Intravenous Pulse Cyclophosphamide Research Articles

Autologous Hematopoietic Stem Cell Transplantation vs Intravenous Pulse Cyclophosphamide in Diffuse Cutaneous Systemic Sclerosis: A Randomized Clinical Trial

Autologous Hematopoietic Stem Cell Transplantation vs Intravenous Pulse Cyclophosphamide in Diffuse Cutaneous Systemic Sclerosis: A Randomized Clinical Trial

Allogenic Mesenchymal Stem Cell Transplantation For Refractory Severe Pyoderma Gangrenosum

Background: Pyoderma Gangrenosum (PG) is a rare and an idiopathic, inflammatory ulcerative condition, which is a diagnosis of exclusion and the treatment are empirical and based on small series or local experience. Mesenchymal stem cells (MSCs) have immunomodulatory and tissue-repairing effects in autoimmune diseases. Objectives: This study aimed to assess the efficacy of UC-MSCT and define whether there is remission of wounded skin in refractory severe PG patient. Methods: Twenty nine year old male PG patient was recuited. UC-MSCs were prepared by the Stem Cell Center of Jiangsu Province (Beike Bio-Technology). The patient underwent two times of UC-MSCT on June 13th, 2012 and June 27th, 2012. The protocol was approved by our Ethics Committee and informed consent was signed from the patient. Results: The PG patient presented with pustules over the lower limbs and was refractory to oral prednisolone (initially 60 mg per day, tapered in 8 weekly steps to 5 mg per day) , pulse intravenous cyclophosphamide (0.6 g per month for 6 months) and he also underwent two times unsuccessful of skin grafting for the lower extremity ulcers. There are no adverse events during the UC-MSCT treatment. After one week, he was free of intense pain and the exudation significantly reduced. Auto-skin grafting was given 4 weeks after UC-MSCT and the grafts came from his back and inner thigh. His ulcers significantly healed with complete resolution of pain 2 months after UC-MSCT. Maintenance therapy followed transplantation included prednisone 5 mg per day and intravenous cyclophosphamide 0.6 g per month. Conclusions: This is the first reported case of successful allogenic UC-MSCT for refractory severe PG. Although additional studies are needed to confirm this finding, we believe that UC-MSCT may be considered a therapeutic option in large area ulcerative PG patients unresponsive to conventional treatments.

FIRST USE OF ALEMTUZUMAB IN BALO CONCENTRIC SCLEROSIS: A CASE REPORT

We describe an unsuccessful treatment of Balo concentric sclerosis (BCS), review the current evidence directing therapy, and propose next steps for exploring this rare and commonly fatal condition.Case ReportA 52–year–old...

Lupus Mesenteric Vasculitis Masquerading as Small Bowel Obstruction

Purpose: A 33-year-old male presented with 4-day history of postprandial abdominal distention, epigastric pain, and vomiting. Past medical history was significant for systemic lupus erythematosus, diagnosed 6 months prior to presentation. The patient had stopped his immunosuppressive medications as he had been asymptomatic. Admission labs included: WBC count: 13.2 x 10E9/L; CRP: 1.38 mg/dL (0-0.80); ESR: 28 mm/h (0-10); ANA 1:640. Twelve hours after admission, patient's clinical status deteriorated as he developed worsening severe abdominal pain and distention. CT abdomen/pelvis was performed, which showed evidence of small bowel obstruction with marked wall thickening, edema, and dilation of the jejunum. There was a large amount of ascites, abnormal bowel wall enhancement (target sign), and engorgement of mesenteric vessels with increased number of visible vessels (comb sign), consistent with mesenteric vasculitis (see Figure). A diagnostic laparoscopy showed no evidence of impending bowel infarction or necrosis. Based on a clinical diagnosis of lupus mesenteric vasculitis, treatment with highdose pulse intravenous steroids and cyclophosphamide was initiated. The patient's symptoms resolved. This case highlights a rare, poorly understood condition associated with lupus along with pathognomonic CT findings. Because of potential fatal consequences, mesenteric vasculitis should be included in the differential diagnosis for patients with lupus that present with abdominal pain. As in this case, response can be rapid if appropriate therapy is instituted promptly.Figure

