LONG-TERM FOLLOW-UP OF PATIENTS WITH HAIRY-CELL LEUKEMIA TREATED WITH PENTOSTATIN - LYMPHOCYTE SUBPOPULATIONS AND RESIDUAL BONE-MARROW INFILTRATION

Peripheral blood lymphocyte (PBL) subsets and bone marrow biopsies were analysed in six patients with hairy cell leukaemia (HCL) treated with 2'-deoxycoformycin (pentostatin, DCF) according to a phase II trial of the EORTC Leukemia Cooperative Group. All patients responded to DCF with four complete and two partial remissions according to conventional criteria. Within the PBL subsets, major changes concerned the CD4+ T cells, which during DCF therapy were distinctly suppressed to nadir values of 0.038-0.18 (median 0.126) x 10(9)/l. In five patients these cells returned to normal 3.0-49.5 (median 14.5) months after the last DCF injection. CD8+ cells were decreased to a lesser extent, and NK cell numbers improved during treatment. Bone marrow immunohistology applying the MoAb B-ly7 demonstrated residual hairy cells (HCs) in all of the six patients following DCF treatment with nadir HC numbers of 0.2-3.0% of bone marrow cells. Immunoglobulin gene rearrangement analysis of DNA obtained from these biopsies showed only germline bands, whereas rearranged bands had been present on the pretreatment specimens. Within the observation period of 15.5-54.0 (median 47.0) months after discontinuation of DCF therapy, immunohistology demonstrated a continuous increase in HC numbers in five of the six patients with clonal rearrangement detectable in bone marrow specimens from three of these patients at last follow-up date. Although established on the basis of a small number of patients, these data suggest that DCF treatment as currently employed in HCL is unable to eradicate the malignant B cell clone.