Onset, duration, and clinical impact of immune-related adverse events in Hodgkin lymphoma.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 95-95
Author(s):  
Alexandra Higgins ◽  
Michael D. Richter ◽  
Shruti Patel ◽  
Kristen Beth McCullough ◽  
Thomas Matthew Habermann ◽  
...  
Keyword(s):  
Adverse Events ◽  
Hodgkin Lymphoma ◽  
Retrospective Chart Review ◽  
Relevant Information ◽  
Incidence Rates ◽  
Time Profile ◽  
Treatment Discontinuation ◽  
Prolonged Duration ◽  
Continue Therapy

95 Background: The incidence of immune-related adverse events (irAEs) in patients (pts) with Hodgkin lymphoma (HL) treated with PD-1 antibodies (ICI) is reported at 28 - 36%. However, clinically relevant information on irAE onset, duration, or impact on ability to continue therapy in HL is lacking. Additionally, these incidence rates reflect CTCAE definition and grading, and not ASCO Clinical Practice Guidelines irAE-specific criteria (Brahmer et al, JCO 2018). The objectives of this study were to evaluate the rate and severity of irAEs in HL pts using ASCO criteria, to characterize irAE time profile and to assess their impact on continued therapy. Methods: HL pts who received a PD-1 inhibitor for the treatment of HL at Mayo Clinic Rochester between January 1, 2011 and March 1, 2018 were identified. We conducted a detailed, longitudinal retrospective chart review with definition and grading of irAEs in accordance with ASCO guidelines. Results: Fifty-one pts were identified (35% women, median age at ICI initiation 35 years [range: 19-87]). Median duration of follow up from ICI start was 30 months (range: 1-70). Thirty-one pts (61%) had any irAE. Most common irAEs were inflammatory/bullous dermatoses (23.5%/5.9% any grade/grade3-4; median onset/duration of 81/57 days[d]), followed by thyroiditis (22%/0%; 86/84 d), colitis (14%/8%; 82/106 d), pneumonitis (14%/10%; 241/182 d), and hepatitis (14%/4%; 71/35 d). Fifteen pts (29%) required treatment with steroids. Among the total cohort, ICI was held for an irAE 28 times (50% of 56 total irAEs). Median treatment cycles held was 2.5 and ICI was permanently discontinued due to irAE in 18%. The most common irAE leading to treatment discontinuation was pneumonitis, followed by neuritis (5.9%/3.9%; 179/374 d), colitis, and rash. Conclusions: The rate of irAEs of 61% in this cohort as defined by ASCO consensus criteria was higher than reported in trials. Most irAEs were characterized by delayed onset of several months and prolonged duration, particularly pneumonitis and neuritis. Treatment discontinuation due to irAEs was infrequent overall. Further studies are needed to determine whether the development or duration of irAEs is predictive of treatment outcomes in HL.

Change in Abdominal Aortic Aneurysm Sac Diameter After Endovascular Repair: A Single-Center Experience From Taiwan

2022 ◽  
pp. 152660282110687
Author(s):  
Hsien-Wei Tseng ◽  
Po-Ya Chang ◽  
Chin-Hao Chang ◽  
I-Hui Wu ◽  
Ron-Bin Hsu ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Adverse Events ◽  
Survival Rates ◽  
Incidence Rates ◽  
Single Center Experience ◽  
Maximal Diameter ◽  
Abdominal Aortic ◽  
Diameter Change

