小剂量三尖杉酯碱联合全反式维甲酸治疗骨髓增生异常综合征

自1988年1月以来,我们试用小剂量三尖杉酯碱联合全反式维甲酸,双重分化诱导治疗骨髓增生异常综合征(MDS)14例。现总结报道如下。临床资料14例均为住院病人。男女各7例。平均年龄42岁(28～67岁)。诊断标准按照1982年 FAB 协作组标准,其中难治性贫血(RA)6例,原始粒细胞增多的难治性贫血(RAEB)5例,转化中的原始粒细胞增多的难治性贫血(RAEB—T)3例。方法三尖杉酯碱1mg 加入10%葡萄糖250ml 静咏滴注,每日一次,10天1疗程,休息5～7天进行下一疗程。全反式维甲酸每日60mg,分三次口服,达到完全缓解后停药。每个疗程结束后复查血象和骨髓象,三个疗程无效者可更换其它方案。疗效评定标准参照全国会议制定的急性白血病及再障疗效评定标准,将 MDS 疗效分为:完全缓解(CR)、部分缓解(PR)、进步、无效。结果 RA6例中获 CR2例、PR1例、进步1例,     

应用HOAP方案治疗急性淋巴细胞白血病355例的疗效

苏州医学院附属一院等六个医院组成江苏省白血病协作组,使用HOAP(高三尖杉酯碱、长春新碱、阿糖胞苷,强的松)方案,治疗急非淋白血病355例,5～7天为一疗程,间歇10～14天。一般接受3～7个疗程,少数用到10个疗程以上。本组年龄自5～64岁,其中儿童56例,成人299     

LD—HA诱导治疗非M3型老年急性髓系白血病疗效观察

目的观察小剂量高三尖杉酯碱＋阿糖胞苷（LD—HA）诱导治疗非M3型老年急性髓系白血病（AML）的疗效和不良反应。方法将35例初治老年AML患者随机分为A组（19例）及B组（16例）。A组采用LD—HA方案：高三尖杉酯碱（H）1～2mg／d,阿糖胞苷（Ara—C）25mg,q12h,第1—14天化疗。B组采用标准剂量HA或DA方案。结果1个疗程结束后,A组和B组的完全缓解（CR）率分别为68．4％和37．5％;病死率分别为10．5％和18．7％,差异有统计学意义。血液学毒性两组差异无统计学意义;非血液学毒性的发生率A组低于B组。结论LD—HA诱导治疗老年AML近期疗效好,不良反应较轻。     

单剂三尘杉酯碱治疗急性非淋巴细胞性白血病55例临床疗效观察

一、病例:急性非淋巴细胞白血病(ANLL)25例,男11,女14名.年龄14～52岁,诊断和疗效按1987年全国白血病标准判定。二、方案诱导缓解: (1)常规剂量:三尖杉脂碱(H)4～6毫克加入5％葡萄糖液500毫升静脉点滴,每日一次,5～7天一疗程,间歇7～15天,达完全缓解后再用原方案巩固3疗程. (2)小剂量H0.5毫克加入5％葡萄糖液500毫升静脉滴,每日一次,10～15天.间歇7～15天,达完全缓解后再用原方案巩固3疗程.     

环孢素A联合小剂量HA方案治疗难治性阵发性睡眠性血红蛋白尿症的临床疗效观察

目的:观察环孢素A联合小剂量HA方案(高三尖杉酯碱+阿糖胞苷)治疗难治性阵发性睡眠性血红蛋白尿症(PNH)的临床疗效及毒副反应。方法:采用环孢素A联合小剂量HA方案治疗15例难治性PNH,分析患者的临床疗效及不良反应。结果:4个疗程后,15例难治性PNH的疗效为14例(93.33%)有效,其中2例(13.33%)达到近期临床痊愈,4例(26.67%)达到近期临床缓解,5例(33.33%)达到近期明显进步,3例(20.00%)达到近期进步;另外1例(6.67%)无效。所有患者均无严重的骨髓抑制及毒副反应。结论:环孢素A联合小剂量HA方案对难治性PNH的治疗安全、有效,毒副反应可耐受。     

