Outcome Of Pregnancy After Autologous Hematopoietic Stem Cell Transplantation (AHSCT) For Autoimmune Diseases (AD): A Retrospective Study Of The EBMT Autoimmune Diseases Working Party (ADWP)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4640-4640
Author(s):  
Emilian Snarski ◽  
John A Snowden ◽  
Manuela Badoglio ◽  
Kristina Carlson ◽  
Joachim Burman ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Adverse Events ◽  
Autoimmune Diseases ◽  
Retrospective Analysis ◽  
Post Partum ◽  
Supplementary Information ◽  
High Dose ◽  
Healthy Children ◽  
Inclusion Criteria ◽  
Serious Adverse Events

Introduction AHSCT is increasing used to control severe and refractory autoimmune diseases (AD). Many patients (pts) are women of reproductive age with a potential desire for pregnancy, especially with control of AD. However, high dose cytotoxic therapy is associated with an age dependent risk of temporary or permanent ovarian and/or endometrial damage. Although childbirth has been sporadically reported after AHSCT for AD, the incidence, complications and outcomes of pregnancy in this group have never been characterised. We present the first multicenter retrospective analysis of pregnancy in patients who underwent AHSCT for AD. Patients and Methods The study was designed as a multicenter retrospective study of data registered in the EBMT database with supplementary information requested with a specific questionnaire sent to each centre. Inclusion criteria were: female pts aged >18 and 50 years receiving AHSCT for AD between 1994-2011. Over this time period 588 adult female patients fulfilling inclusion criteria were identified in the EBMT database and collaborating centres. Results Twenty-two pregnancies were reported in 15 pts between 1997-2010 2013, with 4 pts having 2 pregnancies, and one pt having 4 pregnancies, amounting to approximately 2% of total eligible registrations. Indications for AHSCT included multiple sclerosis (7 pts), systemic sclerosis (5 pts), rheumatoid Arthritis (1 pt), juvenile idiopathic arthritis (1 pt) and Takayasu disease (1 pt). All pts had received standard immunosuppressive +/- cytotoxic treatment for AD prior to mobilisation and AHSCT. The most common mobilization regimen was cyclophosphamide (2-4g/m2) and G-CSF. Conditioning for AHSCT was high dose cyclophosphamide (200mg/kg) in 7 pts, BEAM in 7 pts and one pt received BCNU (300mg/m2) with cyclophosphamide (150g/kg). Serotherapy was used in 10 patients (ATG in 9, ALG in 1). None received TBI. Of the 22 reported pregnancies, 20 were due to natural conception and 2 required assisted conception (two with in vitro fertilization). Fifteen pregnancies (68%) were successful, while seven (38%) were unsuccessful due to ectopic pregnancy (n=1), spontaneous abortion (n=4), and spontaneous fetal death (n=1). and induced abortion (n=1). Other serious adverse events included gestational diabetes mellitus (n=1), congestive heart failure and atrial fibrillation (n=1) and pre-term labor (n=1). Five serious adverse events occurred during first pregnancies, and 2 during second pregnancies. Exacerbations of AD occurred in 2 pts during second pregnancies. In all other patients the AD remained stable throughout pregnancy and post-partum. No maternal mortality was associated with pregnancy or post-partum. The status of the AD at most recent follow up was reported as remission (5 pts), improvement (4 pts), stabilization (3 pts), progression (2 pts) and 1 death due to AD progression. There were no reports of congenital, developmental or any other disease in the children of these pregnancies. Discussion This retrospective analysis confirms that pregnancy is feasible in some pts following AHSCT for severe AD. The outcome of pregnancy is generally good and most lead to the birth of healthy children. It is unclear whether the reported rates of adverse obstetric events exceed that of the general population, but exacerbation of underlying autoimmune disorder is possible. In pts who have undergone AHSCT for AD who wish to plan a pregnancy, we recommend close interdisciplinary collaboration involving obstetricians and relevant AD specialists. However, the reported frequency of pregnancy was relatively rare, and we continue to recommend consideration of embryo or ovum cryopreservation prior to AHSCT as per current ADWP guidelines (Snowden et al BMT 2012;47:770-90) Disclosures: No relevant conflicts of interest to declare.

