Cumulative Dose Of Cyclophosphamide Research Articles

Incidence of sterile hemorrhagic cystitis in tumor-bearing dogs concurrently treated with oral metronomic cyclophosphamide chemotherapy and furosemide: 55 cases (2009-2015).

OBJECTIVE To determine the incidence of sterile hemorrhagic cystitis (SHC) in tumor-bearing dogs concurrently treated with oral metronomic cyclophosphamide chemotherapy and furosemide. DESIGN Retrospective case series. ANIMALS 55 dogs. PROCEDURES Record databases of 2 specialty practices were searched to identify dogs treated with oral metronomic cyclophosphamide chemotherapy in conjunction with furosemide for a minimum of 28 days between January 2009 and December 2015. Information extracted from the records included signalment, tumor diagnosis, cyclophosphamide and furosemide dosages, and concurrent medications. Confirmed SHC was defined as the presence of gross or microscopic hematuria and clinical signs associated with lower urinary tract disease in the absence of infection or neoplasia of the urinary tract; the definition for suspected SHC was the same, except the absence of infection or neoplasia of the urinary tract was not confirmed. RESULTS Cyclophosphamide dosage varied from 6.5 to 18.6 mg/m2 once daily to 6.3 to 49.2 mg/m2 every other day. Median duration of cyclophosphamide administration was 272 days (range, 28 to 1,393 days). Median cumulative dose of cyclophosphamide administered was 2,898 mg/m2 (range, 224 to 14,725 mg/m2). Median furosemide dose was 1.4 mg/kg (0.64 mg/lb). Confirmed or suspected SHC was identified in 2 of 55 (3.6%) dogs. Cyclophosphamide administration was discontinued for the dog with confirmed SHC but not the dog with suspected SHC. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that oral administration of furosemide in conjunction with oral metronomic cyclophosphamide chemotherapy was associated with a low incidence of SHC, which suggested that furosemide may protect against cyclophosphamide-induced SHC.

The First Case of Primary Cardiac Lymphoma, Diffuse Large B-Cell Type, Successfully Treated with EPOCH-R

Introduction:Primary cardiac lymphomas are rare non-Hodgkin lymphomas and account for less than 1% of intrinsic cardiac tumors and extranodal Non-Hodgkin lymphomas. Patients can present with a variety of manifestations including heart failure, chest pain, dyspnea, arrhythmias, and tamponade. Presently, there are no formal established guidelines for treatment of primary cardiac lymphomas.Presentation:This is a case of a 72-year-old white man with past medical history significant for paroxysmal atrial fibrillation and known pulmonary, renal, and cutaneous sarcoidosis who presented with palpitations, dyspnea on exertion and lightheadedness for two-weeks. He was evaluated by his cardiologist who recommended an elective atrial fibrillation radiofrequency ablation (RFA). Prior to the planned procedure a transesophageal echocardiogram was performed which revealed a large tissue density within the pericardial space, adjacent to the free wall of the right ventricle and right atrium, and invading the myocardium with extension through the interatrial septum (Figure 1). The RFA was aborted and the patient was admitted for further evaluation of the new cardiac mass, initially suspected to be cardiac sarcoidosis.Subsequent work up included a cardiac MRI, which displayed a dense 7.5 cm by 3.5 cm mass involving the right ventricle and right atrium, wrapping around the great vessels. Right heart cardiac catheterization with endomyocardial biopsy was performed which revealed clusters of large atypical B lymphoid cells with the following immunophenotype: CD30+, CD79a+, Pax5+, Alk 1-, CD138-, CD 10-, Bcl 2-, Bcl 6-, CD45-, focally CD20+, Ki67: 80-90% (Figure 2). These findings were consistent with diffuse large B cell lymphoma (DLBCL). His PET-CT demonstrated absence of extracardiac lesions, confirming the diagnosis of primary cardiac lymphoma (PCL) (Figure 3).The patient began treatment with a EPOCH-R (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) modified chemotherapy based regimen which consisted of a pre-phase treatment with dexamethasone 12 mg once daily for four days, a cumulative dose of cyclophosphamide 600 mg/m2 over five days and etoposide 50 mg/m2 for three days. Doses of cyclophosphamide and etoposide were initiated at lower doses and titrated upward to reach the target dose. This strategy was invoked based upon prior experiences and studies that suggest that a modest pre-phase cytoreduction reduces the risk of cardiac perforation. Rituximab was given on day six. He was also given granulocyte colony stimulating factor (GCSF).Our patient was observed closely in the cardiac intensive care unit throughout the duration of chemotherapy due to the high risk of fatal arrhythmia, tamponade, perforation and heart failure. Interim restaging, confirmed complete remission of the intracardiac mass. His post chemotherapy TTE demonstrated a slight reduction in ejection fraction (Figure 1). He received a total of three cycles of EPOCH-R and remained hemodynamically stable within the hospital. No further chemotherapy was given due to a decline in the patient's performance status.Conclusion:This is the first documented case of primary cardiac diffuse large B cell lymphoma successfully treated with EPOCH-R consisting of a modest pre-phase cytoreduction with steroids, cyclophosphamide and etoposide. The high area under the curve of doxorubicin in this setting is far less cardiotoxic. This regimen reduces the risk of cardiac perforation in patients with relatively normal ejection fractions. [Display omitted] [Display omitted] [Display omitted] DisclosuresO'Connor:Mundipharma: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Research Funding; TG Therapeutics: Research Funding; Bristol Myers Squibb: Research Funding; Spectrum: Research Funding; Celgene: Research Funding; Bristol Myers Squibb: Research Funding; Celgene: Research Funding; TG Therapeutics: Research Funding.

