Cyclophosphamide Pulse Therapy Research Articles

Clinical trial: cyclophosphamide pulse therapy – a promising therapeutic alternative in refractory Crohn’s disease

In severe steroid-refractory Crohn's disease (CD), established therapies fail in a relevant proportion of patients. Recent pilot studies indicated the efficacy of cyclophosphamide pulse therapy in these patients. To provide further and substantial evidence for the rationale to apply cyclophosphamide pulse therapy as therapeutic option in severe courses of CD. Fifteen patients with steroid-refractory (n = 13) or steroid-dependent (n = 2) CD received 2-6 (median 3) monthly pulses of 750 mg cyclophosphamide in an open-label fashion. Eleven patients were on concomitant immunosuppression (azathioprine/mercaptopurine n = 9; methotrexate n = 2). Thirteen of 15 patients (87%) had a clinical response (CDAI decrease >100). Ten patients (67%) went into remission (CDAI <150) after 8 weeks. Steroid-free remission was achieved in eight patients (54%). Two patients (13%) failed to respond. Median CDAI decreased from 420 (245-550) to 100 (26-538) at week 8. Remission lasted 16 months (median, range 4-40). In three patients, arthritis, erythema nodosum and episcleritis completely resolved. Cyclophosphamide pulse therapy administration was well tolerated in all subjects. Cyclophosphamide pulse therapy is safe and highly effective for induction and maintenance of remission in steroid-refractory/-dependent CD. There is a strong need for additional experience to improve the setting of the encouraging cyclophosphamide treatment in CD.

Low-density lipoprotein apheresis in a pediatric patient with refractory nephrotic syndrome due to focal segmental glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) often leads to refractory nephrotic syndrome (NS). A high level of low-density lipoprotein (LDL) is a risk factor for the progression of NS. An 8-year-old girl presented with severe proteinuria refractory to steroid therapy. She was diagnosed with non-IgA diffuse mesangial proliferative glomerulonephritis. Oral prednisolone, methylprednisolone (mPL) pulse therapy, and cyclosporine and cyclophosphamide therapy failed to achieve remission. Follow-up renal biopsy revealed FSGS. Her serum level of LDL was high, and LDL-apheresis (LDL-A) was performed five times, followed by mPL pulse therapy. Urinary protein decreased from 2-4 g x day(-) to 0.5-1.0 g x day(-). LDL-A may be beneficial in the treatment of multidrug-resistant FSGS.

Early aggressive intra-venous pulse cyclophosphamide therapy for interstitial lung disease in a patient with systemic sclerosis. A case report

Interstitial lung disease is an important cause of mortality and morbidity in patients with systemic sclerosis (SSc). There are currently no recommended guidelines for management of these patients. This is probably due to the rarity of this condition, as well as clinical trials with only a small number of cases. There are published case report and case series along with the two main trials, viz. Scleroderma Lung Study and the Fibrosing Alveolitis Study, but again, there is no consensus on treatment protocols. In this report, we present a case of aggressive interstitial lung disease in a patient with SSc, which improved dramatically on treatment with intra-venous cyclophosphamide and high dose prednisolone therapy.

P094 - Increased antigenic uptake in patients with ulcerative colitis role of CRH and muscarinic receptors

therapy (pancytopenia), but after omission the patient settled into the original condition. 28 patients of the 32 achieved remission after the second infusion of cyclophosphamide. Conclusion: Remission was maintained in all patients for 9 months on he average (mostly by CD patients) and the drug was well tolerated. Our experience suggest that intravenous pulse cyclophosphamide therapy may be a safe and effective treatment for patients with severe IBD unresponsive for conventional treatment, but further controlled study should be considered in the future in more diverse patient population.

P095 - Reducing the time to symptom improvement and resolution for moderately active UC

therapy (pancytopenia), but after omission the patient settled into the original condition. 28 patients of the 32 achieved remission after the second infusion of cyclophosphamide. Conclusion: Remission was maintained in all patients for 9 months on he average (mostly by CD patients) and the drug was well tolerated. Our experience suggest that intravenous pulse cyclophosphamide therapy may be a safe and effective treatment for patients with severe IBD unresponsive for conventional treatment, but further controlled study should be considered in the future in more diverse patient population.

Hemorrhagic cystitis following dexamethasone: Cyclophosphamide pulse therapy

Hemorrhagic cystitis following dexamethasone: Cyclophosphamide pulse therapy

Microscopic polyangiitis in a patient on hemodialysis : A case report.

