Combination Of Prednisone Research Articles

1421P Effect of abiraterone-prednisone in metastatic castration-sensitive prostate cancer (mCSPC) with neuroendocrine and very high-risk features in the PEACE-1 trial

The PEACE-1 trial demonstrated improved overall survival (OS) in de novo mCSPC patients treated with a combination of androgen deprivation therapy, docetaxel, and abiraterone (AA) plus prednisone. Prostate cancers with neuroendocrine differentiation (NEPC) are rare. Most trials exclude de novo NEPC, thus their standard of care remains uncertain. As NEPC was allowed in PEACE-1, we aimed to assess the effect of AA in NEPC and those with very high-risk factors (Gleason >8, liver metastases).

P-198: Real-life experience of the combination of daratumumab, bortezomib, melphalan, and prednisone (DVMP) in patients with newly diagnosed multiple myeloma ineligible for autologous stem cell transplantation

P-198: Real-life experience of the combination of daratumumab, bortezomib, melphalan, and prednisone (DVMP) in patients with newly diagnosed multiple myeloma ineligible for autologous stem cell transplantation

Diagnosis and treatment of autoimmune diseases of the brain and spinal cord in dogs: analysis of the literature review

The main methods of diagnosing these diseases, according to the analysis of world literature data, are the analysis of the patient's cerebrospinal fluid and magnetic resonance imaging (MRI). The analysis of cerebrospinal fluid (CSF) is carried out in order to detect changes characteristic of the diagnosis. With the help of MRI, it is possible to determine the localization of inflammation. A number of studies have been aimed at improving diagnostic methods by detecting new factors characteristic of autoimmune diseases of the nervous system. Data on the detection of antibodies corresponding to human antibodies in the cerebrospinal fluid of dogs and on changes in the concentration of various substances in it are presented. This allows for faster and more accurate diagnostics.As a result of the generalization of the literature data, it was found that immunosuppressive drugs are used for the treatment of autoimmune diseases of the brain and spinal cord of dogs. According to the data presented, the most effective of the known methods of treatment of autoimmune meningoencephalitis is the use of a combination of prednisolone and imatinib mesylate. For the treatment of steroid-dependent meningoarteritis (SRMA), various corticosteroid drugs are used, the most optimal of which is the combination of prednisone and cytarabine.The purpose of our study was to study modern Russian and foreign literature sources on autoimmune diseases of the brain and spinal cord in dogs, methods of diagnosis and treatment of these diseases and to review works that provide new data on their treatment, diagnosis and understanding of etiology and pathogenesis.

Leflunomide versus azathioprine for maintenance therapy of lupus nephritis: a prospective, multicentre, randomised trial and long-term follow-up

ObjectivesPrevious studies have compared mycophenolate mofetil and azathioprine as maintenance therapy for lupus nephritis (LN). Leflunomide is an immunosuppressant widely used in the treatment of rheumatoid arthritis. The aim of...

Histiocytic Sarcoma: Clinical Features and Outcomes of Patients Treated at a Tertiary Cancer Care Center

Histiocytic sarcoma (HS) is an extremely rare histiocytic disorder of unknown etiology. It is not a true sarcoma and is named so, due to the pathological resemblance to mature histiocytes. The clinical presentation of HS is diverse and is related to the involved organs. Due to its aggressive nature, with poor prognosis and lack of a standard treatment regimen of choice, its diagnosis and management pose a challenge to the clinician. Limited literature is available on the management of this entity. Here, we report four patients with HS, diagnosed over 15 years in a tertiary cancer center, with varied clinical presentation, management, and outcomes. The first patient presented with a localized unresectable esophageal mass. He was treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) combination chemotherapy and attained complete remission. The second patient had a painless mass of the hand, treated with wide excision and adjuvant Radiotherapy. She is disease-free for the past 12 years. The third patient had presented with an anterior mediastinal mass. He had progressive disease on chemotherapy. The fourth patient had multifocal disease with generalized lymphadenopathy. She was treated with CHOP chemotherapy and is now disease-free at 13 months. To summarize, the patients with the localized resectable disease did well, with surgical excision and adjuvant radiotherapy, while patients with the multifocal disease did well on CHOP chemotherapy. The take-home message from this case series is - CHOP off whenever you can and if not give CHOP to chop off the disease.

Enhancing Prednisone-Based Arthritis Therapy with Targeted IL-27 Gene Delivery.

