Understanding Hairy Cell Leukemia: A Rare Chronic Blood Cancer

Author: Pratham Sarkar

Credits: Hairy Cell Leukemia Foundation

Hairy Cell Leukemia (HCL) is a rare, slow-growing cancer of the blood in which the bone marrow produces too many B lymphocytes (a type of white blood cell). The cancerous cells, which have "hair-like" projections under the microscope, interfere with the usual production of blood cells and accumulate in the bone marrow, spleen, and liver. Although rare, with about 1,000 new cases annually in the United States, it is a well-defined leukemia with high response rates to treatment.

Pathophysiology and Disease Origin

HCL develops from memory B cells, which in normal circumstances take part in long-term immunity. In individuals with HCL, these B cells are cancerous and begin to grow in the bone marrow, interfering with the production of normal red cells, white cells, and platelets. This leads to pancytopenia—low levels of all blood cells—and is the cause of symptoms such as fatigue, recurrent infections, and bruising or bleeding after minor trauma.

The "hairy" look of lymphocytes, which is typical of the disease, is caused by irregular projections from the cell membrane, as viewed under the microscope.

Subtypes of Hairy Cell Leukemia

There are two general forms of HCL:

1. Classic Hairy Cell Leukemia: The most common form is marked by specific cell surface markers (CD19, CD20, CD11c, CD25, CD103, CD123) and the presence of the BRAF V600E mutation, found in nearly all classic cases.

2. Variant Hairy Cell Leukemia (HCL-V): This variant lacks some of the markers of classical HCL, lacks the BRAF mutation, and is less sensitive to standard purine analog therapy. HCL-V often requires more intensive or experimental treatment strategies.

Accurate diagnosis and classification are critical because treatments and responses vary among these subtypes.

Signs, Symptoms, and Diagnosis

Symptoms may develop insidiously, and because of its indolent nature, most patients do not know they are ill until a blood test reveals abnormalities. Classical clinical presentations include:

1. Fatigue and weakness

2. Recurrent infections due to neutropenia

3. Splenomegaly with abdominal pain

4. Easy bruising or bleeding due to thrombocytopenia

5. Night sweats and weight loss (rarely)

Diagnostic workup includes:

1. Blood Tests: Peripheral blood smear can reveal hairy cells.

2. Bone Marrow Biopsy: Assesses the extent of infiltration and cell type.

3. Immunophenotyping: Establishes cell surface markers to classify the disease.

4. Molecular Testing: Detects the BRAF V600E mutation, a valuable biomarker and therapeutic target in classical HCL.

Treatment Options

Hairy Cell Leukemia, while incurable, is very treatable. The majority of patients enjoy long, healthy lives with proper medical care. The following are the traditional treatment options:

1. Purine Analogs: Cladribine (2-CdA) and Pentostatin are the most common first-line therapies, inducing durable remissions in most patients. Cladribine is typically given as a single cycle, either intravenously or subcutaneously.

2. Monoclonal Antibodies: Rituximab, in combination with cladribine, is effective in patients with refractory or relapsed disease. It targets the CD20 marker on B cells.

3. Targeted Immunotoxins: Moxetumomab pasudotox (Lumoxiti) is FDA-approved for treatment in patients who have failed at least two prior systemic treatments. It binds to CD22 on the hairy cells and delivers a bacterial toxin that kills the cancer cells.

4. Monitoring and Disease Management

After successful treatment, patients typically enter remission, although HCL can relapse even years later. Accordingly, careful follow-up is important. Patients are followed with blood work, physical exams, and occasional imaging for signs of relapse.

Interestingly, the blood counts can take several months to recover. Physicians are advised not to diagnose treatment failure too quickly, especially in the face of residual symptoms like cytopenia that are gradually improving.

Living with Hairy Cell Leukemia

Most patients live normal, active lives after treatment. Support from doctors, researchers, advocacy organizations, and peers reduces the emotional toll of a chronic cancer diagnosis. Many patients experience long-term remission after just one or two rounds of treatment.

Hairy Cell Leukemia is a prime example of how orphan diseases can benefit from focused research, patient advocacy, and precision medicine. Though the disease cannot be cured, it can be managed, and most patients proceed to lead long, healthy lives with the treatments available today. Ongoing research—spurred on by organizations like the HCLF—continues to open up new possibilities for patients with this uncommon form of leukemia.

Works Cited

DeMarco, Cynthia. “Hairy Cell Leukemia: 6 Questions, Answered.” MD Anderson Cancer Center, www.mdanderson.org/cancerwise/hairy-cell-leukemia--6-questions--answered.h00-159539745.html.

“Lymphoma Action | Hairy Cell Leukaemia.” Lymphoma Action, 31 May 2023, lymphoma-action.org.uk/types-lymphoma/hairy-cell-leukaemia.

“Understanding Hairy Cell Leukemia.” Hairy Cell Leukemia Foundation, www.hairycellleukemia.org/hairy-cell-leukemia.

“Vemurafenib and Rituximab for Hairy Cell Leukemia - National Cancer Institute.” Www.cancer.gov, 3 June 2021, www.cancer.gov/news-events/cancer-currents-blog/2021/hairy-cell-leukemia-vemurafenib-rituximab.