A 62-year-old male was admitted to a local hospital due to a clouding of consciousness in October 2006. On admission, his renal function was observed to have severely deteriorated, which is thought to cause disturbance of consciousness. Laboratory data showed blood urea nitrogen to be 160 mg/dl and the serum creatinine level was 25 mg/dl and, as a result, continuous hemodiafiltration (CHDF) was started. Although his general condition improved, his renal function did not recover. Therefore, regular hemodialysis was started in December 2006. The cause of renal dysfunction was uncertain, because MPO-ANCA was negative, and a renal biopsy could not be done due to the lack of a clear corticomedullary border in his kidneys. In January 2008, he was diagnosed to have microscopic polyangiitis (MPA) because of hemoptysis, elevated serum CRP levels and a positive finding for MPO-ANCA (408.0 EU). An alveolar hemorrhage was also ascertained in a broncoscopic examination. Steroid pulse therapy and intravenous pulse therapy of cyclophosphamide were thus started. The patient's clinical symptoms thereafter significantly improved and his MPO-ANCA level became normalized. This is a rare case characterized by a late appearance of MPO-ANCA, which occurred after more than one year after the onset of renal failure in MPA.

Systemic sclerosis and dexamethasone cyclophosphamide pulse therapy

Systemic sclerosis and dexamethasone cyclophosphamide pulse therapy

Long‐term Clinical Outcomes of Synchronized Therapy With Plasmapheresis and Intravenous Cyclophosphamide Pulse Therapy in the Treatment of Steroid‐resistant Lupus Nephritis

In recent years, the vital prognosis of the patients with lupus nephritis (LN) has improved dramatically as a result of steroid therapy and the administration of immunosuppressants including cyclophosphamide, but recurrent cases and complications associated with these therapies are a concern. In this study, a long-term retrospective evaluation was performed over a period of five years concerning the clinical characteristics, remission rate and relapse rate by dividing 38 patients with LN into three groups receiving either plasmapheresis (PP), intravenous cyclophosphamide pulse therapy (IVCY), or both PP and IVCY (synchronized PP-IVCY) as the treatments added to steroid therapy. The complete remission rates of PP, IVCY and PP-IVCY were 5/9 (55.6%), 8/16 (50.0%) and 9/13 (69.2%), respectively. The relapsing rates of PP, IVCY and PP-IVCY were 3/9 (33.3%), 3/16 (18.8%) and 1/13 (7.7%), respectively. Synchronized PP-IVCY therapy might be superior to PP or IVCY in achieving complete remission of LN, and in minimizing the risk of relapse of impaired renal function.

Rapidly progressing central nervous system involvement despite of steroid pulse therapy in a case of systemic lupus erythematosus presented as mononeuritis multiplex

AbstractA 31‐year‐old‐woman with a 6‐month history of systemic lupus erythematosus (SLE) was admitted because of severe mononeuritis multiplex. Although she initially responded well with steroid pulse therapy, she developed unconsciousness again 3 weeks later just after a second course of steroid pulse. Laboratory evaluations revealed a high titre of anti‐DNA antibody, low complement levels, and positive lupus anticoagulant. She was treated with intravenous cyclophosphamide pulse therapy with immediate response. The clinical course of central nervous system involvement was very unusual for the response to steroid pulse therapy.

Hämoptysen und akutes Nierenversagen bei einem 29-jährigen Patienten mit chronischer Hepatitis C

A 29-year-old male patient with chronic hepatitis C infection and interferon alpha therapy in his medical history was admitted to the hospital because of the clinical manifestation of a pulmonary renal syndrome. High titers of proteinase-3-ANCA were detected, while an infectious agent was ruled out. After diagnosis of Wegener's granulomatosis the patient received prednisolone and cyclophosphamide pulse therapy and remission developed rapidly. Chronic hepatitis C infection as well as interferon therapy are frequently associated with autoimmune disorders. We assume that the interferon therapy itself has triggered autoimmune processes resulting in Wegener's granulomatosis in our patient. Thus we recommend to search specifically for autoimmune disorders in the past medical history and if necessary to consider a screening for autoantibodies before starting an interferon therapy. An autoimmune disease should also be taken into account if new symptoms develop under an ongoing interferon alpha therapy.

