In vitro sensitivity of B-CLL cells to fludarabine and interferons.
In this study we evaluated the cytotoxicity of Fludarabine (FAMP) both alone and in combination with alpha and beta interferon (IFN) against B-cells from patients affected by chronic lymphocytic leukemia (CLL). We used an in vitro colorimetric assay based on the bioreduction of the tetrazolium salt XTT by viable cells. Fludarabine concentrations ranging from 0.03 to 30 microM were tested on cells collected from 22 B-CLL patients. For each fludarabine concentration, 800 I.U. of either alpha or beta IFN were added. Interferon alone did not exert any cytotoxic effect, while Fludarabine showed a strong cytotoxicity against B-CLL cells. The concentration of Fludarabine required to induce a 50% cytotoxicity (IC50) was below 3 microM (the achievable serum level after standard dose in vivo administration) for 19 out of 22 patients. After IFNs supplementation to Fludarabine, it was possible to identify three groups of samples. The first in which IFNs addition did not produce almost any significant change in Fludarabine cytotoxicity (13/22), the second in which there was an improvement in FAMP IC50 (6/22), and finally the third group in which IFNs worsened it (3/22). Stage of disease was the only identified factor accounting for these different results. The second group included samples from 5 patients at stage A and one at stage B, while in the third group all three samples were from patients at stage C. Interferon-alpha and -beta induced the same degree of FAMP IC50 variation.(ABSTRACT TRUNCATED AT 250 WORDS)
Di Raimondo
F
F
Institute of Hematology, Ospedale Ferrarotto, University of Catania, Italy.
Palumbo
G A
GA
Romeo
M A
MA
Cacciola
E
E
Milone
G
G
Impera
S
S
Giustolisi
R
R
Cacciola
E
E
D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D002478:Cells, Cultured; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology
D015703:Antigens, CD; D000970:Antineoplastic Agents; D016898:Interferon-alpha; D016899:Interferon-beta; D014740:Vidarabine; C024352:fludarabine