Proliferative Hairy Cell Leukaemia (HCL-v) Resistant to Alpha-Interferon: Clinical, Diagnostic and In-Vitro Cellular...

This report details the clinical and cellular features of a patient with 'proliferative' hairy cell leukaemia (HCL-v) who presented with a WBC count of 345 x 10(9)/1. In contrast to typical HCL, there was no significant clinical response to splenectomy or treatment with alpha-interferon but leucophoresis was found to be important in maintaining a stable WBC count. Additionally, morphological (light and electron microscopy), cytochemical (ANAE +, AcP +, TRAcP -) and immunophenotypic (CDlc +, CDllc +, CD19 +, CD20 +, CD23-, CD25-, FMC7 +, HC2-) studies of HCL-v cells were undertaken together with an extensive analysis of cellular characteristics (including RNA/DNA synthesis) following in-vitro culture. In contrast to typical HCL cells, but in common with CLL/PLL cells, TPA did not induce the 'acquisition' of long fibroblast-like cytoplasmic extensions. However, plasmacytoid features could be induced by culture in the presence of TPA plus the calcium ionophore A23187. Furthermore, although some TRAcP isoenzyme synthesis could be induced by TPA, its level of staining (IEF) did not reach the same intensity as that usually observed for HCL. In-vitro culture studies, with TPA and TPA/A23187 as well as a number of immunomodulators, were also used to examine the rates of immunoglobulin (Ig) and beta(2)-microglobulin (B(2)m) secretion. TPA alone was the most potent stimulator of both Ig and B(2)m production whereas the addition of A23187 to TPA cultures induced a marked suppression of Ig production but only minimally affected B(2)m secretion. For comparison, bryostatin-1, r IFN-lambda, r IL-2 and r TNF were all considerably less effective than TPA in the induction of B(2)m production. These observations further support the contention that HCL-v represents a leukaemia subtype intermediate between HCL and B-PLL and that recognition of this variant is of particular importance in therapeutic management.