Dynamics of serum angiopoietin-2 levels correlate with efficacy of intravenous pulse cyclophosphamide therapy for interstitial lung disease associated with systemic sclerosis

Objective Angiopoietin-2 (Ang2) regulates the transition between vascular quiescence and angiogenesis in a context-dependent manner. In systemic sclerosis (SSc), serum Ang2 levels correlate with its disease activity. Therefore, we investigated the clinical significance of monitoring serum Ang2 levels during intravenous pulse cyclophosphamide (IVCY) therapy in SSc patients with interstitial lung disease (ILD).Methods Serum Ang2 levels were determined by a specific enzyme-linked immunosorbent assay in seven SSc patients treated with IVCY and 20 healthy controls. In the patient group, serum samples were drawn the day before each IVCY therapy.Results Serum Ang2 levels tended to be higher in SSc patients before IVCY than in healthy controls and significantly correlated with KL-6, surfactant protein D, erythrocyte sedimentation rate, and C-reactive protein in SSc patients with ILD. In sera drawn before the last IVCY, Ang2 levels were significantly decreased compared with initial levels. Notably, Δ serum Ang2 levels between baseline and after the first IVCY significantly correlated with Δ ILD score between before and after the entire IVCY therapy (r = 0.90, p < 0.01).Conclusion Monitoring Ang2 levels during IVCY treatment may be useful to evaluate and predict the efficacy of this treatment for SSc-ILD.

Effect of Rituximab in Patients with Cyclophosphamide-non-responsive Connective Tissue Disease-Related Interstitial Lung Disease: A Case Series Study

Objective: To report our experience of intravenous cyclophosphamide pulse therapy and the effect of rituximab (RTX) therapy in patients with cyclophosphamide-non-responsive connective tissue disease associated interstitial lung disease (CTD-ILD).Methods: We retrospectively evaluated the medical records of patients with CTD-ILD. All patients received intravenous cyclophosphamide pulse (IVCYC) therapy. The patients who received IVCYC+RTX were non-responsive to IVCYC treatment. At 0 to 6 months prior to the treatment, these patients underwent a pulmonary function test (PFT). High resolution computed tomography was performed before the initiation of treatment.Results: Ten patients were enrolled in this study. A significant percentage of patients showed stabilization or improvement of pulmonary function after treatment. The response rates of the IVCYC and IVCYC+RTX groups were 50% (5/10) and 60% (3/5), respectively.Conclusions: Patients with CTD-ILD who received IVCYC with or without RTX therapy showed a significant improvement in lung function. RTX therapy could be employed as a salvage therapy and combined with IVCYC early for refractory CTD-ILD.

Oral Cyclophosphamide Confounds the Relationship between CYP2C19 and CYP2B6 Pharmacogenetics and Cyclophosphamide-induced premature Ovarian Failure in Lupus Nephritis Patients

Cyclophosphamide treatment of lupus nephritis is associated with ovarian toxicity. Four separate studies have previously demonstrated a lower risk of cyclophosphamide induced premature ovarian failure (POF) in carriers of the CYP2C19*2 null function allele. This hepatic enzyme bioactivates cyclophosphamide. CYP2B6 is also important in the activation of this prodrug however, genetic variants of CYP2B6 have not been associated with POF risk. The aim of this study was to determine the relationship between CYP2C19 and CYP2B6 loss of function variants and prevalence of ovarian toxicity following treatment with monthly pulses of intravenous cyclophosphamide in lupus nephritis patients. In 28 pre-menopausal female patients, there was a 25% incidence of POF. In contrast to previous studies of a similar size we could not detect a significant relationship between the risk of POF and genetic variants of CYP2C19, alone or in combination with variants of CYP2B6. However, 71.4% of the cases with POF had been treated with additional daily oral cyclophosphamide compared with only 4.7% of controls (P < 0.02; OR 14.29 (95% CI, 1.4-144.5). Thus the effect of daily oral cyclophosphamide administration in addition to pulsed intravenous monthly doses may have obscured any protective effect of CYP2C19 loss of function in this cohort.