Purpose: The purpose of this study was to investigate the change in the diameter of infrarenal abdominal aortic aneurysm (AAA) sacs after endovascular aortic repair (EVAR) in Taiwanese patients and to depict its association with clinical outcomes. Materials and Methods: This retrospective cohort study was conducted on patients who underwent EVAR for infrarenal AAA between January 2011 and December 2016. All preoperative and follow-up computed tomography (CT) images were reviewed. Postoperative CT angiography was arranged after 1 month and annually thereafter. The maximal diameter on the axial plane and the maximal diameter perpendicular to the centerline on the coronal and sagittal planes were measured. The study examined post-EVAR sac diameter change over time and compared the differences in adverse events (AEs) among groups. Results: The survey included a total of 191 patients with a median follow-up duration of 2.5 (interquartile range: 1.1–2.9) years. Overall survival rates at 1, 2, and 5 years were 92%, 81%, and 76%, respectively. According to their last CT scans, the patients were categorized into 3 groups as follows: shrinkage, stationary, and enlargement, which comprised 58 (30.4%), 118 (61.8%), and 15 (7.9%) patients, respectively. Pre-EVAR characteristics and sac diameters were similar among the groups. Sac shrinkage was exclusively observed in the first 2 years, whereas sac enlargement developed at all follow-up periods. Patients with sac enlargement had higher incidence rates of endoleaks, complications, and reintervention than the other groups. Conclusion: Based on our observations, post-EVAR sac shrinkage only occurs in the first 2 years; however, post-EVAR sacs may enlarge at any point and even after 5 years. In our study, patients with sac enlargement had higher rates of adverse events and reintervention.

CML Patients Outcome after TKI Discontinuation: A Single Institution Experience in the US

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1923-1923 ◽  
Author(s):  
Kamal Chamoun ◽  
Hagop M. Kantarjian ◽  
Mary Beth Rios ◽  
Rita Assi ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Adverse Events ◽  
Relapse Rate ◽  
Research Funding ◽  
Cytogenetic Response ◽  
Advisory Board ◽  
Treatment Discontinuation ◽  
Molecular Response ◽  
Single Institution ◽  
Complete Cytogenetic Response

Abstract Chronic myeloid leukemia (CML) patients who achieve a complete cytogenetic response (CCyR) with tyrosine kinase inhibitor (TKI) have an expected survival rate comparable to that of the general population. It is practice to continue TKI therapy indefinitely. However, this chronic therapy may impact patient's lives either by its associated adverse events, or its influence on real-life events (eg. pregnancy, financial burden). Therefore, treatment discontinuation has been increasingly sought. Discontinuation of therapy for patients with sustained MR4.5 has been associated with 30-50% sustained molecular response in previous studies. However, patients may sometimes choose to discontinue therapy for various reasons regardless of the response. We retrospectively analyzed the outcome of 95 patients with CML who discontinued TKI therapy at a single institution. Median age at diagnosis was 50 years (range 26 - 75), 56 (59%) were females. Median follow up from diagnosis to treatment discontinuation was 120 months. TKI was the initial therapy in 62 patients (41 imatinib, 7 nilotinib, 12 dasatinib, 1 bosutinib, 1 ponatinib) and interferon in 33 patients (34%). At time of discontinuation, 67 patients (71%) were receiving their first TKI (48 imatinib, 6 nilotinib, 12 dasatinib, 1 ponatinib) while 25 (26%) and 3 (3%) patients were receiving their second and third TKI respectively. All patients achieved complete cytogenetic response (CCyR) and major molecular response (MMR) in a median of 3 (range 2-93) and 9 months (range 2-132) respectively. MR4.5 was achieved in 92 (97%) patients at a median of 17 months. Three patients had MMR as their best response. Patients received TKI for a median of 104 months (range 8-203) before discontinuation. Fifty two patients (54%) discontinued therapy due to adverse events, 27 (28%) electively due to sustained MR4.5, 7 (7%) due to pregnancy, 6 (6%) for financial reasons and 3 (3%) due to the occurrence of a second cancer. At time of discontinuation all patients were in CCyR; 90 patients (95%) were in MR4.5 and 5 patients (5%) in MMR. The median MR4.5 duration before discontinuation was 75 months (range 1-178); 84 had a sustained MR4.5 for at least 2 years and 59 for at least 5 years. After a median follow-up from treatment discontinuation of 23 months (0 to 113 months), 38 (40%) patients have lost their response at a median of 4 months (range 1-34) after discontinuation; 10 patients lost response after 12 months from discontinuation. Among patients with MR4.5 at discontinuation, molecular relapse occurred in 33 patients (37%) at a median of 4 months (range 1-34; 8 after 12 months from discontinuation). All 5 patients with MMR at discontinuation loss their response at a median of 8 months (range 2-14). Patients receiving imatinib, dasatinib or nilotinib had a median TKI treatment duration of 117, 64 and 65 months before discontinuation, and lost their response at a rate of 33%, 56% and 46%, respectively. Relapse rate for patients with MR4.5 sustained >2 years was 32%, whereas those with <2 years it was 82%; a similar analysis with cutoff of 5 years yielded a relapse rate of 15% and 77%, respectively. Among patients with b3a2 with MR4.5 at discontinuation, 35% lost response, compared to 33% for those with b2a2 and 53% for those with both b3a2 and b2a2. Twenty four relapsing patients were eventually retreated; 21 re-gained the response they had at the time of discontinuation in a median of 4.5 months after resumption of therapy. At last follow up, 82 (86%) patients were in MR4.5, 4 (4%) in MMR, 5 (5%) in CCyR, 3 (3%) in PCyR and 1 (1%) in mCyR. This analysis shows that patients with less than MR4.5 at time of discontinuation have higher risk of relapse. The lower percentage of relapse seen in patients who had been on imatinib likely represents the longer period of treatment before discontinuation compared to the 2nd generation TKIs. Late relapses (e.g., beyond a year) occur in a subset of patients. Although the majority of patients who lose their response after discontinuation respond to retreatment, treatment discontinuation is still not recommended outside clinical trials. Disclosures Jain: Pfizer: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; Genentech: Research Funding; Servier: Consultancy, Honoraria; Seattle Genetics: Research Funding; Abbvie: Research Funding; Infinity: Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Novimmune: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Incyte: Research Funding; BMS: Research Funding. Daver:BMS: Research Funding; Karyopharm: Honoraria, Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Research Funding; Kiromic: Research Funding; Sunesis: Consultancy, Research Funding; Otsuka: Consultancy, Honoraria. Konopleva:Calithera: Research Funding; Cellectis: Research Funding. DiNardo:Abbvie: Research Funding; Daiichi Sankyo: Other: advisory board, Research Funding; Novartis: Other: advisory board, Research Funding; Celgene: Research Funding; Agios: Other: advisory board, Research Funding. Jabbour:ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy. Cortes:ARIAD: Consultancy, Research Funding; Bristol-Myers Squib: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding.