诱导分化治疗白血病

诱导分化治疗白血病是近年来在联合化疗方面取得的重要进展。我们采用小剂量三尖杉酯碱,加维甲酸作为联合诱导分化方案治疗急性早幼粒细胞性白血病(APL)及继发于骨髓增殖异常综合征(MDS)的急性白血病(AL)。现报道如下: 临床资料11例均为男性患者,年龄21～50岁,诊断AML(M_3)8例。MDS发展为急性白血病3例(1例M_6,2例M_2),均为初治病例。治疗方法:11例均以三尖杉酯碱1mg加0.9%     

HHT联合Ara-C治疗慢性粒细胞白血病临床研究

对35例慢性粒细胞白血病慢性后期（病程〉12个月）且对α-干扰素反应差者采用高三尖杉酯碱和小剂量阿糖胞苷联合治疗，治疗1～12个周期后，79％（22／28）慢性期及29％（2／7）加速期患者达血液学完全缓解，无明显副作用。     

小剂量^131碘治疗儿童Graves病42例疗效观察

目的 探讨小剂量^131碘(^131I)治疗儿童Graves病的疗效。方法 ^131I剂量降至常规计算用量的1／2～2／3，1次顿服，3个月为1个疗程，进行疗效复查，总剂量37～185MBq。结果 42例患儿中，痊愈38例，治愈率为90．5％；显效2例，占4．8％；无效1例，占2．4％；1例出现早发甲状腺功能低下(甲低)，经治疗后恢复。治愈总疗程1～3个，时间3～9个月。痊愈病例中，服药1个疗程治愈17人(44．8％)，2个疗程治愈16人(42．1％)，3个疗程治愈5人(13．1％)，观察3～5年，38例治愈患者中未出现甲状腺功能亢进症复发或晚发甲低。结论 小剂量^131I是治疗儿童Graves病安全、有效的方法。     

高三尖杉酯碱联合全反式维甲酸治疗老年急性早幼粒细胞白血病的疗效

目的 观察高三尖杉酯碱联合全反式维甲酸治疗老年急性早幼粒细胞白血病的疗效.方法 对48例老年急性早幼粒细胞白血病的初始治疗使用高三尖杉酯碱联合全反式维甲酸,对患者的一般临床表现、用药疗效以及生存率进行观察.同时选取45例单用全反式维甲酸的老年急性早幼粒细胞白血病病例作为对照组.结果 观察组48例患者中,有39例(81.25％)得到了临床的完全缓解(CR),诱导治疗期间的死亡率为18.75％.在对患者进行平均3年的临床随访发现,有3例患者死于维持治疗阶段.对照组CR仅为64.44％.结论 高三尖杉酯碱联合全反式维甲酸治疗老年急性早幼粒细胞白血病的疗效较好,患者的初始治疗临床完全缓解率高,死亡率较低.     

酶酚酸酯治疗难治性狼疮肾炎的临床观察

狼疮肾炎 (ＬＮ)是系统性红斑狼疮 (ＳＬＥ)最常见和最严重的内脏损害 ,而难治性ＬＮ[1] 病情更重 ,对常规皮质激素和细胞毒药物无效 ,治疗困难。我院于 1998年以来采用酶酚酸酯 (ＭＭＦ ,商品名骁悉 )配合小剂量激素治疗难治性ＬＮ 9例 ,取得较好疗效 ,现总结如下。1　材料与方法1 1　病例选择　本组 9例均系在我院住院的病人。女性7例 ,男性 2例。年龄 11～ 5 8(31 1± 11 3)岁 ,病程 3～ 318(5 0 6± 39 6 )个月。均符合美国风湿病学会 1982年ＳＬＥ诊断标准 ,经 2个月以上皮质激素加ＩＶ ＣＴＸ标准治疗或免疫抑制剂反复治疗 ,临床症状…     

