Cumulative Dose Of Cyclophosphamide Research Articles

Combination treatment with rituximab, low-dose cyclophosphamide and plasma exchange for severe antineutrophil cytoplasmic antibody-associated vasculitis

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis can present with life-threatening lung-kidney syndromes. However, many controlled treatment trials excluded patients with diffuse alveolar hemorrhage or severely impaired glomerular filtration rates, and so the optimum treatment in these cases is unclear. In this retrospective cohort study, we report the outcomes of 64 patients with life-threatening disease treated with a combination regimen of rituximab, low-dose intravenous cyclophosphamide, oral glucocorticoids, and plasma exchange. At entry, the median estimated glomerular filtration rate was 9 mL/min, 47% of patients required dialysis, and 52% had diffuse alveolar hemorrhage. All patients received a minimum of seven plasma exchanges, and the median cumulative doses of rituximab, cyclophosphamide, and glucocorticoid were 2, 3, and 2.6 g, respectively, at six months. A total of 94% of patients had achieved disease remission (version 3 Birmingham Vasculitis Activity Score of 0) at this time point, and 67% of patients who required dialysis recovered independent kidney function. During long-term follow-up (median duration 46 months), overall patient survival was 85%, and 69% of patients remained free from end-stage kidney disease, which compares favorably to a historic cohort with severe disease treated with a conventional induction regimen. Combination treatment was associated with prolonged B cell depletion and low rates of relapse; 87% of patients were in continuous remission at month 36. The serious infection rate during total follow-up was 0.28 infections/patient/year, suggesting that combination treatment is not associated with an enduring risk of infection. Thus, we suggest that combination immunosuppressive therapy may permit glucocorticoid avoidance and provide rapid and prolonged disease control in patients with severe ANCA-associated vasculitis.

Pregnancy in patients with systemic lupus erythematosus after cyclophosphamide therapy.

Systemic lupus erythematosus (SLE) often affects females of reproductive age and Cyclophosphamide, an alkylating agent leading to premature ovarian insufficiency (POF) and labelled category D for pregnancy is used as induction therapy for severe manifestations of lupus. There have been multiple case series reflecting variable outcomes of pregnancies after cyclophosphamide use for cancers and autoimmune diseases. With increasing maternal age, we have an increasing population of lupus patients who may wish to conceive after having received cyclophosphamide therapy. The objective of our study was to improve our understanding of the impact of cyclophosphamide exposure on fertility and pregnancy outcomes in patients with SLE.We retrospectively reviewed the charts of all patients who had received intravenous cyclophosphamide at our academic institute in the time period from 2000-2018 and identified 440 patients which included 157 female patients of reproductive age. There were 37 documented pregnancies after the cyclophosphamide infusion, of which 23 patients had successful outcomes; 4 elective abortion and 10 miscarriages. There were 17 patients who developed POF, of which 7 also had end stage renal disease. The average cumulative dose of cyclophosphamide in the patients who had successful pregnancy was 4080.37 mg compared to 2806.25 mg in those who had a miscarriage (p 0.164) and 5526.47 mg in those who developed POF (p 0.046). Using multiple regressions to evaluate risk factors impacting pregnancy outcomes, when taken as a set, the predictors including race, serological profile, exposure to steroids and Mycophenolate mofetil, age at cyclophosphamide infusion, age at pregnancy, and cumulative cyclophosphamide dose accounted for 46.29% of the variance in outcome of pregnancy (p 0.23) and 39.58% of the variance in development of premature ovarian failure (p 0.008). We noted statistical significance in the impact of maternal age at time of pregnancy (p 0.04) and duration of time between the last infusions to subsequent pregnancy (p 0.02) to pregnancy outcome.Our findings suggest that a longer time interval between the last cyclophosphamide infusion and subsequent pregnancy was favorable for a successful outcome and higher cumulative cyclophosphamide dose is more likely to be associated with premature ovarian failure.

Nebivolol protects against cyclophosphamide-induced nephrotoxicity through modulation of oxidative stress, inflammation, and apoptosis.