Drug survival of the first and second course of anti-tumour necrosis factor agents in juvenile idiopathic arthritis

2008 ◽  
Vol 68 (4) ◽  
pp. 552-557 ◽  
Author(s):  
P Tynjälä ◽  
P Vähäsalo ◽  
V Honkanen ◽  
P Lahdenne
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Adverse Events ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Treatment Discontinuation ◽  
Inactive Disease ◽  
Infliximab Treatment ◽  
Drug Survival ◽  
Necrosis Factor

Objectives:To evaluate drug survival (continuation rates on drug) of anti-tumour necrosis factor (TNF) agents in juvenile idiopathic arthritis (JIA) and predictors for treatment discontinuation.Methods:A retrospective observational study on JIA patients taking etanercept (n  =  105) or infliximab (n  =  104) with at least one year follow-up. Kaplan–Meier curves and log-rank statistics were used to compare treatments and a proportional hazards model to assess risk factors for discontinuation.Results:Etanercept versus infliximab treatment survival at 12 months was 83% versus 80%, at 24 months 68% versus 68%, at 36 months 64% versus 53%, at 48 months 61% versus 48% (p = 0.194), respectively. Reasons for discontinuing the first biological treatment were inefficacy (etanercept 28% vs infliximab 20%, p = 0.445), adverse events (7% vs 22%, p = 0.002) or inactive disease (10% vs 16%, p = 0.068). Women (hazard ratio (HR) 2.8, 95% CI 1.3 to 5.8), patients with systemic JIA (HR 7.8, 95% CI 1.7 to 34.9) or those taking infliximab (HR 2.0, 95% CI 1.2 to 3.3) were at higher risk of treatment discontinuation. One-third of the patients were switched to the second anti-TNF therapy, which was discontinued less frequently than the first. At 12 months treatment survival of etanercept was 60%, infliximab 58% and adalimumab 66% as the second-line anti-TNF therapy.Conclusions:Although infliximab was discontinued more often than etanercept because of adverse events, during a 48-month follow-up the overall treatment survival of etanercept and infliximab as the first biological agent in JIA was comparable. A switch from one anti-TNF agent to another appears a reasonable therapeutic option.

