The effect of cytosine arabinoside on CFU-GM from patients with myelodysplastic syndrome.

CFU-GM clonal growth was examined in bone marrow from patients with myelodysplastic syndrome (MDS) in the presence of Ara-C at 10(-8) M and 4 X 10(-8) M and the response compared to the effect on progenitors from normal subjects. Seventy-three percent of marrow cultures from patients with MDS showed colony growth below the 95% confidence limits for normal subjects in the presence of 10(-8) M Ara-C. At 4 X 10(-8) M Ara-C 43% of marrow cultures had subnormal colony growth. These results suggest that CFU-GM from patients with MDS may have a greater than normal sensitivity to Ara-C.

The effect of etoposide on human CFU-GM.

Etoposide is being used increasingly in the treatment of a variety of malignant conditions and in conjunction with autologous bone marrow transplantation. We have examined the effect of the drug on human CFU-GM as an indication of the response of these bone marrow progenitor cells to measured plasma concentrations. When etoposide is present in the routine assay for 7 days, 50% growth of colony-forming CFU-GM occurs at a concentration of 0.0098 micrograms ml-1. When bovine serum albumin or human serum albumin is present this value is increased to 0.042 and 0.375 micrograms ml-1. Protein binding therefore plays an important part in modifying in vitro response and possibly in vivo response of these progenitor cells to etoposide.

Effect of medium osmolality on the growth of murine continuous marrow cultures.

The effect of medium osmolality was examined in primary, continuous bone-marrow cultures established from TO strain mice. The non-adherent cell population increased exponentially between weeks 2 and 5 and thereafter declined steadily. The number of CFU-GM followed a similar pattern but showed greater variability. The optimum osmolality in 4 week old cultures was found to be about 345 mosmol/kg which was higher than the plasma osmolality (n = 20; mean = 323.3 mosmol/kg; range = 313-331). Maximum non-adherent cell numbers were found at about 345 mosmol/kg (better than half-maximum between 320 and 370 mosmol/kg). CFU-GM numbers in the culture supernatant were maximal at about 355 mosmol/kg (better than half-maximum between 320 and 400 mosmol/kg). An adherent layer developed over a wider range of osmolality than supported granulopoiesis (better than half-maximum between 258 and 402 mosmol/kg). It was necessary to increase the osmolality of Fischer's medium in order to obtain maximum growth.

Effect of adriamycin on CFUGM at plasma concentrations found following therapeutic infusions.

The effect of adriamycin on human and mouse CFUGM was examined at concentrations and times suggested by plasma clearance data derived from the results of a number of published studies. Our results suggest that the high concentrations of drug present in the plasma for short periods of time following infusion are only weakly cytotoxic towards the CFUGM when incubated for similar times. In contrast, there was a considerably greater cytotoxic effect when the drug was examined at low concentrations for periods similar to those described for the terminal phase of adriamycin clearance. The principal metabolite, adriamycinol, was poorly cytotoxic.

Use of logistic regression analysis to improve prediction of prognosis in acute myeloid leukaemia.

The prognostic usefulness of a range of factors has been examined for patients with acute myeloid leukaemia. Although there was a statistical association between some of these factors and remission rate, the association was only partial. To improve the usefulness of the data, multiple logistic regressional analysis was used. The features selected for use in the analysis were age, blood blast count, FAB classification and colony growth pattern. The last three features could be used as categorical variables, since blood blast counts of greater than 100 X 10(9)/1, FAB group 1 and a prolific pattern of colony growth were associated with a low remission rate. Age was used as a continuous variable. Using these features, eight regression groups were defined. Thus when this data for an individual patient is analysed, it is possible to obtain a value for the probability of that patient achieving remission.