The usefulness of cyclophosphamide (CP) in the treatment of multiple human malignancies and immunological diseases is hindered by the danger of developing nephrotoxicity. The toxic metabolites of CP are suggested to be responsible for oxidative stress resulted from the production of reactive oxygen species (ROS) and stimulation of lipid peroxidation. Nebivolol (NEB) is a third-generation selective B1 adrenoceptor antagonist, but it has also various pharmacological properties such as anti-inflammation, anti-apoptotic, and antioxidant activities. Thus, the present study aims to explore the potential protective effect of NEB against CP-induced nephrotoxicity. A cumulative dose of CP (75mg/kg) was administered to albino rats by intraperitoneal injection. The protective effect of NEB was investigated by co-administration of NEB (10mg/kg orally daily). Administration of NEB with CP significantly improved renal functions and reduced the oxidative renal changes induced by CP injection. Co-administration of NEB ameliorated apoptosis and inflammatory markers that were markedly exaggerated by CP. Our results indicated that NEB could be used as a protective agent against CP-induced nephrotoxicity.

Efficacy and tolerability of VCD chemotherapy in a UK real‐world dataset of elderly transplant‐ineligible newly diagnosed myeloma patients

There are limited data on the efficacy and tolerability of VCD chemotherapy in transplant-non-eligible (TNE) newly diagnosed myeloma (NDMM) patients. In this retrospective study, we set out to evaluate this triplet combination in this setting across Thames Valley Cancer Network (UK). The primary end point was overall response rate (ORR). Secondary outcomes included event-free survival (EFS), overall survival (OS) and adverse events (AEs). In a total cohort of 158 patients, ORR for total cohort was 72.1%. Median EFS was 10.5months, and for subgroups by age (<75:11.7 vs ≥75:10.3months, P=.124), by Charlson Co-morbidity Index (CCI) (<5:11.1 vs ≥5:8.2months, P=.345). The 4-month landmark analysis showed the following median EFS results: by cumulative bortezomib dose (≥26mg/m2 : 9.0months vs <26mg/m2 : 6.4, P=.13), by cumulative cyclophosphamide dose (≥7000mg: 9.2 vs <7000mg: 7.0months, P=.02) and by cumulative dexamethasone dose (>600mg: 7.8 vs ≤600mg: 8.3months, P=.665). Median OS was 46.9months. The incidence rate of AE was as follows: any grade (76.8%), ≥G3 (27.1%), ≥G3 haematological AEs (7.9%), any grade infections (31.1%) and ≥G3 infections (11.9%). This study demonstrated a good ORR achieved from fixed duration VCD, which was reasonably well tolerated. This was followed by modest median EFS. We envisage that the latter may be improved in this patient group with the use of a higher cumulative bortezomib dose (≥26mg/m2 ) which showed a trend for improved EFS although without statistical significance (P=.13), and with the use of a higher cumulative cyclophosphamide doses (≥7000mg, P=.02), subject to tolerability and close monitoring.

Burkitt lymphoma: Age Specific Fertility Rate in 113 long-term female survivors after treatment with cyclophosphamide.

Reduced fertility risk is a risk in females treated with a high cumulative cyclophosphamide (CPM) dose. The objective of this study is to establish the age at menarche, record all pregnancies, calculate age-specific fertility rate (ASFR) in female BL survivors, treated in Cameroon, in the age groups 15-19 and 20-24 years, and association with an increasing cumulative CPM dose. Data collection included personal data and telephone interviews for female survivors, aged ≥12 years with regards to menarche age, their mothers' menarche age, incidence and outcome of all pregnancies. The cumulative CPM/m2 dose was categorized as low (<4723 mg/m2), medium (4724-10 635 mg/m/2) or high (>10 635 mg/m2). The median age at first treatment for 113 patients was 8 years (range 3-17 years), with median current age 17 years (range 12-26 years); the median duration of follow-up was 9 years (range 1.2-13.3 years). The median age of patients at menarche (n = 109; 4 unknown) was 14 years (range 10-17 years, SD 1.19) and that of their mothers (n = 68; 45 unknown) 15 years (range 10-17 years, SD 1.53). The median time to first pregnancy following menarche (the fertility time) was 3.04 years (n = 10) with low-dose CPM, 6.09 years with medium-dose CPM (n = 81) and 6.04 years with high-dose CPM (n = 32) (log rank difference p = 0.420). The ASFR in the age group 15-19 years was 82.19 (n = 73) and in the age group 20-24 years was 863.6 (n = 22), with significantly lower ASFR (p > 0.001) in children treated before the age of 10 years. Fertility rates of girls treated for BL with CPM were normal but reduced in patients who commenced treatment before the age of 10 years.