scholarly journals 755. Posaconazole versus voriconazole as antifungal prophylaxis for invasive fungal diseases in patients with hematological malignancies

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S425-S425
Author(s):  
Reem F Almutairy ◽  
Mansoor Khan ◽  
Majed Alshamrani ◽  
Hassan Marhabi ◽  
Doaa Naeem
Keyword(s):  
Adverse Events ◽  
Retrospective Chart Review ◽  
Cost Effective ◽  
Antifungal Prophylaxis ◽  
Incidence Rates ◽  
Fungal Diseases ◽  
Comparable Efficacy ◽  
Efficacy And Safety ◽  
International Guidelines ◽  
Invasive Fungal Diseases

Abstract Background The incidence of Invasive Fungal Diseases (IFDs) has dramatically increased in patients with hematologic malignancies due to prolonged neutropenia. IFDs are associated with significant morbidity and mortality. Due to these risks, international guidelines have recommended antifungal prophylaxis for Acute Myeloid Leukemia (AML) and Myelodysplastic syndromes (MDS) patients. Posaconazole has been recommended as the prophylactic agent of choice. Also, voriconazole has been recommended by guidelines with different levels of recommendations. Data on a direct comparison between Posaconazole delayed-release tablets (DR) and Voriconazole for IFD prophylaxis are lacking. Therefore, we aim to compare the efficacy and safety of the fungal prophylaxis; voriconazole versus posaconazole in AML/MDS patients at Princess Nourah Oncology Center, Jeddah Methods Retrospective chart review study for eligible patients from January 2017 to February 2019 to identify the breakthrough IFD rates and assess the frequency of adverse events within AML/MDS patients at PNOC, Saudi Arabia Results A total of 48 patients (130 chemo cycles) were included in the study: 50 using posaconazole (DR) and 80 using oral voriconazole as antifungal prophylaxis. The incidence rates of IFD in the posaconazole group was 8 % (4/50) of those 2 were probable, and 2 were possible infections while 6.26 % (5/80) of patients in the voriconazole group have developed IFD of them 4 had a possible infection, and one had a probable infection (p=0.7325). A higher percentage of patients in the voriconazole group discontinued prophylaxis due to adverse events (5 patients vs. 2 patients). Use of voriconazole as antifungal prophylaxis for 15 days in 130 cycles in 48 AML/MDS patients would cost 175,500 SR in comparison to the cost of the posaconazole for the same duration of 1,350,130 SR. So, use of voriconazole would save 1.13 million SR and is more cost effective when used as antifungal prophylaxis in AML/MDS patients in comparison to posaconazole although later is category 1 recommended antifungal prophylaxis in international guidelines Conclusion Our study has shown that both posaconazole and voriconazole have comparable efficacy and safety in the prevention of IFD in AML and MDS receiving chemotherapy but voriconazole is more cost effective Disclosures All Authors: No reported disclosures

Patient characteristics associated with dose-limiting sunitinib adverse events

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16110-e16110
Author(s):  
B. Atkinson ◽  
J. Hart ◽  
E. Lin ◽  
N. Tannir ◽  
E. Jonasch
Keyword(s):  
Adverse Events ◽  
Tyrosine Kinases ◽  
Univariate Analysis ◽  
Cell Cancer ◽  
Multivariate Logistic Regression Analysis ◽  
Retrospective Chart Review ◽  
Continuation Methods ◽  
Eligibility Criteria ◽  
The Impact

