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ABSTRACT: We report a case of steroid-induced acute tumor lysis syndrome and review the literature. A 60-year-old woman was started on steroid therapy for dyspnea due to bilateral pleural effusion and a large mass involving the anterior mediastinum. The final diagnosis was precursor T-lymphoblastic lymphoma-leukemia. Following steroid therapy, the patient developed acute renal failure and laboratory evidence of metabolic changes induced by massive cytolysis. She received vigorous hydration, diuretic and allopurinol therapy, and haemodialysis. Her diuresis, renal function and laboratory data returned to normal within 2 weeks. A review of the medical literature on T-cell lymphoma revealed only one similar case of steroid-induced acute tumor lysis syndrome, a life-threatening metabolic emergency. This risk should be kept into account in the management of patients with lymphoproliferative disorders.
Leukemia and Lymphoma 06/2002; 43(5):1129-32. · 2.58 Impact Factor
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ABSTRACT: Circulating myeloid (CFU-GM) and erythroid (BFU-E) progenitor levels were evaluated weekly throughout 3 courses of treatment with vinorelbine (VNB) ifosfamide (IFO) and filgrastim (G-CSF) with or without addition of cisplatin (DDP) in 20 stage IIIB or IV non small-cell lung cancer patients. In IFO, VNB, DDP-treated patients, BFU-E mobilization in peripheral blood following chemotherapy and G-CSF was completely lacking, in contrast with the patients treated with IFO, VNB plus G-CSF. CFU-GM release, however, was of the same order in the 2 groups of patients. Further investigations are needed to explain why presence of DDP in this chemotherapeutic protocol hinders erythroid progenitor release in peripheral blood.
European Journal Of Haematology 08/1998; 61(1):65-70. · 2.61 Impact Factor
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ABSTRACT: Early diagnosis of local and distant recurrences of colorectal cancer remains difficult and there is no agreement on the effectiveness of follow-up in these patients. The aim of this study is to assess the value of our method of follow-up. We consider 239 patients with colorectal cancer and at least 2 years follow-up following radical resection. A local recurrence appeared in 26 patients (10.9%), a distant metastasis in 41 (17.1%), while in seven (2.9%) local and distant recurrences appeared simultaneously. Local recurrence was detected because of an increase in carcinoembryonic antigen (CEA) level in 15 patients (57.7%), during a scheduled endoscopy in four (15.4%) and because of symptoms in seven (26.9%). In seven patients (26.9%) a radical resection was possible. Distant metastases were detected by CEA levels in 20 patients (48.8%), by ultrasonography (U.S.) in 12 (29.3%) and by chest X-ray in five (12.2%). In 13 of 26 patients with liver metastases a resection was performed. This study shows that few patients benefit from follow-up and only CEA levels and liver U.S. performed intensively between 15 and 36 months after surgery are useful in early detection of recurrences. A modification of the follow-up to the single patient, according to the stage, location and grading of cancer, could improve the results, so lowering the costs of this expensive practice.
European Journal of Surgical Oncology 01/1998; 23(6):522-5. · 2.50 Impact Factor
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R Lerza,
M O Vannozzi,
G Tolino,
M Viale,
G B Bottino, G Bogliolo,
A Cerruti,
G Castello,
M Mencoboni,
G Reggiardo,
I Pannacciulli,
M Esposito
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ABSTRACT: Cisplatin (DDP) and carboplatin (CBDCA) are two of the most effective drugs in a locoregional approach. Since simultaneous combined treatment with intrapleural DDP and CBDCA has not been reported in humans, we investigated its use in patients with malignant effusions, focusing on pharmacokinetics.
The pharmacokinetics of DDP and CBDCA were studied in 10 patients with malignant pleural effusion treated intrapleurally with a combination of DDP (60 mg/m2) and CBDCA (270 mg/m2) and in additional patients who received the same doses of drugs administered intravenously as single agents or in combination. Platinum (Pt) species originating from DDP (metabolites plus unchanged DDP) and intact CBDCA in plasma and pleural fluid ultrafiltrates were measured by means of high performance liquid chromatography and atomic absorption spectrometry.
