In:
British Journal of Haematology, Wiley, Vol. 110, No. 1 ( 2000-07), p. 188-196
Abstract:
Hepatosplenic γδ + T‐cell lymphoma represents a rare neoplasm of post‐thymic phenotype, characterized by an aggressive clinical course and a poor response to conventional chemotherapy. In the present study, we have examined the cytotoxic effects of the purine analogue 2′‐deoxycoformycin (dCF) on cultured mononuclear cells and purified γδ + tumour cells from bone marrow or peripheral blood of four patients with hepatosplenic γδ + T‐cell lymphoma. At a concentration of 10 µ m , dCF, in the presence of 2′‐deoxyadenosine (dAdo), displayed an early and selective cytotoxic effect on γδ + tumour T cells. After 48 h of in vitro exposure to dCF, the absolute number of viable CD3 + /γδ + tumour T cells was reduced by more than 90% in all samples with respect to control cultures, with absolute counts of viable CD3 + /αβ + lymphocytes being reduced only by 6–40% of the initial cell input. Analysis of cultures after 5 d of exposure to dCF plus dAdo revealed the persistence of normal CD3 + /αβ + T cells, which accounted, however, for only 20–25% of the initial cell input. Accordingly, the combination of dCF (10–100 µ m ) plus dAdo was able to induce a dose‐dependent inhibition of clonogenic growth and [ 3 H]‐thymidine incorporation in purified CD3 + /CD4 − /CD8 − γδ + tumour cells. We also report that one patient with hepatosplenic γδ + T‐cell lymphoma in terminal leukaemic phase showed a striking haematological response to single‐agent dCF given as fourth‐line treatment. In particular, the selective clearance of γδ + tumour T cells in peripheral blood and bone marrow was observed starting after the second course of treatment. Our results suggest that dCF may represent a potentially active drug for the management of this aggressive form of T‐cell lymphoma.
Type of Medium:
Online Resource
ISSN:
0007-1048
,
1365-2141
DOI:
10.1046/j.1365-2141.2000.02129.x
Language:
English
Publisher:
Wiley
Publication Date:
2000
detail.hit.zdb_id:
1475751-5
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