e16110 Background: Sunitinib, an inhibitor of multiple tyrosine kinases, is FDA approved for metastatic renal cell cancer (mRCC). Though better tolerated than historical therapies, sunitinib is associated with adverse events (AEs) that may require dose modifications (DM). We sought to identify 1) baseline patient (pt) characteristics that predispose for DM, 2) the most common AEs requiring DM in a non-protocol setting, and 3) the impact of dose limiting AEs on treatment continuation. Methods: Single-center, retrospective chart review. Pts ≥ 18 years of age with mRCC of clear-cell histology on sunitinib therapy with active follow-up at MDACC were eligible. Univariate and multivariate logistic regression analysis of 66 pt variables (demographics, laboratory analysis, past medical and treatment history, etc) and dose-limiting AEs was completed, with a 6 month endpoint of sunitinib continuation, alternative therapy, or death. Results: From January 1, 2006 through September 30, 2007, 146 pts were identified meeting eligibility criteria. By univariate analysis, increased age (p=0.04; OR 1.04, 1.002–1.081 CI) and elevated BUN (p=0.03; OR 1.06, 1.006 –1.108 CI) were directly associated with increased incidence of dose-limiting AEs. ECOG PS of 2 (p=0.04; OR 0.3, 0.114–0.951 CI) was associated with a decreased incidence of dose limiting AEs. In a multivariate analysis, only BUN remained significant. 57% of patients (n= 83) had dose-limiting AEs. DM were often attributed to multiple AEs (55%), with fatigue, mucositis, hand-foot syndrome and nausea being the most common. At 6 months follow-up, 63% of pts with dose-limiting AEs remained on sunitinib vs. 37% (p=0.18). There was no difference in death rate at 6 months between the two groups. Conclusions: Elevated baseline BUN is associated with an increased rate of DM in patients with RCC receiving sunitinib. Despite the high-incidence of AEs, pts can be maintained on sunitinib with DM and without an adverse impact on outcome. Whether specific AEs are biologic indicators of activity should be evaluated in a larger clinical trial. [Table: see text]

scholarly journals Evaluating Resident Training in Oculoplastic Surgery: A Case Series of 104 Eviscerations

2018 ◽  
Vol 10 (01) ◽  
pp. e108-e113
Author(s):  
Brittany Simmons ◽  
Anna Artymowicz ◽  
Mithra Gonzalez
Keyword(s):  
Adverse Events ◽  
Chart Review ◽  
Case Series ◽  
Retrospective Chart Review ◽  
Resident Training ◽  
Complication Rates ◽  
Surgical Performance ◽  
Resident Participation ◽  
Oculoplastic Surgery

Purpose The aim of this study is to evaluate resident surgical performance based on complications after ocular evisceration. Methods A retrospective chart review of eviscerations performed between October 2011 and May 2017 by ophthalmology residents as the primary or assistant surgeon under the guidance of a single oculofacial plastic surgeon (M.O.G.) was completed. Data collected included reason for evisceration, resident participation in the case and resident's month of oculoplastic training, surgical technique, subsequent complications, and duration of follow-up. Results There were no significant differences in complication rates or surgical sequelae in resident-led versus attending-led surgeries. The complication rate for all cases in total was 5.77%. A slight negative correlation existed between the resident's month of training and the presence of postoperative complications. The number of adverse events was found to be significantly correlated with the duration of patient follow-up. Discussion Ocular eviscerations performed by ophthalmology residents as primary surgeons achieve outcomes equivalent to published reports, suggesting ocular eviscerations are a safe, effective procedure wherein residents can refine surgical skills. Some surgical sequelae may be linked to particular surgeons, implying evisceration outcomes can be used to assess resident surgical performance. Fewer adverse events arose as the resident's length of oculoplastic training increased, but this finding did not reach significance. Larger studies are needed to explore these trends.