Prevalence and clinical associations with premature ovarian insufficiency, early menopause, and low ovarian reserve in systemic sclerosis.

The low prevalence of pregnancy in women with systemic sclerosis (SSc) is due to multi-factorial causes, including premature ovarian insufficiency (POI). The study aimed to determine the prevalence of POI, early menopausal status, and any clinical associations of these among Thai female SSc patients. An analytical cross-sectional study was conducted among female SSc patients between 18 and 45years of age. The eligible patients underwent blood testing for follicle stimulating hormone and anti-mullerian hormone levels, gynecologic examination, and transvaginal ultrasound for antral follicle count. We excluded patients having surgical amenorrhea, previous radiation, and history of hormonal contraception < 12weeks and pregnancy. A total of 31 patients were included. The majority (67.7%) had diffuse cutaneous systemic sclerosis. Three patients were POI with a prevalence of 9.7%. The factors associated with POI were a high cumulative dose of cyclophosphamide (CYC) (p = 0.02) and the long duration of CYC used (p = 0.02). After excluding POI, early menopause was detected in 10 patients with a prevalence of 35.7%. The factors associated with early menopause were long disease duration (p = 0.02), high cumulative dose of CYC (p = 0.03), and high cumulative dose of prednisolone (p = 0.02). Low ovarian reserve according to POSEIDON definition was found in 28 patients with the prevalence of 90.3%. POI in Thai SSc was uncommon, whereas early menopause and low ovarian reserve were frequently revealed. A high cumulative dose of CYC was associated with both POI and early menopause. Physicians should be aware of reproductive outcomes and advise patients at risk. Key Points • POI is revealed in patients with SSc particularly in who received high cumulative dose of cyclophosphamide, while early menopause and low ovarian reserve were major reproductive problem among SSc. • Prescriptions for CYC for female SSc-both for young patients of reproductive age and premenopausal middle-aged women-should be concerned of the long-term effects on gonadal function.

A Multi-Center Analysis of the Impact of Dose Level of R-EPOCH on Outcomes of Patients with Double/Triple-Hit B-Cell Lymphoma

A Multi-Center Analysis of the Impact of Dose Level of R-EPOCH on Outcomes of Patients with Double/Triple-Hit B-Cell Lymphoma

Histologic Analysis of Testes from Prepubertal Patients Treated with Chemotherapy Associates Impaired Germ Cell Counts with Cumulative Doses of Cyclophosphamide, Ifosfamide, Cytarabine, and Asparaginase.

Cryopreservation of immature testicular tissue is an experimental strategy for the preservation of fertility in prepubertal boys that will be subjected to a gonadotoxic onset, as is the case of oncologic patients. Therefore, the objective of this study was to assess the impact of chemotherapeutic treatments on the testicular histologic phenotype in prepubertal patients. A total of 56 testicular tissue samples from pediatric patients between 0 and 16years old (28 with at least one previous chemotherapeutic onset and 28 untreated controls) were histologically analyzed and age-matched compared. At least two 5-μm sections from testis per patient separated by a distance of 100μm were immunostained for the germ cell marker VASA, the spermatogonial markers UTF1, PLZF, UCHL1, and SALL4, the marker for proliferative cells KI67, and the Sertoli cell marker SOX9. The percentage of tubule cross-sections positive for each marker and the number of positive cells per tubule cross-section were determined and association with the cumulative dose received of each chemotherapeutic drug was statistically assessed. Results indicated that alkylating agents, cyclophosphamide and ifosfamide, but also the antimetabolite cytarabine and asparaginase were associated with a decreased percentage of positive tubules and a lower number of positive cells per tubule for the analyzed markers. Our results provide new evidences of the potential of chemotherapeutic agents previously considered to have low gonadotoxic effects such as cytarabine and asparaginase to trigger a severe testicular phenotype, hampering the potential success of future fertility restoration in experimental programs of fertility preservation in prepubertal boys.

