Hairy Cell Leukemia - Hairy Cell Leukemia Variant - Japanese Variant

Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. It is usually classified as a sub-type of chronic lymphoid leukemia. Hairy cell leukemia makes up approximately 2% of all leukemias, with fewer than 2,000 new cases diagnosed annually in North America and Western Europe combined.

Hairy cell leukemia was originally described as histiocytic leukemia, malignant reticulosis, or lymphoid myelofibrosis in publications dating back to the 1920s. The disease was formally named leukemic reticuloendotheliosis and its characterization significantly advanced by Bertha Bouroncle and colleagues at The Ohio State University College of Medicine in 1958. Its common name, which was coined in 1966, is derived from the "hairy" appearance of the malignant B cells under a microscope. 

Classification

When not further specified, the "classic" form is often implied. However, two variants have been described: Hairy cell leukemia-variant, which usually is diagnosed in men and a Japanese variant. The non-Japanese variant is more difficult to treat than either 'classic' HCL or the Japanese variant HCL. 

Hairy cell leukemia-variant

Hairy cell leukemia-variant, or HCL-V, is usually described as a prolymphocytic variant of hairy cell leukemia. It was first formally described in 1980 by a paper from the University of Cambridge's Hayhoe lab. About 10% of HCL patients have this variant form of the disease, representing about 60-75 new HCL-V patients each year in the U.S. While classic HCL primarily affects men, HCL-V is somewhat more evenly divided between males and females. While the disease can appear at any age, the median age at diagnosis is over 70.

Similar to B-PLL in Chronic Lymphocytic Leukemia, HCL-V is a more aggressive disease. It is less likely to be treated successfully than classic HCL and remissions tend to be shorter. Many treatment approaches, such as Interferon-alpha, CHOP and common alkylating agents like cyclophosphamide provide very little benefit. Pentostatin and cladribine provide some benefit to many HCL-V patients, but with shorter remissions and lower response rates compared to classic HCL. More than half of patients respond partially to splenectomy.

In terms of B cell development, the prolymphocytes are less developed than lymphocyte cells or plasma cells, but are still more developed than their lymphoblastic precursors.

HCL-V differs from classic HCL principally in these respects:

• High white blood cell counts, sometimes in excess of 100,000 cells per microliter;
• More aggressive course of disease that requires more frequent treatment;
• Cells with an unusually large nucleolus for their size;
• Little excess fibronectin (which is produced by classic hairy cells) to interfere with bone marrow biopsies; and
• Low or no expression of CD25 (also called the Interleukin-2 [IL-2] receptor alpha chain or p55) on cell surfaces.

The lack of CD25, which is part of the receptor for a key immunoregulating hormone, may explain why HCL-V cases are normally resistant to treatment by immune system hormones.

HCL-V, which has a high proportion of hairy cells without a functional p53 tumor suppressor gene, is somewhat more likely to transform into a higher-grade disease, with Daniel Catovsky suggesting a typical transformation rate of 5% in the U.K., which is similar to the Richter's transformation rate for SLVL and CLL and reporting 6% in one group of patients. Among HCL-V patients, the most aggressive cases normally have the least amount of p53 gene activity. Hairy cells without the p53 gene tend, over time, to displace the less aggressive p53+ hairy cells. 

Hairy cell leukemia-Japanese variant

Hairy cell leukemia-Japanese variant or HCL-J. There is also a Japanese variant, which is more easily treated. Treatment with cladribine has been reported.

Wikipedia