Rheumatoid arthritis (RA) is a chronic autoimmune disease which is characterized primarily by synovial hyperplasia and accumulation of several types of immune infiltrates that promote progressive destruction of the articular structure. Glucocorticoids are often prescribed to treat RA because of their strong anti-inflammatory and immunosuppressive effects. However, their application must be limited to the short-term due to a risk of adverse events. In the present study, we examined the potential combination of low-dose prednisone with gene delivery of an agent of promising and complementary effectiveness in RA, interleukin (IL)-27. IL-27 has been shown to have anti-inflammatory potential, while also acting as an effective bone-normalization agent in prior reports. The present report examined a version of IL-27 targeted at the C-terminus with a short ‘peptide L’ (pepL, LSLITRL) that binds the interleukin 6 receptor α (IL-6Rα) upregulated during inflammation. By focusing on this targeted form, IL-27pepL or 27pL, we examined whether the anti-inflammatory potential of prednisone (at a relatively low dose and short duration) could be further enhanced in the presence of 27pL as a therapy adjuvant. Our results indicate that 27pL represents a novel tool for use as an adjuvant with current therapeutics, such as prednisone, against inflammatory conditions.

837-P: Hypoxemic COVID-Pneumonia, Diabetes Mellitus: Combination of Tailored Prednisone, Colchicine, Antithrombotics, Diuretic Improves Prognosis (CocAA-CoLa PLUS Study)

In patients (pts) with diabetes mellitus (DM) , Covid-pneumonia mortality rate >20% has been reported. A low fixed dose of intravenous dexamethasone (Dx) for days (RECOVERY study, 6 mg/d, i.e 0.5 mg/kg/d prednisone equivalent) has been shown to effectively reduce Covid-pneumonia mortality. In an observational study, prognosis was improved with an oral combination of prednisone fixed dose (1mg/kg/d) , direct anticoagulant/aspirin/colchicine/furosemide (DOAACF) . We hypothesized prednisone tailored doses driven by clinical evolution (extra 1mg/kg/d for every increase of O2 flow) added-on DOAACF for days would decrease morbi-mortality. In our monocentric, retrospective study (03.2020-05.2021) , pts with Covid-pneumonia requiring O2 out of the Intensive Care Unit (ICU) were included. According to the Physicians discretionary caring decisions, a control group (no corticoid) , a Dx group, an oral tailored prednisone ≥1mg/kg/d-DOAACF group were compared. The primary endpoint was Day 28 ICU requirement or mortality. Out of 3pts included for hypoxemic Covid-pneumonia, 132 pts had DM (43%) (control n = 28; Dx n = 46; tailored prednisone-DOAACF n = 58) : median age 69y; Males/Females 2.8; BMI 28 kg/m2; cardiovascular history 40%; median SpO2 at room air 92%; median maximal O2 flow 4L/min. Pts characteristics were non statistically different. Prednisone median dose (1.5mg/kg/d) and aspirin-colchicine-furosemide use were significantly higher in the tailored prednisone-DOAACF group in which events rate (12%) was significantly lower (control 50%, p = 0.0003, Dx 37%, p = 0.004) . In the tailored group, no statistical difference observed with pts without DM (13.3%, p = 1) . Out of the ICU, in pts with DM, a five oral drugs combination made of tailored prednisone ≥1mg/kg/d, anti-inflammatory, antithrombotics, diuretic improves hypoxemic Covid-pneumonia prognosis. A randomized trial is needed. Disclosure J.Kevorkian: None. B.Mégarbane: None. F.Féron: None. J.Riveline: None. F.Mauvais-jarvis: Consultant; Mithra Pharmaceutical. J.Gautier: Other Relationship; Novo Nordisk, Sanofi, Speaker's Bureau; Eli Lilly and Company.

New-Onset Diabetes after Transplantation (NODAT) in Renal Transplant Recipients, A Retrospective Single Centre Study

Objective: New onset diabetes after transplant (NODAT) is a known post-transplant complication contributing to morbidity and mortality. This study was aimed to find out the frequency of NODAT in kidney disease patients after one year. Methods and subjects: The study was conducted retrospectively on 275 Asian patients who underwent kidney transplant. The demographic and clinical data was evaluated at the time, as well as 3, 6, and 12 months after kidney transplant. The etiology of end-stage renal disease (ESRD) or comorbidities was also documented. Every patient received a combination of Tacrolimus (Tac), Mycophenolate Mofetil (MMF), and Prednisone (Pred) as post-transplant immunosuppression. Patients who developed NODAT were compared with those who did not. RESULTS: One year after the transplantation, the incidence of NODAT was 4.3 percent. Patients diagnosed with NODAT were older (p = 0.001) and had renal failure owing to Chronic glomerulonephritis with hypertension (p = 0.001), according to the results of the univariate analysis. The NODAT group had significantly greater rates of high blood pressure after transplantation (p = 0.01), heart failure (p = 0.02), and dyslipidemia (p = 0.001) than the other groups. Through the use of logistic regression, it was shown that high blood pressure after transplant, and dyslipidemia are all independently linked with NODAT. Conclusion: Asian patients who had high blood pressure and dyslipidemia had a higher incidence of NODAT compared to those who did not have. Keywords: kidney transplantation, prevalence, new-onset diabetes after trasplant

Treatment efficacy of carrelizumab in metastatic castration-resistant prostate cancer, and the significance of circulating tumor DNA fraction

