中西医结合治疗狼疮肾炎56例疗效观察

目的：探讨中西医结合治疗狼疮肾炎的疗效。方法：将１０６例狼疮肾炎住院病人随机分为中西医结合治疗组（５６例）和单纯西医组（５０例）予以治疗、观察评定疗效。结果：中西医结合组有效率达９３％,复发率７％,不良反应３９％;而对照组有效率为７８％,复发率２２％,不良反应８０％,两组各项对比有显著性差异（Ｐ〈０．０５）。结论：中西医结合治疗组在提高疗效,减少复发和不良反应方向,均显著优于西医组。     

Fever after peripheral blood stem cell infusion in haploidentical transplantation with post-transplant cyclophosphamide

Objective/backgroundNoninfection-related fever can occur after peripheral blood stem cell infusion in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide. The objective of this study was to analyze the incidence of fever and characterize some clinical features of affected patients.MethodsA retrospective case-series study with 40 patients who received haploidentical hematopoietic stem cell transplantation was carried out.ResultsThirty-three patients (82.5%) developed fever; no baseline characteristic was associated with its development. Median time to fever onset was 25.5 h (range, 9.5–100 h) and median peak temperature was 39.0 °C (range, 38.1–40.5 °C). Not a single patient developed hemodynamic or respiratory compromise that required admission to the intensive care unit. Fever was not explained by infection in any case. Ninety-one percent of the febrile episodes resolved within 96 h of cyclophosphamide administration. No significant difference in overall survival, event-free survival, or graft versus host disease-free/relapse-free survival was found in the group of febrile individuals after peripheral blood stem cell infusion.ConclusionFever after peripheral blood stem cell infusion in this clinical setting was common; it usually subsides with cyclophosphamide administration. The development of fever was not associated with an adverse prognosis.     

Myocarditis of Mixed Connective Tissue Disease: Favourable Outcome after Intravenous Pulsed Cyclophosphamide

A 30-year-old woman with mixed connective tissue disease was admitted with Wernicke’s aphasia and progressive dyspnoea with chest pain. Multiple brain infarcts on a computed tomographic scan were compatible with a thromboembolic aetiology. Echocardiography showed marked hypokinesia of the posterior wall, biventricular dilatation and a decreased left-ventricle ejection fraction (40%). A diagnosis of myocarditis was made on myocardial biopsies disclosing interstitial lymphocytic infiltrates and myocardial fibre necrosis. A treatment with steroids and monthly pulsed cyclophosphamide was introduced. The heart function rapidly improved as assessed by a left-ventricle ejection fraction of 55% and remained stable 17 months thereafter. Received: 10 November 1997 / Accepted: 22 June 1998     

Dramatic regression of mesenteric abnormalities demonstrated on angiography following prednisolone and cyclophosphamide combination therapy in a patient with polyarteritis nodosa associated with Sjögren’s syndrome

Abstract

A 63-year-old woman, who had been followed for Sjögren’s syndrome, was admitted due to cryoglobulinemia, leukocytoclastic vasculitis, and mononeuritis multiplexa. In spite of the administration of 60 mg prednisolone, fecal occult blood was strongly positive. The colonoscopy showed multiple colonic ulcers, and a diagnosis of polyarteritis nodosa (PAN) was made because abdominal angiography revealed markedly serpentine and narrowed superior and inferior mesenteric arteries. After steroid pulse therapy and daily oral administration of cyclophosphamide were initiated, her symptoms improved and abdominal angiographic findings were finally normalized. Although there are only three case reports on improvements in abdominal angiographic findings of PAN in the literature, our case and previously reported cases suggest that improvements in angiographic findings may reflect a good prognosis of PAN.     

