Proliferation studies on chromosome preparations of bone marrow in hematological disease

Abstract

The growth rate of neoplastic cells has been the subject of numerous scientific and diagnostic approaches. The study presented here analyses the relationship between mitotic activity in standardised cytogenetic bone marrow preparations from three haematological diseases and diagnostic and clinical parameters, most importantly the outcome. The disorders studied were: Acute lymphoblastic leukemia (ALL) (N=107), chronic myeloid leukemia (CML) (N=166) and aplastic anemia in childhood (AA) (N=39). A strict protocol of quantitative standardisation of cytogenetic slides was adhered to ensuring comparability both cross-sectionally and longitudinally. The samples were studied after short-term incubation without mitogenic in vitro stimuli. The most important findings include: i) ALL: Immunological subtypes can be differentiated according to their proliferation profile; there is a striking difference between childhood and adult ALL in proliferation activity; most importantly initial proliferation is much higher in patients who will relapse than in those with stable remission. ii) CML: Philadelphia-positive CML shows proliferation activities quite distinct from Philadelphia-negative CML; however there is only a small change in the proliferative activity from the chronic phase to the accelerated phase or blast crisis. iii) AA: Very low proliferation scores rise quickly to near normal levels during immunosuppressive therapy in most patients. Higher levels at diagnosis are associated with a faster and better response to therapy. In conclusion, assessment of the proliferative activity in cytogenetic preparations made from bone marrow samples of patients with haematological disease may add valuable information as to diagnostic sub-groups and clinical course and may contribute to therapeutic decisions.