Purpose: To explore the efficacy of carrelizumab in the treatment of metastatic castration-resistant prostate cancer (mCRPC), and the significance of circulating tumor DNA (ctDNA) fraction in the process.Methods: 100 mCRPC patients who were treated in the Oncology Department of Harbin Medical University Cancer Hospital in a time frame of January 2018 to January 2019 were enrolled and assigned (1:1) into control and study groups and were given a regimen consisting of a combination of docetaxel and prednisone. Prognosis of patients with high and low ctDNA fractions relative to baseline ctDNA level, was compared.Results: The study group obtained considerably higher objective response rate (ORR) in relation to the control group (p < 0.05). Serum levels of prostate-specific antigen (PSA) and testosterone (TTE) were significantly lower in the study group versus control group. Better quality of life and bladder function were witnessed in the study group when compared to control group (p < 0.05). The proportion of patients with ctDNA fraction < 2 % in the study group significantly increased, but there was no significant change in ctDNA in the control group. The clinical prognosis of patients with low ctDNA fraction was significantly better than that of patients with high fraction (p < 0.05).Conclusion: Combined use of carrelizumab and docetaxel-prednisone regimen for mCRPC patients substantially improved clinical efficacy, quality of life, and long-term prognosis, while reducing ctDNA levels. Thus, the combination regimen has promise for the treatment of mCRPC patients.

Progressive Multifocal Leukoencephalopathy Presenting as Expressive Aphasia in a Lung Transplant Recipient

IntroductionProgressive multifocal leukoencephalopathy (PML) is a demyelinating brain disease caused by reactivation of JC virus in immunocompromised patients. PML typically manifests with subacute neurologic deficits including altered mental status, motor deficits, limb ataxia, gait ataxia, and visual symptoms. We report an atypical presentation of PML in a lung transplant recipient (LTR).Case ReportA 71-year-old LTR received rituximab induction followed by a combination of mycophenolate mofetil, tacrolimus, and prednisone. He had a single episode of minimal acute cellular rejection early after LT, but never required significantly augmented immunosuppression. Notably, he had mild leukopenia throughout his post-LT course (WBC count 3-4 thousand/µL), and he had no response to 4 doses of the Pfizer SARS-CoV-2 vaccine, suggesting advanced immunosuppression. At 14 months after LT, the patient reported progressive anomia and aphasia, but no other neurologic deficits. MRI showed an abnormal increased T2/FLAIR signal in the left posterior parieto-occipital subcortical white matter, involving subcortical U fibers, characteristic of PML (Figure A, C). Serum JC virus PCR showed low-level viremia, but CSF from 2 lumbar punctures was PCR negative. Thus, he was diagnosed with possible PML, and immunosuppression was narrowed to a combination of tacrolimus (goal trough 4-6) and prednisone, 5 mg daily. Despite reduced immunosuppression, a repeat MRI 2 months after the initial diagnosis showed worsening PML (Figure B, D) and his symptoms progressed to severe anomia, aphasia, and cortical blindness, but still no motor deficits.SummaryPML is a rare, albeit well described, complication of LT, but presentation with only anomia and aphasia is unusual. Without CSF viral isolation, a definitive diagnosis requires brain tissue; however, MRI changes involving subcortical U fibers in the parieto-occipital area are highly characteristic. Early recognition allows for expeditious management. Progressive multifocal leukoencephalopathy (PML) is a demyelinating brain disease caused by reactivation of JC virus in immunocompromised patients. PML typically manifests with subacute neurologic deficits including altered mental status, motor deficits, limb ataxia, gait ataxia, and visual symptoms. We report an atypical presentation of PML in a lung transplant recipient (LTR). A 71-year-old LTR received rituximab induction followed by a combination of mycophenolate mofetil, tacrolimus, and prednisone. He had a single episode of minimal acute cellular rejection early after LT, but never required significantly augmented immunosuppression. Notably, he had mild leukopenia throughout his post-LT course (WBC count 3-4 thousand/µL), and he had no response to 4 doses of the Pfizer SARS-CoV-2 vaccine, suggesting advanced immunosuppression. At 14 months after LT, the patient reported progressive anomia and aphasia, but no other neurologic deficits. MRI showed an abnormal increased T2/FLAIR signal in the left posterior parieto-occipital subcortical white matter, involving subcortical U fibers, characteristic of PML (Figure A, C). Serum JC virus PCR showed low-level viremia, but CSF from 2 lumbar punctures was PCR negative. Thus, he was diagnosed with possible PML, and immunosuppression was narrowed to a combination of tacrolimus (goal trough 4-6) and prednisone, 5 mg daily. Despite reduced immunosuppression, a repeat MRI 2 months after the initial diagnosis showed worsening PML (Figure B, D) and his symptoms progressed to severe anomia, aphasia, and cortical blindness, but still no motor deficits. PML is a rare, albeit well described, complication of LT, but presentation with only anomia and aphasia is unusual. Without CSF viral isolation, a definitive diagnosis requires brain tissue; however, MRI changes involving subcortical U fibers in the parieto-occipital area are highly characteristic. Early recognition allows for expeditious management.

