ABSTRACT
We evaluated in vitro the inhibitory effect of cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate (DPR) on colony formation by granulocyte/macrophage (CFU-GM) peripheral blood progenitor cells, representing a method to quantitate the toxicity of drugs to the hematopoietic system, and human leukemic cell lines. The results were compared with those obtained exposing cells to cisplatin and carboplatin. Our data showed that while DPR had a significantly better cytotoxic activity than cisplatin and carboplatin against HL60 and K562, and than carboplatin against Molt 4 cells, it showed 12 and 43 times less inhibitory effect on CFU-GM than cisplatin and carboplatin, respectively. These results suggest that the myelosuppressive activity of DPR could be lower than that of cisplatin and carboplatin, and, furthermore, that leukemic cells represent a preferential target for its cytotoxic activity compared to normal committed hemopoietic progenitor cells. All our results speak in favor of a better therapeutic index for DPR than for the other platinum compounds considered here.
Subject(s)
Antineoplastic Agents/pharmacology , Cisplatin/analogs & derivatives , Cisplatin/pharmacology , Hematopoietic Stem Cells/drug effects , Organoplatinum Compounds/pharmacology , Procaine/analogs & derivatives , Procaine/pharmacology , Antineoplastic Agents/adverse effects , Carboplatin/pharmacology , Cisplatin/adverse effects , Colony-Forming Units Assay , Drug Evaluation, Preclinical , Drug Resistance, Neoplasm , Drug-Related Side Effects and Adverse Reactions , Granulocytes/drug effects , Granulocytes/metabolism , HL-60 Cells/drug effects , Humans , In Vitro Techniques , K562 Cells/drug effects , Macrophages/drug effects , Macrophages/metabolism , Organoplatinum Compounds/adverse effects , Procaine/adverse effectsABSTRACT
This article describes two cases of malignant lymphoma in which the finding of a striking epithelioid granulomatosis was the main clinical manifestation at the outset of the patients' history. Despite some suggestive clinical and laboratory data, the final diagnosis of lymphoproliferative disorder was made only after repeated histological studies in both patients. Although the association between a severe granulomatous reaction and a B-cell neoplasm is rare, the latter should be taken into account as a possible primary disease. The pathogenetic mechanisms postulated by the literature as the cause of granulomatous reactions in lymphoproliferative disorders are reported and discussed in relation to the two cases.
Subject(s)
Granuloma/etiology , Lymphoma, Non-Hodgkin/pathology , Bone Marrow Cells/pathology , Epithelial Cells/pathology , Fatal Outcome , Granuloma/pathology , Humans , Male , Middle AgedABSTRACT
The multilineage hematological effects of the chemoprotective agent amifostine suggested administration of the drug to patients with myelodysplastic syndromes. Partial but encouraging responses were seen. The aim of this research was to further evaluate amifostine activity on the hemopoietic progenitor cells of myelodysplastic patients. We determined amifostine effects on in vitro growth of pre-treatment peripheral blood and bone marrow hemopoietic progenitor cells from myelodysplastic patients, and colony forming unit granulocyte-macrophage and burst forming unit erythroid levels in the peripheral blood of 7 myelodysplastic patients during and following a 3-week treatment with amifostine (200 mg/m2 i.v., three times a week). No variations were observed for hemoglobin, platelets, white blood cells and reticulocyte values. The peripheral blood levels of both colony forming unit granulocyte-macrophage and burst forming unit erythroid, however, showed a significant and sustained increase. In vitro a significant effect exerted by the drug was observed in single cases, but the in vitro effect did not predict the in vivo increase of peripheral blood levels of hemopoietic progenitor cells. These results appear to provide evidence that amifostine has a significant impact on early events of hemopoiesis in myelodysplastic patients.