CD4 cell count and CD4/CD8 ratio increase during rituximab maintenance in granulomatosis with polyangiitis patients.

IntroductionRituximab (RTX) is a B cell-depleting agent approved for the treatment of granulomatosis with polyangiitis (GPA). RTX reduces antibody producing precursor plasma cells and inhibits B and T cells interaction. Infections related to T cell immunodeficiency are not infrequent during RTX treatment. Our study investigated CD4 cell count and CD4/CD8 ratio in GPA patients during the first two years of long-term RTX treatment.MethodsA single centre cohort study of 35 patients who received median total cumulative dose of cyclophosphamide (CYC) of 15 g and were treated with RTX 2 g followed by retreatment with either 2 g once annually or 1 g biannually. Serum levels of total immunoglobulin (Ig) and lymphocytes subsets were recorded at RTX initiation and at 3, 6, 12, 18 and 24 months. Low CD4 count and inverted CD4/CD8 ratio were defined as CD4 < 0.3 × 109/l and ratio < 1.ResultsThe CD4 cell count and CD4/CD8 ratio decreased slightly following the initial RTX treatment and then increased gradually during maintenance treatment. While the proportion of patients with low CD4 cell count decreased from 43% at baseline to 18% at 24 months, the ratio remained inverted in 40%. Oral daily prednisolone dose at baseline, CYC exposure and the maintenance regimen did not influence the CD4 cell count and ratio. Being older (p = 0.012) and having a higher CRP (p = 0.044) and ESR (p = 0.024) at baseline significantly increased the risk of inverted CD4/CD8 ratio at 24 months. Inverted ratio at baseline associated with lower total Ig levels during the study.ConclusionsOverall, the CD4 and CD4/CD8 ratio increased during maintenance RTX therapy in GPA with no discernible impact of other immunosuppressive therapy. However the increase in CD4 was not followed by an increase in the CD4/CD8 ratio, especially in older patients. Inverted CD4/CD8 ratio associated with lower Ig levels, suggesting a more profound B cell depleting effect of RTX with a relative increase in CD8+ lymphocytes.

No Evidence for the Benefit of Gonadotropin-Releasing Hormone Agonist in Preserving Ovarian Function and Fertility in Lymphoma Survivors Treated With Chemotherapy: Final Long-Term Report of a Prospective Randomized Trial.