Antibodies to Full-Length Agrin Protein in Chinese Patients With Myasthenia Gravis.

This study aimed to establish a cell-based assay (CBA) for the detection of agrin antibodies (Agrin-Ab) to explore the clinical features of agrin antibody-positive Chinese patients with myasthenia gravis (Agrin-MG). We developed a CBA based on the human full-length agrin protein expressed in HEK293T cells for the reliable and efficient detection of Agrin-Ab. Clinical data and serum samples were collected from 1948 MG patients in 26 provinces in China. The demographic and clinical features of Agrin-MG patients were compared with those of other MG patient subsets. Eighteen Agrin-MG cases were identified from 1948 MG patients. Nine patients were Agrin-Ab positive, and nine were AChR-Ab and Agrin-Ab double-positive (Agrin/AChR-MG). Eleven (61.11%) patients were males older than 40 years of age. The initial symptom in 13 (81.25%) cases was ocular weakness. Occasionally, the initial symptom was limb-girdle weakness (two cases) or bulbar muscle weakness (one case). Agrin-MG patients demonstrated slight improvement following treatment with either acetylcholinesterase inhibitor or prednisone; however, the combination of the two drugs could effectively relieve MG symptoms. In China, Agrin-MG demonstrated seropositivity rates of 0.92%. These patients were commonly middle-aged or elderly men. The patients usually presented weakness in the ocular, bulbar, and limb muscles, which may be combined with thymoma. These patients have more severe diseases, although the combination of pyridostigmine and prednisone was usually effective in relieving symptoms.

Influence of Bisphosphonates or Recombinant Human Parathyroid Hormone on in Vitro Chemotherapy Sensitivity in Acute Lymphoblastic Leukemia Cells

BACKGROUNDOsteonecrosis and low bone mineral density (BMD) are serious osteogenic side effects of acute lymphoblastic leukemia (ALL) treatment. Bisphosphonates and recombinant human parathyroid hormone (rPTH) tend to be used to ameliorate osteonecrosis-related symptoms as well as to enhance bone mineral density in children with ALL and severe bone fragility. Only one preclinical study on the safety of bisphosphonates during ALL treatment is available, which raises concerns about their impact on leukemic drug sensitivity. Here, we assessed the influence of various bone-modifying agents (zoledronate, pamidronate and rPTH) on in vitro cytotoxicity of chemotherapeutic agents (vincristine (VCR), daunorubicin (DNR), dexamethasone (DEXA), 6-mercaptopurine (6-MP), PEG-asparaginase (PEG-ASP)) and prednisone (PRED) that are commonly used in ALL treatment.METHODSPotential cytotoxic effects of the bone-modifying agents on leukemia cell viability and on in vitro cytotoxic responses of chemotherapeutic agents were tested in various T-cell and B-cell leukemia cell lines using methyl-thiazol-tetrazolium (MTT) assays. Bone-modifying agents were added at concentrations up to a five-fold of their physiological peak plasma concentration. For each assay, 50th percentile of maximal inhibitory concentration was determined. To quantify the combined effects of the bone-modifying agents on chemotherapeutic agent-induced cytotoxicity, median (interquartile range) combination indexes (CI) were calculated. We considered a median CI of < 0.8 as synergism and > 1.2 as antagonism (based on the method of Chou).RESULTSZoledronate, pamidronate or rPTH in combination with DNR, 6-MP and PEG-ASP showed median CI values between 0.8 and 1.2. Variable inconclusive results were obtained in combination with VCR. Only the combination of a five-fold peak plasma concentration of zoledronate or pamidronate with DEXA resulted in median CI values of 1.15 (range, 1.08-1.48), and 1.34 (range, 1.07-1.62), respectively. Additional experiments using DEXA as well as PRED in combination with one-, three- or five-fold physiological peak plasma concentrations of zoledronate or pamidronate revealed that median CI values stay within 0.8 and 1.2, except for DEXA exposed leukemia cells in combination with a five-fold physiological peak plasma concentration of pamidronate which repeatedly showed a median CI value above 1.2 (1.34, range 1.04-1.86).CONCLUSIONSZoledronate, pamidronate or rPTH do not seem to influence drug sensitivity of DNR, 6-MP or PEG-ASP, even at a five-fold physiological peak plasma concentration. Nevertheless, our findings suggest a minimal effect of pamidronate on DEXA-induced leukemia cell death. This suggests that even though zoledronate or pamidronate do not seem to negatively influence DEXA- or PRED- induced toxicity in expected physiological concentrations (one- to three-fold physiological peak plasma concentrations), these bone-modifying agents may only be considered with caution in individual cases, and preferably in clinical trial settings before being applied on a large scale in children with ALL. DisclosuresNo relevant conflicts of interest to declare.