scholarly journals Open-Label Clinical Trials of Oral Pulse Dexamethasone for Adults with Idiopathic Nephrotic Syndrome

2019 ◽  
Vol 49 (5) ◽  
pp. 377-385 ◽  
Author(s):  
Monique E. Cho ◽  
Mary H. Branton ◽  
David A. Smith ◽  
Linda Bartlett ◽  
Lilian Howard ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Adverse Events ◽  
Idiopathic Nephrotic Syndrome ◽  
High Dose ◽  
Open Label ◽  
Serious Adverse Events ◽  
Oral Dexamethasone ◽  
Dose Oral ◽  
Pulse Dexamethasone ◽  
Daily Prednisone

Background: In adults with primary focal segmental glomerulosclerosis (FSGS), daily prednisone may induce complete remissions (CR) and partial remissions (PR), but relapses are frequent and adverse events are common. Methods: We carried out 2 open-label, uncontrolled trials to explore the efficacy and tolerability of pulse oral dexamethasone as an alternative to daily prednisone. We enrolled adult patients with proteinuria > 3.5 g/day despite the use of renin-angiotensin-aldosterone blockade. In the first trial, we enrolled 14 subjects with FSGS and administered 4 dexamethasone doses (25 mg/m2) daily for 4 days, repeated every 28 days over 32 weeks. The second trial involved a more intensive regimen. Eight subjects received 4 dexamethasone doses of 50 mg/m2 every 4 weeks for 12 weeks, followed by 4 doses of 25 mg/m2 every 4 weeks for 36 weeks; subjects were randomized to 2 doses every 2 weeks or 4 doses every 4 weeks. Results: In the first trial, we enrolled 13 subjects with FSGS and 1 with minimal change disease and found a combined CR and PR rate of 36%. In the second trial, we enrolled 8 subjects. The combined CR and PR rate was 29%. Analysis combining both trials showed a combined CR and PR rate of 33%. Adverse events were observed in 32% of subjects, with mood symptoms being most common. There were no serious adverse events related to the study. Conclusion: We conclude that high dose oral dexamethasone is well tolerated by adults with idiopathic nephrotic syndrome and may have some efficacy.

scholarly journals The Effect of Early Treatment with Intravenous Magnesium Sulfate on the Incidence of Cardiac Comorbidities in Hospitalized Stroke Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Kameron Bechler ◽  
Kristina Shkirkova ◽  
Jeffrey L. Saver ◽  
Sidney Starkman ◽  
Scott Hamilton ◽  
...  
Keyword(s):  
Adverse Events ◽  
Acute Stroke ◽  
Magnesium Sulfate ◽  
Serum Magnesium ◽  
High Dose ◽  
Stroke Patients ◽  
Serious Adverse Events ◽  
Intravenous Magnesium ◽  
Prophylactic Measures ◽  
Cardiac Adverse Events