We have reported previously that after 1-year follow up, gonadotropin-releasing hormone agonist (GnRHa) did not prevent chemotherapy-induced premature ovarian failure (POF) in patients with lymphoma, but may provide protection of the ovarian reserve. Here, we report the final analysis of the cohort after 5 years of follow up. A total of 129 patients with lymphoma were randomly assigned to receive either triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) during chemotherapy. Ovarian function and fertility were reported after 2, 3, 4, and 5 to 7 years of follow up. The primary end point was POF, defined as at least one follicle-stimulating hormone value of > 40 IU/L after 2 years of follow up. Sixty-seven patients 26.21 ± 0.64 years of age had available data after a median follow-up time of 5.33 years in the GnRHa group and 5.58 years in the control group (P = .452). Multivariate logistic regression analysis showed a significantly increased risk of POF in patients according to age (P = .047), the conditioning regimen for hematopoietic stem cell transplant (P = .002), and the cumulative dose of cyclophosphamide > 5 g/m(2) (P = .019), but not to the coadministration of GnRHa during chemotherapy (odds ratio, 0.702; P = .651). The ovarian reserve, evaluated using anti-Müllerian hormone and follicle-stimulating hormone levels, was similar in both groups. Fifty-three percent and 43% achieved pregnancy in the GnRHa and control groups, respectively (P = .467). To the best of our knowledge, this is the first long-term analysis confirming that GnRHa is not efficient in preventing chemotherapy-induced POF in young patients with lymphoma and did not influence future pregnancy rate. These results reopen the debate about the drug's benefit in that it should not be recommended as standard for fertility preservation in patients with lymphoma.

Brief Report: Menopause and Primary Ovarian Insufficiency in Women Treated for Antineutrophil Cytoplasmic Antibody-Associated Vasculitides.

One of the side effects of cyclophosphamide is earlier menopause and primary ovarian insufficiency. This study was undertaken to investigate the onset of menopause and the incidence of primary ovarian insufficiency in women with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), especially after treatment with orally administered cyclophosphamide. We retrospectively studied the onset of menopause and the influence of cyclophosphamide in women diagnosed as having AAV in our center between 1970 and 2012. Ninety-four premenopausal women diagnosed as having AAV were included. Sixty-seven patients received cyclophosphamide, and 27 received other, mostly immunosuppressive, medication. Forty-six cyclophosphamide-treated women developed menopause, 22 of whom were considered to have primary ovarian insufficiency. None of the patients who were not treated with cyclophosphamide developed primary ovarian insufficiency. There was a significant association between a cumulative cyclophosphamide dose of >16.6 gm, versus a cumulative dose of <16.6 gm, and menopause (χ(2) = 8.72, P = 0.003; odds ratio [OR] 2.60 [95% confidence interval 1.38-4.90]). In addition, there was a significant association between a cumulative cyclophosphamide dose of <16.6 gm, versus no cyclophosphamide exposure, and menopause (χ(2) = 16.37, P < 0.001; OR 7.32 [95% confidence interval 2.79-19.20]). Both women who received cyclophosphamide and those who did not experienced involuntary childlessness. Earlier menopause and primary ovarian insufficiency frequently develop after oral cyclophosphamide therapy in premenopausal women with AAV. Involuntary childlessness is common after the development of primary ovarian insufficiency, but it also occurs in women not treated with cyclophosphamide. These findings emphasize the importance of the use of drugs that are not toxic to gonadal function in women of childbearing age.