Interim Results of a Phase II Study of Dasatinib and Prednisone As an Oral, Chemo-Free Induction and Consolidation Regimen for Adults with Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

BackgroundTyrosine kinase inhibitors (TKIs) combined with intensive chemotherapy as a first-line treatment regimen significantly improved the prognosis of Philadelphia (Ph) chromosomal positive acute lymphoblastic leukemia (Ph+ALL). However, it has been reported that 74% of patients fail to complete 8 cycles of chemotherapy, and the early mortality rate during induction was as high as 13%. Our previous retrospective study determined an oral, chemo-free regimen (dasatinib plus prednisone) as induction and consolidation yields 100% of complete remission (CR) rates in Ph+ ALL with minimal induction death (Li XY, et al. Br J Haematol. 2020;189:e231-e234). To further verify the effectiveness of this completely oral and chemo-free regimen, we conducted a phase II, one-arm and multicenter trial (ChiCTR200038053).MethodsAdults ≥16 years of age with new diagnosed Ph+ALL were eligible. Induction (Course I) used dasatinib 100 mg daily on days 1-28 and prednisone 1mg/kg/daily on days 1-21, 0.5 mg/kg/daily on days 22-28. Patients not in CR/CRi received Course I as second induction again. Two courses of consolidation (Course II and III) used dasatinib 100 mg daily on days 1-28 and prednisone 1mg/kg/daily on days 1-7. CNS prophylaxis used intrathecal cytarabine and dexamethasone. Patients 16-65 years old underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) if they had a HLA-matched donor; otherwise they received 6 cycles of hyper-CVAD chemotherapy alternating regimen-B (methotrexate, cytarabine) and regimen-A (cyclophosphamide, doxorubicin, vincristine, dexamethasone). The dose of chemotherapy was reduced by a third in patients 60-70 years old and by half in patients over 70 years. The primary objectives were to determine induced complete remission rate and major molecular response of the dasatinib/prednisone oral, chemo-free regimen.ResultsTo date, 32 patients from 10 centers enrolled. Median age was 54 years (range: 15-84). The dominant BCR-ABL1 isoform was p190 in 72%, p210 in 18%, rare types in 6.3% and not reported in 3.1%. Patients received an average of 2.5 courses of dasatinib/prednisone regimen (Course I-III). Most patients were tolerable the dose of dasatinib, and two patients were reduced to 50mg daily due to severe pleural effusion. Allo-HSCT was performed in 10 patients, 50% after remission and 50% after marrow relapse.As shown in Figure 1, the CR rate was 97% with one induction death due to sepsis. The major molecular response (MMR was defined as: 3-log reduction in BCR-ABL1 transcript) was 50% and the complete molecular response (CMR was defined as: the absence of a detectable BCR-ABL1 transcript with 0.01% sensitivity/4.5-log) was 40% either at 3 months after starting induction or before HSCT, respectively. From Course I to Course II, the CMR increased from 18.5% to 48%, but accompanied by an increase in marrow relapse rates, which were 16% and 18.75% at course II and course III, respectively. Marrow relapse occurred in 9 patients, all occurred within 6 months after starting induction. T315I mutation in ABL1 KD was detected in 5 of 7 marrow relapses (72%). With a median follow up of 232 days (range: 77-392 days), 1-year OS and 1-year event-free survival (events were defined as marrow relapse and death) was 97% and 54%, respectively (Figure 2). The cumulative molecular relapse rate (defined as BCR-ABL1:ABL1 ratio rises after reaching the CMR level) was 35% at 3 months, 48% at 6 months, and 54% at 1 year (Figure 2).ConclusionsThe chemotherapy-free, oral combination of dasatinib and prednisone appears promising induction efficacy in de novo Ph+ ALL; the high CR rates and acceptable molecular response rates were similar to results reported by GIMEMA LAL2116 study (Foà R, et al. N Engl J Med. 2020;383:1613-1623). However, two subsequent consolidation courses of the chemo-free regimen led to early molecular relapse with T315I mutations, which urged us to modify the study protocol such as strengthening consolidation therapy or incorporating promising drug blinatumomab. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Triple Combination of Ruxolutinib, Nilotinib and Prednisone Is Safe and Shows Promising Activity for the Treatment of Myelofibrosis Patients, Results of a Phase Ib Clinical Trial (RUNIC)