Urine NGAL and KIM-1: tubular injury markers in acute lymphoblastic leukemia survivors

IntroductionNephrotoxicity is a potential adverse effect of anticancer treatment in childhood. Cytostatics, abdominal radiotherapy, total body irradiation (TBI) and some agents used in supportive care may induce acute kidney injury (AKI) or lead to chronic kidney disease (CKD). The aim of this study was to test the hypothesis whether urinary kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are increased in acute lymphoblastic leukemia (ALL) survivors.MethodThe study cohort consisted of 86 patients (42 females) previously treated for ALL. The median time after cessation of treatment was 6.55 (IQR: 1.96–9.93) years and median age at the time of study: 12 (IQR: 6.76–16.00). The control group included 53 healthy peers. Immunoenzymatic ELISA commercial kits were used to measure urine KIM-1 and NGAL levels.ResultsThe median levels of urine uNGAL (p < 0.05), uNGAL/creatinine (cr.) ratio (p < 0.0001) and uKIM-1/creatinine ratio (p < 0.0001) were significantly higher in ALL survivors in comparison with healthy controls. Female patients had significantly higher levels of NGAL and NGAL/cr. than males (mean 8.42 ± 7.1 vs. 4.59 ± 4.5 ng/mL and 86.57 ± 77 vs. 37.7 ± 37 ng/mg, respectively; p < 0.01). Of all the study participants, 11 (13%) presented eGFR below 90 mL/min/1.73 m2. The NGAL/cr. ratio seemed to be the best predictor of decreased eGFR (AUC = 0.65). The cumulative dose of methotrexate and cyclophosphamide did not predict the values of the urine NGAL, NGAL/cr., KIM-1/cr. and eGFR.Five years after the end of treatment, the patients had higher levels of uKIM-1 (1.02 ± 0.8 vs. 0.62 ± 0.6 ng/mL, p < 0.01), uNGAL (7.9 ± 6.7 vs. 4.6 ± 5 ng/mL, p < 0.01) and lower eGFR (114 ± 29 vs. 134 ± 35 mL/min/1.73 m2, p < 0.01) in comparison with ALL survivors with the observation period of less than 5 years.ConclusionWe demonstrated that ALL survivors have higher levels of urine NGAL, NGAL/cr. and uKIM-1/cr. ratio as compared to the control group. Further long-term follow-up studies are necessary to assess the significance of the NGAL and KIM-1 and their relationship to kidney damage after anticancer treatment in childhood.

Ovarian dysfunction with moderate-dose intravenous cyclophosphamide (modified NIH regimen) and mycophenolate mofetil in young adults with severe lupus: a prospective cohort study

