology

Treatment Strategies for Classic HCL

At a Glance

Classic Hairy Cell Leukemia (HCL) is a slow-growing cancer that may initially be managed with a watch and wait approach. When treatment is needed, frontline therapies like cladribine or pentostatin are highly effective and can lead to deep, durable remissions that last for a decade or more.

Because Classic Hairy Cell Leukemia (HCL) is a slow-growing (indolent) disease, the goal of treatment is not just to clear the cancer, but to do so in a way that maximizes your quality of life over many years. For many patients, treatment is so effective that they achieve deep, durable remissions that last a decade or more [1][2].

The “Watch and Wait” Approach

Not every person diagnosed with HCL needs to start treatment immediately. If you have no symptoms and your blood counts are near normal, your doctor may recommend active surveillance, also known as “watch and wait” [3][4].

This is a standard and safe management strategy. During this time, you will have regular check-ups and blood tests to monitor the disease. Treatment only begins when the leukemia starts to interfere with your health [5][4].

When is it Time for Treatment?

There is no “magic number” on a lab report that says treatment must start today. Instead, doctors look at a combination of factors [6]:

  • Significant Cytopenias: This means your blood counts have dropped to levels that increase your risk of problems (e.g., hemoglobin below 10–12 g/dL, or platelets below 100,000/μL) [7].
  • Recurrent Infections: Frequent fevers or infections that won’t go away often indicate a need for intervention [5].
  • Symptomatic Splenomegaly: An enlarged spleen that causes pain or makes it hard to eat [5].

Frontline Treatment: The Gold Standard

If treatment is necessary, the standard of care involves Purine Nucleoside Analogs (PNAs) [8]. The two primary drugs used are:

  • Cladribine: Usually given as a single 5-to-7-day course, either continuously in the hospital or as daily outpatient infusions [2].
  • Pentostatin: Given as an injection every few weeks for several months [1].

These drugs are remarkably effective, with cladribine alone inducing complete remission in about 72% of patients [9]. Increasingly, doctors may add rituximab (an immunotherapy) to these drugs to achieve an even deeper remission [10].

Important Safety Information During Treatment:
While highly effective, PNAs will cause an initial, temporary worsening of your blood counts. You will likely experience a significant drop in white blood cells and may develop neutropenic fever, which sometimes requires hospitalization. To protect you during this severe immune suppression, your doctor will prescribe prophylactic (preventative) antibiotics and antiviral medications to prevent serious infections like PCP pneumonia or shingles [11].

Options for Relapsed or Refractory HCL

If the leukemia returns (relapses) or does not respond to the first treatment (refractory), there are several highly effective secondary options [12][13]:

  1. Retreatment: If your first remission lasted a long time (typically more than 2–5 years), you may simply repeat a course of purine analogs, often combined with rituximab [14][15].
  2. BRAF Inhibitors: For patients with the BRAF V600E mutation, targeted oral drugs like vemurafenib or dabrafenib can “turn off” the cancer’s growth switch. These are often used when chemotherapy isn’t an option [13][16].
  3. Targeted Combinations: Sometimes BRAF inhibitors are combined with MEK inhibitors (like trametinib) or rituximab to overcome resistance [17]. Additionally, drugs used in other leukemias, like BTK inhibitors (ibrutinib) or BCL2 inhibitors (venetoclax), are increasingly being studied in clinical trials for HCL.

Even if HCL comes back, it remains very treatable, and new targeted therapies continue to improve the long-term outlook for all patients [18].

Common questions in this guide

Why isn't my doctor starting treatment immediately for my Hairy Cell Leukemia?
Because HCL is a slow-growing disease, doctors often use a safe approach called watch and wait. Treatment is only necessary when your blood counts drop significantly or you develop symptoms like recurrent infections or an enlarged spleen.
What is the standard frontline treatment for HCL?
The standard of care involves drugs called Purine Nucleoside Analogs, primarily cladribine or pentostatin. These are highly effective and are sometimes combined with rituximab immunotherapy to achieve deeper remissions.
What side effects should I expect during HCL treatment?
Treatment often causes a temporary worsening of your blood counts, particularly a drop in white blood cells. This increases your risk of neutropenic fever and infections, so your doctor will likely prescribe preventative antibiotics and antivirals to protect you.
What happens if my Hairy Cell Leukemia comes back after treatment?
Relapsed HCL remains highly treatable. Depending on how long your first remission lasted, your doctor may repeat your initial treatment or use targeted therapies like BRAF inhibitors to control the cancer's growth.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Based on my current blood counts and symptoms, why is treatment recommended (or not recommended) at this time?
  2. 2.If we choose 'watch and wait,' how often will I need blood tests and what specific changes would trigger starting treatment?
  3. 3.Which purine analog—cladribine or pentostatin—do you recommend for me, and will it be combined with rituximab?
  4. 4.What are the most common side effects I should expect during and after treatment?
  5. 5.If my leukemia returns in the future, what are the next steps for treatment?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (18)
  1. 1

    Relative survival reaches a plateau in hairy cell leukemia: a population-based analysis in The Netherlands.

    Dinmohamed AG, Posthuma EFM, Visser O, et al.

    Blood 2018; (131(12)):1380-1383 doi:10.1182/blood-2017-12-820381.

    PMID: 29382643
  2. 2

    Prospective long-term follow-up after first-line subcutaneous cladribine in hairy cell leukemia: a SAKK trial.

