CD154 expression triggered by purine analogues in vitro: Correlation with treatment response and autoimmune events in chronic lymphocytic leukemia.
OBJECTIVE
Despite a fludarabine-based treatment is the first choice of therapy in chronic lymphocytic leukemia (CLL), not all patients achieve a partial or complete response and some of them develop autoimmune manifestations. The aim of this study was to evaluate the influence of CD154 on these adverse effects because CD154 is involved in both B-cell survival and autoimmunity.


METHODS
Peripheral blood mononuclear cells (PBMC) from 36 patients with CLL were cultured in vitro with fludarabine or 2-chlorodeoxyadenosine for 24, 48, and 72 hours.


RESULTS
Seven patients (19.4%) presented CD154 expression in PBMC cultured with purine analogues in vitro for 24 and/or 48 hours, while no expression was found when cultured in media alone. These seven patients showed a decreased apoptotic rate in vitro after purine analogues compared with those patients who did not express CD154 (p = 0.01 for fludarabine; p < 0.001 for 2-chlorodeoxyadenosine). CD154 expression was found to have prognostic value for response to fludarabine in vivo and was associated with the development of autoimmune manifestations (odds ratio = 25; 95% confidence interval = 3.5-166.7; p < 0.001).


CONCLUSIONS
Our preliminary results suggest that CD154 expression in CLL patients, which may be induced by purine analogues, is associated with resistance to fludarabine and with development of autoimmune manifestations.
Citores
Maria Jesus
MJ
Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro Majadahonda, Universidad Autónoma de Madrid, Majadahonda, Madrid, Spain. mjcitores@telefonica.net
Castejon
Raquel
R
Villarreal
Mercedes
M
Rosado
Silvia
S
Garcia-Marco
Jose Antonio
JA
Vargas
Juan Antonio
JA
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology; D015551:Autoimmunity / Q000187:drug effects; D023201:CD40 Ligand / Q000096:biosynthesis*; D002478:Cells, Cultured; D017338:Cladribine / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods; D011379:Prognosis; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; D023201:CD40 Ligand; D017338:Cladribine; D014740:Vidarabine; C024352:fludarabine