Introduction

Hairy cell leukaemia (HCL) is a rare clonal B-cell chronic lymphoproliferative disorder.¹ Around 1600 new cases are diagnosed in Europe per year.² Without many therapeutic options in the past decades, interferon-alpha was the first substantial therapeutic intervention for this untreatable chronic leukaemia in 1984 with a response rate of 80-90%.³ This treatment was once extremely widely used, but it is now mostly used on pregnant people assigned female at birth (AFAB) or patients who are neutropenic, relapsed/refractory, or fragile and are not suitable for chemotherapy.¹ 

Understanding hairy cell leukaemia

Hairy cell leukaemia (HCL) is a type of rare blood cancer affecting the hematopoietic system leading to the accumulation of abnormal B lymphocytes and is a subdivision of chronic lymphocytic leukaemia (CLL) and it is characterised as a long-term health disorder that often lasts through an individual's entire life. Under a microscope, the leukaemia cells in this particular case appear "hairy," hence the term "hairy cell leukaemia.⁴

This disorder accounts for 2% of lymphoid leukaemia and is broadly classified into two categories, variant (HCLv) and classical (HCLc), with HCLc being the most common type, accounting for around 90-95% of HCL cases. It is a male-dominant disorder with a ratio of 4:1 (people assigned male at birth (AMAB): people AFAB). Patients are generally diagnosed between the ages of 55-58.⁵ Whereas, HCLv is a very uncommon disorder accounting for only 0.4% of CLL, with a median age of 71 years in patients and no gender predominance.² 

HCLc is easily detected since it is mostly caused by a mutation of BRAFV600E that causes constitutive over-activation of the MEK/ERK pathway. HCLv is more difficult to diagnose and is distinguished from HCLc by the absence of several variables, the most significant of which is the absence of the BRAFV600E mutation.⁵

Interferon therapy

Definition and explanation of interferon

Interferons are glycoproteins produced by cells in the body as part of the early immune response to viral infections, particularly at mucosal surfaces, which are crucial sites for pathogen exposure.⁶ Interferon and are synthetic drug and they help our immune system to find and attack viruses and cancers to stop their growth and prevent them from infecting other cells. 

Interferon- is the major type of interferon protein used in HCL cases, however, the and forms are used very rarely and in small number of patients with the disorder as they have been observed to be far less active than Interferon- thus are not mainly taken as a treatment option in HCL. Both Interferon-2a and Interferon-2b are produced using recombinant DNA technology and both the treatments were FDA-approved for HCL in 1986.⁷

Mechanism of action in treating hairy cell leukaemia

Interferon inhibits the growth of aberrant B-cells in HCL by differentiating them into a state where they respond less strongly to growth factors. This makes them less susceptible to a decrease in the growth capacity of the hairy cell band and causes them to divide more slowly than they did initially. 

Interferon proteins have antiviral and antitumor properties. They have the capability to inhibit protein synthesis, deactivate viral RNA, while enhancing phagocytic and cytotoxic mechanisms. Interferons are administered through intramuscular and subcutaneous routes. The most usual method of administration is through intramuscular injections with a dose running from 1-10 million units.⁸ 

Clinical studies and trials supporting interferon use

A study was conducted on 70 patients who were divided into three groups. Group A included patients who were above 65 years of age and receiving front-line interferon-alpha treatment. Group B included patients who were below 65 years of age and had multiple health conditions or women desiring pregnancy.

Group C included patients who had a deteriorated condition after receiving other treatments and were therefore receiving interferon-alpha as a further line of action. Out of the total of 70 patients, 52 (74%) were able to reach a partial remission and 18 (25%) reached a complete remission. These groups had 5-years progression-free survival rates of 95%, 68% and 96%, respectively. These results prove that interferon-alpha is a positive option to consider for patients with HCL.⁹ 

Based on a case study, patients with HCL were treated with recombinant interferon alpha-A. The study involved seven previously untreated cases, and it concluded with nine complete and 17 partial remissions. All patients' peripheral blood haematologic indexes either remained normal or improved. The study's findings revealed that 71% of previously untreated patients achieved complete remission, while only 17% of previously treated patients did.

The median time between diagnosis and the initiation of the treatment was shorter for previously untreated patients than previously treated patients. The study shows that previously untreated patients demonstrated better response rates with shorter time to treatment initiation, lower leukaemia infiltrate, and improvements in spleen and liver condition.¹⁰

Treating HCL in elderly and frail patients can be very challenging. However, interferon-alpha-2a could still be used as a first-line therapy with the hope of positive results. During a health diagnosis, a patient came with a life-threatening condition that included severe neutropenia (low white blood cell count) and splenomegaly (enlarged spleen) with a high risk of splenic rupture.

They opted for monotherapy with pegylated interferon-alpha-2a, and after six months of treatment, the palpable splenomegaly and peripheral hairy cells disappeared without any side effects. Interferon is a potentially effective and safe alternative for elderly patients who are not eligible for therapies like purine analogues or targeted treatments.¹¹

Side effects of interferon therapy

Side effects due to interferon-alpha therapy may occur in almost every organ system and most of the side-effects are dose-dependent. Some of the side effects are as follows.

• Nausea
• Fatigue
• Flu-like syndromes
• Gastrointestinal complaints
• Body pain
• Hematological toxicity
• Weight loss^12,13

FAQs

Can hairy cell leukaemia be cured?

Although hairy cell leukaemia is not curable, it can be controlled with proper treatment and care. Patients who seek help from experienced doctors and receive good therapy can lead a relatively normal life. However, it is worth noting that even after achieving complete remission, there is a chance that the disorder may return.

Can I go through chemotherapy for hairy cell leukaemia?

Chemotherapy is the most common treatment for hairy cell leukaemia. It works by circulating anti-cancer drugs throughout the body to destroy cancer cells while preventing them from multiplying. Two drugs that are commonly used for this disorder are cladribine and pentostatin. 

What are the side effects of hairy cell leukaemia?

The signs and symptoms of hairy cell leukaemia can vary from person to person. Some common symptoms include fatigue, unexplained bruising and bleeding, recurrent infections, fever, night sweats, abdominal discomfort, and weight loss. If you experience any of these symptoms, it's important to seek medical attention as soon as possible. Your doctor can perform a physical exam, blood tests, and bone marrow biopsy to diagnose the disorder and determine the best treatment plan for you.

Summary

Hairy cell leukaemia (HCL) is a long-lasting disorder leading to abnormal B-cell production in the bone marrow. Interferon was the first therapeutic man-made drug that had a high response rate when treating HCL. This therapy was used a lot in the past, however, it is not mostly used on pregnant people AFAB or fragile and elderly patients or patients with neutropenic or worsen stage and who are not suitable for chemotherapy.

Chemotherapy is the first line of action in the general treatment of HCL. There are two types of HCL: HCLv and HCLc. The most prevalent and primary cause of HCL is HCLc. HCLv accounts for only 0.4% of cases of chronic lymphocytic leukaemia. Interferon-alpha is the most common type of interferon protein used in HCL cases.

It helps in controlling the growth of abnormal B-cells and also helps in killing the cancer cells in the bloodstream. This drug is most commonly administered using intramuscular injections. Interferon has frequently assisted patients in achieving either full or partial remission. Interferon therapy does have certain adverse effects, though, including nausea, weight loss, pain, and exhaustion. Patients are advised to contact their doctors if they have any difficulty. Hairy cell leukaemia may not be a curable disorder but it can still be controlled and treated efficiently if the patient commits to the treatment plan.