霉酚酸酯与环磷酰胺治疗重症过敏紫癜性肾炎的疗效比较

目的:比较霉酚酸酯(MMF)与间断环磷酰胺(CTX)静脉冲击疗法治疗重症过敏紫癜性肾炎(HSPN)的临床疗效。方法:39例重症HSPN患者,分别采用激素联合MMF治疗(MMF组,n=21),或采用激素联合CTX间断静脉冲击治疗(CTX组,n=18)。MMF剂量1.5或2g/d,诱导疗程均≥6个月;CTX剂量为0.6～0.75g/m2·体表面积,每月静脉滴注一次,6个月后改为每3个月一次。两组患者基础病情无差异。MMF组失访1例,CTX组失访4例,退出2例。其余患者随访时间≥12个月。疗效指标包括完全缓解、部分缓解、蛋白尿和血尿缓解及复发率。比较观察两组治疗的临床疗效和副作用。结果:①临床缓解率:治疗6、9和12个月时完全缓解率MMF组高于CTX组,分别为25%vs8.3%、40%vs25%和55%vs25%(P>0.05)。部分缓解率两组相近,分别为40%vs50%、45%vs33.3%和40%vs33.3%(P>0.05)。总缓解率分别为65%vs58.3%、85%vs58.3%和95%vs58.3%(P>0.05)。②尿蛋白变化:MMF组尿蛋白缓解率高于CTX组,治疗6个月和12个月时两组完全缓解率分别为45%vs16.7%(P>0.05)和70%vs25%(P<0.05)。③尿红细胞变化:MMF组治疗6个月时血尿缓解率高于CTX组(45%vs16.7%),12个月时两组相近(65%vs66.7%)。④肾功能:MMF组6例治疗初有肾功能不全,5例治疗3个月降至正常;1例6个月降至正常。CTX组4例治疗3个月降至正常。随访末两组SCr均正常。⑤副作用:MMF组并发带状疱疹和上呼吸道感染各1例。CTX组2例明显消化道症状,各有1例并发带状疱疹、细菌性肺炎、白细胞下降、肝酶升高、脱发。1例因副作用严重而退出。⑥复发:MMF组2例(10.5%),CTX组5例(41.7%)。结论:激素联合MMF治疗重症HSPN缓解率高于CTX静脉冲击疗法,能更有效降低蛋白尿和血尿。MMF副作用发生率和复发率均低于CTX疗法。     

槐白皮水提物对免疫抑制小鼠的免疫作用

目的 探讨槐白皮水提物对免疫抑制小鼠免疫功能的影响。方法 昆明小鼠随机分为正常组,模型组,香菇多糖组和槐白皮水提物低、中、高剂量组,除正常组外,其余各组连续3 d腹腔注射环磷酰胺复制免疫抑制模型。造模后连续灌胃给药14 d,血细胞计数仪测定小鼠外周血白细胞数目、称量并计算免疫器官系数、MTT法测定脾淋巴细胞增殖和NK细胞活性,ELISA检测血清IL-2、IFN-γ和TNF-α水平。结果 槐白皮水提物中、高剂量组明显提高免疫抑制小鼠的外周血白细胞水平和免疫器官系数,显著增加LPS诱导的脾淋巴细胞增殖,显著增强脾NK细胞活性,提高免疫抑制小鼠血清IL-2、IFN-γ水平;槐白皮水提物高剂量组明显提高ConA诱导的脾淋巴细胞增殖,显著提高免疫抑制小鼠血清TNF-α水平。结论 槐白皮水提物可以提高免疫抑制小鼠的免疫功能。     

Symptomatic hyponatremia induced by low-dose cyclophosphamide in patient with systemic lupus erythematosus: A case report

Rationale:Cyclophosphamide (CY) is an alkylating agent used widely to treat cancer and autoimmune diseases. Hyponatremia is a common adverse effect of high-dose and moderate-dose of intravenous CY, but is rare in patients treated with low-dose (<15 mg/kg).Patient concerns:A 52-year-old woman with new-onset systemic lupus erythematosus (SLE) was treated with low-dose cyclophosphamide (8 mg/kg, CY), but showed sudden headaches, disorientation and weakness. Laboratory examinations revealed severe isovolumic hyponatremia along with low-serum osmolality and high urine osmolality.Diagnosis:The acute hyponatremia was consistent with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and was an adverse event of low-dose CY, with no evidence of endocrine, cancer, pulmonary, or cerebral abnormalities relevant to the SIADH.Intervention:The hyponatremia was resolved after the supplementation of NaCl solution.Outcomes:The hyponatremia was resolved without any complications.Lessons:Hyponatremia induced by low-dose CY should be recognized as an underlying life-threatening complication in clinical practice.     