BackgroundOvarian toxicity is a dreaded complication of cyclophosphamide (CYC). With the use of lower cumulative doses of intravenous CYC (modified NIH regimens) and availability of better markers of ovarian toxicity, the incidence of ovarian dysfunction needs reassessment. Lupus disease activity, by itself, is also believed to affect ovarian function negatively.MethodsThis single-centre prospective cohort study recruited 50 female patients of severe lupus aged 18–40 years. Twenty-five patients each received induction with either monthly intravenous CYC (0.5–0.75 g/m2) for 6–9 months or daily oral mycophenolate mofetil (MMF). Details of menstrual irregularities; serum levels of FSH, LH, estradiol, AMH, and inhibin B; and sonographic assessment of ovarian volume and antral follicular count were done at baseline and 6 months after treatment. Amenorrhoeic patients were re-evaluated at 1 year.ResultsMean (SD) age of subjects in the CYC and MMF groups was 31.4 (6.3) and 28.4 (4.4) years, respectively. Mean (SD) SLEDAI at the initiation of therapy was 7.2 (2.5) in the CYC group and 5.8 (3.4) in the MMF group. The mean cumulative dose of CYC used was 4.6 (1.8) g. Three patients in the CYC group (versus none in MMF) had amenorrhoea at 6 months—two of these regained menses within 6 months, while only one (4%) developed sustained amenorrhoea (lasting more than 12 months) at 41 years of age, likely menopause. Serum FSH levels increased (p = 0.03), while AMH (p = 0.002) and inhibin B (p < 0.001) levels decreased significantly with 6 months of CYC therapy. Ovarian volume also reduced significantly (p = 0.005) with 6 months of CYC therapy, while antral follicular count reduced numerically (p = 0.32). Levels of AMH, inhibin-B, estradiol, ovarian volume, and antral follicular count after 6 months therapy were significantly lesser in the CYC group compared to the MMF group, despite being similar before the start of therapy.ConclusionsOvarian dysfunction with monthly intravenous CYC (modified NIH regimen) was predominantly subclinical, with a negative effect on ovarian reserve. No premature ovarian failure was noted at 1 year. No ovarian dysfunction occurred in the MMF group, despite having patients with severe background lupus. Use of intravenous CYC for induction may thus not be restricted in young lupus females with incomplete families for fear of gonadotoxicity, especially in life- or organ-threatening situations, where the benefits outweigh this subclinical risk.

Impact of cyclophosphamide on gonadotropins in menopausal systemic lupus erythematosus patients: Relation to disease activity and damage

BackgroundSystemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that affects females at reproductive age, where lupus patients experience menopause at younger age. It is debated whether early menopause in lupus patients results from gonadotoxic effect of cyclophosphamide treatment or an autoimmune mediated ovarian injury. Aim of the workTo identify menopausal symptoms and characteristics in an Egyptian cohort of SLE females and its relation to disease activity, disease damage, lupus nephritis and treatment. Patients and methods120 consecutive SLE female patients above the age of 35 were studied. Disease activity was assessed by SLE Disease Activity Index (SLEDAI), and accumulated damage by Systemic Lupus International Collaborative Clinics-Damage Index (SLICC-DI). Laboratory assessment was done including follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. ResultsThe mean age of the patients was 45.1 ± 8.2 years (35–63 years) and the age at menopause was 45.2 ± 7.3 years (26–54 years). Their mean disease duration was 5.1 ± 5.7 years (1 month to 21 years). The mean SLEDAI was 4.7 ± 3.5 and SLICC-DI was 0.63 ± 0.82. 24 (20%) of patients had premature menopause, 29.2% had natural menopause and 50.8% were menstruating. There was a significant negative correlation between LH and SLEDAI. There was a significant correlation of FSH and LH with the cumulative cyclophosphamide dose. ConclusionSLE patients have early mean age of menopause at 45 years. High LH is associated with lower disease activity. High cumulative cyclophosphamide dose is associated with high FSH and LH. cyclophosphamide is potentially associated with premature menopause.

Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma

SummaryOver the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763–0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses.

Prevalence and risk factors of herpes zoster infection in patients with biopsy proven lupus nephritis undergoing immunosuppressive therapies

