Subsequent Pulse Cyclophosphamide Research Articles

Sustained benefit from combined plasmapheresis and allogeneic mesenchymal stem cells transplantation therapy in systemic sclerosis

BackgroundSystemic sclerosis (SSc) is an autoimmune disease involving the skin and several internal organs. Most therapies available for this disease are symptomatic. Given the difficulty in treating SSc, we conducted this study to investigate the effect of combined plasmapheresis (PE) and allogeneic mesenchymal stem cells transplantation (MSCT) therapy on SSc.MethodsFourteen patients underwent three repeated PE treatments with subsequent pulse cyclophosphamide on days 1, 3 and 5. Patients received a single MSCT (1 × 106 cells/kg of body weight) on day 8. During follow up, evaluations performed included complete physical examination, serologic testing, and organ function.ResultsThe mean modified Rodnan skin score (MRSS) improved from 20.1 ± 3.1 to 13.8 ± 10.2 (P < 0.001) at 12 months of follow up. Three patients had interstitial lung disease, all had improvement of lung function and improved computed tomography (CT) images after 12 months of combined therapy. This combined treatment also significantly decreased the anti-Scl70 autoantibody titer and serum transforming growth factor-β and vascular endothelial growth factor levels during follow up.ConclusionThe results indicate that PE combined with MSCT is a feasible treatment associated with possible clinical benefit for SSc patients.Trial registrationClinicalTrials.gov, NCT00962923. Registered on 19 August 2009.

Intensivierte Therapie des schweren Lupus erythematodes

14 female patients (mean age 28 [18-56] years) with severe systemic lupus erythematosus (SLE) were treated after discontinuing previous immunosuppressive therapy, according to an intensified protocol, with three plasmaphereses (days 1-3), followed by pulse cyclophosphamide (12 mg/kg i.v. each on days 3-5) and then oral immunosuppression (cyclophosphamide 1-5 mg/kg daily, depending on white blood cell count; prednisone equivalent 2.0 decreasing to 0.1 mg/kg, according to response, for 6 months). The aim of "synchronization" of plasmaphereses with subsequent cyclophosphamide pulse-therapy is to damage pathogenic lymphocyte clones during maximal compensatory activation induced by plasmapheresis. In all patients there was rapid improvement from the nephritis, pneumonitis, cytopenia, CNS abnormalities and polyserositis. The lupus activity index (SLAM) fell clearly, from initially 28.4 (13-37) points to 8.9 (2-13) after 6 months. Treatment was discontinued after this fall in 12 patients. A recurrence was observed in two patients, at 12 and 39 months respectively. Another patient died from liver cirrhosis of unknown aetiology. Nine patients are under observation but without treatment at present, in essential remission after 2 years (5-51 months), with a SLAM of 2.8 (0-7) points. "Synchronization" of plasmaphereses with subsequent pulse cyclophosphamide achieved rapid improvement and it resulted, for the first time, repeatedly in long-term treatment-free clinical remissions.

Erstmanifestation einer diffusen proliferativen Lupus-Nephritis unter immunsuppressiver Langzeittherapie mit Mycophenolatmofetil

A now 34-year old female patient with long-standing systemic lupus erythematosus (SLE) had successfully been treated with mycophenolate mofetil (MMF) because of former pleuropericardial and pulmonal lupus manifestations when she was admitted with edema for the first time. Laboratory investigations of urine and blood showed findings compatible with lupus nephritis. Kidney biopsy revealed lupus nephritis type IV. Despite the initiation of cyclophosphamide bolus and corticosteroid therapy, the kidney function and renal hypertension worsened and the patient developed cerebral manifestations. Finally, synchronization of plasmapheresis with subsequent pulse cyclophosphamide led to remission of SLE. Although MMF is a promising innovative agent for induction and maintenance therapy of lupus nephritis that can be used instead of cyclophosphamide, there may be cases like the one reported here, in which MMF cannot prevent lupus flares in first manifestation of severe renal disease.