Long-term effects of combination treatment with fludarabine and low-dose pulse cyclophosphamide in patients with lupus nephritis

OBJECTIVES: To determine the safety and efficacy of a short course of fludarabine combined with cyclophoshamide in lupus nephritis. METHODS: A phase I/II open label pilot study. Thirteen patients with active proliferative lupus nephritis received monthly oral boluses of low-dose cyclophoshamide (0.5 gm/m(2) on day 1) and subcutaneous fludarabine (30 mg/m(2) on days 1-3) for 3-6 cycles. Concomitant prednisone was aggressively tapered from 0.5 mg/kg/day to a low-dose, alternate-day schedule. Patients were followed for at least 24 months after therapy. The primary outcome was the number of patients achieving renal remission defined as stable creatinine, proteinuria <1 gm/day and inactive urine sediment for at least 6 months. RESULTS: The study was terminated early because of bone marrow toxicity. Eleven patients who received at least three cycles were evaluated for efficacy. Ten patients improved markedly with seven patients achieving complete remission and three patients achieving partial remission. There were three serious haematological adverse events during the treatment with one death due to transfusion-associated graft vs host disease. Profound and prolonged CD4 (mean CD4: 98/microl at 7 months and 251/microl at 12 months) and CD20 lymphocytopenia was noted in most patients. Three patients developed Herpes zoster infections. CONCLUSIONS: A short course of low-dose fludarabine and cyclophoshamide can induce long-lasting remissions in patients with proliferative lupus nephritis, but severe myelosuppression limits its widespread use.     

Die Nierenbeteiligung beim systemischen Lupus erythematodes

Renal involvment in patients with systemic lupus erythematosus displays a broad variety of clinical symptoms ranging from asymptomatic hematuria to rapidly progressing glomerulonephritis. The histopathological findings in renal biopsy are classified in six different forms reflecting this diversity. Mild forms of lupus nephritis do not require immunosuppressive therapy whereas the diffuse-proliferative lupus nephritis (classified as type IV) as the most aggressive form with the worst prognosis demands immediate treatment. Recent approaches aimed to achieve remission in the early induction phase with reduced side effects (e.g. low-dose cyclophosphamide, mycophenolate). Novel therapeutic concepts promise further improvement in lupus nephritis treatment.     

Treatment of proliferative lupus nephritis: a slowly changing landscape

Proliferative lupus nephritis is the most severe form of lupus nephritis. Outcomes of this disease are affected by ethnicity, clinical characteristics, irreversible damage on renal biopsy, initial response to treatment and future disease course (for example, the occurrence of renal flares). Initial intensive (induction) treatment of proliferative lupus nephritis is aimed at achieving remission, but optimal duration and intensity are not well defined. A combination of intravenous cyclophosphamide and corticosteroids have been shown to decrease the risk of end-stage renal disease, but are associated with substantial acute toxic effects (such as infections) and chronic toxic effects (such as ovarian failure). In white populations, low-dose cyclophosphamide is a reasonable alternative to high-dose cyclophosphamide as it is similarly effective and associated with less toxicity. Mycophenolate mofetil is as effective as high-dose intravenous cyclophosphamide in terms of inducing remission and similar in terms of safety. Although most patients respond to induction treatment, remission is often only achieved after patients are switched to maintenance treatment. As maintenance treatment, mycophenolate mofetil is superior to azathioprine and azathioprine is similarly effective to ciclosporin in terms of prevention or reducing the risk of relapse. Rituximab should be reserved for patients with refractory disease. Treatment of lupus nephritis should be individually tailored to patients, with more aggressive therapy reserved for patients at high risk of renal dysfunction and progression of renal disease.     

