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In vitro drug testing in patients with acute leukemia with incubations mimicking in vivo intracellular drug concentrations
Author(s) -
Tidefelt Ulf,
SundmanEngberg Britt,
Rhedin AnnSofie,
Paul Christer
Publication year - 1989
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1989.tb00323.x
Subject(s) - in vivo , anthracycline , incubation , in vitro , cytotoxicity , acute lymphocytic leukemia , acute leukemia , medicine , leukemia , chemotherapy , pharmacology , intracellular , cytotoxic t cell , gastroenterology , biology , lymphoblastic leukemia , cancer , biochemistry , microbiology and biotechnology , breast cancer
The differential staining cytotoxicity (DiSC) assay was evaluated as a predictive test for response to therapy in patients with acute non‐lymphoblastic leukemia. Incubations were designed in such a way that the intracellular concentrations of cytostatic drugs in vitro parallelled those in vivo. Leukemic cells were isolated from 53 patients with acute non‐lymphocytic leukemia. 13 of these patients died early due to supportive care failure and were not evaluable for the predictive drug testing. Of the remaining 40 patients, 25 entered a complete remission (CR) and 15 had a resistant disease (RD). According to the patients randomization to therapy the cells were incubated with anthracyclines and Ara‐C separately and in combination. After 4 days of culturing in liquid medium the in vitro cytotoxicity was determined by dye exclusion according to Weisenthal. The cytotoxic effect in vitro was significantly higher on cells from patients who achieved a CR compared to patients with RD after incubations with anthracyclines 0.2 μmol/l (p ≤ 0.005), Ara‐C 0.5 μmol/l (p ≤ 0.05) and with the combination of anthracyclines with Ara‐C (p ≤ 0.0005). The best predictive value was achieved when incubations with 0.2 μmol/l anthracyclines and 0.5 μmol/l Ara‐C were analyzed together. With these incubations cells from 20 out of 21 patients who achieved CR showed either ≤ 60% surviving cells after the anthracycline incubation or ≤ 35% surviving cells after the Ara‐C incubation. Cells from 11 out of 13 patients with RD did not fulfill either of these criteria. In vitro drug sensitivity was signiñcantly correlated to a prolonged survival (p < 0.01). We conclude that, when performed with incubations that mimic in vivo tumor cell exposure to cytostatic drugs, the DiSC assay shows a high correlation to clinical outcome for patients with acute non‐lymphocytic leukemia.