Hans H. Euler

Randomized controlled trial of pulse/synchronization cyclophosphamide/apheresis for proliferative lupus nephritis

To assess the efficacy of pulse/synchronization cyclophosphamide/apheresis in patients with proliferative lupus nephritis.

Antibody depletion and cytotoxic drug therapy in severe systemic lupus erythematosus

Abstract The established treatment of severe systemic lupus erythematosus (SLE) includes corticosteroids and cytotoxic drugs. Therapeutic plasmapheresis may provide additional rapid relief, but this is only temporary. Controlled trials have repeatedly demonstrated that long-term improvement cannot be achieved if plasmaphereses are performed in addition to long-term oral immunosuppression, as is the usual procedure. This might be an indication that the organism has a considerable ability to re-establish the status quo ante. By contrast, uncontrolled case reports indicate that both rapid and longterm benefits may be achieved by combining plasmapheresis with subsequent pulses of an alkylating agent. The approach used in these studies theorizes that antibody depletion induces increased proliferation of pathogenic clones and that it should be possible to exploit this increased proliferation for the enhanced deletion of pathogenic clones by the subsequent application of pulse cyclophosphamide. The present paper reviews the literature and summarizes the results achieved with the treatment of severe SLE using cytotoxic agents and antibody elimination. Additionally, the authors discuss how the organisms ability to achieve rapid counterregulation might be utilized to improve the therapeutic results, and they attempt to develop perspectives for the future.

A Randomized Trial of Plasmapheresis and Subsequent Pulse Cyclophosphamide in Severe Lupus: Design of the Lpsg Trial

A group of clinics cooperating as the Lupus Plasmapheresis Study Group (LPSG) is starting an international multicenter study of the treatment of severe systemic lupus erythematosus. The primary goal of this randomized and prospective trial is to establish whether treatment with plasmapheresis and subsequent pulse cyclophosphamide improves the outcome compared to treatment with pulse cyclophosphamide alone. The underlying rationale assumes that plasmapheresis: a) eliminates pathogenic autoantibodies and immune complexes and b) induces a compensatory activation of pathogenic lymphocyte clones through a feedback between circulating antibodies and their respective antibody-producing clones. Synchronization of plasmapheresis with subsequent pulse cyclophosphamide should enhance the deletion of pathogenic clones during the period of greatest vulnerability. This overview reviews the first results of treatment approaches based on this concept and summarizes the design of the LPSG trial

Recognition and Management of Systemic Lupus Erythematosus

SummarySystemic lupus erythematosus (SLE) is an inflammatory systemic disease that causes organ damage by the deposition of autoantibodies and complement activating immune complexes or by vascular occlusion due to procoagulant states associated with antiphospholipid antibodies. The vast majority of cases occur in women of childbearing age. SLE is diagnosed on the basis of its clinical manifestations and the demonstration of characteristic immunological phenomena, especially anti-nuclear antibodies.The prognosis in SLE has shown a distinct improvement over recent decades, the 5-year survival rate now approaching or exceeding 90%. The 15-year survival rate of 63 to 79%, on the other hand, underscores the need for further advances in diagnosis and treatment of the disease.Management of the disease includes regular monitoring of disease activity, avoidance of predisposing factors and close supervision of therapy. Drug therapy is guided by the activity and severity of the leading organ manifestations and ranges from nonsteroidal antirheumatic drugs to intensive treatment with cytotoxic agents. Corticosteroids remain irreplaceable for the control of acute flares. Antimalarials and azathioprine are important long term drugs for treating mild or moderate disease activity. Intravenous pulse cyclophosphamide is safer than other regimens and at least as effective as oral cyclophosphamide for severe lupus nephritis. It is also effective in the treatment of central nervous disease and of other organ-threatening manifestations. Recently, an intensified protocol which included cyclophosphamide induced long term treatment-free remission in 60% of patients. The toxicity of cyclophosphamide is considerable, but can be ameliorated by various measures. The value of several new immunosuppressants and other compounds remains to be determined.