Late Nephrotoxicity of Intensive Modified Program NHL-BFM-90 in Adult Poor Prognosis Patients with Diffuse Large B-Cell Lymphoma

Aim. To evaluate late nephrotoxicity of intensive modified program NHL-BFM-90 (mNHL-BFM-90) in adult poor-prognosis patients with diffuse large B-cell lymphoma (DLBCL).Materials and methods. The data of laboratory tests of blood and urine of 40 patients with DLBCL which received mNHL-BFM-90 protocol in the Hematology Research Center in the period from 2002 to 2009 years was analyzed. Group consisted of 20 men, 20 women, aged from 31 to 76 years, median age - 56.5 years at the time of the survey, the median period after therapy- 6 years. Individual cumulative dose of ifosfamide - 8-12 g / m2, cyclophosphamide - 2-3 g / m2, methotrexate - 6-9 g / m2. Comparison group included 19 patients (8 men and 11 women), aged from 39 to 78 years, median age - 70 years at the time of the survey, who received therapy to CHOP or R-CHOP. The median period after therapy - 5,5 years. Individual cumulative dose of cyclophosphamide - 3-6 g / m2. Laboratory tests of blood and urine were performed before chemotherapy and after 5 years after treatment.Results. From all 40 patients with DLBCL received mNHL-BFM-90, signs of chronic kidney disease were found in 32 (80%) patients, only 2 (5%) of them showed a decrease in creatinine clearance daily. In comparison group signs of chronic kidney disease were found in 12 (63%) patients, 2 patients (10.5%) showed a reduction in the daily creatinine clearance. No significant differences in the manifestations of nephrotoxicity in the long term between comparison groups were found. No significant differences in the manifestations of nephrotoxicity in the long term period were found between two groups of patients (who underwent and not underwent acute renal failure during high-dose chemotherapy). Amount of nephrotoxicity signs was significantly dependent on the presence of hypertensive disease in history (p = 0.02).Conclusion. Nephrotoxicity of high-dose mNHL-BFM 90 exceeds significantly nephrotoxicity program CHOP / R-CHOP. Conducting high-dose chemotherapy in 10 (25%) patients complicated by acute renal failure, 2 (20%) patients required hemodialysis in contrast to the group of standard chemotherapy without such complications (p=0,01). However, in the long term observations there weren't significant differences in the nephrotoxic manifestations between two groups. Impaired renal function in the long term period observed in 100% of patients undergoing acute renal failure during treatment and only in 71% of patients without acute renal failure (p=0,04). It was comparable repairing of renal function in the long term in patients undergoing high-dose therapy between patients with and without acute renal failure among those who showed signs of chronic kidney disease. DisclosuresNo relevant conflicts of interest to declare.

Prevalence of premature ovarian failure in systemic lupus erythematosus patients treated with immunosuppressive agents in Thailand.

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects most women of reproductive age. The prevalence of premature ovarian failure (POF) in SLE patients is higher than that in the general population. However, the data on this condition are limited in Asian countries. To determine the prevalence and associated factors of POF in SLE patients who received immunosuppressive therapy. Women aged 18-40 years who were diagnosed with SLE according to the 1997 revised criteria for the classification of SLE or patients with biopsy-proven lupus nephritis were evaluated. All patients had received at least one of the following immunosuppressive agents: cyclophosphamide (CYC), azathioprine, mycophenolate mofetil, chlorambucil or cyclosporine for more than six months. POF was diagnosed in those who had sustained amenorrhea for more than six consecutive months, with a level of estradiol ≤ 110 pmol/L (30 pg/mL) and follicle stimulating hormone ≥40 IU/L. Ninety two SLE patients were included in this study. Mean age at enrollment was 30 ± 6.9 years and disease duration was 103 ± 67.5 months. The mean Systemic Lupus International Collaborating Clinics/ American College of Rheumatology (SLICC/ACR) damage index was 1.7 ± 1.7. Seventy five patients (82%) had lupus nephritis. Sixty four patients (70%) received CYC. Eleven patients (12%) with POF were observed. For the binary logistic regression model, CYC cumulative dosage of more than 10 g was the only independent risk factor of POF (hazard ratio 17.0, 95% CI 1.96-147.72, p = 0.01). From our data, 12% of SLE patients developed POF. A cumulative dose of CYC of more than 10 g was the only risk factor for POF. To prevent these events, systematic evaluation and early recognition of POF should be promoted in the care of SLE patients.