Propranolol for infantile haemangiomas: initiating treatment on an outpatient basis

2011 ◽  
Vol 22 (4) ◽  
pp. 424-429 ◽  
Author(s):  
Joshua L. Dyme ◽  
Ashis Thampan ◽  
Eugenia J. Han ◽  
Themba L. Nyirenda ◽  
Mohy E. Kotb ◽  
...  
Keyword(s):  
Adverse Events ◽  
Physical Examination ◽  
Chart Review ◽  
Retrospective Chart Review ◽  
Outpatient Basis ◽  
Cardiac Evaluation ◽  
Pre Treatment ◽  
Clinically Significant ◽  
Infantile Haemangiomas

AbstractIntroductionPropranolol was recently discovered to be an effective treatment for infantile haemangiomas, and varying doses and monitoring regimens have been proposed. Adverse events, although uncommon, have been reported.Materials and methodsThis was a retrospective chart review of infants with haemangiomas who were started on propranolol at a dose of 3 milligrams per kilogram per day on an outpatient basis. After a baseline cardiac evaluation including an electrocardiogram and an echocardiogram, treatment was initiated during 6 hours of observation.ResultsA total of 15 patients were identified; however, only 13 returned for at least one follow-up visit. This cohort was followed up for a median of 2.8 months with a range from 0.2 to 10.0. No hypotension, hypoglycaemia, bronchospasm, or clinically significant bradycardia occurred during treatment. All patients had clinical improvement of their haemangiomas.ConclusionsThis study suggests that initiating treatment during outpatient observation may be a reasonable alternative to inpatient admission. In addition, expensive testing may not be necessary during pre-treatment screening when the physical examination is normal.

Operative versus nonoperative treatment for adult symptomatic lumbar scoliosis at 5-year follow-up: durability of outcomes and impact of treatment-related serious adverse events

2021 ◽  
pp. 1-13
Author(s):  
Justin S. Smith ◽  
Michael P. Kelly ◽  
Elizabeth L. Yanik ◽  
Christine R. Baldus ◽  
Thomas J. Buell ◽  
...  
Keyword(s):  
Adverse Events ◽  
Operative Treatment ◽  
Nonoperative Treatment ◽  
Incidence Rates ◽  
Mean Difference ◽  
Patient Counseling ◽  
Serious Adverse Events ◽  
Lumbar Scoliosis ◽  
The Impact

OBJECTIVE Although short-term adult symptomatic lumbar scoliosis (ASLS) studies favor operative over nonoperative treatment, longer outcomes are critical for assessment of treatment durability, especially for operative treatment, because the majority of implant failures and nonunions present between 2 and 5 years after surgery. The objectives of this study were to assess the durability of treatment outcomes for operative versus nonoperative treatment of ASLS, to report the rates and types of associated serious adverse events (SAEs), and to determine the potential impact of treatment-related SAEs on outcomes. METHODS The ASLS-1 (Adult Symptomatic Lumbar Scoliosis–1) trial is an NIH-sponsored multicenter prospective study to assess operative versus nonoperative ASLS treatment. Patients were 40–80 years of age and had ASLS (Cobb angle ≥ 30° and Oswestry Disability Index [ODI] ≥ 20 or Scoliosis Research Society [SRS]–22 subscore ≤ 4.0 in the Pain, Function, and/or Self-Image domains). Patients receiving operative and nonoperative treatment were compared using as-treated analysis, and the impact of related SAEs was assessed. Primary outcome measures were ODI and SRS-22. RESULTS The 286 patients with ASLS (107 with nonoperative treatment, 179 with operative treatment) had 2-year and 5-year follow-up rates of 90% (n = 256) and 74% (n = 211), respectively. At 5 years, compared with patients treated nonoperatively, those who underwent surgery had greater improvement in ODI (mean difference −15.2 [95% CI −18.7 to −11.7]) and SRS-22 subscore (mean difference 0.63 [95% CI 0.48–0.78]) (p < 0.001), with treatment effects (TEs) exceeding the minimum detectable measurement difference (MDMD) for ODI (7) and SRS-22 subscore (0.4). TEs at 5 years remained as favorable as 2-year TEs (ODI −13.9, SRS-22 0.52). For patients in the operative group, the incidence rates of treatment-related SAEs during the first 2 years and 2–5 years after surgery were 22.38 and 8.17 per 100 person-years, respectively. At 5 years, patients in the operative group who had 1 treatment-related SAE still had significantly greater improvement, with TEs (ODI −12.2, SRS-22 0.53; p < 0.001) exceeding the MDMD. Twelve patients who received surgery and who had 2 or more treatment-related SAEs had greater improvement than nonsurgically treated patients based on ODI (TE −8.34, p = 0.017) and SRS-22 (TE 0.32, p = 0.029), but the SRS-22 TE did not exceed the MDMD. CONCLUSIONS The significantly greater improvement of operative versus nonoperative treatment for ASLS at 2 years was durably maintained at the 5-year follow-up. Patients in the operative cohort with a treatment-related SAE still had greater improvement than patients in the nonoperative cohort. These findings have important implications for patient counseling and future cost-effectiveness assessments.