▪Background: Ruxolitinib is the standard of care for myelofibrosis (MF). However not all patients respond to ruxolitinib and other lose response while on treatment or require discontinuation due to adverse events. Therefore, several clinical trials with ruxolitinib in combination with other drugs are being conducted. We previously showed the synergistic effect of the combination ruxolitinib/nilotinib/prednisone in ex vivo models of peripheral blood mononuclear cells from MF patients and cell lines.Aims: This phase Ib/II study, non-randomized, open-label, evaluates safety and tolerability of ruxolitinib in combination with nilotinib and prednisone in patients with naïve or ruxolitinib-resistant MF.Methods:Between November 2017 and June 2020, 21 patients were included in RUNIC (EudraCT Number:2016-005214-21) at 6 Spanish sites. Six patients were considered screening failures. A total of 15 patients received at least one dose of ruxolitinib and were included in the intention-to-treat (ITT) or the per-protocol (PP) populations. The study design is summarized in figure 1.Out of 15 evaluable patients whose median age was 66.5 years (53.4-70.8). Six patients (40%) had a diagnosis of primary MF, 4 patients (26.7%) post-polycythemia vera MF, and 4 patients (26.7%) post-essential thrombocythemia MF. Most patients had International Prognostic Scoring System (IPSS) intermediate-1 or -2 disease (5 [33.3%] and 4 [26.7%], respectively), and 9 patients (60%) had JAK2 V617F mutation. Most of the patients (n=13; 86.7%) had received ruxolitinib as previous anti-neoplastic therapy for MF.Results:Eight patients completed 7 cycles (53.3%), and six patients 12 cycles (40%) and nine patients withdrawn because of disease progression, lack of efficacy, or no clinical benefit (n=5), withdrawal of consent (n=2), adverse event (AE) (pulmonary thromboembolism, n=1), and investigator's medical judgment (n=1).All patients experienced at least one AE during the study (the most common were hyperglycemia, asthenia and thrombocytopenia, and 14 patients registered at least one treatment-related AE (the most common were hyperglycemia (22.2%), thrombocytopenia (13.3%), and anemia (8.9%)). Five treatment-related serious adverse events (SAEs) were reported in 2 patients (13.3%), all of them related to nilotinib: one patient had pericardial effusion and bilateral pleural effusion, the other had congestive heart failure, pleural effusion, and pulmonary hypertension. No deaths were registered throughout the study.There were 2 patients with at least one adverse event meeting criteria for dose-limiting toxicity: grade 4 anemia and lumbar pain.Only eight patients were evaluated for spleen lengths at screening and cycle 7 (Figure 2B). Of these, 6 experienced a palpable spleen reduction, 4 of them with a 100% reduction. In contrast, one patient remained with the same spleen length, and one patient experienced a 25% increase.Six patients had both symptom evaluation at screening and cycle 7 (Figure 2D). Four experienced a total symptom score reduction, one patient remained with the same total symptom score, and two patients reported an increase.Six patients had spleen length measures recorded both at screening and at cycle 12. From those, 4 showed a spleen length reduction, 3 of them with a 100% reduction.Conclusions: Ruxolitinib in combination with nilotinib and prednisone showed relevant clinical activity in patients with naïve or ruxolitinib-resistant MF. The tolerability of this combination was acceptable, and the hyperglycemia was the treatment-related AE most frequent. The main cause of trial withdrawn was disease progression, lack of efficacy, or no clinical benefit. Based on these results, this triple combination should be explored in phase II/III clinical trials. [Display omitted] DisclosuresAyala: Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria; Celgene: Honoraria. Garcia Gutierrez: BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Osorio: Janssen, Abbvie, Roche: Consultancy. Sanchez: Janssen, Jazz Pharmaceuticals, Gilead, Novartis, Amgen: Consultancy. Martínez-López: Janssen, BMS, Novartis, Incyte, Roche, GSK, Pfizer: Consultancy; Roche, Novartis, Incyte, Astellas, BMS: Research Funding.

Frontline Therapy with Bendamustine-Rituximab (BR) in Patients with Treatment-Naïve Waldenstrom's Macroglobulinemia Confers Similar Long-Term Outcomes to R-CVP in a Real-World Setting: A Population-Based Analysis

Frontline Therapy with Bendamustine-Rituximab (BR) in Patients with Treatment-Naïve Waldenstrom's Macroglobulinemia Confers Similar Long-Term Outcomes to R-CVP in a Real-World Setting: A Population-Based Analysis

Cost of Disease Progression after Frontline (1L) R-CHOP in Diffuse Large B-Cell Lymphoma (DLBCL)

Cost of Disease Progression after Frontline (1L) R-CHOP in Diffuse Large B-Cell Lymphoma (DLBCL)

Five Year Results of Short Course Complete Androgen Blockade With Abiraterone Acetate and LHRH Agonist for Unfavorable Intermediate and Favorable High Risk Prostate Cancer

