ABSTRACT
High-dose anticancer drugs have been shown to induce an increase in serum erythropoietin (sEpo) levels not mediated by hypoxia. In this study, sEpo was assessed in seven patients who had been administered a course of 5-day leucovorin-modulated 5-fluorouracil (5-FU-LV) as an adjuvant therapy after the removal of colon cancer. During this study, the mean hemoglobin (Hb) concentration stayed at a constant level, peripheral blood (PB) reticulocytes showed an early, sharp decline, and sEpo levels progressively increased for 15 days after the start of chemotherapy. These results appear to indicate that the increase in sEpo, which was not related to anemia, may have followed from the administration of a cytotoxic drug at doses used in routine, clinical practice.
Subject(s)
Erythropoietin/blood , Fluorouracil/administration & dosage , Leucovorin/administration & dosage , Aged , Colonic Neoplasms/drug therapy , Erythropoiesis/drug effects , Female , Humans , Male , Middle Aged , Reticulocyte Count , Time FactorsABSTRACT
Changes of granulocyte macrophage colony forming units (CFU-GM) were assessed in peripheral blood of patients treated with 5-Fluorouracil-Leucovorin adjuvant chemotherapy after removal of colon cancer. The clinical and hematological state of the patients was steady and as far normal as possible. Leucocyte counts did not show significant changes. The mean peripheral blood level of CFU-GM significantly decreased following 5FU-LV infusion, reaching nadir by day 15. These changes of hemopoietic progenitors, not detected by routine hematic cell counts, point to a perturbation of the granulopoietic system by the 5FU-LV association also at doses used in adjuvant chemotherapy.
Subject(s)
Colonic Neoplasms/drug therapy , Fluorouracil/adverse effects , Granulocytes/drug effects , Hematopoietic Stem Cells/drug effects , Leucovorin/adverse effects , Macrophages/drug effects , Aged , Chemotherapy, Adjuvant , Colony-Forming Units Assay , Female , Fluorouracil/antagonists & inhibitors , Fluorouracil/therapeutic use , Humans , Leucovorin/therapeutic use , Male , Middle AgedABSTRACT
Interstitial lung lesions were induced in mice by high-dose methotrexate with high frequency. They appeared early after treatment; their onset, evolution and recovery parallelled those of lesions to the hemopoietic tissues and the intestine. The pathogenesis of methotrexate lung toxicity in mice is discussed. Leucovorin rescue was ineffective in preventing the lung lesions induced by high-dose methotrexate.
Subject(s)
Leucovorin/therapeutic use , Lung Diseases/chemically induced , Methotrexate/toxicity , Animals , Female , Lung/pathology , Lung Diseases/prevention & control , Male , Methotrexate/administration & dosage , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Pulmonary Atelectasis/chemically inducedABSTRACT
Haematologic effects of delayed 16 h administration of leucovorin (LV) following high-dose methotrexate (HDMTX) were analyzed in C57Bl X C3H F1 mice. Results show that 16 h administration of LV significantly reduces the toxic effects of HDMTX on hemopoietic progenitors and bone marrow cells. At 12 days after HDMTX administration, the bone marrow level of CFUs was significantly higher in HDMTX-LV treated mice than in HDMTX treated animals. In comparison with previous data obtained when LV was injected 2 h after HDMTX, the delay in administration of LV does not appear to reduce the protective effect of the vitamin.
Subject(s)
Hematopoietic Stem Cells/drug effects , Leucovorin/administration & dosage , Methotrexate/administration & dosage , Animals , Colony-Forming Units Assay , Drug Administration Schedule , Leucovorin/pharmacology , Leukocytes/drug effects , Methotrexate/antagonists & inhibitors , Mice , Reticulocytes/drug effectsABSTRACT
This study compares the effects of a high dose of methotrexate (HDMTX) to that of a high dose of methotrexate plus leucovorin protection on the hemopoietic stem cells in a murine model. C57BL X C3H F1 mice were treated with a single large bolus (500 mg/kg body weight) of methotrexate or with the same dose of the drug plus leucovorin administered in fractionated doses during the following 24 hr. At 1 to 2 days after the administration of HDMTX, there was a large bone marrow and spleen depopulation of pluripotent stem cells and of committed and recognizable progenitors. At 2 to 3 days, a severe fall of white blood cells and reticulocytes ensued. The recovery process of hemopoietic precursors followed alternate phases of overshooting and secondary falls. Leucovorin administration appeared to protect all stages of hemopoiesis and prevented the severe drops of bone marrow cellularity and stem cell content which followed the HDMTX bolus. However, the effect of leucovorin on peripheral blood cell reduction was less significant. After treatment with HDMTX, the recovery of bone marrow cells and the burst of splenic hemopoietic activity followed a pattern similar in both leucovorin-protected and unprotected animals, but in the former, the increase in stem cells and hemopoietic progenitors appeared to reach higher values and to last longer. In particular, the overshooting of colony-forming units, culture and erythroid, reached a higher peak in leucovorin-treated mice and was more prolonged. Our results indicate that, in HDMTX-treated mice, leucovorin protection involves the earliest stages of hemopoiesis, assuring the maintenance of a satisfactory endowment of stem and progenitor cells.
Subject(s)
Hematopoietic Stem Cells/drug effects , Leucovorin/administration & dosage , Methotrexate/administration & dosage , Animals , Blood Cell Count/drug effects , Bone Marrow/drug effects , Bone Marrow/pathology , Colony-Forming Units Assay , Drug Administration Schedule , Female , Hematopoiesis/drug effects , Male , Mice , Mice, Inbred Strains , Spleen/drug effects , Spleen/pathology , Time FactorsABSTRACT
A report is presented of the effects upon the liver and enteric mucosa of rats treated chronically with azathioprine (AZA) and cyclophosphamide (CY) in equiactive doses three times greater. The groups treated either with equiactive doses of AZA and CY or with doses three times greater of AZA and CY presented limited and moderate morphological alteration in the liver and in the mucosa of the small intestine, while all rats treated with high dose of CY died in the first phase of the experiment.