Incidence of Cyclophosphamide-induced Urotoxicity and Protective Effect of Mesna in Rheumatic Diseases.

To assess bladder toxicity of cyclophosphamide (CYC) and uroprotective effect of mesna in rheumatic diseases. Data of 1018 patients (725 women/293 men) treated with CYC were evaluated in this retrospective study. All of the following information was obtained: the cumulative CYC dose, route of CYC administration, duration of therapy, concomitant mesna usage, and hemorrhagic cystitis. Cox proportional hazard model was used for statistics. We identified 17 patients (1.67%) with hemorrhagic cystitis and 2 patients (0.19%) with bladder cancer in 4224 patient-years. The median time for diagnosis to hemorrhagic cystitis was 10 months (4-48) and bladder cancer was 8 years (6-10.9). There were 583 patients (57.2%) who received mesna with intravenous CYC therapy. We observed similar incidence rate for hemorrhagic cystitis in both patient groups concomitantly treated with or without mesna [9/583 (1.5%) vs 8/425 (1.8%) respectively, p = 0.08]. Cumulative CYC dose (HR for 10-g increments 1.24, p < 0.001) was associated with hemorrhagic cystitis. Cumulative dose was the only risk factor for hemorrhagic cystitis in patients treated with CYC. No proof was obtained for the uroprotective effect of mesna in our cohort.

Frequency, risk factors and prophylaxis of infection in ANCA-associated vasculitis.

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are potentially life-threatening disorders. Even though immunosuppressive therapy improves the prognosis, adverse events, either attributable to persistent disease activity or side effects of treatment remain a challenge. Infectious complications are the leading cause of death in the first year after diagnosis and a major cause of morbidity and mortality thereafter. Their incidence in clinical trials varies considerably but opportunistic and life-threatening infections, such as Pneumocystis jirovecii pneumonia or systemic cytomegalovirus infections, are frequent and thus predisposing/risk factors need to be defined. Pneumocystis jirovecii pneumonia has been associated with a lymphocyte count below 300/mm(3) . Additionally, besides the aggressiveness of the immunosuppressive regimen administered (especially the cumulative dose of steroids and cyclophosphamide), an elevated serum creatinine or dialysis dependency, older age and pulmonary involvement increase the rate of infectious complications. We suggest to routinely prescribe trimethoprim-sulfamethoxazole or antimicrobial agents such as pentamidine in case of intolerance or contraindication in the early phase of induction therapy irrespective of the immunosuppressive strategy used and to continue therapy, together with other targeted measures (antiviral, antimycotic or antibiotic) in the presence of risk factors for a prolonged period of time. Finally, there is an urgent need to standardize the reporting of infectious complications in clinical trials to enable comparing the adverse event spectrum of distinct treatment approaches more appropriately.

Age-related toxicity in patients with rhabdomyosarcoma: a report from the children's oncology group.

On the Fourth Intergroup Rhabdomyosarcoma study, older children experienced excessive neurotoxicity, whereas younger children had increased myelosuppression. The purpose of this study was to determine whether the same pattern of toxicity was seen on the successor study when use of growth factor was required and dosing of chemotherapy was different by performing a retrospective cohort analysis on patients treated on Children's Oncology Group protocol D9803. Toxicity data were analyzed by stratifying children into 4 age groups. The frequency of grade 3/4 neurotoxicity, myelosuppression, infection, and mucositis was predicted for each age group. The cumulative doses of vincristine and cyclophosphamide administered were measured as percent of protocol-prescribed dose. Adolescents (aged 15+) were more likely to experience neurotoxicity compared with younger patients (odds ratio, 3.6; P<0.0001). There was no difference in myelosuppression, infection, or mucositis. The mean percent protocol-prescribed doses administered for vincristine and cyclophosphamide did not differ much by age group. Adolescents experienced more neurotoxicity with vincristine compared with younger patients. No differences in other toxicities were observed between age groups. As adolescents received at least 85% of protocol-prescribed doses of vincristine, it is difficult to attribute the poorer survival in this age group to inadequate protocol-delivered therapy.

