Hairy cell leukemia classification

Overview
Two variants have been described: Hairy cell leukemia-variant, which usually is diagnosed in older men (median age above 70), and a Japanese variant. The non-Japanese variant is more difficult to treat than either 'classic' HCL or the Japanese variant HCL.

Variants
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.

Similar to B-PLL in Chronic Lymphocytic Leukemia, HCL-V is a more aggressive disease which is harder to treat successfully than classic HCL. 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 transformation rate of 5% in the U.K., which is similar to the Ricther's transformation rate for SLVL and CLL. 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 or HCL-J. There is also a Japanese variant, which is more easily treated.