Purpose/Objective(s)Androgen deprivation therapy (ADT) and radiotherapy (RT) are synergistic, and the combination results in improved survival outcomes for aggressive prostate cancers. However, long-term ADT carries substantial burden of toxicity and morbidity. We hypothesized that a combination of definitive prostate RT and short-term complete androgen blockade (CAB) in men with unfavorable intermediate or favorable high-risk localized PC would provide excellent biochemical control and allow high rates of testosterone recovery. This combination would allow an escalation of therapy for unfavorable intermediate risk and de-escalation for favorable high-risk patients. We tested this hypothesis in a prospective trial of neoadjuvant/concurrent/adjuvant abiraterone acetate, prednisone, and LHRH agonist given for 6 months in conjunction with definitive prostate external beam RT. We now report the mature results of this trial.Materials/Methods37 men were enrolled in an IRB-approved NCT-registered prospective multi-center single arm investigator-initiated trial between January 2014 and August 2016. Eligibility required unfavorable intermediate risk of low volume high risk (NCCN) prostate cancer. All men were treated with 6 months of abiraterone acetate (1000mg daily), prednisone (5mg daily), and depot LHRH agonist initiated 8 weeks prior to standard fractionation RT to prostate/seminal vesicles +/- pelvis. Endpoints included PSA and testosterone (T) kinetics, biochemical progression-free survival (PFS), metastasis-free survival (MFS), overall survival (OS), and patient-reported quality-of-life.ResultsEnrolled patients were low volume (T1-2 disease and PSAs < 20 ng/ml), with Grade Group 1 (11%), 2 (11%), 3 (35%), 4 (27%), and 5 (16%); 43% were high-risk. The median follow-up time among all 37 surviving patients is 58months (range 24-65). Treatment was well tolerated and has been reported previously. In the entire cohort, 5-year BPFS was 92% (95% CI 72-98%). 32 out of 37 men recovered T to at least 150 ng/dl; the median time to T recovery was 9.2 mo (95% CI: 9.0-12.2). In men with T recovery, the 5-year BPFS was also 92% (95% CI: 71-98%). Hormonal/sexual function declined at six months but had improved by 24 mo and remained stable thereafter.ConclusionFor select men with aggressive prostate cancer, short course CAB with abiraterone acetate plus prednisone in combination with definitive prostate RT allows rapid T recovery and can provide excellent biochemical control up to 5 years. Short-course CAB is feasible for favorable high risk prostate cancer and may support optimization of patient quality of life. Prospective randomized trials should be considered. Androgen deprivation therapy (ADT) and radiotherapy (RT) are synergistic, and the combination results in improved survival outcomes for aggressive prostate cancers. However, long-term ADT carries substantial burden of toxicity and morbidity. We hypothesized that a combination of definitive prostate RT and short-term complete androgen blockade (CAB) in men with unfavorable intermediate or favorable high-risk localized PC would provide excellent biochemical control and allow high rates of testosterone recovery. This combination would allow an escalation of therapy for unfavorable intermediate risk and de-escalation for favorable high-risk patients. We tested this hypothesis in a prospective trial of neoadjuvant/concurrent/adjuvant abiraterone acetate, prednisone, and LHRH agonist given for 6 months in conjunction with definitive prostate external beam RT. We now report the mature results of this trial. 37 men were enrolled in an IRB-approved NCT-registered prospective multi-center single arm investigator-initiated trial between January 2014 and August 2016. Eligibility required unfavorable intermediate risk of low volume high risk (NCCN) prostate cancer. All men were treated with 6 months of abiraterone acetate (1000mg daily), prednisone (5mg daily), and depot LHRH agonist initiated 8 weeks prior to standard fractionation RT to prostate/seminal vesicles +/- pelvis. Endpoints included PSA and testosterone (T) kinetics, biochemical progression-free survival (PFS), metastasis-free survival (MFS), overall survival (OS), and patient-reported quality-of-life. Enrolled patients were low volume (T1-2 disease and PSAs < 20 ng/ml), with Grade Group 1 (11%), 2 (11%), 3 (35%), 4 (27%), and 5 (16%); 43% were high-risk. The median follow-up time among all 37 surviving patients is 58months (range 24-65). Treatment was well tolerated and has been reported previously. In the entire cohort, 5-year BPFS was 92% (95% CI 72-98%). 32 out of 37 men recovered T to at least 150 ng/dl; the median time to T recovery was 9.2 mo (95% CI: 9.0-12.2). In men with T recovery, the 5-year BPFS was also 92% (95% CI: 71-98%). Hormonal/sexual function declined at six months but had improved by 24 mo and remained stable thereafter. For select men with aggressive prostate cancer, short course CAB with abiraterone acetate plus prednisone in combination with definitive prostate RT allows rapid T recovery and can provide excellent biochemical control up to 5 years. Short-course CAB is feasible for favorable high risk prostate cancer and may support optimization of patient quality of life. Prospective randomized trials should be considered.

Study on the Effect of Combination of Prednisone and Vitamin D in the Treatment of Primary Nephrotic Syndrome in Children.