To study the prevalence of herpes zoster infection in patients with biopsy-confirmed lupus nephritis undergoing immunosuppressive therapies. Patients who had histologically active lupus nephritis between 2004 and 2018 were retrospectively reviewed. Clinical and laboratory data at baseline and six months post-therapy were collected. The incidence of herpes zoster reactivation within two years of lupus nephritis treatment was calculated. Risk factors for herpes zoster reactivation were studied by logistic regression. Patients (N = 251) with 311 episodes of lupus nephritis were studied (92% women; age 34.2 ± 14.2 years; histological classes III/IV ± V (69%)). Within two years of therapy, 55 (18%) episodes of lupus nephritis were complicated by herpes zoster infection (incidence 8.84/100 patient-years). Fourteen episodes (25%) of herpes zoster were treated by intravenous anti-viral drugs in hospital but disseminated disease or mortality was not reported. Significant post-herpetic neuralgia developed in 9% of the episodes. Patients with herpes zoster reactivation, compared with those without, were more likely to have first-time renal disease and a shorter systemic lupus erythematosus duration at lupus nephritis than those without. Disease activity, treatment response and other clinical/laboratory parameters were not significantly different between patients with and without herpes zoster reactivation. Herpes zoster-infected patients had been treated with a significantly higher dose of prednisolone as induction therapy. Logistic regression revealed that first-time renal disease, peak daily mycophenolate mofetil dose and cumulative cyclophosphamide dose during induction therapy were significantly associated with herpes zoster reactivation. Herpes zoster reactivation is common in lupus nephritis patients but unpredictable from clinical parameters. Although adverse outcomes of herpes zoster infection are uncommon, using the minimally effective doses of mycophenolate mofetil and cyclophosphamide during induction therapy may help reduce the risk of herpes zoster infection.

Leukocyte nadir as a predictive factor for efficacy of adjuvant chemotherapy in breast cancer. Results from the prospective trial SBG 2000–1

Background: Retrospective studies have suggested that chemotherapy-induced leukopenia is associated with improved recurrence-free or overall survival. The SBG 2000–1 trial was designed to verify the favorable prognosis associated with chemotherapy-induced leukopenia in early breast cancer. Patients not experiencing chemotherapy-induced leukopenia were randomized into standard dosed or individually escalated chemotherapy doses based on the grade of leukopenia after a first standard dose.Patients and methods: 1452 women in Sweden and Denmark with operable node-positive or high-risk node-negative breast cancer aged 18–60 years were recruited to participate in this trial. Participants received a first FEC cycle at standard doses (600/60/600 mg/m2). Patients (n = 1052) with nadir leukopenia grade 0–2 after the first cycle were randomized between either 6 standard FEC or 6 tailored FEC courses with doses of epirubicin and cyclophosphamide escalated during courses 2 and 3 and thereafter aimed at achieving grade 3 leukopenia. Patients with nadir leukopenia grade 3–4 after the first course continued treatment with standard FEC. Results of the randomized comparison has been published previously. The present study focuses on chemotherapy-induced leukopenia as a covariable with outcome in randomized and non-randomized patients. The prognostic value of leukopenia after course 3, was studied in a Cox model adjusted for cumulative doses of epirubicin and cyclophosphamide. The association of chemotherapy-induced leukopenia with prognosis was a preplanned secondary endpoint for this trial.Results: The eight-year distant disease-free survival was 73%, 77%, 78% and 83% for patients with leucocyte nadir grade 0, 1, 2 and 3–4, respectively. Higher degree of leukopenia was highly significantly associated to improved distant disease-free survival (HR 0.84, 95% CI 0.74–0.96, p = .008) and overall survival (HR 0.87 (0.76–0.99, p = .032).Conclusion: This prospective study confirms that chemotherapy-induced leukopenia is a covariable with outcome in primary breast cancer, even after adjustment for chemotherapy doses.

Therapeutic efficacy of combined glucocorticoid, intravenous cyclophosphamide, and double-filtration plasmapheresis for skin sclerosis in diffuse systemic sclerosis