Acquired hemophilia in a patient with systemic lupus erythematosus: a case report and literature review

We report the case of a 38-year-old female patient with systemic lupus erythematosus (SLE) who developed acquired hemophilia caused by factor VIII (FVIII) inhibitors. She manifested spontaneous bleeding symptoms such as ecchymoses and hematuria. Laboratory findings showed an isolated prolongation of the activated partial thromboplastin time, reduced FVIII activity, and a high titer of FVIII inhibitors. She was successfully treated with oral predonisolone and cyclosporine in combination with steroid and cyclophosphamide pulse therapy.

Whipple Disease: Unusual Presentation of a Protean and Sometimes Confusing Disease

To describe an unusual case of Whipple disease (WD) with confusing clinical features at onset and to discuss the diagnostic challenges for the clinician. Description of a new case of this rare disease and thorough discussion of the atypical clinical manifestations at onset. A literature review, concerning the unusual onset, by means of a MEDLINE search from 1966 to 2007 was done. A 39-year-old man with sudden bilateral blurred vision due to retinal vasculitis and concomitant rapidly evolving symmetrical neurosensory bilateral hearing loss as initial features of WD is described. Due to the clinical manifestations resembling systemic vasculitis, high-dose corticosteroid and pulse cyclophosphamide therapy were started with subsequent appearance of gastrointestinal symptoms (diarrhea and weight loss) and spiking fever, suggesting superimposed infection. After a complete evaluation, including gastroscopy, extensive duodenal-jejunal mucosal involvement was seen, while diffuse infiltration of the duodenal lamina propria with periodic acid-Schiff-positive foamy macrophages was observed on the histological sample. The diagnosis was confirmed by reverse transcriptase-polymerase chain reaction for the DNA of Tropheryma whippelii. To our knowledge, no previous similar clinical onset of WD has been described. To avoid misdiagnosis and therapeutic mistakes, clinicians should be aware of unusual presentations of WD. Because this etiological agent is a difficult to isolate bacterium, diagnosis may be especially problematic in cases without intestinal involvement at onset.

Vesical varices and telangiectasias in a patient with ataxia telangiectasia

A Japanese boy with ataxia telangiectasia (AT) developed severe gross hematuria and recurrent bladder tamponade, requiring an extensive blood transfusion. He had received intermittent intravenous cyclophosphamide pulse therapy (cumulative dose of 1.3 g) for refractory steroid-resistant and intravenous immunoglobulin-resistant severe autoimmune thrombocytopenia 3 years previously. A cystoscopy revealed multiple varices and severe telangiectasias in the bladder wall. The intensive treatment, such as repeatedly selective embolization of the vesical arteries, proved to be partially effective. Finally, a surgical cystotomy resulted in a gradual improvement in clinical symptoms. To the best of our knowledge, this is the first report of a patient with AT who developed refractory bladder hemorrhage caused by widespread vesical telangiectasias.

Intravenous Cyclophosphamide Pulse Therapy in the Treatment of Systemic Sclerosis-Related Interstitial Lung Disease: A Long Term Study

Objective: Interstitial lung disease (ILD) frequently complicates systemic sclerosis (SSc). Cyclophosphamide (CYC) is a promising immunosuppressive therapy for SSc-related ILD. Our objective was to investigate the effectiveness of an intravenous CYC (iv CYC) pulse regime in SSc-related ILD during treatment and thereafter.Methods:In a prospective observational study ten consecutive patients with SSc-related ILD were treated with iv CYC in a pulse regime lasting from 6 to 24 months. Clinical status, pulmonary functional testing (PFT) and high resolution computed tomography (HRCT) of the chest were evaluated at enrolment and 6, 12 and 24 months thereafter. After treatment withdrawal, patients were followed up every 6 months with PFT and chest HRCT to monitor lung disease.Results:Clinical improvement was apparent in 8 out of 10 patients. The median values of forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and diffusion lung capacity for carbon monoxide (DLCO) as well as ground-glass pattern on HRCT did not change significantly after 6, 12 and 24 months of therapy. The follow-up continued in 8 out of 10 patients after treatment withdrawal for a median of 26.5 months (range: 12-48 months). The final median FVC was 54.5% of predicted value (interquartile range, IQR= 31.6%-94%). Only one patient suffered a FVC deterioration greater than 10%, even though less than 160 ml. The final median DLCO was 68% of predicted value (IQR=38.3-83.6%). Only 2 patients who developed pulmonary arterial hypertension deteriorated their DLCO values of more than 15%.Conclusions:An iv CYC pulse regimen over 24 months may stabilize pulmonary activity in patients with SSc-related ILD during the course of treatment and for a median of 26.5 months thereafter.