Background. Cardiac adverse events are common among patients presenting with acute stroke and contribute to overall morbidity and mortality. Prophylactic measures for the reduction of cardiac adverse events in hospitalized stroke patients have not been well understood. We sought to investigate the effect of early initiation of high-dose intravenous magnesium sulfate on cardiac adverse events in stroke patients. Methods. This is a secondary analysis of the prehospital Field Administration of Stroke Therapy-Magnesium (FAST-MAG) randomized phase-3 clinical trial, conducted from 2005-2013. Consecutive patients with suspected acute stroke and a serum magnesium level within 72 hours of enrollment were selected. Twenty grams of magnesium sulfate or placebo was administered in the ambulance starting with a 15-minute loading dose intravenous infusion followed by a 24-hour maintenance infusion in the hospital. Results. Among 1126 patients included in the analysis of this study, 809 (71.8%) patients had ischemic stroke, 277 (24.6%) had hemorrhagic stroke, and 39 (3.5%) with stroke mimics. The mean age was 69.5 (SD13.4) and 42% were female. 565 (50.2%) received magnesium treatment, and 561 (49.8%) received placebo. 254 (22.6%) patients achieved the target, and 872 (77.4%) did not achieve the target, regardless of their treatment group. Among 1126 patients, 159 (14.1%) had at least one CAE. Treatment with magnesium was not associated with fewer cardiac adverse events. A multivariate binary logistic regression for predictors of CAEs showed a positive association of older age and frequency of CAEs (R=1.04, 95% CI 1.03-1.06, p<0.0001). Measures of early and 90-day outcomes did not differ significantly between the magnesium and placebo groups among patients who had CAEs. Conclusion. Treatment of acute stroke patients with magnesium did not result in a reduction in the number or severity of cardiac serious adverse events.

An Open-Label Study of CEP-701 in Patients with JAK2 V617F-Positive Polycythemia Vera and Essential Thrombocytosis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 99-99 ◽  
Author(s):  
Alison R Moliterno ◽  
Gail J. Roboz ◽  
Martin Carroll ◽  
Selina Luger ◽  
Elizabeth Hexner ◽  
...  
Keyword(s):  
Adverse Events ◽  
Polycythemia Vera ◽  
Performance Status ◽  
Jak2 V617f ◽  
Spleen Size ◽  
Inclusion Criteria ◽  
Essential Thrombocytosis ◽  
Serious Adverse Events ◽  
Hematopoietic Stem ◽  
Secondary Endpoints

Abstract Polycythemia vera (PV) and essential thrombocytosis (ET) are clonal hematopoietic stem cell disorders characterized by the over production of phenotypically normal circulating blood cells. Most PV and approximately half of ET patients harbor the activating mutation JAK2 V617F. CEP-701 is an orally available, potent low nanomolar inhibitor of both the wild-type and mutated JAK2 tyrosine kinase, with its inhibitory effect demonstrated both in enzymatic and cellular assays and in vivo, where CEP-701 significantly inhibited the growth of JAK2 V617F-positive HEL.92 xenografts in mice. These findings suggest that CEP-701 is an attractive candidate for clinical evaluation in JAK2 V617F-positive myeloproliferative disorders. The purpose of this study is to test the safety and efficacy of CEP-701 administration in JAK2 V617F positive ET and PV patients. The primary endpoint is reduction in JAK2 V617F neutrophil allele burden; secondary endpoints are reduction in phlebotomy rates, improvement in hemoglobin, white cell and platelet counts, reduction in hydroxyurea (HU) dose, and reduction in spleen size. The secondary endpoints include the pharmacokinetics and pharmacodynamics of CEP-701 and the safety of CEP-701 treatment in patients with JAK2 V617F-positive PV and ET. This is a multicenter study with an anticipated enrollment of 40 PV and ET patients. Inclusion criteria include JAK2 V617F-positive PV and ET patients; patients with PV either have a neutrophil count greater than 7,000/ul or are receiving HU, while ET patients are receiving concomitant HU. Other inclusion criteria include an ECOG performance status of 0, 1 or 2, and 18 years of age or older. Exclusion criteria include the active use of anegrelide or interferon, or a recent history of venous or arterial thrombosis. This is an 18 week trial with an optional 1 year extension period; doses will escalate from 80 mg twice daily to a maximum of 120 mg twice daily. To date, 20 subjects, 11 PV and 9 ET, comprised of 11 females and 9 males, ages 34 to 74, have enrolled. Approximately 27% of the PV patients were taking HU. The most common adverse events have been gastrointestinal (GI) and constitutional in nature. No related serious adverse events have been observed. Five patients have discontinued study participation, all for adverse events: 1 due to disease progression, 1 leg cramps, and 3 GI. To date, 7 patients have completed 18 weeks of therapy and 6 of these patients will continue to receive CEP-701 on the extension phase of the trial. Five of 8 subjects with splenomegaly have responded with reductions in spleen size evident within 6 weeks of therapy initiation. Updated results on current and future patients will be presented at the meeting.