Crystallization of Cyclophosphamide Monohydrate During Lyophilization

The purpose of this study was to investigate the phase behavior of cyclophosphamide (CPA) during various stages of lyophilization, with special emphasis on obtaining crystalline CPA monohydrate (CPA-MH) in the lyophilized product. Subambient differential scanning calorimetry and low-temperature X-ray diffractometry (LTXRD) were used to study the phase behavior of CPA solution (3.7% w/v). In situ lyophilization in LTXRD chamber was used to monitor the phase transitions occurring during the drying stages. Finally, the implications of these findings were confirmed by freeze-drying the aqueous solution in a laboratory-scale freeze-dryer. The results suggested that CPA remains amorphous during freeze concentration, with a T_g' of ?50°C. However, its crystallization as CPA-MH can be induced by annealing the frozen solution between ?5°C and ?10°C. In situ lyophilization in LTXRD showed that the CPA-MH crystallized during annealing, rapidly dehydrated during primary drying, thereby causing structural collapse. The dehydration of CPA-MH can be prevented by lowering the escaping tendency of water molecules from the crystal lattice of CPA-MH by maintaining the chamber pressure to 300, 400, or 500 mTorr. This study highlights the relationship of process parameters used during lyophilization with the solid form of lyophilized CPA.     

Successful treatment of childhood pilocytic astrocytomas metastatic to the leptomeninges with high-dose Cyclophosphamide

Leptomeningeal dissemination of childhood pilocytic astrocytoma (PA) is a rare event with little information available regarding therapy. We report here four children with disseminated PA whom we treated with high doses of cyclophosphamide with clinical benefit. The patients were aged 2.5 to 8 years. Three patients presented with PA localized in the posterior fossa, initially treated with surgical resection (n = 3) and radiotherapy (n = 1). Leptomeningeal dissemination occurred at 32, 44, and 8 months from diagnosis, respectively. The fourth patient presented with an optic pathway tumor with leptomeningeal dissemination at diagnosis. At commencement of cyclophosphamide therapy, disease was present in the subarachnoid space (intracranial, n = 2; spinal, n = 4), cerebral ventricles (n = 2), and primary site (n = 3). Histology was identical at diagnosis and recurrence in the two biopsied cases and cerebrospinal fluid was negative in all cases. Treatment was with cyclophosphamide 4–5 g/m²/cycle given every 4 weeks for a total of two cycles (n = 1) and four cycles (n = 3). One patient achieved disease stabilization (duration 27 months at the time of publication) and three patients experienced significant reductions in tumor burden. Subsequent intrathecal therapy was administered to two patients. Two patients developed disease progression at 10 and 9 months from cessation of chemotherapy. The one re-treated patient responded to further, lower dose, cyclophosphamide. This is the first report of the use of high dose cyclophosphamide for disseminated PA. The recurrence of disease in two cases with a further response to lower dose cyclophosphamide has implications for the optimal duration of therapy for these low grade, aggressive tumors. © 1996 Wiley-Liss, Inc.     

重组人成骨生长肽对化疗小鼠白细胞减少的影响

目的 研究重组人成骨生长肽(rhOGP)对环磷酰胺(Cy)化疗损伤小鼠白细胞减少的影响;观察rhOGP对人肺腺癌Anip细胞和人胃癌SGC-7901细胞增殖的影响.方法 用Cy腹腔注射每日100mg/kg,连续3d,造成小鼠的化疗损伤模型.拮抗实验中,分别给予低、高剂量的rhOGP,连续13d,采用皮下注射给药途径,于第0d、第4d(Cy造模后)、第9d、第14d检测外周血白细胞(WBC)数变化.预防实验中,分别给予rhOGP、DTT与生理盐水,连续10d,并于第8、9、10d同时给予Cy,分别于实验前、实验后记取外周血WBC数.利用MTT法和细胞生长曲线观察rhOGP对人肺腺癌Anip细胞和人胃癌SGC-7901细胞增殖的影响.结果 rhOGP能促进Cy损伤小鼠WBC数的恢复,高、低剂量组间略有差异.rhOGP能明显降低Cy损伤小鼠外周血白细胞减少的幅度.rhOGP对人肺腺癌Anip细胞及人胃癌SGC-7901细胞的增殖无明显促进作用.结论 rhOGP可促进Cy损伤小鼠外周血白细胞的恢复,rhOGP对Cy化疗小鼠白细胞数减少有预防作用,且对人肺腺癌Anip细胞和人胃癌SGC-7901细胞的增殖无促进作用,提示rhOGP作为肿瘤治疗辅助用药的潜在价值.     

Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide Using Non–First-Degree Related Donors

Outcomes of nonmyeloablative (NMA) haploidentical (haplo) blood or marrow transplant (BMT) with post-transplantation cyclophosphamide (PTCy) using non–first-degree relatives are unknown. We evaluated 33 consecutive adult patients (median age, 56 years) with hematologic malignancies who underwent NMA haplo T cell–replete BMT with PTCy at Johns Hopkins using second- or third-degree related donors. Donors consisted of 10 nieces (30%), 9 nephews (27%), 7 first cousins (21%), 5 grandchildren (15%), and 2 uncles (6%). Thirty-one patients (94%) reached full donor chimerism by day 60. The estimated cumulative incidence (CuI) of grades II to IV acute graft-versus-host disease (aGVHD) at day 180 was 24% (90% confidence interval [CI], 9% to 38%). Only 1 patient experienced grades III to IV aGVHD. At 1 year the CuI of chronic GVHD was 10% (90% CI, 0% to 21%). The CuI of nonrelapse mortality at 1 year was 5% (90% CI, 0% to 14%). At 1 year the probability of relapse was 31% (90% CI, 12% to 49%), progression-free survival 64% (90% CI, 48% to 86%), and overall survival 95% (90% CI, 87% to 100%). The 1-year probability of GVHD-free, relapse-free survival was 57% (90% CI, 41% to 79%). NMA haplo BMT with PTCy from non–first-degree relatives is an acceptably safe and effective alternative donor platform, with results similar to those seen with first-degree relatives.     

Sequential therapy with cyclophosphamide and mycophenolic acid in patients with progressive immunoglobulin A nephropathy: a long‐term follow‐up

In progressive immunoglobulin (Ig)A nephropathy (IgAN), cyclophosphamide pulse therapy (CyP), high‐dose intravenous immunoglobulins (IVIg) and mycophenolic acid (MPA) have been used to stop progressive loss of renal function, but disease progression may occur after the end of the initial treatment. Here, we report the long‐term follow‐up of patients with progressive IgAN with MPA as maintenance therapy after CyP (CyP‐MPA). In a median observation time of 6·2 years, we analysed the slopes of the loss of renal function of 47 patients with biopsy‐proven IgAN and treated with CyP. Thirty‐one patients with further progression were treated with MPA maintenance for a median time of 5·2 years. Follow‐up was compared with symptomatic therapy and IVIg as historically matched control groups. Median loss of renal function was reduced significantly from 0·9 ml/min to 0·1 ml/min per month with CyP (P < 0·05), and with MPA in patients with a relapse from ?0·4 ml/min to ?0·1 ml/min per month (P < 0·05) until the end of the study. Proteinuria decreased significantly from 1·6 g/l to 1·0 g/l after CyP, and during MPA treatment to 0·6 g/l (P = 0·001 Friedman test). Median renal survival time was in patients with CyP 10·5 years (range = 3·2–17·8), with CyP‐MPA 10·7 years (range = 8·3–13·1), with IVIg 4·7 years (range = 2·6–6·6), and in untreated patients 1·2 years (range = 0·8–1·6; log‐rank test P < 0·01). In patients with progressive IgAN, our long‐term follow‐up observation indicates that sequential CyP‐MPA therapy maintains renal survival significantly.     

狼疮性肾炎94例的治疗总结

目的:探讨中西医结合治疗狼疮性肾炎(IN)的疗效。方法:随机设置中西医组和西医组,分别为94例、84例,两组进行有效率、复发率、副作用的比较。结果:西医组总有效率80.9％,复发率21.4％,副作用发生率77.1％;中西医组总有效率94.6％,复发率4.2％,副作用发生率38.0％,中西医组总有效率高于西医组(P<0.05)。结论:中西医结合治疗在提高疗效,减少复发及减轻副作用均显著优于西医组。