    Benz R, Arn K, Andres M, et al.

    Blood advances 2020; (4(15)):3699-3707 doi:10.1182/bloodadvances.2020002160.

    PMID: 32777066
  3. 3

    Hairy cell leukemia and COVID-19 adaptation of treatment guidelines.

    Grever M, Andritsos L, Banerji V, et al.

    Leukemia 2021; (35(7)):1864-1872 doi:10.1038/s41375-021-01257-7.

    PMID: 33947938
  4. 4

    Almost a Near Miss: Hairy Cell Leukemia.

    Parkash J, Bansro V, Chhabra GS, Mujahid Z

    Cureus 2023; (15(1)):e33949 doi:10.7759/cureus.33949.

    PMID: 36820110
  5. 5

    Lytic Bone Lesion: An Unusual Presentation of Hairy Cell Leukemia.

    Fasulo SM, Narvaneni S, Kumar V, et al.

    Cureus 2021; (13(1)):e12959 doi:10.7759/cureus.12959.

    PMID: 33659114
  6. 6

    Expert consensus opinion on the management of hairy cell leukemia in elderly patients.

    Tadmor T, Demeter J, Fagarasanu A, et al.

    Leukemia & lymphoma 2025; (66(14)):2611-2617 doi:10.1080/10428194.2025.2562961.

    PMID: 41069242
  7. 7

    Classic hairy cell leukemia with an aggressive presentation.

    Fugere T, Harley S, Godbole A

    Proceedings (Baylor University. Medical Center) 2021; (34(6)):721-723 doi:10.1080/08998280.2021.1934344.

    PMID: 34733001
  8. 8

    Hairy cell leukemia (HCL) and HCL-like disorders: present, emergent treatment options and future directions.

    Troussard X

    Expert review of hematology 2024; (17(12)):907-915 doi:10.1080/17474086.2024.2427660.

    PMID: 39535173
  9. 9

    A 3-decade multicenter European experience with cladribine as upfront treatment in 384 patients with hairy cell leukemia.

    Broccoli A, Argnani L, Cross M, et al.

    Blood advances 2022; (6(14)):4224-4227 doi:10.1182/bloodadvances.2022007854.

    PMID: 35584397
  10. 10

    Long-term follow-up of patients with hairy cell leukemia in the south of Iran.

    Dehghani M, Kashkooe A, Namdari N, et al.

    Expert review of hematology 2023; (16(4)):289-295 doi:10.1080/17474086.2023.2174520.

    PMID: 36709461
  11. 11

    Single-center study of outcomes of patients with hairy cell leukemia who contracted SARS-CoV-2.

    Annunzio K, Ozga M, Huang Y, et al.

    EJHaem 2023; (4(4)):1200-1202 doi:10.1002/jha2.764.

    PMID: 38024604
  12. 12

    Recommendations for the Management of Patients with Hairy-Cell Leukemia and Hairy-Cell Leukemia-like Disorders: A Work by French-Speaking Experts and French Innovative Leukemia Organization (FILO) Group.

    Paillassa J, Maitre E, Belarbi Boudjerra N, et al.

    Cancers 2024; (16(12)) doi:10.3390/cancers16122185.

    PMID: 38927891
  13. 13

    Single agent vemurafenib or rituximab-vemurafenib combination for the treatment of relapsed/refractory hairy cell leukemia, a multicenter experience.

    Yiğit Kaya S, Mutlu YG, Malkan ÜY, et al.

    Leukemia research 2024; (140()):107495 doi:10.1016/j.leukres.2024.107495.

    PMID: 38599153
  14. 14

    Outcome of hairy cell leukemia patients treated with cladribine - a 10-year single-center experience in Pakistan.

    Zahid MF, Mehdi MQ, Ali N

    Hematology, transfusion and cell therapy 2019; (41(2)):134-138 doi:10.1016/j.htct.2018.08.006.

    PMID: 31084763
  15. 15

    Long-term results of the sequential combination of cladribine and rituximab in Hairy cell leukemia.

    Marvin-Peek J, Jen WY, Kantarjian HM, et al.

    Leukemia & lymphoma 2024; (65(9)):1325-1334 doi:10.1080/10428194.2024.2349700.

    PMID: 38749022
  16. 16

    Safety and efficacy of the BRAF inhibitor dabrafenib in relapsed or refractory hairy cell leukemia: a pilot phase-2 clinical trial.

    Tiacci E, De Carolis L, Simonetti E, et al.

    Leukemia 2021; (35(11)):3314-3318 doi:10.1038/s41375-021-01210-8.

    PMID: 33731847
  17. 17

    Patients with relapsed/refractory hairy-cell leukemia.

    Paillassa J, Troussard X

    Cancer reports (Hoboken, N.J.) 2022; (5(3)):e1495 doi:10.1002/cnr2.1495.

    PMID: 34250762
  18. 18

    Vemurafenib and Rituximab in Patients with Hairy Cell Leukemia Previously Treated with Moxetumomab Pasudotox.

    Robak T, Janus A, Jamroziak K, et al.

    Journal of clinical medicine 2021; (10(13)) doi:10.3390/jcm10132800.

    PMID: 34202156

This page explains treatment strategies for Classic Hairy Cell Leukemia for educational purposes only. Always consult your hematologist or oncologist to determine the most appropriate treatment plan for your specific condition.

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