Both in the plasma and pleural fluid, the total levels of free Pt represented the additive result of the individual concentrations of CBDCA and Pt-species derived from DDP. After intrapleural combination, high pleural-plasma ratios of the peak concentrations and AUCs were observed both for CBDCA and DDP-derived Pt species, highlighting a distinct local pharmacological advantage. However, the Pt species originating from DDP were absorbed more rapidly from the pleural cavity than CBDCA (Ka = 86 x 10(-3) vs. 37 x 10(-3) min-1, P < 0.05). Intrapleural combination of CBDCA and DDP produced therapeutic plasma levels of reactive (free) DDP species and increased the extent of their residence time (MRT) compared with single intravenous DDP treatment [peak concentration: 1.1 +/- 0.1 (SD) vs. 1.6 +/- 0.2 microgram/ml; MRT: 5.2 +/- 1.9 vs. 0.5 +/- 0.06 h]. Furthermore, the plasma AUC of free CBDCA after intrapleural combined treatment (2.1 +/- 0.5 mg/ ml x min) was similar to that after intravenous administration of CBDCA alone (2.1 +/- 0.2 mg/ml x min). The intrapleural treatment was well tolerated by all patients. Toxicity consisted of mild nausea and vomiting (grade 1-2 according to the WHO scale) in four patients. Myelosuppression (grade 1-2) was remarkable only in two heavily pretreated patients. No evidence of recurrence of the pleural effusion was observed in six patients (complete response), while an asymptomatic minimal fluid reaccumulation not requiring drainage (partial response) was observed in four patients.
The pharmacologic results seem to exclude a pharmacokinetic interaction between CBDCA and DDP and suggest that a dose of CBDCA 2-fold higher than that used in this study associated intrapleurally with 60 mg/m2 DDP could induce an acceptable and predictable myelosuppression.
Annals of Oncology 05/1997; 8(4):385-91. · 6.43 Impact Factor
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ABSTRACT: In vitro growth of human normal bone marrow granulocyte-macrophage colony forming units (CFU-GMs) and erythroid burst forming units (BFU-Es) was dose-dependently inhibited by 3'-azido-3'deoxythymidine (AZT) (from 0.1 microM to 4 microM) and 2',3'-dideoxycytidine (ddC) (from 0.01 microM to 1.0 microM). These ranges included minimum in vitro inhibitory concentrations to HIV-1 and concentrations corresponding to plasma level achievable in vivo. A synergistic inhibitory effect, statistically highly significant, was observed when combinations of the two drugs were added to cultures. This severe in vitro toxicity of ddC and the synergistic toxicity of AZT-ddC combinations on hemopoietic progenitor cells should be considered when the two drugs are administered in concurrent or alternating regimens.
Experimental Hematology 04/1997; 25(3):252-5. · 2.90 Impact Factor
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ABSTRACT: Changes in routine hematologic data and in circulating granulocyte-macrophage colony-forming units (CFU-GM) during granulocyte colony-stimulating factor (G-CSF) administration were evaluated in non-small cell lung carcinoma (NSCLC) patients treated with a combination of 5-fluorouracil (5-FU) and cisplatin (DDP) with and without the addition of interferon-alpha (IFN-alpha). The patterns of leukocyte changes following chemotherapy plus G-CSF were similar in both the IFN-alpha-inclusive and the IFN-alpha-devoid courses. However, the twofold increase in CFU-GM observed in patients receiving chemotherapy plus G-CSF was completely absent following the course including IFN-alpha. The activity of G-CSF on the hematologic pattern is seemingly affected by its combination with IFN-alpha treatment. Mechanisms of the possible in vivo interaction among IFNs and hematopoietic growth factors remain to be elucidated.