Efficacy and safety of fludarabine and cyclophosphamide combined therapy in patients with refractory/recurrent B-cell chronic lymphocytic leukaemia (B-CLL)-Polish multicentre study

The aim of this study was to investigate the efficacy of a combination of fludarabine (F) and cyclophosphamide (C) in the treatment of patients with refractory/recurrent B-cell chronic lymphocytic leukaemia (B-CLL). Between November 1999 and December 2001, 63 patients with B-CLL (median age 60 years) received a regimen that consisted of F 25 mg/m² and C 250 mg/m², days 1 - 3, intravenously, every 4 weeks, for a maximum of 6 courses. Response and toxicity were assessed according to current criteria (NCI-WG and WHO). Complete and partial remissions were achieved in 17.5% and 55.6% of patients, respectively; 19% of patients had stable disease and 7.9% of patients showed disease progression. The median follow-up was 16.5 (range 1.5 - 32) months. The median duration of progression-free survival (PFS) has not been reached among patients treated with FC regimen as second-line therapy.The median PFS was 13 (range 8 - 26) months in the 19 responding patients treated with FC regimen as third-line therapy. The most frequent side-effects were neutropenia (45%), thrombocytopenia (42%) and infections (57%). We conclude that the combination of fludarabine and cyclophosphamide demonstrated significant efficacy in pretreated, advanced B-CLL patients, with tolerable toxicity.     

Modulation of thalidomide pharmacokinetics by cyclophosphamide or 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in mice: the role of tumour necrosis factor

Purpose There is considerable current interest in the use of thalidomide as a single agent or in combination with drugs such as cyclophosphamide in the treatment of multiple myeloma and other cancers. Our previous work has shown that thalidomide potentiates the antitumour activity of both cyclophosphamide and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) against murine Colon 38 tumours. In both of these cases, thalidomide extends the half-life (t_1/2) of the other drug. We wished to determine whether cyclophosphamide and DMXAA altered the t_1/2 of thalidomide. Since both thalidomide and DMXAA modulate tumour necrosis factor (TNF), we also wished to determine the role of TNF in this interaction.Methods Mice with Colon 38 tumours were treated with cyclophosphamide (220 mg/kg) and/or thalidomide (20 mg/kg) or DMXAA (25 mg/kg) and thalidomide (100 mg/kg), combinations that have previously demonstrated synergistic activity. Plasma and tumour tissue drug concentrations were analysed by high-performance liquid chromatography. To determine the role of TNF, similar experiments were performed using mice defective in the TNF gene (TNF^–/–) or the TNF receptor-1 gene (TNFR1^–/–).Results Coadministration of cyclophosphamide increased the thalidomide t_1/2 by 3.9- and 3.6-fold, respectively, in plasma and tumour tissue, with a corresponding increase in the concentration-time curve (AUC). The corresponding values following coadministration of DMXAA were 3.0- and 4.6-fold, respectively. Coadministration of cyclophosphamide had similar effects on thalidomide t_1/2 in C57Bl/6, TNF^–/– and TNFR1^–/– mice, while coadministration of DMXAA did not alter the t_1/2 or AUC in TNF^–/– and TNFR1^–/– mice.Conclusions Both cyclophosphamide and DMXAA have a pharmacokinetic interaction with thalidomide, increasing t_1/2 and AUC. TNF mediates the effect of DMXAA on thalidomide pharmacokinetics but not that of cyclophosphamide.This work was supported by the Auckland Medical Research Foundation, the Marsden Fund and the Auckland Cancer Society. Francisco Chung is a recipient of an Asian Development Bank Scholarship.     

