Hairy cell leukemia (HCL) and hairy cell leukemia variant (HCL-v)

  • Method:
  • Anticoagulant:
  • Recommendation:
  • Method:
    Cytomorphology
  • Anticoagulant:
    EDTA
  • Recommendation:
    obligatory
  • Method:
    Immunophenotyping
  • Anticoagulant:
    EDTA or Heparin
  • Recommendation:
    obligatory
  • Method:
    Chromosome analysis
  • Anticoagulant:
  • Recommendation:
    no
  • Method:
    FISH
  • Anticoagulant:
  • Recommendation:
    no
  • Method:
    Molecular genetics
  • Anticoagulant:
    EDTA or Heparin
  • Recommendation:
    obligatory

Hairy cell leukemia (HCL) is a rare disease, which is usually indolent. The incidence is 0.3/100,000 persons. The main age of onset of the disease is about 50 years. Men fall ill four to five times more frequently than women. Clinically, the disease is usually characterized by pronounced splenomegaly and pancytopenia. Characteristic is the appearance of hairy cells, with fine, hairy-like cytoplasmic spurs.

Classification of Hairy cell leukemia and Hairy cell leukemia variant

According to the WHO classification 2017, hairy cell leukemia belongs to the mature B-cell neoplasms. The central molecular genetic finding today is the BRAF mutation V600E, which is detectable in practically all patients with classic hairy cell leukemia and is helpful in differentiating it from other indolent non-Hodgkin lymphomas. According to the new WHO classification, the variant form of hairy cell leukemia (HCL-v) must be distinguished from hairy cell leukemia (see Table 1).

>90%

of HCL patients have a BRAF V600E mutation

(Oncopedia Guideline HCL)

Table 1: WHO 2017 classification of hairy cell leukemia (HCL) and the variant form of hairy cell leukemia (HCL-v)

(Swerdlow et al. 2017)
Mature B-cell neoplasms

Hairy cell leukemia (HCL)

BRAF V600E-mutant mature memory B-cell

Hairy cell leukemia variant (HCL-v)

Wildtype BRAF

Hairy cell leukemia and its variant form differ especially in clinical and genetic aspects. Patients with HCL-v are older compared to patients with classic hairy cell leukemia, and men are similarly more likely to develop the disease than women (Matutes et al. 2001). However, the most important diagnostic difference is the absence of a BRAF mutation. In contrast to classical hairy cell leukemia, HCL-v shows a more aggressive course with shorter survival times and poorer response to conventional therapy approaches. Despite similarities in phenotype and immunophenotype, there are also differences (see Diagnostics).

Hairy cell leukemia and Hairy cell leukemia variant - Diagnostics

Prognosis of Hairy cell leukemia

The majority of patients with hairy cell leukemia have a normal life expectancy

Classical hairy cell leukemia has a good prognosis in the majority of patients and about 70% of patients have a normal life expectancy (Onkopedia Guideline HCL 2020). The decisive factor is the response to therapy. Patients who achieve complete remission have a significantly better prognosis compared to patients with partial remission (e.g. Else et al. 2009, Rosenberg et al. 2014, Grever et al. 2017, Onkopedia Guideline HCL 2020). It is still controversial whether the risk of secondary tumors is increased (e.g. Maitre et al. 2019). In contrast to classical hairy cell leukemia, HCL-v shows a more aggressive course with shorter survival times (Swerdlow et al. 2017).

Therapy of Hairy cell leukemia

Frequent recurrence despite initial high response rate

The therapy of patients with hairy cell leukemia is usually carried out with purine nucleoside analogues (cladribine, pentostatin), which can also be given in combination with anti-CD20 monoclonal antibodies (rituximab) if necessary (Grever 2010, Grever et al. 2017). Thus, for ~80 - 85% of the patients a permanent complete remission of the disease can be achieved over several years, even if a relapse occurs in about 40 - 50% of the patients (Grever 2010).

New targeted treatment options, especially for patients with relapse, include the use of BRAF and MEK inhibitors (vemurafenib, dabrafenib, trametinib) that inhibit the RAS-RAF-MEK-ERK signaling pathway overactivated by the BRAF V600E mutation. In two clinical trials with vemurafenib, very good response rates were achieved (overall response 96% and 100%, complete remission at 35% and 42%, respectively) (Tiacci et al. 2015, Falini et al. 2016). However, these patients also showed a high rate of recurrence due to the development of resistance to the BRAF inhibitors. Future therapeutic strategies should therefore focus on reducing the development of resistance, for example by using new BRAF inhibitors, combining BRAF and MEK inhibitors or combining BRAF inhibitors with anti-CD20 monoclonal antibodies (Falini et al. 2016). Further therapeutic approaches for relapsed/refractory hairy cell leukemia are the immunotoxin moxetumomab pasudotox, which is directed against CD22, and the bruton tyrosine kinase inhibitor ibrutinib (Maitre et al. 2019).

For patients with the variant form of hairy cell leukemia, the overall response to cladribine monotherapy was below 50%, with a complete remission rate of 8% (Kreitmann et al. 2013). However, by combining cladribine with the anti-CD20 antibody rituximab, the proportion of complete remissions could be increased to 86% when administered sequentially (Chihara et al. 2016) and to 90% when given in combination (Kreitmann et al. 2013). Cladribine/rituximab therapy is therefore currently recommended as first-line therapy (Maitre et al. 2019). Therapeutic options for relapsed/refractory HCL-v include: a repetition of cladribine/rituximab therapy, participation in clinical trials, treatment with moxetumomab pasudotox and treatment with ibrutinib (as monotherapy or combination therapy with the BCL2 inhibitor Venetoclax) (Maitre et al. 2019).

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