Autologous Hematopoietic Stem Cell Transplantation In Neuromyelitis Optica: A Retrospective Study Of The EBMT Autoimmune Diseases Working Party In Collaboration With The University Of Sao Paulo, Ribeirao Preto, Brazil

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2125-2125
Author(s):  
Raffaella Greco ◽  
Attilio Bondanza ◽  
Manuela Badoglio ◽  
Myriam Labopin ◽  
Maria Carolina Oliveira ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cell ◽  
Retrospective Study ◽  
Stem Cell Transplantation ◽  
Autoimmune Diseases ◽  
Working Party ◽  
High Dose ◽  
Free Survival ◽  
Disease Response

Abstract Background Neuromyelitis optica (NMO) is an inflammatory and demyelinating disorder of the central nervous system. Recently NMO has been recognized as an autoimmune astrocytopathy, distinct from multiple sclerosis and hallmarked by pathogenic anti-aquaporin 4 (AQP4) antibodies (Kim et al, Mult Scler, 2013). Currently NMO carries a poorer prognosis than multiple sclerosis (MS) and its response to various immunosuppressive treatments remains largely unsatisfactory. Use of Autologous stem cell transplantation (ASCT) has been reported worldwide as a tool for inducing prolonged restoration of self-tolerance in MS and other severe autoimmune diseases (AD), refractory to conventional treatments. In this context, NMO treatment resistant cases were considered for ASCT on a ‘Clinical Option’ basis, according to EBMT guidelines (Snowden et al, Bone Marrow Transplant, 2012). Only 2 isolated NMO cases with contradictory results (Matiello et al, Arch Neurol, 2011; Peng et al, Neurologist, 2010) and a Chinese report of 21 opticospinal multiple sclerosis patients treated by ASCT (Xu et al, Ann Hematol, 2011) are reported in the literature. Therefore, the EBMT Autoimmune Diseases Working Party (ADWP) conducted a survey to address NMO disease response following ASCT. Methods This retrospective study followed the EBMT study guidelines. All centers were invited to participate. Sixteen patients with aggressive forms of NMO refractory to standard treatments treated by ASCT between 2001 and 2011 had been reported to the EBMT registry. For each case, a specific questionnaire was sent to complete information by referring haematologist and neurologist about NMO, ASCT and outcome including disease response, relapse and progression. Results are reported as median. Results Patients (13 females and 3 males) had a median age of 37 years at transplant. Previous treatments had included high-dose steroids (12/16), immunoglobulins (5/16), iv cyclophosphamide (Cy, in 8/16), rituximab (5/16), mitoxantrone (2/16), plasma exchanges (8/16), azathioprine (5/16) and methotrexate (1/16). Median time between NMO diagnosis and transplant was 24 months. Before ASCT, the median EDSS (the Kurtzke Expanded Disability Status Scale) was of 6.5, 10/16 patients were positive for AQP4 antibodies and 11/16 had active lesions on magnetic resonance imaging (MRI). Peripheral blood stem cells mobilization, high-dose alkylating agent such as Cy (14/16) or monoclonal antibodies as Rituximab (2/16), followed by granulocyte colony stimulating factor (G-CSF), was successfully achieved in all cases (16/16). The conditioning regimen consisted of BEAM plus anti-thymocyte globulin (9/16) or Thiotepa-Cy (3/16) or Cy and anti-thymocyte globulin (4/16). Hematopoietic recovery was documented in all patients within 10 days (range 3-25) after ASCT, both for neutrophils and platelets, with a median number of 4 red blood cells and 5 platelet units transfusions. Infectious complications required specific treatment in 9 patients (6 febrile neutropenia, 5 CMV and 2 VZV reactivations, 1 aspergillosis). All patients responded initially. Relapse, necessitating further treatments, occurred in 13/16 at a median of 7 months after ASCT, presenting a median EDSS of 7 (range 3-8.5) and a worsening of MRI (11 cases). NMO progression was observed in 9/16 patients at a median of 10 months after ASCT. In the eight patients evaluable for AQP4 antibodies in the follow-up phase, the pathogenic autoantibodies remained positive after ASCT. Disease-free survival at 3 and 5 years were 31% and 10%, respectively, while progression-free survival at 3 and 5 years were 48%. No secondary malignancy was documented. All patients, but one patient who died from disease progression, are alive at a median follow up of 47 months after ASCT. Conclusions This EBMT retrospective study further demonstrates the potential of ASCT to reduce the highly inflammatory picture typical of NMO, at least in the short term, together with a low incidence of toxicities. Despite transient response after ASCT in the majority of cases, NMO relapsed at later time points underlying the need to investigate maintenance strategies to improve disease outcome in the long term after ASCT. Disclosures: No relevant conflicts of interest to declare.