Plasma exchange in systemic lupus erythematosus

Abstract Standard treatment for severe systemic lupus erythematosus (SLE) consists of corticosteroids and immunosuppressive drugs. A number of controlled studies purport to show that parallel application of plasmapheresis is no longer tenable since it imparts no additional benefit. Three indications for plasmapheresis in SLE appear to remain: (1) emergency intervention; (2) contraindication of cytotoxic drugs in severe SLE; and (3) so-called “synchronization”, which combines plasmapheresis with subsequent high-dose pulse cyclophosphamide and has achieved repeatedly long-term, treatment-free remission in severe SLE. Immunoadsorption, especially employing an anti-immunoglobulin adsorber, appears to represent a further useful technological advance. It is questionable whether photopheresis, lymphapheresis, and cascade filtration will have a role to play in the treatment of SLE. An additional indication for apheresis may be the new procedure of autologous transplantation of purged stem cells.

Effect of antigen-specific immunoadsorption on antibody kinetics in a rat model

The investigation of antibody kinetics following antigen-specific immunoadsorption in alkaline phosphatase immunized rats revealed significantly lower antibody levels than in untreated controls over a follow-up period of 6 weeks. A rebounding antibody synthesis as a result of specific depletion was not observed. Non-adsorption of specific antiidiotypic antibodies may explain these findings.

Analyse prognostischer Faktoren beim Plasmozytom

SummaryFor analysis of prognostic factors the clinical course of 109 patients with multiple myeloma was evaluated. Survival curves of immunoglobulin (Ig)G- and IgA-myelomas were identical (Fig. 1) with median survival times of 52 and 42 months, respectively, whereas patients with IgD- and Bence-Jones-myeloma had short survival times (median 3 months). Most important risk factors were anemia, renal insufficiency, and hypercalcemia (Figs. 7 and 8). Median survival time dropped from 52 months (Hb above 100 g/l) to 22 (Hb 85–100 g/l) and 1 month (Hb below 85 g/l). Patients with serum creatinine values below 2 mg/dl lived significantly longer than those with values above. Median survival times were 52 and 1 month, respectively. All seven hypercalcemic patients had a renal insufficiency and were in a very poor condition; their median survival time was 1 month. Analysis of the widely used staging system of Durie and Salmon [16] gave disappointing results. Survival curves of the three A-stages ran close together with median survival times of 58, 51, and 36 months. Only the A-B classification according to renal function (A: creatinine under 2 mg/dl; B: creatinine above 2 mg/dl) proved prognostically relevant.For analysis of prognostic factors the clinical course of 109 patients with multiple myeloma was evaluated. Survival curves of immunoglobulin (Ig)G- and IgA-myelomas were identical (Fig. 1) with median survival times of 52 and 42 months, respectively, whereas patients with IgD- and Bence-Jones-myeloma had short survival times (median 3 months). Most important risk factors were anemia, renal insufficiency, and hypercalcemia (Figs. 7 and 8). Median survival time dropped from 52 months (Hb above 100 g/l) to 22 (Hb 85-100 g/l) and 1 month (Hb below 85 g/l). Patients with serum creatinine values below 2 mg/dl lived significantly longer than those with values above. Median survival times were 52 and 1 month, respectively. All seven hypercalcemic patients had a renal insufficiency and were in a very poor condition; their median survival time was 1 month. Analysis of the widely used staging system of Durie and Salmon gave disappointing results. Survival curves of the three A-stages ran close together with median survival times of 58, 51, and 36 months. Only the A-B classification according to renal function (A: creatinine under 2 mg/dl; B: creatinine above 2 mg/dl) proved prognostically relevant.

[Goodpasture's syndrome--rapid remission after early plasmapheresis and high-dose cyclophosphamide therapy (author's transl)].

SummaryIn a 21-year old patient, complete remission of the first manifestation of Goodpastures-syndrome was attained within two days by large-volume centrifugation plasmapheresis and high-dose treatment with cyclophosphamide. The course and therapy procedure are discussed.ZusammenfassungBei einem 21jährigen Patienten wurde die vollständige Remission der Erstmanifestation eines Goodpasture-Syndroms innerhalb von zwei Tagen erreicht durch großvolumige Zentrifugations-Plasmapherese und hochdosierte Stoßbehandlung mit Cyclophosphamid. Verlauf und therapeutisches Vorgehen werden diskutiert.