Response to Treatment in Acute Non‐lymphatic Leukaemia: Prognostic Value of Colony Forming and Colony Stimulating Capacities of Bone Marrow and Blood Cells Compared to Other Parameters

Abstract

Growth of bone marrow and mononuclear white blood cells (MWBC) in soft-agar cultures was studied in 26 patients with untreated acute non-lymphocytic leukaemia (ANLL). Marrow and MWBC from 30 healthy volunteers served as controls. All ANLL patients revealed an abnormal growth in vitro. Patients with an increased number of clones in marrow cultures and large cluster predominance ('excessive growth') responded poorly to therapy with only one of 10 patients entering remission. On the contrary, only two of the 15 patients with a decreased clone number ('low growth') failed to achieve remission. The number of colonies and clusters in both bone marrow and blood cultures was significantly lower at presentation in patients who later entered remission than in those who did not. The correlations between the number of colonies and clusters in the blood and the marrow cultures were statistically significant. No significant correlations were found between prognosis or colony formation, on one hand, and the production of colony stimulating activity (CS)bA), by bone marrow and blood cells of ANLL patients, on the other. Nor could such correlations be found between prognosis, blood cell counts, and age. It is concluded that the growth pattero cytostatic drugs and particularly in selecting patients with a high probability to respond poorly to current cytostatic regimes.

Prognostic value of in vitro growth pattern of colony forming cells in adult acute leukaemia

“…The divergent pattern of blood and marrow culture growth in our patients with AML and ALL (clu) (Beran et al, 1980), AML patients showing an increased number of clones in marrow cultures responded poorly to therapy, but those with a decreased clone number, predominantly clusters, and a high percentage of negative leukaemias achieved significantly more frequent complete remission. In the circulating blood, the situation was opposite to that in bone marrow viz.…”

“…Determination of colony formation has become a useful tool for investigating the abnormal regulation of haematopoiesis. Therefore, several investigators have tried to correlate the in vitro growth pattern of granulopoietic progenitor cells with the prognostic outcome (Keating et al, 1980;Elias & Greenberg, 1977;Moore et al, 1974;Hornsten et al, 1977;Beran et al, 1980;Gustavsson et al, 1981). However, the results have been conflicting due to poor reproducibility and differences in culture technique, sources of colony stimulating activity, classification of growth pattern, therapeutic regimens, selection of patients, and inadequate statistical analysis.…”

Regrowth of granulocyte‐macrophage progenitor cells (GM‐CFC) in suspension cultures of bone marrow depleted of GM‐CFC with 4‐hydroperoxycyclophosphamide (4‐HC)*

“…GM-CFCs were assayed using a standard double layer agar system (14) with colony-stimulating factor present in medium conditioned with human placenta (HPCM) incorporated into underlayer. Bone marrow cells were incorporated in the overlayer.…”

Advances in the management of adult acute myelogenous leukaemia.

“…Samples from patients with acute myelogenous leukaemia produce either poor growth or an increased number of colonies and clusters, and patients whose blood or bone marrow shows an excessive growth pattern with a predominance of clusters respond poorly to treatment. 59 In summary, therefore, the prospects for adults with acute myelogenous leukaemia have changed substantially in recent years. Remission induction rates of 700 % or more are being reported, and the preliminary results ofmarrow transplantation suggest that a cure is possible for those patients who reach remission and have an HLA-matched sibling donor.…”