Journal of Interferon & Cytokine Research 12/1996; 16(11):953-6. · 3.06 Impact Factor
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ABSTRACT: The toxic effects of a combination of 2-chloro-2'-deoxyadenosine (CDA) and interferon alpha (IFN-alpha), with and without addition of interleukin 1 (IL-1) and/or granulocyte macrophage colony stimulating factor (GM-CSF), on the in vitro growth of peripheral blood granulocyte macrophage committed progenitors (CFU-GM) from 10 normal subjects were investigated. CDA concentration ranged from 15.6 nmol/l to 1 mumol/l, IFN-alpha sole concentration was 10 IU/ml. IL-1 and/or GM-CSF were added at concentrations of 2000 pg/ml and 10 ng/ml, respectively. CDA induced a dose dependent inhibitory effect on CFU-GM growth. Addition of IFN-alpha increased CFU-GM inhibition induced by CDA only at lower concentrations of the latter. IL-1 and GM-CSF, separately or in combination, did not counteract the inhibitory activity of the CDA-IFN-alpha combination.
Leukemia Research 10/1996; 20(9):777-80. · 2.92 Impact Factor
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ABSTRACT: This paper reports on the production of tumor necrosis factor (TNF) and granulocyte macrophage colony-stimulating factor (GM-CSF) by cultured mononuclear adherent cells derived from bone marrow of 25 patients affected by myelodysplastic syndrome (MDS) of different FAB subtypes. Mean production of GM-CSF was much lower than in controls, without significant differences among different subtypes. Mean production of TNF was similar in MDS patients and in controls, but noteworthy differences were observed between patients with RA, RAEB and RAEB-t and patients with RARS and CMML. Growth of bone marrow granulocyte macrophage and erythroid progenitors did not correlate with TNF and GM-CSF production, although in MDS subtypes with higher GM-CSF levels, colony growth was slightly higher than in subtypes with lower GM-CSF production.
European Journal Of Haematology 04/1996; 56(3):148-52. · 2.61 Impact Factor
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ABSTRACT: In previous researches recombinant interferon alpha (IFN-alpha) has been demonstrated to significantly control red cell mass and thrombocytemia in patients with polycythemia vera (PV). Further evaluation of drug effectiveness and of modalities of maintenance therapy is warranted. We treated four patients with PV according to PVSG criteria with IFN-alpha (3 MU subcutaneously three times a week) for five months. Thereafter the starting dose was reduced to 1.5 MU three times a week. Treatment with IFN-alpha at the higher dosage induced regression in sizes of the spleen and a return to normal levels of peripheral blood platelets and leukocytes. Phlebotomies, previously performed to keep under control hematocrit values, were no more needed. During maintenance treatment with IFN-alpha reduced dose platelet level remained in the normal range, spleen size did not show further variation but hematocrit slowly rose and phlebotomies had to be resumed. These results confirm IFN-alpha effectiveness in PV, but suggest the need of relatively high dosages of the drug and difficulties in switching to a maintenance treatment.
Recenti progressi in medicina 02/1996; 87(1):7-11.
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ABSTRACT: The in vivo effects of hydroxyurea (HU) on circulating erythroid (BFU-E) and granulocyte-macrophage progenitors (CFU-GM) in patients with polycythemia vera (PV) have been evaluated. HU induced a strong decrease of both BFU-E and CFU-GM in the first month of treatment. During the following 4 months of treatment the level of circulating progenitors remained at very low values, until the end of the period of observation. HU activity involved both erythroid and myeloid committed progenitors and both erythropoietin-stimulated (normal) and endogenous (derived from the abnormal PV clone) BFU-E.
Annals of Hematology 10/1995; 71(3):119-21. · 2.62 Impact Factor
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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.