Treatment of multiple myeloma: a randomized study of three different regimens

The results of an Italian multicentric trial for treatment of symptomatic Multiple Myeloma (MM) are reported. One hundred and thirty-three previously untreated patients were singled out at random for three different chemotherapy schedules: Melphalan plus Prednisone (M.P.) X 6 monthly cycles; Vincristine plus Melphalan plus Cyclophosphamide plus Prednisone (VMCP) X 6 monthly cycles; Peptichemio, Cyclophosphamide, BCNU. Drugs in this latter schedule were administered sequentially, for a period of six months. Criteria for response, progression and relapse were those of the Southwestern Oncology Group. Fifteen patients in MP chemotherapy (35%) and 20 patients in VCMP chemotherapy (46%) achieved an objective response (decrease of at least 50% in the synthesis index of Monoclonal Component (M.C.], while only 3 out of the other 21 patients assigned to the third schedule responded to treatment. No significant differences were noted in the survival curves in either of the three treatment groups. The 38 responding patients did not receive maintenance therapy; no significant difference was found in remission duration between patients in MP and VCMP arms, with a median duration of 16 months for the whole group. No statistical difference was observed between survival and remission curves of patients with a 'response' (M. spike reduction greater than 75%) and those with 'improvement' (M. spike reduction between 75 and 50%). The authors conclude that the inclusion of Vintristine in a combination chemotherapy does not produce clear survival benefits; a longer induction period (12 cycles) could allow a better differentiation between MP and VMCP regimens.     

Modification of tumor response to cyclophosphamide and irradiation by preirradiation of the tumor bed: prolonged growth delay but reduced curability

The effect of tumor bed irradiation (TBX) on subsequent tumor response to treatment with cyclophosphamide (CY) or further irradiation was studied in mice. Using the growth delay assay, the therapeutic response was enhanced by prior TBX: for example, in mice receiving 3000 rad TBX 1 day before fibrosarcoma cell inoculation, the growth delay from 8 to 12 mm produced by CY (150 mg/kg) was 18.8 days compared with 9.4 days without prior TBX. This effect was independent of time between TBX and tumor cell inoculation over the range 1-56 days. When tumor cure experiments were performed, however, the effect of prior TBX was to decrease significantly the proportion of tumors controlled by either CY or irradiation and to make the dose-response curve for radiocurability less steep. These data are best interpreted by postulating that TBX increases the environmental heterogeneity of tumors growing in preirradiated sites, with an overall net decrease in the cell kill achieved by a given dose of CY or radiation. This results in increased resistance to cure and a lack of dose response. However, the TBX also causes slower regrowth of surviving cells, so that an increase in tumor growth delay is realized. Thus, although eradication of postirradiation recurrences by chemotherapy is compromised, their palliation may actually be enhanced.     

1例环磷酰胺用于合并肺间质纤维化的AASV患者的药学实践

摘 要抗中性粒细胞胞浆抗体(ANCA)相关性小血管炎(AASV)的推荐一线治疗方案为糖皮质激素联合环磷酰胺,而环磷酰胺有明确引起肺间质纤维化(PF)的不良反应,对于临床上合并PF的AASV患者,在选用环磷酰胺时有无禁忌,本文结合1例合并PF的AASV患者环磷酰胺是否该继续使用进行分析。     

Growth pattern of tumor xenografts in wistar rats after treatment with cyclophosphamide,total lymphoid irradiation and/or cyclosporin A

Wistar rats treated with cyclophosphamide, total lymphoid irradiation (TLI and/or cyclosporin A (CSA) develop a state of immune suppression permitting the growth of tumor xenografts. Experiments were carried out on this newly developed model to investigate the growth patterns of a mouse osteosarcoma and a human colon adenocarcinoma. The combination of cyclophosphamide and CSA permitted a limited period of growth of the mouse osteosarcoma with a tumor take rate of 66%. No takes were observed with the human adenocarcinoma. The combination of cyclophosphamide and TLI resulted in a period of immunosuppression followed by recovery of the immune status. During the period of immunosuppression, tumor xenografts showed a 100% take rate. The most efficient immunosuppression was achieved by a combination of cyclophosphamide, TLI and CSA administered on alternate days. Wistar rats subjected to this treatment showed prolonged tolerance to mouse osteosarcoma and human adenocarcinoma xenografts. There was no alteration in the tumor doubling time or histological morphology of the xenografts in the adapted host as compared with those in the donor tumors. The tumor growth curve showed a pattern of of initial growth, a period of stagnation, followed by a steady but slower growth phase. The significance of the results and the advantages of the rat model described in this paper for human tumor xenotransplantation are discussed.