Objective To study the effect of prednisone combined with vitamin D in the treatment of primary nephrotic syndrome in children. Method 73 cases of primary nephrotic syndrome admitted to the nephrology department of our hospital were randomly selected and retrospectively analyzed. 36 cases were treated with prednisone as the control group, and 37 cases were treated with prednisone combined with vitamin D as the observation group. The efficacy was compared after 3 months of continuous treatment. Result After 3 months of treatment, the blood calcium of the observation group was higher than that of the control group, PTH was lower than that of the control group, and 25-(OH)2D3 and 1,25-(OH)2D3 were higher than those of the control group (P < 0.05). After 1, 2, and 3 months of treatment in the observation group, Scr and 24-h urine protein quantification were lower than those in the control group and eGFR was higher than that in the control group (P < 0.05). CD4+ and CD4+/CD8+ were lower in the observation group than in the control group after 3 months of treatment (P < 0.05). The serum sTfR and TGF-β1 levels were lower in the observation group than in the control group after 3 months of treatment (P < 0.05). The total effective rate of the observation group was 83.78% after 3 months of combined treatment with prednisone and vitamin D, which was significantly higher than the total effective rate of the control group of 61.11% (P < 0.05). The incidence of nausea and vomiting, heartburn, headache, dry cough, hypercalcemia, and constipation during treatment in the observation group was not statistically different from that in the control group (P > 0.05). Conclusion Combined treatment of primary nephrotic syndrome in children with prednisone and vitamin D can more significantly improve the level of clinical indicators, improve renal function and immune function, and obtain more satisfactory efficacy, without significantly affecting the safety of treatment.

Carnosine Remedial Effect on Fertility of Male Rats Receiving Cyclophosphamide, Hydroxydaunomycin, Oncovin and Prednisone (CHOP).

Chemotherapeutic agents can impair gonadal function triggering infertility. Here, we probed the properties of carnosine as an antioxidant in reproductive disorders caused by the combination of cyclophosphamide, hydroxydaunomycin (doxorubicin), oncovin (vincristine) and prednisone (CHOP); this combination is mostly used in treating non-Hodgkin lymphoma. Animals were distributed into four groups: Group I was the control. Group II received carnosine (250mgkgday-1 , i.p.); Group III received CHOP: cyclophosphamide (27mg/kg/cycle), doxorubicin (1.8mg/kg/cycle) and vincristine (0.05mg/kg /cycle) by i.p. plus oral prednisone (1.47mgkg-1 day-1 /cycle) for five days. Group IV received carnosine plus CHOP. The study involved 4 cycles each of 3weeks. Also, we explored the effect of combining carnosine with CHOP on the development of solid Ehrlich carcinoma in mice. CHOP lowered genitals weight, sperm count and motility, testicular function marker enzymes, serum testosterone level and gene expression of 3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein. Furthermore, CHOP elevated testicular oxidative stress, serum follicle-stimulating hormone, luteinising hormone and triggered DNA damage. Morphometric and histopathological examinations of testicular tissues buttressed the biochemical results. Importantly, administration of carnosine ameliorated CHOP-induced alterations without diminishing CHOP's antineoplastic action. These results indicated that carnosine may ameliorate reproductive disorders induced by CHOP.

Pregnancy after liver transplant: maternal and perinatal outcomes

BackgroundLiver transplantation is a life-saving and successful therapeutic procedure which is more and more frequent worldwide, also among women of reproductive age. Consequently, there is an increasing number of reports of pregnancy following liver transplantation, but doubts still exist regarding preconception counseling and the optimal method of managing pregnancy. The aim of this study was to report and evaluate pregnancy outcomes in women who had undergone liver transplantation.MethodsWe retrospectively analyzed female patients after orthotopic liver transplantation who reported pregnancy and were under medical care of a single transplant center.ResultsWe identified 14 pregnancies in 10 women who had undergone liver transplantation (12 childbirths, one induced abortion due to fetal death in the first trimester, one pregnancy is still ongoing). Causes of transplantation include congenital or acquired disorders and the most common indication was autoimmune hepatitis (50%).The mean age at the point of transplantation was 28.5 (range 21–36), mean maternal age at pregnancy was 32 (range 26–43), and transplant-to-pregnancy interval was 4.07 years (range 1.5–7). The mean gestational week was 36.67 (range 31–40). Immunosuppression was maintained with combinations of prednisone (n = 11), tacrolimus (n = 13), and azathioprine (n = 8) prior to and during pregnancy. Two pregnancies were unintended, so women took mycophenolate mofetil in the first weeks of gestation. Another two women stopped taking azathioprine due to increasing anemia. Maternal complications included increase of aspartate transaminase and alanine transaminase (n = 2), anemia (n = 4) and hyperthyroidism (n = 2). Among the 12 childbirths, five (41.67%) were preterm. Only five women entered labor spontaneously, while seven (58,33%) had cesarean delivery.ConclusionsPregnancy after liver transplantation can achieve relatively favorable outcomes. Liver transplantation does not influence women’s fertility and, during pregnancy, we report low rates of minor graft complications. A multidisciplinary team should be involved in contraceptive, fertility and consequently pregnancy counseling of female transplant recipients.