Experimental Hematology 01/1995; 22(13):1261-3. · 2.90 Impact Factor
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ABSTRACT: In four patients with polycythaemia vera (PV) who received interferon alpha (IFN-alpha) (3 MU subcutaneously three times a week) for 5 months, peripheral blood levels of granulocyte-macrophage colony-forming units and erythroid burst-forming units were assessed monthly. Circulating progenitors significantly decreased throughout the treatment period. Moreover, we observed an inhibitory activity of IFN-alpha on haemopoietic progenitor cells (HPC) from patients with PV in vitro. The data presented confirm previous research which has shown an inhibitory effect of IFN-alpha on HPC from patients with myeloproliferative disorders. Significant improvement in the patients' clinical and haematological conditions should encourage larger studies on IFN-alpha administration in PV patients.
British Journal of Haematology 08/1994; 87(3):621-3. · 4.94 Impact Factor
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ABSTRACT: The authors report a feasibility study of intrapleural cisplatin in a patient with inoperable malignant pleural mesothelioma.
Total and filterable platinum in pleural effusion and in plasma were monitored for two intrapleural courses of 120 mg/m2 cisplatin, and a weekly schedule was adopted. Platinum concentrations in pleural effusion, plasma, and urine were determined by flameless atomic absorption spectroscopy.
A lower peak of filterable platinum in plasma, a decrease in systemic filterable platinum exposure (AUC [area under the concentration-time curve]), and a greater pleural exposure to filterable platinum were observed after Course 2 compared with Course 1. After the second cycle of intrapleural treatment, the systemic AUC for filterable platinum was reduced by 40%.
The authors' findings may have some implications for the clinical use of intrapleural chemotherapy with high doses of cisplatin. Both infusions of cisplatin were generally well tolerated by the patient and were associated with the local pharmacologic advantage of sustained exposure to cisplatin of the pleural cavity. No sign of myelosuppression, neuropathy, or ototoxicity was observed, and acute toxicity consisted of mild nausea, vomiting, and prolonged anorexia. A transient presence of granular casts was the only observed nephrotoxic effect of cisplatin. Excellent local control of the disease with absence of recurrence of the effusion was observed.
Cancer 02/1994; 73(1):79-84. · 4.77 Impact Factor
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ABSTRACT: The ability of procaine hydrochloride (P.HCl) to modulate the effects of cisplatin (DDP) on pluripotent (CFU-S) and committed (CFU-GM) murine hemopoietic stem cells was investigated. DBA/2NCrlBRF1 mice received DDP alone (10 and 16 mg/kg body wt. single i.p. injection) or in combination with P.HCl (40 mg/kg body wt. single i.p. injection). Hemopoietic progenitor cell (HPC) time survival curves were determined up to 14 days following treatment. The simultaneous administration of the lower DDP dose together with P.HCl greatly reduced the hemotoxicity of the antitumoral drug, while this protection was not significant with the higher DDP dose. These results support a role for P.HCl in protecting against DDP hematological toxicity.
Cancer Letters 06/1992; 64(1):55-60. · 4.24 Impact Factor
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ABSTRACT: In the past few years tumor necrosis factor (TNF), also known as cachectin, has been isolated, cloned and now human recombinant TNF is available. This cytokine has numerous actions, which can be divided into four groups: 1) antitumor function; 2) immunomodulating activity and function in the inflammatory response; 3) effects on metabolism; 4) other functions. TNF was first identified for its anticancer activity; it is able to induce hemorrhagic necrosis in subcutaneously implanted tumors, due to the induction of free radicals in tumor cells and to vascular damage. It can also activate T-lymphocytes to become lymphokine-activated killer cells (LAK cells) against tumors. TNF also plays an important role in the inflammatory response: it mediates many of the immunologic features of T-cell function and of infection, and is essential in septic shock. TNF is a cause of the hypertriglyceridemia and the cachexia that characterize chronic infections and neoplasms. In vitro this cytokine causes growth of vascular endothelial cells; this observation suggests that it could have an atherogenic role. In in vivo experiments severe hepatic ischemia-reperfusion injury results in TNF release with subsequent local and systemic injury that was significantly reduced by anti-TNF antiserum pretreatment. Thus, TNF could be a cause of ischemic tissue damage. In conclusion, while TNF is known to play many roles, the intercellular network of the cytokines is not yet sufficiently understood and so we are only just beginning to comprehend the full implication of this important molecule in both histology and pathology.