We treated skin sclerosis with triple therapy consisting of a glucocorticoid, intravenous cyclophosphamide, and double-filtration plasmapheresis. The objective of this study was to analyze its effectiveness in a case series of patients who received triple therapy.We enrolled 8 patients with diffuse cutaneous systemic sclerosis (dcSSc) who received triple therapy at our hospital from 2008 to 2016. We analyzed the mean change in the modified Rodnan skin score (mRSS), percentage of the predicted forced vital capacity (%FVC), percentage of the predicted carbon monoxide diffusing capacity (%DLCO), and serum KL-6 levels from baseline to follow-up.All patients were treated with an intermediate dose of oral prednisolone (30.6 ± 2.1 mg/day) initially. The mean cumulative dose of intravenous cyclophosphamide was 1.4 ± 0.2 g. The mean mRSS decreased significantly at follow-up compared with that at baseline (27.0 ± 3.3 vs 15.8 ± 3.5; P = .03). At the end of the treatment, the mean %FVC and %DLCO were improved moderately, although the differences were not significant. The serum KL-6 levels decreased from 578.9 ± 146.5 to 205.3 ± 43.1 U/ml (P = .02). No significant correlation was found between the change in mRSS or disease duration and the initial skin score severity.Triple therapy may improve skin sclerosis, with effectiveness equal or superior to other reported treatments. This preliminary case series demonstrates the potential of triple therapy for treating dcSSc. However, prospective studies with long-term follow-up should be performed to assess its role.

Treatment and its side effects in ANCA-associated vasculitides – Study based on POLVAS registry data

PurposeThe aim of this study is to present the treatment modalities and associated side effects in a Polish nation-wide ANCA-associated vasculitides (AAV) patients’ cohort. Materials and methodsRetrospective analysis of patients diagnosed with AAV between 1990 and 2016, included in the POLVAS registry was performed. Standard descriptive statistic methods were used with an emphasis on the treatment modalities. ResultsThere were 625 patients diagnosed with AAV included in this study: 417 cases of granulomatosis with polyangiitis (GPA; 66.7%), 106 cases of microscopic polyangiitis (MPA; 17.0%) and 102 cases of eosinophilic granulomatosis with polyangiitis (EGPA; 16.3%). The mean age at the date of diagnosis was 50.4 (±15.7) years and the median observational period amounted to 4.0 (2.0–8.0) years.Glucocorticosteroids (GCs) were the medicaments most frequently used for remission induction (593/622; 95.3%), followed by cyclophosphamide (487/622; 78.3%), rituximab (44/622; 7.1%), and methotrexate (39/622; 6.3%). GCs were also most frequently administered for maintenance therapy (499/592; 84.3%), followed by azathioprine (224/592; 37.8%), methotrexate (136/592; 23.0%) and mycophenolate mofetil (99/592; 16.7%). The median cumulative doses of cyclophosphamide and rituximab equalled 7.99 g (4.18–14.0) and 2000 mg (1500–2800), respectively. The most commonly observed adverse events included: infections - 214/551 cases (38.8%), which were associated with the time of observation (OR = 1.05; 95% CI 1.01–1.10), the use of GCs intravenous pulses (OR = 2.76; 95% CI 1.68–4.54) and need for haemodialysis (OR = 1.73; 95% CI 1.10–2.71). ConclusionsPolish patients with AAV were predominantly treated according to appropriate guidelines. The most frequent adverse events were typical for usually administered immunosuppressive treatment.

Cardiac complications in patients who underwent to hematopoietic stem cell transplantation.

Cardiac complications may be observed after hematopoietic stem cell transplantation (HSCT). Despite significant improvement in supportive care, HSCT may be associated with significant morbidity and mortality. In this study, the aim was to evaluate the frequency of clinically serious cardiac complications after HSCT in our patients. This is a retrospective study. Cardiac complications were analyzed in 75 patients undergone to HSCT with physical examination, electrocardiography, echocardiography, and cardiac monitorization. The median age was 12 years (range 11-16) and M/F ratio was 2/3 = 0.66. There are five patients with six complications among the retrospective cohort of 75. These were pericardial effusion in three patients, and sinus bradycardia in two patients and ventricular tachycardia in one patient. The incidence of cardiac complications among 75 patients with HSCT was 6.7%. The mortality rates of patients with and without cardiac complication were 40% and 34%, and both of them with cardiac complication had pericardial effusion. However, the cardiac complication was not found statistically significant factor on survival ( P = 0.82). Poor risk factors of patients, myocarditis, pericarditis, and heart failure owing to cumulative doses of anthracycline, cyclophosphamide, cytomegalovirus infection or other infections, mediastinal irradiation, and cryopreserved stem cell product with dimethyl sulfoxide may be effective on the development of cardiac complications individually. Early intervention can prevent death related to this complication.