A Protocol for the Pharmacokinetics of Enteric Coated Mycophenolate Sodium in Lupus Nephritis (POEMSLUN): an open-label, randomised controlled trial

IntroductionMycophenolate sodium, an enteric-coated tablet (EC-MPS), is as effective and safe as mycophenolate mofetil (MMF) in preventing transplant rejection. EC-MPS and MMF improve the outcome of severe lupus nephritis (LN)...

Evaluation of cyclophosphamide pulse therapy as an adjuvant to oral corticosteroid in the management of pemphigus vulgaris

Corticosteroids are the mainstay of treatment for pemphigus. However, despite the introduction of adjuvant therapy for PV, the mortality rate has remained static over the past 2 decades, and consequently, a new adjuvant therapy that is both safe and effective is needed. Intravenous pulse cyclophosphamide has shown encouraging results in few studies, with a better safety profile than the oral formulation, and with better treatment compliance. We undertook a randomized, prospective, non-blinded trial to assess the efficacy of cyclophosphamide pulse therapy (CPT) as an adjuvant to oral corticosteroid in pemphigus vulgaris (PV). We enrolled 60 patients with mild to moderate active disease to receive either daily oral prednisolone or intravenous CPT prednisolone for 1 year, and they were then followed up for another year. At the end of the study period, the time taken to initiate response was similar in both groups, but in the group who received pulse cyclophosphamide, there was a reduced time to remission, a greater proportion of cases who achieved remission, a lower number of patients who relapsed while on treatment or after stopping treatment, and a lower cumulative dose of corticosteroid. Hence, the overall trend was in favour of CPT, although this was not significant. CPT also had a good safety profile. Based on the results of this trial, CPT may be a useful adjuvant in PV in terms of reducing time to remission, relapse rates and cumulative dose of steroid, and it has a good safety profile.

Efficacy and Limitations of Pulse Cyclophosphamide Therapy in Polymyositis and Dermatomyositis

To assess the therapeutic response of intravenous (IV) pulse cyclophosphamide therapy in polymyositis and dermatomyositis. Data of 9 patients (M:F = 2:7) who received IV pulse cyclophosphamide therapy were retrospectively analyzed. The mean symptom duration was 11.33 ± 10.6 months (range, 2-34 months). The cohort comprised (1) primary idiopathic polymyositis (n = 1), (2) primary idiopathic dermatomyositis (n = 1), (3) childhood type associated with vasculitis (n = 1), and (4) associated with collagen vascular disease (n = 6). All patients improved and became clinically asymptomatic after a mean period of 12.33 ± 6.5 months (range, 4-24 months); 5 remained asymptomatic at the end of a median follow-up period of 22 months. All patients received concomitant steroid therapy, and in 6, steroids could be tapered after the initiation of IV pulse cyclophosphamide therapy. In this cohort of polymyositis/dermatomyositis, treatment with IV pulse cyclophosphamide was associated with improvement; the therapeutic response was sustained in majority of the patients.

THU0299 Factors Associated with Long-Term Renal Function Deterioration in Lupus Nephritis Treated Initially with Combined Prednisolone and Mycophenolate Mofetil (MMF) or Tacrolimus (TAC)

ObjectivesTo study the risk factors for renal function decline in patients with lupus nephritis treated initially with combined steroid and MMF or Tac.MethodsData were extracted from a randomized controlled trial...

AB0618 Comparison of mycophenolate mofetil and intravenous cyclophosphamide as induction therapy in korean patients with lupus nephritis

ObjectivesAlthough intravenous cyclophosphamide (IVC) pulses are generally accepted as standard therapy for induction treatment of active proliferative lupus nephritis (LN), several clinical trials have suggested that mycophenolate mofetil (MMF) is...