Cyclophosphamide pulse therapy did not impact disease progression in a patient with childhood cerebral X-linked adrenoleukodystrophy

Cyclophosphamide pulse therapy did not impact disease progression in a patient with childhood cerebral X-linked adrenoleukodystrophy

Vascularite urticarienne hypocomplémentémique

Hypocomplementemic urticarial vasculitis is a rare disorder characterized by the presence of C1q precipitins associated with a syndrome of urticarial vasculitis, arthralgias, ocular inflammation and obstructive-lung disease. We report the case of a 48-year-old woman with hypocomplementemic urticarial vasculitis. Because of dependance to corticosteroids, cyclophosphamide-pulse therapy was started and resulted in significant clinical improvement. Mycophenolate mofetil was effective as maintenance therapy and resulted in complete resolution of rash, arthralgias, arthritis and uveitis, but had no effect on the obstructive-lung disease.

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.

Current regimen of pulse therapy for pemphigus: Minor modifications, improved results

If administered properly, dexamethasone cyclophosphamide pulse (DCP) therapy has the potential to effect lifelong recovery from pemphigus. The objective of this paper is to highlight various parameters of DCP therapy and also, to report the effects of a few modifications in the regimen. An analysis of 123 patients treated with the DCP/DP regimen over a period of five years (1998 to 2002) is presented here. Seventeen patients who did not start/continue the treatment and three patients who died during the treatment have been excluded from the analysis. Twenty patients who had not yet started families were given only dexamethasone pulses (DPs) while 103 patients received DCPs. Low dose (50 mg/day) cyclophosphamide was used as in the standard regimen. The three modifications introduced into the regimen were: (1) an additional daily dose of oral betamethasone sufficient to control the disease activity during phase I, which was progressively tapered off completely as the patient recovered, (2) use of systemic antibiotics if the patient had skin lesions, and oral anti-candida drugs if the patient had oral ulcers until complete healing, and (3) insistence on thorough cleaning of the skin and scalp with a normal soap and shampoo, and proper maintenance of oral hygiene in spite of skin/mucosal lesions. The regimen consisted of DCP/DP repeated in exactly 28-day cycles, along with 50 mg cyclophosphamide per day, insistence on completing the treatment and avoiding irregular pulses in all patients. The number of DCPs/DPs during phase I varied in different patients depending upon the dose of betamethasone used and the rate of recovery, but phase II (nine DCPs/DPs in exactly 28-day cycles along with 50 mg cyclophosphamide per day) and phase III (only 50 mg cyclophosphamide per day) was fixed at nine months each. This was followed by posttreatment follow-up (phase IV). At present, all the patients are in complete remission. The confirmed period of posttreatment, disease-free follow-up period has already been more than five years in 62 patients, 3-5 years in 41 patients, 2-3 years in three patients and less than two years in six patients. Eight DCP patients and three DP patients developed a relapse (the relapse rates thus being 7.7 and 15% respectively) and received a second course of pulse therapy. They are also in remission at present. The duration of phase I was three months in 62 patients, 4-5 months in 28 patients, 6-9 months in 13, 10-12 months in nine patients and more than 12 months in 11 patients. The maximum daily dose of betamethasone used in these patients was nil in 17 patients, 1-2 mg in 85, 3-4 mg in 16, and> 4 mg in five patients. The modifications employed in this study could ensure the cure of all pemphigus patients by using DCP therapy administered at a private clinic.

Complete Resolution of Dermatomyositis with Refractory Cutaneous Vasculitis by Intravenous Cyclophosphamide Pulse Therapy

Cutaneous ulcers associated with vasculitis are rarely reported in adult-onset dermatomyositis (DM), and are often resistant to treatment, resulting in a poor prognosis. There is no general treatment strategy and the effects of various treatments have never been confirmed histopathologically. A 43-year old man with DM developed refractory multiple cutaneous ulcers which were revealed as vasculitis by skin biopsy. Repeated intravenous cyclophosphamide pulse therapy (IV-CY) without high-dose corticosteroid therapy resulted in complete resolution of the ulcers without adverse effects or severe complications. A repeat biopsy confirmed complete remission of vasculitis. Repeated IV-CY is a useful treatment for induction of clinical remission of DM with cutaneous vasculitis.