Shorter-Duration Therapy Using Vincristine, Dactinomycin, and Lower-Dose Cyclophosphamide With or Without Radiotherapy for Patients With Newly Diagnosed Low-Risk Rhabdomyosarcoma: A Report From the Soft Tissue Sarcoma Committee of the Children's Oncology Group

Intergroup Rhabdomyosarcoma Study Group (IRSG) studies III and IV showed improved failure-free survival (FFS) rates with vincristine, dactinomycin, and cyclophosphamide (VAC; total cumulative cyclophosphamide dose, 26.4 g/m(2)) compared with vincristine and dactinomycin (VA) for patients with subset-one low-risk embryonal rhabdomyosarcoma (ERMS; stage 1/2 group I/II ERMS or stage 1 group III orbit ERMS). The objective of Children's Oncology Group ARST0331 was to reduce the length of therapy without compromising FFS for this subset of low-risk patients by using VA in combination with lower-dose cyclophosphamide (total cumulative dose, 4.8 g/m(2)) plus radiotherapy (RT). This noninferiority prospective clinical trial enrolled newly diagnosed patients with subset-one clinical features. Therapy included four cycles of VAC followed by four cycles of VA over 22 weeks. Patients with microscopic or gross residual disease at study entry received RT. With a median follow-up of 4.3 years, we observed 35 failures among 271 eligible patients versus 48.4 expected failures, calculated using a fixed outcome based on the FFS expected for similar patients treated on the IRSG D9602 protocol. The estimated 3-year FFS rate was 89% (95% CI, 85% to 92%), and the overall survival rate was 98% (95% CI, 95% to 99%). Patients with paratesticular tumors had the most favorable outcome. Three-year cumulative incidence rates for any local, regional, or distant failures were 7.6%, 1.5%, and 3.4%, respectively. Shorter-duration therapy that included lower-dose cyclophosphamide and RT did not compromise FFS for patients with subset-one low-risk ERMS.

Cyclophosphamide: As bad as its reputation? Long-term single centre experience of cyclophosphamide side effects in the treatment of systemic autoimmune diseases

Despite new treatment modalities, cyclophosphamide (CYC) remains a cornerstone in the treatment of organ or life-threatening vasculitides and connective tissue disorders. We aimed at analysing the short- and long-term side-effects of CYC treatment in patients with systemic autoimmune diseases. Chart review and phone interviews regarding side effects of CYC in patients with systemic autoimmune diseases treated between 1984 and 2011 in a single university centre. Adverse events were stratified according to the "Common Terminology Criteria for Adverse Events" version 4. A total of 168 patients were included. Cumulative CYC dose was 7.45 g (range 0.5-205 g). Gastro-intestinal side effects were seen in 68 events, hair loss occurred in 38 events. A total of 58 infections were diagnosed in 44/168 patients (26.2%) with 9/44 suffering multiple infections. Severity grading of infections was low in 37/58 cases (63.8%). One CYC-related infection-induced death (0.6%) was registered. Amenorrhoea occurred in 7/92 females (7.6%) with 5/7 remaining irreversible. In females with reversible amenorrhoea, prophylaxis with nafarelin had been administered. Malignancy was registered in 19 patients after 4.7 years (median, range 0.25-22.25) presenting as 4 premalignancies and 18 malignancies, 3 patients suffered 2 premalignancies/malignancies each. Patients with malignancies were older with a higher cumulative CYC dose. Death was registered in 28 patients (16.6%) with 2/28 probably related to CYC. Considering the organ or life-threatening conditions which indicate the use of CYC, severe drug-induced health problems were rare. Our data confirm the necessity to follow-up patients long-term for timely diagnosis of malignancies. CYC side-effects do not per se justify prescription of newer drugs or biologic agents in the treatment of autoimmune diseases.

Urine uromodulin estimation in partial bladder outlet obstruction and cyclophosphamide-induced haemorrhagic cystitis models in rats.