Recenti progressi in medicina 02/1992; 83(1):15-7.
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ABSTRACT: This study reports the effects of a combination of azidothymidine (AZT) plus acyclovir (ACV) on both pluripotent (spleen colony-forming units, CFU-S) and committed (granulocyte-macrophage colony-forming units, CFU-GM; erythroid burst-forming units, BFU-E) murine hemopoietic progenitors. Administration of AZT alone was associated with severe hemotoxicity, as shown by the marked decrease of all the hemopoietic progenitor populations tested, that is, CFU-S, CFU-GM, and BFU-E. This, however, was followed by a prompt recovery of hemopoiesis. Administration of ACV alone did not modify the hematological parameters studied, whereas the combined administration of AZT and ACV led to changes in peripheral blood cells and bone marrow hemopoietic progenitors that were, on the whole, not significantly different from those observed with AZT alone. Only the decrease in CFU-S was significantly more severe, but their recovery was as rapid as that of the committed progenitors. Thus, in this experimental setting, the addition of ACV to AZT does not appear to increase the hemotoxicity of the latter.
Experimental Hematology 10/1991; 19(8):838-41. · 2.90 Impact Factor
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ABSTRACT: 9 beta-D-Arabinofuranosyladenine (adenine arabinoside, vidarabine, ara-A), is employed as an antiviral compound mainly against herpes virus infections. Toxicity of ara-A is of concern in clinical applications. This work reports quantitative changes of bone marrow hemopoietic progenitors in mice treated with ara-A. The experimental model is based on time survival curves following repeated intraperitoneal injections (200, 400 or 800 mg/kg twice a day for 4 days) of different doses of the drug. Our results show that ara-A causes damage to the hemopoietic progenitors. The induced damage is roughly proportional to the injected amount of the drug. Following termination of ara-A administration all tested populations rapidly recovered.
Chemotherapy 02/1990; 36(3):240-4. · 1.82 Impact Factor
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ABSTRACT: Germinal tumours compose about 1-2% of all human neoplasms. The most common histotypes appear to be seminoma and teratocarcinoma. These are the most frequent neoplasms in 15 to 35 years old males. Up until 15 years ago, the prognosis of these tumours was almost always poor. New combined chemo-radiotherapy approaches permit prolonged survival or a cure in most cases. We describe the case of a patient who benefitted from these new therapeutic protocols. A review of these new treatments is also presented.
Giornale di clinica medica 04/1989; 70(3):187-93.
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ABSTRACT: The toxicity of the antiviral drug 3'-azido-3'-deoxythymidine was studied in vivo on murine hemopoietic progenitor cells and peripheral blood cells. The drug induced a marked decrease of all tested populations, showing a severe toxicity on hemopoiesis.
Experimental Hematology 01/1989; 16(11):938-40. · 2.90 Impact Factor
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ABSTRACT: The possible protective action of sodium-2-mercaptoethanesulfonate (mesna) on hemotoxicity induced by anticancer drugs was tested in normal mice. Mesna (100 mg/kg b.w.) was injected i.v. 1 h before the i.v. administration of cyclophosphamide (10, 120, and 200 mg/kg b.w.), doxorubicin (4.32, 7.2, and 12 mg/kg b.w.) and cis-diamminedichloroplatinum (5.4, 9, and 15 mg/kg b.w.). Results show that in this experimental model mesna does not seem to protect against toxicity of the tested anticancer drug on hemopoietic progenitor cells.
Tumori 07/1988; 74(3):333-7. · 0.86 Impact Factor
