Hairy Cell Leukemia variant

What is Hairy Cell Leukemia variant?

Hairy cell leukemia variant (HCL-V) is an unclassifiable splenic B-cell leukemia/lymphoma. According to the World Health Organization classification of diseases, it is not biologically related to classic hairy cell leukemia. HCL-V is a more aggressive disease than the classic form.

Epidemiology

Hairy cell leukemia variant is a rare disorder accounting for approximately 0.4% of chronic lymphoid malignancies and 10% of all HCL cases. The disease affects the elderly population without sexual predominance. The median age of the patients is 71 years.

Diagnosis

A diagnosis of hairy cell leukemia variant should be established by morphological analysis (referring to the structure and shape of cells) and flow cytometric analysis (referring to a method of measuring certain characteristics of cells) of peripheral blood, bone marrow and/or spleen specimens. The features of hairy cell leukemia variant are intermediate between those of classical HCL and prolymphocytic leukemia (PLL).

Patients with HCL-V have elevated white blood cells as well as unique morphology (structure and shape) and immunophenotype (types of markers on the surface of cells). HCL-V cells are CD19+, CD20+ and CD22+, and are positive for B-cell antigens on flow cytometric analysis. Leukemic cells are also positive for CD103 and CD11c and negative for CD25. In contrast to the classic hairy cell leukemia, patients with HCL-V have no monocytopenia (deficiency of monocytes, a type of immune cell that is made in the bone marrow), and the leukemic leukocytes lack CD25 antigens. Moreover, HCL-V is not associated with the BRAF V600E mutation.

Treatment

There is currently no curative treatment for hairy cell leukemia variant. The results of therapy with cladribine or pentostatin are rather poor. An analysis of 19 cases reported in various treatment centers showed a response rate of 55%, including only two complete remissions. In addition, the majority of HCL-V patients required more than one cycle to maintain a partial remission. Pentostatin induced a partial remission in 8 out of 15 (54%) patients, but no complete remission was observed.

Rituximab alone or splenectomy followed by rituximab therapy can induce complete remission in patients with hairy cell leukemia variant. More recently, cladribine combined with rituximab was found to be more effective than cladribine alone or rituximab alone. Kreitman et al report a case of 10 patients with HCL-V treated simultaneously with cladribine and rituximab. Nine patients (90%) achieved a complete remission with this regimen, compared with 3 of 39 cases (8%) reported in the literature who were treated with cladribine alone. In addition, 7 patients (88%) had a complete remission with minimal residual disease negativity at 12-38 months of follow-up. These results indicate that patients with HCL-V could be initially treated with cladribine combined with rituximab.

Alemtuzumab is an active agent in selected cases with hairy cell leukemia variant. Splenectomy can induce clinical responses and correct cytopenias (lower-than-normal number of blood cells) in some patients with HCL-V. In one study, splenectomy resulted in good partial remission in 2/3 patients. Some case studies indicate that autologous transplantation (blood-forming stem cells are removed, stored, and later given back to the same person) or allogenic hematopoietic cell transplantation (a person receives blood-forming stem cells from a genetically similar, but not identical, donor) can be effective in patients who don’t respond to other treatments.

Moxetumomab pasudotox, an anti-CD22 immunotoxin, was more recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with hairy cell leukemia or hairy cell leukemia variant who received at least two prior systemic therapies, including treatment with a purine nucleoside analog. Approval was based on a clinical study of 80 patients with HCL or HCL variant: 77 with classic HCL and 3 with HCL variant. 41% of patients experienced complete remission (CR) and most CRs were without minimal residual disease, which may cause relapse.

Emerging Drugs

The B-cell antigen receptor (BCR) signal transduction inhibitors, ibrutinib (PCI-32765) and idelalisib (GS-1101, CAL-101), represent a promising new strategy for the treatment of hairy cell leukemia and possibly hairy cell leukemia variant.