Uromodulin (UMOD) is a glycoprotein excreted by the thick ascending limb of the Henle's loop and distal convoluted tubule cells, playing various, yet still unclear roles. An abnormal urinary UMOD excretion is observed in many pathophysiological conditions. The aim of our study was to assess urine UMOD excretion in experimental partial bladder outlet obstruction (PBOO), reflecting BPH in humans, and in cyclophosphamide-induced haemorrhagic cystitis (CP-HC). PBOO and CP-HC rats and two appropriate control groups were studied. The PBOO model was surgically induced by partial proximal urethral obstruction and CP-HC by four i.p. cyclophosphamide administrations (every two days). 24-hour urine collections were performed in both PBOO (on 3rd, 7th, 12th and 15th day after surgery) and CP-HC rats (on 1st, 3rd, 5th and 7th day). UMOD was determined with the ELISA method. Both 24-hour urinary UMOD excretion and urinary UMOD concentrations were determined. In the overall assessment, PBOO rats were characterized by decreased mean urinary UMOD concentration. However, as the urine volume, except for transient drop on 3rd day following PBOO operation, was steadily increasing, the daily urinary uromodulin excretion did not differ from the control one. Contrary to PBOO, CP-HC rats demonstrated mean urinary concentration similar to that of the control rats, while their 24hr UMOD excretion in urine was almost doubled due to urine volume increase (from 1.6 up to almost 3 fold). The highest UMOD urinary output was observed after the 3rd and 4th doses of cyclophosphamide. A reduced urinary UMOD excretion in early PBOO phase may be considered as a marker of distal tubular cells damage due to incomplete bladder emptying and increased pressure retrograding to distal tubules. This effect disappears with structural, adaptive histological changes of the bladder wall leading to an improved voiding. In CP-HC animals, the elevated urinary UMOD level may be associated with complex inflammatory response due to the cytotoxic CP action. UMOD assessment in this model may reflect renal and urological toxicity as UMOD excretion rises with the cumulative cyclophosphamide dose.

Anti-müllerian Hormone in Reproductive Age Women With Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune systemic and chronic disease. Fertility in SLE patients is considered normal; factors that have been associated in these patients with ovarian failure are: disease activity, autoantibodies, and the use of cytotoxic agents. The anti-Müllerian hormone (AMH) is a marker that helps to determine the follicular reserve. ObjectiveThe objective was to determine AMH levels in women of reproductive age with SLE. Material and methodsWe included 65 women with SLE classified according to the 1997 ACR criteria, 18–40-years old. We obtained demographic, clinical, obstetric, and gynecological characteristics as well as serum levels of AMH. We performed a bivariate analysis among patients with low ovarian reserve and those with normal ovarian reserve. We also performed a correlation analysis between activity and damage index and between the cumulative cyclophosphamide dose and AMH levels. ResultsWe found a median of serum AMH in SLE patients of .61ng/ml. The prevalence of low ovarian reserve in our study was 3.07%. We found a median MEX-SLEDAI score of 1 point and the median SLICC score was 2 points. Twenty-five patients (38.4%) had used cyclophosphamide and their cumulative average dose was 7.5g. ConclusionsWe found a median of AMH of .61ng/ml in our population. The prevalence of low ovarian reserve in SLE patients was 3.07%. We did not find a correlation between AMH levels, the use of cyclophosphamide, and disease activity.

Regular menstrual cycles do not rule out ovarian damage in adult women with systemic lupus erythematosus

