In vitro chemosensitivity testing of selected myeloid cells in acute myeloid leukemia.
In several studies different chemosensitivity assays have been examined in acute myeloid leukemia (AML). Some have shown that in vitro chemosensitivity testing is an independent prognostic factor but so far no one has been able to show that the use of these methods can improve treatment outcome. In an attempt to improve in vitro chemosensitivity testing in AML we wanted to establish and evaluate a new flow cytometry chemosensitivity assay. After 4 days of incubation viable mononuclear myeloid cells were identified by the exclusion of propidium iodide in CD13 or CD33 positive cells. Sixty-eight samples from 64 AML patients were included. In this study, we showed that the flow cytometry method is feasible in AML and we also found some correlations to clinical data. The secondary AML at diagnosis showed an in vitro resistance to etoposide and amsacrine that was significantly higher compared to de novo AML at diagnosis (p = 0.04 and p = 0.02). When AML patients at diagnosis were compared to resistant disease/relapse patients there was a significantly higher effect of ara-C in the diagnosis group (p = 0.03). Responders and non-responders were compared in vitro but we found no significant differences. In vitro mitoxantrone was more effective in multidrug resistance (MDR) negative cells compared to MDR positive cells (p < 0.01). This new method is feasible and makes it possible to selectively evaluate the effect of cytotoxic drugs in myeloid cells. Further studies with a larger group of patients are needed to evaluate the predictive value of the assay.
Möllgård
Lars
L
Department of Hematology, Huddinge University Hospital, S-141 86 Stockholm, Sweden. lars.mollgard@hs.se
Prenkert
Malin
M
Smolowicz
Adam
A
Paul
Christer
C
Tidefelt
Ulf
U
D000208:Acute Disease; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018826:CD13 Antigens / Q000032:analysis; D002452:Cell Count; D002470:Cell Survival; D019008:Drug Resistance, Neoplasm; D005240:Feasibility Studies; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D016130:Immunophenotyping; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000473:pathology*; D022423:Myeloid Cells / Q000473:pathology*; D063268:Sialic Acid Binding Ig-like Lectin 3
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3; D018826:CD13 Antigens