JASPAC 06: Observational study of FOLFIRINOX therapy for unresectable and recurrent pancreatic cancer—Preliminary report on serious adverse events.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 407-407
Author(s):  
Masato Ozaka ◽  
Akiko Todaka ◽  
Keita Mori ◽  
Narikazu Boku ◽  
Nobumasa Mizuno ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Observational Study ◽  
Clinical Data ◽  
Preliminary Report ◽  
Japanese Patients ◽  
Inclusion Criteria ◽  
Serious Adverse Events ◽  
Recurrent Pancreatic Cancer ◽  
Ecog Ps

407 Background: In Japan, indication of FOLFIRINOX for unresectable and recurrent pancreatic cancer was approved in 2013. Because clinical data of FOLFIRINOX in Japanese patients based on only one exploratory trial is limited, this observational study was conducted to survey practical use of FOLFIRINOX and to evaluate incidences of adverse events in Japanese patients. Methods: The subjects were patients with unresectable or recurrent pancreatic cancer who received FOLFIRINOX therapy during one year from Dec. 20, 2013 (approval date of this study). All the subjects were registered and their clinical data were sent to the data center. In this preliminary report, we analyzed patients’ characteristics related to serious adverse event (SAE). This study was approved by the IRB in each institution. Results: Four hundred patients (pts) were registered from 27 institutions in Japan. Median age was 63 years (range 27-80). Sixty-four percent (n = 254) had no prior treatment and 254 pts (60%) had distant metastatic lesions. The UGT1A1 genotype was wild-type in 56.8% of the subjects, heterozygous (*1/*6, *1/*28) in 39.3%, and homozygous (*6/*6, *6/*28, *28/*28) in 3.9%. One hundred forty-one SAEs in 115 pts (28.8％) were reported until Aug. 10, 2015. Most common SAEs were febrile neutropenia (n = 26), neutrophil count decreased (n = 26), anorexia (n = 21) and biliary tract infection (n = 18). Of these 141 events, five events were results in death. The proportion of patients who met the inclusion criteria (as follows: ECOG PS of 0 or 1; age 20-75 years; adequate hematological, liver and renal functions) used in the phase II trial of FOLFIRINOX for Japanese patients was significantly lower in the subjects with SAEs than those without SAE (60.5% vs. 72.4%, p = 0.023). Four of the 5 pts who resulted in death did not fulfill the inclusion criteria; C-reactive protein in 4, platelet count in 1 and hemoglobin in 1. Conclusions: This is a first report to evaluate the safety profile of FOLFIRINOX in Japanese pancreatic cancer patients. These data highlight the importance of patient selection for FOLFIRINOX. The final safety and efficacy results of this study will be reported at the coming meeting. Clinical trial information: UMIN000014658.