FRI0385 Long term follow-up after systemic sclerosis patients treated with intravenous cyclophosphamide pulse therapy for interstitial lung disease: a single eustar center (042) experience.

BackgroundTwo RCT and several open-labeled studies demonstrated various efficacy of cyclophosphamide (CYC) for treatment of Systemic sclerosis-associated interstitial lung disease (SSc-ILD) with follow up for 1-4 years.ObjectivesTo analyze the changes...

Two Systemic Lupus Erythematosus Patients With Severe Pleurisy: Similar Presentations, Different Causes

History of the present illness. A 25-year-old woman was diagnosed with systemic lupus erythematosus (SLE) 2 years prior to admission, after she presented with fever, malaise, lymphadenopathy, arthritis, myalgias, malar rash, and positive serologies for antinuclear antibody (ANA) and anti–double-stranded DNA (anti-dsDNA). Additional serology tests were negative for anti-Ro/SSA, anti-La/SSB, RNP, and Sm antibodies, as well as antiphospholipid antibodies (aPL). She was treated with intermittent courses of glucocorticoids (GC) for disease flares. Eight months before admission, she had a severe flare that manifested with high fevers, weight loss, delirium, spastic bladder, and non-nephrotic proteinuria. She was ultimately diagnosed with gray matter transverse myelitis of the conus medullaris and lupus nephritis. She was treated aggressively with pulse GC and intravenous (IV) cyclophosphamide (CYC), which led to resolution of all symptoms. After completion of a 6-month course of IV CYC, she was maintained on 20 mg of prednisone. One month prior to admission, she was admitted to another hospital with leftsided pleurisy, dyspnea, and high fever. A chest computed tomography (CT) scan excluded pulmonary embolism, but showed bilateral lung lower lobe consolidations with pleural effusions (left larger than right) and a small fluid collection adjacent to her spleen. Her blood cultures grew Salmonella. Her symptoms improved with cefepime and high-dose GC, and she was discharged home 2 weeks later on 60 mg of daily prednisone and oral levofloxacin for a total of 3 weeks of antibiotics. In addition, she was discharged on trimethoprim/sulfamethoxazole (TMP/SMX) 160/800 mg 3 times weekly for Pneumocystis jiroveci pneumonia (PCP) prophylaxis. One week before her current admission, she was started on 1,000 mg of mycophenolate mofetil (MMF) daily. She then presented to our hospital with acute left-sided pleuritic chest pain, dyspnea, and arthralgias. She did not have fever or cough.

Pediatric lupus nephritis: more options, more chances?

Lupus nephritis (LN) is more common and severe in childhood-onset systemic lupus erythematosus (SLE) than in adults. It is one of the major causes of acute kidney injury (AKI) and chronic kidney disease (CKD) in children. Steroid therapy has been used as the first-line treatment for SLE since 1970, and has improved the survival of SLE patients from ∼ 50% to >80%. Over the years many immunosuppressive drugs, including pulse methylprednisolone, oral cyclophosphamide, pulse intravenous cyclophosphamide, mycophenolate mofitil, rituximab, and tacrolimus, have been combined with prednisolone, further improving survival rates to 90%-95%. However, the effectiveness of these drugs is still uncertain, as most seem very good in the beginning, but in studies examining longer-term follow-up the remission of disease does not remain. Fatal infection is still a major complication of aggressive chemotherapy, and the potential benefits as well as adverse events from each drug need to be considered. Induction of remission is the major aim of therapy, with safe and effective maintenance therapy for long-term remission. The survival rates of many published studies vary widely because of differences in patients and treatment modalities, severity of disease, renal histopathology, racial factors, and duration of follow-up. Finding the optimal treatment for SLE and related co-morbidities is highly challenging, and will likely involve a complex combination of different drugs for different patients in the search for giving them an opportunity to be free from this debilitating disease.