Treatment‐free remission in severe systemic lupus erythematosus following synchronization of plasmapheresis with subsequent pulse cyclophosphamide

To investigate the effect of an intensified treatment protocol synchronizing plasmapheresis with subsequent pulse cyclophosphamide for severe systemic lupus erythematosus (SLE). A protocol of plasmapheresis (3 x 60 ml/kg) and subsequent high-dose pulse cyclophosphamide (36 mg/kg) followed by 6 months of peroral immunosuppression was used to treat 14 patients with severe SLE. Rapid improvement was achieved in all patients. Immunosuppressants, including corticosteroids, were withdrawn at month 6 in 12 patients. Eight patients continued without treatment for a mean observation period of 5.6 years (46-91 months). The results demonstrate that treatment-free clinical remission can be achieved in some patients with severe SLE.

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 feed-back 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.

Plasmapheresis and subsequent pulse cyclophosphamide versus pulse cyclophosphamide alone in severe lupus: Design of the LPSG trial

A group of clinics are collaborating in the Lupus Plasmapheresis Study Group (LPSG) to investigate whether repeated plasmapheresis prior to pulse cyclophosphamide improves the therapeutical results in severe systemic lupus erythematosus (SLE). The underlying rationale is the hypothesis that plasmapheresis 1) eliminates pathogenic autoantibodies and immune complexes and 2) induces compensatory lymphocyte activation via feedback mechanisms between circulating antibodies and their respective clones ("antibody rebound"). It should be possible to utilize this enhanced activity for increased clonal deletion if pulse cyclophosphamide is applied shortly after plasmapheresis. Accordingly, in a randomized study, the LPSG will be comparing the repeated application of pulse cyclophosphamide alone with a treatment involving repeated plasmapheresis prior to the cyclophosphamide pulses in severe SLE. A third arm of the study will be gathering experience with a more intensified procedure. This overview summarizes the most important details of the planned study.

Combination of plasmapheresis with subsequent pulse cyclophosphamide as initial treatment of severe Wegener's granulomatosis

Combination of plasmapheresis with subsequent pulse cyclophosphamide as initial treatment of severe Wegener's granulomatosis

Plasmapheresis and Pulse Cyclophosphamide Therapy in Pemphigus Vulgaris: A Novelty or a Reappraisal?

To the Editor.— I have read with interest the article published in the September 1987 issue of theArchivesdealing with long-lasting and complete remission in a patient with refractory pemphigus vulgaris using an experimental treatment protocol based on synchronization of plasmapheresis with subsequent pulse cyclophosphamide therapy. 1 Plasmapheresis was applied both as a means of rapid elimination of circulating intercellular antibodies (abs) and also as a means for rebound stimulation of the ab-producing cells (feedback cycle between circulating abs and their production). In that way, the subsequent high-dose cyclophosphamide treatment, by exerting its cytotoxic effect during the period of assumed maximum proliferation and, thus, vulnerability of abproducing cell clones, could act optimally. In the Comment section of their article, the authors have pointed out that two new elements characterized the therapeutic approach in the case reported: the high dose of cyclophosphamide (total dose of the cyclophosphamide pulse, 1500 mg)

Synchronization of Plasmapheresis and Pulse Cyclophosphamide Therapy in Pemphigus Vulgaris

Long-lasting and complete remission was obtained in a 48-year-old patient with refractory pemphigus vulgaris by an experimental treatment protocol that tries to synchronize plasmapheresis with subsequent pulse cyclophosphamide therapy. The rationale of the approach tries to utilize the plasmapheresis-induced increased proliferation of pathogenic cell clones for partial deletion of these clones through application of maximum pulse immunosuppression treatment during the period of assumed maximum proliferation and, thus, maximum vulnerability of the antibody-producing cells. The treatment schedule consisted of initial withdrawal of immunosuppressive drug therapy, repeated large-volume plasmaphereses substituted with immunoglobulin-free albumin solutions, subsequent application of high-dose (36 mg/kg of body weight) cyclophosphamide therapy, and low-dose maintenance immunosuppression for several months. As a result, our patient remained disease free over a follow-up period of 40 months without any further immunosuppressive treatment. Stimulation of postexchange antibody production and subsequent application of high-dose cytotoxic drugs might be a valuable tool in the management of refractory pemphigus vulgaris and, possibly, in the management of other autoantibody-mediated diseases.