Phase 1 Safety and Immunogenicity Study of a Respiratory Syncytial Virus Vaccine With an Adenovirus 26 Vector Encoding Prefusion F (Ad26.RSV.preF) in Adults Aged ≥60 Years

2020 ◽  
Vol 222 (6) ◽  
pp. 979-988 ◽  
Author(s):  
Kristi Williams ◽  
Arangassery Rosemary Bastian ◽  
Robert Allen Feldman ◽  
Edmund Omoruyi ◽  
Els de Paepe ◽  
...  
Keyword(s):  
Older Adults ◽  
Respiratory Syncytial Virus ◽  
Adverse Events ◽  
Immune Responses ◽  
Phase 1 ◽  
Geometric Mean ◽  
High Dose ◽  
Serious Adverse Events ◽  
Syncytial Virus ◽  
Vector Particles

Abstract Background Despite the high disease burden of respiratory syncytial virus (RSV) in older adults, there is no approved vaccine. We evaluated the experimental RSV vaccine, Ad26.RSV.preF, a replication-incompetent adenovirus 26 vector encoding the F protein stabilized in prefusion conformation. Methods This phase 1 clinical trial was performed in healthy adults aged ≥60 years. Seventy-two participants received 1 or 2 intramuscular injections of low-dose (LD; 5 × 1010 vector particles) or high-dose (HD; 1 × 1011 vector particles) Ad26.RSV.preF vaccine or placebo, with approximately 12 months between doses and 2-year follow-up for safety and immunogenicity outcomes. Results Solicited adverse events were reported by 44% of vaccine recipients and were transient and mild or moderate in intensity. No serious adverse events were related to vaccination. After the first vaccination, geometric mean titers for RSV-A2 neutralization increased from baseline (432 for LD and 512 for HD vaccine) to day 29 (1031 for LD and 1617 for HD). Pre-F–specific antibody geometric mean titers and median frequencies of F-specific interferon γ–secreting T cells also increased substantially from baseline. These immune responses were still maintained above baseline levels 2 years after immunization and could be boosted with a second immunization at 1 year. Conclusions Ad26.RSV.preF (LD and HD) had an acceptable safety profile and elicited sustained humoral and cellular immune responses after a single immunization in older adults.

Rate of Serious Adverse Events Associated with Diazoxide Treatment of Patients with Hyperinsulinism

2019 ◽  
Vol 91 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Paul Thornton ◽  
Lisa Truong ◽  
Courtney Reynolds ◽  
Tyler Hamby ◽  
Jonathan Nedrelow
Keyword(s):  
Pulmonary Hypertension ◽  
Adverse Events ◽  
Retrospective Analysis ◽  
First Line ◽  
Serious Adverse Events ◽  
Infants Of Diabetic Mothers ◽  
Drug Agency ◽  
Different Types ◽  
The Difference ◽  
Diabetic Mothers

Introduction: Diazoxide is the first line and only Federal Drug Agency approved pharmacological agent for the treatment of hyperinsulinism. Its use has increased over the years to include patients with various genetic forms of hyperinsulinism, perinatal stress hyperinsulinism and infants of diabetic mothers with more babies than ever being exposed to this therapy. Methods: We performed a retrospective analysis of 194 patients with hyperinsulinism in our clinic and looked for those who had experienced serious adverse events (SAE) including pulmonary hypertension and neutropenia. We compared the rates of SAE in the different types of hyperinsulinism. Results: Out of 194 patients with hyperinsulinism, 165 (85.1%) were treated with diazoxide. There were 17 SAEs in 16 patients including 8 cases of pulmonary hypertension and 8 of neutropenia. These data show that overall the frequency of SAE associated with diazoxide use is 9.7%, but that those with perinatal stress hyperinsulinism have a much higher rate than those with genetic forms of hyperinsulinism (16.7 vs. 3.6%; p = 0.01). We also found diazoxide is associated with pulmonary hypertension (4.8% of patients treated). Although more patients with perinatal stress hyperinsulinism (7.6%) were affected than genetic hyperinsulinism (1.2%), the difference was not significant (p = 0.088). Conclusion: The rate of SAEs associated with (not necessarily caused by) diazoxide has been demonstrated. The rate of SAE in newborns with perinatal stress hyperinsulinism is significantly higher than that of otherwise healthy babies with genetic forms of hyperinsulinism, suggesting that caution should be used when prescribing diazoxide to this population. This information should help balance the risk benefit of treatment and provide guidance on screening for these complications in the population of treated patients.