Analysis of a Novel Protocol of Pulsed Intravenous Cyclophosphamide for Recalcitrant or Severe Ocular Inflammatory Disease

To analyze the success rate of pulsed intravenous (IV) cyclophosphamide (CyP) for noninfectious ocular inflammatory disease and to identify risk factors for failure of therapy. Retrospective, interventional, noncomparative cohort study. One hundred ten eyes of 65 patients. Through a computer search of the Massachusetts Eye Research and Surgery Institution's database, we identified patients who were treated with IV CyP between May 2005 and April 2012. We obtained demographic and clinical information through review of the electronic health record of each patient. Clinical response, corticosteroid-sparing effect, recurrence rate, calculated "risk factors" for failure, visual acuity, and adverse reactions. Pulsed IV CyP achieved complete remission of inflammation (for ≥ 2 visits) in 54 patients (84.4%). Sustained remission of inflammation occurred in 70% of patients within 3 months, 86.6% of patients within 6 months, and 91.7% within 9 months. The mean time to achieving quiescence was 3.5 months. The success rate in reducing corticosteroid to prednisone ≤ 10 mg/d within 6 months, while maintaining control of ocular inflammation, was 89.7% (95% confidence interval [CI], 81.1-93.5%). The mean duration of clinical remission for those patients who had a positive response to CyP was 32.67 months (95% CI, 25.91-39.43). Relapse of vasculitis was observed in 1 patient (1.5%) after completing the course of therapy. Early initiation of therapy during the course of the disease was correlated with a lesser rate of recurrence (P = 0.028). The most common adverse effects were nausea (29%) and transient lymphopenia (26%). The mean best-corrected visual acuity (BCVA) improved from 0.59 ± 0.66 at baseline to 0.30 ± 0.54 at 6 months of follow-up (P<0.001). The mean follow-up period was 31.61 ± 20.47 months. Pulsed IV CyP employing our protocol results in an extremely high rate of sustained complete remission in patients with recalcitrant and fulminant, vision-threatening ocular inflammatory disorders, with an excellent safety profile in the hands of physicians trained and skilled in the art of this therapy. It also allows tapering and discontinuing corticosteroids in most patients. Early initiation of therapy may decrease the risk of relapses. The authors have no proprietary or commercial interest in any materials discussed in this article.

Microscopic polyangiitis complicated with ileal involvement detected by double-balloon endoscopy: a case report

BackgroundMicroscopic polyangiitis is characterized by pauci-immune, necrotizing small-vessel vasculitis and an anti-neutrophil cytoplasmic antibody-associated vasculitis. Although gastrointestinal involvement in microscopic polyangiitis is not rare, endoscopic observation of it is extremely rare. To the best of our knowledge, this is the first case report of small intestinal involvement in microscopic polyangiitis detected and followed up by double-balloon endoscopy.Case presentationA 70-year-old Japanese woman was transferred to our hospital for close examination of suspected small intestinal lymphoma. Retrograde double-balloon endoscopy revealed various forms of ulcers with redness and edema in the ileum. Histological findings suggested ischemic changes. Because mononeuritis multiplex and a fever spike appeared later, vasculitis was suspected. The perinuclear anti-neutrophil cytoplasmic antibody titer was elevated. Nerve biopsy results suggested vasculitis. From these findings, microscopic polyangiitis was diagnosed. It was suggested that microscopic polyangiitis caused the intestinal involvement. Intravenous pulse cyclophosphamide and oral predonisolone were started. After treatment, perinuclear anti-neutrophil cytoplasmic antibodies decreased to the normal range. Retrograde double-balloon endoscopy after treatment showed ulcer scars and no ulcer.ConclusionThe cause of gastrointestinal involvement in microscopic polyangiitis is ischemia due to vasculitis. It is difficult to diagnose small-vessel vasculitis by endoscopic biopsy. Although histological evidence of microscopic polyangiitis is important, the treatment should not be delayed by repeating the biopsy, because such delay can result in adverse sequela.This case report shows that microscopic polyangiitis should be considered as a differential diagnosis when small intestinal changes like those in the present case are observed by endoscopy.