Proceedings to the 6th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA): 14-16 October 2019, Hosted by Miami Cancer Institute, part of Baptist Health South Florida, Miami, FL, USA.

Proceedings to the 6th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA): 14-16 October 2019, Hosted by Miami Cancer Institute, part of Baptist Health South Florida, Miami, FL, USA.

The VAC regimen for adult rhabdomyosarcoma: Differences between adolescent/young adult and older patients.

Compared to pediatric patients, adult rhabdomyosarcoma (RMS) patients have poor prognoses, but the differences in prognoses and treatment sensitivity between adolescent/young adult (AYA) patient and older RMS patients have not been established. To evaluate and compare the efficacy and safety of the vincristine/dactinomycin/cyclophosphamide (VAC) regimen, that is, the standard combination chemotherapy regimen for pediatric RMS, in AYA and older patients. We retrospectively reviewed the clinical records of adolescent and adult RMS patients treated at our institution and patients treated with the VAC were enrolled in the analyses. The differences in the efficacy and safety of VAC between the AYA patients (15-39 years old) and older patients (≥40 years old) were compared. Total of 23 patients were enrolled (14 AYA patients and nine older patients) were enrolled. With the median follow-up of 89.4weeks (range 17.7-263.1weeks), the median progression-free survival (PFS) and overall survival (OS) of the VAC regimen were 61.4weeks (95% CI, 32.6-90.3) and 104.0weeks (95% CI, 43.8-164.2), respectively, with no significant differences in the PFS or OS between the AYA and older patients. There were no differences in the response rate of the VAC between AYA (64.3%) and older (66.7%), either. Safety profiles were similar between the AYA and older groups, but exposure to antitumor drugs of the VAC tended to be lower in the older group; median number of total cycle of the VAC was 13 in AYA and 10 in older, cumulative cyclophosphamide dose was 16.8g/m2 in AYA and 12.8g/m2 in older, and number of vincristine skips was six in AYA and 12 in older, respectively. There were no significant differences in responses to the VAC among AYA and older patients with RMS. With the appropriate dose modification, the VAC regimen could be a feasible treatment option for RMS patients>40 years old.

Malignancies in Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis: A Population-based Cohort Study.

Patients with ANCA-associated vasculitides (AAV) exhibit higher rates of malignancy than the general population. We assessed whether the cancer risk is increased in a well-characterized population-based cohort of AAV in southern Sweden, followed for a median time of 8 years. With case record review, the outcomes and malignancy development in a cohort of 195 patients with AAV [granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA] diagnosed between 1997 and 2010 were assessed. The patients were followed until death or December 31, 2015. The age- and sex-standardized incidence ratios (SIR) were estimated using the Swedish population data as a reference. During the observation period of about 1500 person-years, we found 60 cancers in 52 of the 195 patients. SIR (95% CI) was 2.8 (2.1-3.6) for cancers at all sites, 1.8 (1.3-2.5) for all cancers excluding squamous cell carcinoma (SCC), 12.9 (8.4-18.8) for SCC, 4.3 (1.4-10.0) for bladder cancer, and 7.0 (1.4-20.5) for pancreatic cancer. Cumulative doses of cyclophosphamide (CYC) < 10 g were not associated with higher incidence of cancers other than SCC (SIR 1.63, 95% CI 0.8-2.9). In contrast to previous publications assessing malignancy risk in patients with AAV, we show in this population-based cohort of patients a persistent increased risk for overall malignancy, bladder cancer, and pancreatic cancer as well as a markedly increased risk for SCC. There was no increase in incidence of cancers other than SCC for those treated with < 10 g CYC.