Efficacy and safety of pharmacological cachexia interventions: systematic review and network meta-analysis

2020 ◽  
pp. bmjspcare-2020-002601
Author(s):  
Manit Saeteaw ◽  
Phitjira Sanguanboonyaphong ◽  
Jukapun Yoodee ◽  
Kaitlyn Craft ◽  
Ratree Sawangjit ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Meta Analysis ◽  
Total Body Weight ◽  
Megestrol Acetate ◽  
High Dose ◽  
Efficacy And Safety ◽  
Pharmacological Interventions ◽  
Serious Adverse Events ◽  
Significant Difference

AimsRandomised controlled trials (RCTs) demonstrated benefits of pharmacological interventions for cachexia in improving weight and appetite. However, comparative efficacy and safety are not available. We conducted a systematic review and network meta-analysis (NMA) to evaluate the relative efficacy and safety of pharmacological interventions for cachexia.MethodsPubMed, EmBase, Cochrane, and ClinicalTrials.gov were searched for RCTs until October 2019. Key outcomes were total body weight (TBW) improvement, appetite (APP) score and serious adverse events. Two reviewers independently extracted data and assessed risk of bias. NMA was performed to estimate weight gain and APP score increase at 8 weeks, presented as mean difference (MD) or standardised MD with 95% CI.Results80 RCTs (10 579 patients) with 12 treatments were included. Majority is patients with cancer (7220). Compared with placebo, corticosteroids, high-dose megestrol acetate combination (Megace_H_Com) (≥400 mg/day), medroxyprogesterone, high-dose megestrol acetate (Megace_H) (≥400 mg/day), ghrelin mimetic and androgen analogues (Androgen) were significantly associated with MD of TBW of 6.45 (95% CI 2.45 to 10.45), 4.29 (95% CI 2.23 to 6.35), 3.18 (95% CI 0.94 to 5.41), 2.66 (95% CI 1.47 to 3.85), 1.73 (95% CI 0.27 to 3.20) and 1.50 (95% CI 0.56 to 2.44) kg. For appetite improvement, Megace_H_Com, Megace_H and Androgen significantly improved standardised APP score, compared with placebo. There is no significant difference in serious adverse events from all interventions compared with placebo.ConclusionsOur findings suggest that several pharmacological interventions have potential to offer benefits in treatment of cachexia especially Megace_H and short-term use corticosteroids. Nonetheless, high-quality comparative studies to compare safety and efficacy are warranted for better management of cachexia.

Management Of Immunotherapy Adverse Events In Oncological Patients: Anti-Ctla-4, Anti-Pd-1/Pd-L1

2020 ◽  
Vol 15 ◽  
Author(s):  
Mattia Brigida ◽  
Alessia Perricelli ◽  
Fausto Sposato ◽  
Maria Giovanna Spadafora ◽  
Angelo Pomillo ◽  
...  
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Corticosteroid Treatment ◽  
High Dose ◽  
Emergency Setting ◽  
Serious Adverse Events ◽  
Oncological Patients ◽  
Grade Ii ◽  
Dose Corticosteroid