Clinical significance of monitoring serum adiponectin levels during intravenous pulse cyclophosphamide therapy in interstitial lung disease associated with systemic sclerosis

Objective: To investigate the clinical significance of monitoring serum adiponectin levels during intravenous pulse cyclophosphamide (IVCY) in systemic sclerosis (SSc) patients with interstitial lung disease (ILD).Methods: Serum adiponectin levels were determined by a specific enzyme-linked immunosorbent assay in eight SSc patients with active ILD who underwent IVCY and 27 healthy controls. In patients, serum samples were drawn the day before each IVCY.Results: Serum adiponectin levels were significantly decreased in SSc patients with active ILD before the first IVCY compared with healthy controls [median (25–75 percentile): 3.21 (2.70–4.19) vs. 7.42 (6.06–10.82) μg/ml; P < 0.01). After the completion of whole IVCY, serum adiponectin levels were significantly increased [17.55 (6.47–39.45) μg/ml; P < 0.05] compared with the initial levels, and this increase significantly correlated with the decrease in ILD scores. Importantly, the dynamics of serum adiponectin levels during the IVCY therapy reflected its efficacy against SSc-ILD over the treatment and the follow-up period.Conclusion: The monitoring of serum adiponectin levels during the IVCY treatment may be useful to identify SSc patients with ILD refractory to the treatment and at high risk for exacerbations during the follow-up period.

Efficacy of low-dose intravenous cyclophosphamide in systemic lupus erythematosus presenting with Guillain-Barré syndrome-like acute axonal neuropathies: report of two cases

There are few cases of Guillain-Barré syndrome (GBS), particularly of atypical variants, occurring in association with systemic lupus erythematous (SLE). Reports addressing a specific therapy thus remain almost anecdotal. It is therefore challenging to determine the treatment that is best suited for this subset of patients, especially if initial conventional therapy for GBS fails. We present two cases of GBS-like acute axonal neuropathies, one with acute motor axonal neuropathy (AMAN), and another with acute motor sensory axonal neuropathy (AMSAN), presenting early in the course of SLE. The first case failed to respond to therapy with intravenous immunoglobulins (IVIG) and plasmapheresis, but achieved a favorable outcome when high-dose glucocorticoids along with low-dose intravenous (IV) cyclophosphamide pulses were given. The second case responded favorably to high-dose glucocorticoids, IVIG, and low-dose IV cyclophosphamide pulses. Both patients have remained in clinical remission and without neurologic sequelae after 10 and three years of follow-up, respectively.

AP-VAS 2012 case report: a case of lupus nephritis with predominant synchronous cellular crescent formation and myeloperoxidase-antineutrophil cytoplasmic antibody seropositivity.

Several cases with an overlap of antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) and lupus nephritis (LN) features have been reported in recent years. However, the clinical and the pathologic features of this condition, including mode of development, histology, and response to treatment, are not fully understood. We report a 77-year-old woman who was diagnosed with Sjögren syndrome 15years previously. The patient presented with acute worsening of renal function and was diagnosed with new-onset systemic lupus erythematosus. A renal biopsy specimen revealed proliferative LN with synchronous cellular crescents. She was also seropositive for myeloperoxidase-ANCA. Together with the positive staining for immunoglobulins and complement factors on immunofluorescence microscopy and scant subendothelial deposits by electron microscopy, we reached a diagnosis of ANCA-associated crescentic GN overlapping with LN. Although immunosuppressive treatment with methylprednisolone pulse therapy and intravenous cyclophosphamide followed by oral predonisolone was initiated, along with intermittent hemodialysis, these treatments did not induce remission of her GN. Therefore, she continued regular intermittent hemodialysis. However, she died because of candida pneumonia 4months after admission. Generally, the glomeruli of patients with ANCA-associated GN exhibit different stages of crescents, namely cellular, fibrocellular, or fibrous. The histologically synchronous crescents in this case indicate that ANCA-associated GN overlapping with LN can progress more rapidly than that without LN. This overlapping type of GN may be resistant to conventional immunosuppressive therapies.