Clinical and serological spectrum of systemic lupus erythematosus in greek children

Summary In the present study 19 Greek Caucasian children with systemic lupus erythematosus (SLE), onset before the age of 16, were followed up for 1–12 years (mean 5.6 yrs.). Diagnosis was determined early in 14 patients and delayed by 2 to 6 years in 5. The clinical manifestations and laboratory findings did not differ significantly from those reported in adults with lupus. The major organ system involvement at onset and early course were skin and joints (80%) followed by kidneys (42%). During the course of the disease 26% of the children developed central nervous system (CNS) involvement. All the patients were treated with steroids and/or cytotoxic drugs in severe uncontrolled progressive disease. At the mean 5.6 years follow-up most patients were in remission on small doses of steroids; one patient still presents signs of active lupus nephritis and one patient died from sepsis. All the patients with CNS involvement recovered without permanent CNS residue.     

Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial,a randomized trial of low-dose versus high-dose intravenous cyclophosphamide

OBJECTIVE: Glomerulonephritis is a severe manifestation of systemic lupus erythematosus (SLE) that is usually treated with an extended course of intravenous (IV) cyclophosphamide (CYC). Given the side effects of this regimen, we evaluated the efficacy and the toxicity of a course of low-dose IV CYC prescribed as a remission-inducing treatment, followed by azathioprine (AZA) as a remission-maintaining treatment. METHODS: In this multicenter, prospective clinical trial (the Euro-Lupus Nephritis Trial [ELNT]), we randomly assigned 90 SLE patients with proliferative glomerulonephritis to a high-dose IV CYC regimen (6 monthly pulses and 2 quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose IV CYC regimen (6 fortnightly pulses at a fixed dose of 500 mg), each of which was followed by AZA. Intent-to-treat analyses were performed. RESULTS: Followup continued for a median of 41.3 months in the low-dose group and 41 months in the high-dose group. Sixteen percent of those in the low-dose group and 20% of those in the high-dose group experienced treatment failure (not statistically significant by Kaplan-Meier analysis). Levels of serum creatinine, albumin, C3, 24-hour urinary protein, and the disease activity scores significantly improved in both groups during the first year of followup. Renal remission was achieved in 71% of the low-dose group and 54% of the high-dose group (not statistically significant). Renal flares were noted in 27% of the low-dose group and 29% of the high-dose group. Although episodes of severe infection were more than twice as frequent in the high-dose group, the difference was not statistically significant. CONCLUSION: The data from the ELNT indicate that in European SLE patients with proliferative lupus nephritis, a remission-inducing regimen of low-dose IV CYC (cumulative dose 3 gm) followed by AZA achieves clinical results comparable to those obtained with a high-dose regimen.     

Hydroxychloroquine use predicts complete renal remission within 12 months among patients treated with mycophenolate mofetil therapy for membranous lupus nephritis

The objective of this study was to identify clinical predictors of response to initial mycophenolate mofetil (MMF) therapy for membranous lupus nephritis (MLN). We observed the clinical outcomes of patients in the Hopkins Lupus Cohort within the first year of initiation of treatment with MMF therapy for newly diagnosed MLN, classified according to the new International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification. Complete renal remission was defined as proteinuria less than 500 mg/24 hours. Demographic, clinical, treatment and laboratory data were examined for their association with renal remission. Twenty-nine MLN patients treated with MMF were identified. Eleven (38%) patients achieved complete renal remission by 12 months. Of those taking hydroxychloroquine, 7/11 (64%) were in remission within 12 months compared to only 4/18 (22%) of those not on hyroxychloroquine (P = 0.036 based on a log-rank test). This association persisted after controlling for the presence of anti-ds-DNA (P = 0.026). Our results provide evidence that hydroxychloroquine has a benefit for renal remission when MMF is used as the initial therapy for MLN. Although hydroxychloroquine is frequently stopped in patients with lupus nephritis, this study suggests it should be started or maintained.     