Background: The widespread use of immunotherapy drugs in the oncological field has led to the spread of new toxicities compared to the more common chemotherapy treatments. This is because immunotherapy with anti-CTLA-4 (Cytotoxic T Lymphocytes-Associated Antigen 4), anti-PD-1 and anti-PD-L1 monoclonal antibodies has become the standard-of-care in a growing number of indications. Any organ or tissue can be involved, but more commonly side effects are reported regarding skin, colon, endocrine glands, liver, lung and kidney. Other less frequent, but more serious, adverse events are neurological and myocarditis. Methods: We performed an electronic search on PUBMED of the literature concerning immunotherapy-related toxicities and their management in oncological patients from 2007 to 2020, with particular attention to the most recent publications. Aim: To summarize the different types of immunotherapy-related toxicities, together with their incidence and diagnosis, and to simplify their management, especially in the emergency setting. Conclusion: Usually, for grade I toxicities it is not recommended to stop immunotherapy; for most of grade II toxicities, immunotherapy should be postponed to when toxicity will have regressed to grade I, considering the possibility of a corticosteroid treatment for most of toxicities. The majority of grade III and IV require administration of high-dose corticosteroid intravenous therapy and suspension of immunotherapy. Mortality related to immune checkpoint inhibitors’ toxicity, occurring at a rate of 0.3-1.3%, is well below fatality rates due to other oncologic interventions and should not discourage the promising results so far reached by immunotherapy.

Outpatient administration of high-dose methotrexate for osteosarcoma treatment in Brazil

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10038-10038 ◽  
Author(s):  
C. R. Macedo ◽  
A. M. Cappellano ◽  
D. T. Noguchi ◽  
A. P. Martinho ◽  
C. G. Dias ◽  
...  
Keyword(s):  
Adverse Events ◽  
Patient Adherence ◽  
Elevated Serum ◽  
Serum Levels ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Serious Adverse Events ◽  
Early Introduction ◽  
Dose Methotrexate ◽  
Metronomic Treatment

10038 Background: We describe the experience with outpatient administration of high dose methotrexate (HDMTX) and leucovorin rescue for osteosarcoma treatment at Instituto de Oncologia Pediátrica. Methods: HDMTX (12g/m2) is administered as part of the Brazilian Osteosarcoma Treatment Group Protocol in an ambulatory basis. Daily MTX serum levels and fluid controls follows until the serum level is <0,2 μ/L. Families were oriented to measure urinary pH and volume, PO intake and to adjust leucovorin dose as needed. To achieve treatment adherence, a family education program was developed. Concomitantly to HD chemotherapy, low dose oral cyclophosphamide and MTX (metronomic treatment) were provided to metastatic (M) patients. This is a retrospective analysis of the HDMTX courses administered between 2006 and 2008. Results: Out of 341 HDMTX infusions, administered to 42 patients, 42.5% had abnormal serum levels at hour 24, 8.8% at hour 48 and 33.2% at hour 72. After required interventions, 2.9% (n = 8) had serum levels >0.2 μ/L at hour 72 leading to delayed excretion. Of these, 7 had also creatinine elevation and main adverse events were mucositis, reversible transaminasis elevation and one sepsis. In the overall analysis, other toxicities included mucositis grade II (20%), nefrotoxicity (5.6%) and neutropenia grades III and IV (25.4%). Serious adverse events of seizure, allergic reaction, and Steven Johnson's Syndrome lead to suspension of future HDMTX administration in 4 patients (01 metastatic). The main differences found between M and non-M patients were 16.8% versus 8.7% of leucopenia grade IV and 12.1% versus 6.6% of anemia grades III and IV. Conclusions: Similar to other authors’ experience, outpatient administration of HDMTX lead to elevated serum levels in 42.5% of the infusions, demonstrating the importance of a well trained staff and early introduction of supportive therapies to avoid associated toxicities. To a developing country, this approach helps lowering treatment costs and infection risks and increases patient adherence to treatment, with acceptable toxicities, even with the introduction of metronomic treatment. No significant financial relationships to disclose.

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