The aim of this study was to evaluate ovarian reserve markers in women with systemic lupus erythematosus (SLE) and regular menstrual cycles, and explore the relationship of such markers with clinical and treatment features. This was a case–control study including 27 women with SLE and 27 controls. All participants were aged 18–40 years, were eumenorrheic and had not used hormone therapy or hormone contraceptives in the past six months. Clinical manifestations of SLE, past and current use of immunosuppressive therapy and organ damage index were assessed at a regular follow-up visit, while antral follicle count (AFC), serum anti-Mullerian hormone (AMH) and follicle-stimulating hormone (FSH) were assessed at early follicular phase of menstrual cycle. AFC was significantly reduced in SLE women [median (interquartile interval) 7 (5–11) versus 11 (7–12), p = 0.029]. AMH levels were more heterogeneous in SLE patients compared to the control group [1.23 (0.24–4.63) ng/ml versus 1.52 (1.33–1.88) ng/ml]. The SLE and control groups had similar serum FSH levels [6.44 (4.19–7.69) versus 7.5 (6.03–8.09) IU/L, p = 0.135]. AFC was inversely correlated with organ damage index (p = 0.046) and cumulative dose of cyclophosphamide (p = 0.028), while AMH levels were negatively correlated with the maximal dose of corticosteroid ever used (p = 0.003). These findings suggest that ovarian reserve may be decreased in women with SLE despite regular menstrual cycles.

SAT0034 Assessment of Ovarian Reserve with Anti-MÜLlerian Hormone in Female Patients with Systemic Lupus Erythematosus

BackgroundWomen with SLE have a higher risk of developing menstrual irregularities compared to a healthy population. Anti-Müllerian hormone (AMH) has been shown to have great promise as a possible marker...

THU0031 Factors Associated with Fatigue in Systemic Lupus Erythematosus Patients

Backgroundevidence exists that fatigue is a significant problem for systemic lupus erythematosus (SLE) patients (pts). The causes of fatigue aren't enough investigated. SLE activity and depression are confounding fatigue factors.Objectivesto...

FRI0468 Chronic Nasal Carriage of Staphylococcus Aureus Does not Increase the Risk of Relapse and Severe Infections in Granulomatosis with Polyangiitis Patients When Receiving Rituximab Maintenance Treatment

BackgroundChronic nasal carriage of Staphylococcus aureus (SA) has been shown to increase the risk of relapse in patients with Granulomatosis with polyangiitis (GPA). B cell depletion with Rituximab (RTX) is...

Which dose of steroids and which cytotoxics for severe lupus?

There have been a number of major advances in the treatment of systemic lupus erythematosus and we are now in the era of biologic therapies for this multisystem autoimmune disorder. There has been a greater awareness of the toxicities of the traditional therapies including the recognition that the doses of corticosteroids used in the past have been excessive, resulting in unacceptable toxicities. Other advances have included the development of lower cumulative doses of cyclophosphamide and the widespread acceptance of mycophenolate mofetil for the treatment of lupus nephritis. This review addresses the current management of severe lupus with corticosteroids and cytotoxic agents.

Hormona anti-mülleriana en mujeres en edad reproductiva con lupus eritematoso sistémico

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune systemic and chronic disease. Fertility in SLE patients is considered normal; factors that have been associated in these patients with ovarian failure are: disease activity, autoantibodies, and the use of cytotoxic agents. The anti-Müllerian hormone (AMH) is a marker that helps to determine the follicular reserve. ObjectiveDeterminate the objective was to determine AMH levels in women of reproductive age with SLE. Material and methodsWe included 65 women with SLE classified according to the 1997 ACR criteria, 18- to 40-years old. We obtained demographic, clinical, obstetric, and gynecological characteristics as well as serum levels of AMH. We performed a bivariate analysis among patients with low ovarian reserve and those with normal ovarian reserve. We also performed a correlation analysis between activity and damage index and between the cumulative cyclophosphamide dose and AMH levels. ResultsWe found a median of serum AMH in SLE patients of .61 ng/mL. The prevalence of low ovarian reserve in our study was 3.07%. We found a median MEX-SLEDAI score of 1 point and the median SLICC score was 2 points. Twenty-five patients (38.4%) had used cyclophosphamide and their cumulative average dose was 7.5 grams. ConclusionsWe found a median of AMH of .61 ng/mL in our population. The prevalence of low ovarian reserve in SLE patients was 3.07%. We did not find a correlation between AMH levels, the use of cyclophosphamide, and disease activity.