Lupus nephritis: Clinical course as related to morphologic forms and their transitions

An intensive study of the course of lupus nephritis has been undertaken in 88 patients in whom strict morphologic criteria were utilized in classification. All were treated with steroid, and 17 received cytotoxic drugs in addition. Focal proliferative lupus nephritis generally follows a benign course except in the occasional instances when transition to the diffuse proliferative or membranous forms occurs. Membranous lupus nephritis, when characterized by persistent nephrotic syndrome, leads slowly to renal failure, but this progression is aborted in the one-third in whom remission of the nephrotic syndrome can be achieved. A fatal outcome occurs within five years in the majority of those with diffuse proliferative lupus nephritis and the nephrotic syndrome, often in association with necrotizing renal vasculitis, severe hypertension and accelerated renal failure. A small number with the diffuse proliferative form have a remission and then show only mesangial abnormalities, usually, however, with the appearance of glomerular sclerosis. Progressive glomerular sclerosis is observed in some patients and may be a sequel of the remission of the diffuse or focal proliferative lesions, or it may represent still another form of lupus nephritis. Mesangial immune deposits with or without proliferation, at times in the absence of clinical renal disease, are observed early in the course of systemic lupus erythematosus (SLE) and may proceed to the diffuse proliferative or membranous forms.     

Mycophenolate mofetil in lupus nephritis

The treatment of severe lupus nephritis is based on the combination of steroids and cytotoxic drugs. Intravenous cyclophosphamide administered in "pulses" is effective in the induction of remission but other therapeutic alternatives are sought in refractory cases or severely relapsing patients. Mycophenolate mofetil, used in renal transplantation, also can be useful in severe lupus nephritis. We describe the evolution of 6 patients (5 women and 1 man; age 17-45 years) with severe lupus nephropathy who after achieving remission with intravenous cyclophosphamide and steroids (5 cases) or cyclosporin A (1 case) showed relapse of proteinuria and were treated with mycophenolate mofetil (dose 1000-2000 mg/day). Two patients have completed 24 months, 1 patient two cycles of 12 months, 2 patients 18 months and 1 patient 6 months. After this treatment, all patients have achieved remission (3 partial and 3 complete). There was no treatment failure and no one patient discontinued medication; however 1 case relapsed. There were no changes in leucocytes, haemoglobin, serum creatinine and serum albumin. ANA and alpha DNA antibodies decreased. Proteinuria (measured as protein/creatinine urine ratio: initial 3 and final 0.3) and dose of steroids (initial: 17.5 mg/d and final 5 mg/d) decreased significantly (p < 0.05 Wilcoxon t-test). The most common side effects were nausea and abdominal discomfort that improved without discontinuation of treatment. We conclude that mycophenolate mofetil is effective and a safe drug in severe relapsing lupus nephritis.     

Low dose cyclosporine A in the treatment of resistant proliferative lupus nephritis

Objective: This study aimed to evaluate long-term efficacy of low dose cyclosporine A (CsA) in the treatment of resistant proliferative lupus nephritis.

Methods: In this retrospective study, patients with biopsy proven proliferative lupus nephritis who were unresponsive to combination therapy with steroid plus mycophenolate mofetil (MMF) or cyclophosphamide (CYC) and had been treated with CsA were included. Efficacy monitoring was based on the systemic lupus erythematosus (SLE) disease activity index, dose of prednisolone, serum complement, anti–double stranded DNA (anti-dsDNA) titration, urine analysis, proteinuria, creatinine clearance, remission of the renal disease, renal survival and involvement of other organs.

Results: This study included 27 consecutive patients (22 females, 5 males) with resistant proliferative lupus nephritis. Mean duration of follow up and treatment with CsA were 40.7?±?24.9 and 35.2?±?19.1 months, respectively. Complete and partial renal remission occurred in 66.9% and 25.7% patients, respectively. Creatinine clearance was stable, proteinuria and anti-dsDNA titer decreased, and C3 and C4 increased significantly during the treatment with CsA. Severe complications such as death, dialysis, kidney transplantation and severe infection did not occur in the studied patients during the follow-up period.

Conclusions: Low-dose CsA could induce renal remission and ameliorate the SLE disease activity in patients with resistant proliferative lupus nephritis and it would be a safe drug for treatment of these patients.