A 57-year-old female patient, admitted for an acute abdominal syndrome, was found to have an extensive proliferation of mast cells both in the peripheral blood and the bone marrow. Cytochemical studies confirmed the mast cell characteristics of the pathological cell population, while the immunophenotype strongly suggested a bone marrow origin of this malignancy. The course of the disease was not affected by antiproliferative treatment and the patient, after progressive general deterioration, died of intractable haemorrhage. On both clinical and haematological criteria it seems possible to distinguish this rare case of primary mast leukaemia from the more common form of tissue mastocytosis with secondary leukaemia.
In a group of 14 patients with primary thrombocythaemia (PT) the study of erythropoietic colony formation in vitro showed the development of so-called 'endogenous' colonies, namely colonies with no added erythropoietin (Ep), in all but one case. In the presence of added Ep the colony formation increased slightly in the PT group, but the rise in the control group was so pronounced that any statistical difference between the two groups disappeared. No 'endogenous' colonies were observed in cases of secondary thrombocytosis. This finding reinforces the view that PT is a myeloproliferative disorder and establishes that some erythroid progenitors show the same high sensitivity to Ep as that found in polycythaemia vera; it is of interest that, in the patients studied, there was no apparent involvement of erythropoiesis.
Summary.-The activity against murine anaplastic MT tumours of the chemotherapeutic agent melphalan, either alone or in combination with one of 6 nitroimidazole compounds, was assayed using an in vivo-in vitro tumour excision assay. The melphalan alone proved cytotoxic to the tumour, whereas relatively little cytotoxicity was produced by any of the nitroimidazoles alone. When the nitroimidazole were given in combination with melphalan, dose-modifying potentiation of its cytotoxicity was observed. Maximum potentiation occurred when the nitroimidazoles were given 0-30 min before the melphalan, although some potentiation was still evident when they were given up to 2 h before or after. There was no threshold in nitroimidazole dose required to produce this potentiation, the degree of potentiation increrasing with dose, albeit at a diminishing rate, to give maximum dose-modification factors of about 3.The 6 nitroimidazole compounds in order of increasing effectiveness as potentiators of melphalan activity were: METRO, Ro 05-9963, MISO, RSU 1047, Ro 03 -8800 and Ro 03 -8799. This order corresponds to the increasing electron affinity of these compounds. The most effective compound here, Ro 03-8799, was about twice as effective as the most widely used nitroimidazole in such studies, MISO.
This is a study of in vitro production of erythropoietic colonies from peripheral blood and bone marrow of normal subjects and patients with different polycythaemic conditions. Proliferative stimuli included: 1. Fetal calf serum (FCS) only. 2. FCS plus a source of erythropoietic-stimulating activity (ESA). 3. FCS + ESA + erythropoietin (Ep). It was found that normal subjects and patients with secondary polycythaemia (SP) exhibited full colony growth only in the presence of both ESA and Ep, while patients with primary proliferative polycythaemia (PPP) showed colony production with FCS alone, further enhanced in the presence of ESA and Ep. A group of patients with idiopathic erythrocytosis (IE), namely with an increase of red cell mass not accompanied by other signs of myeloproliferative disorder, and without underlying cause, showed a heterogeneous response to ESA which in some patients was significantly greater than in normal subjects or in SP patients. It appears therefore that sensitivity of erythropoietic colony formation to Ep and ESA may be helpful in differentiating among various forms of polycythaemia; this study also establishes the heterogenicity of the IE group.
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