scholarly journals Dose Dependency of Iatrogenic Glucocorticoid Excess and Adrenal Insufficiency and Mortality: A Cohort Study in England

2019 ◽  
Vol 104 (9) ◽  
pp. 3757-3767 ◽  
Author(s):  
Teumzghi F Mebrahtu ◽  
Ann W Morgan ◽  
Adam Keeley ◽  
Paul D Baxter ◽  
Paul M Stewart ◽  
...  
Keyword(s):  
Cohort Study ◽  
Adverse Events ◽  
Adrenal Insufficiency ◽  
Cushing Syndrome ◽  
Inflammatory Diseases ◽  
Absolute Risk ◽  
Incidence Rates ◽  
Hazard Ratios ◽  
Increased Risk

Abstract Context Adrenal insufficiency and Cushing syndrome are known adverse events of glucocorticoids. However, no population estimates of dose-related risks are available. Objective To investigate dose-related risks of adrenal dysfunction and death in adults with six chronic inflammatory diseases treated with oral glucocorticoids. Design and setting Retrospective, record-linkage, open-cohort study spanning primary and hospital care in England. Patients A total of 70,638 oral glucocorticoid users and 41,166 nonusers aged ≥18 years registered in 389 practices in 1998 to 2017. Main outcome measures Incidence rates and hazard ratios (HRs) of diagnosed adrenal dysfunction and death. Results During a median follow-up of 5.5 years, 183 patients had glucocorticoid-induced adrenal insufficiency and 248 had glucocorticoid-induced Cushing syndrome. A total of 22,317 (31.6%) and 7544 (18.3%) deaths occurred among glucocorticoid users and nonusers, respectively. The incidence of all outcomes increased with higher current daily and cumulative doses. For adrenal insufficiency, the increases in HRs were 1.07 (95% CI: 1.04 to 1.09) for every increase of 5 mg per day and 2.25 (95% CI: 2.15 to 2.35) per 1000 mg of cumulative prednisolone-equivalent dose over the past year. The respective increases in HRs for Cushing syndrome were 1.09 (95% CI: 1.08 to 1.11) and 2.31 (95% CI: 2.23 to 2.40) and for mortality 1.26 (95% CI: 2.24 to 1.28) and 2.05 (95% CI: 2.04 to 2.06). Conclusion We report a high glucocorticoid dose-dependent increased risk of adrenal adverse events and death. The low observed absolute risk of adrenal insufficiency highlights a potential lack of awareness and a need for increased physician and patient education about the risks of adrenal dysfunction induced by glucocorticoids.

scholarly journals Brentuximab Vedotin Plus ESHAP (BRESHAP) Is a Highly Effective Combination for Inducing Remission in Refractory and Relapsed Hodgkin Lymphoma Patients Prior to Autologous Stem Cell Transplant: A Trial of the Spanish Group of Lymphoma and Bone Marrow Transplantation (GELTAMO)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1109-1109 ◽  
Author(s):  
Ramon Garcia-Sanz ◽  
Anna Sureda ◽  
Ana Pilar Gonzalez ◽  
Fatima De la Cruz ◽  
Blanca Sanchez-Gonzalez ◽  
...  
Keyword(s):  
Stem Cell ◽  
Adverse Events ◽  
Hodgkin Lymphoma ◽  
Abdominal Sepsis ◽  
Brentuximab Vedotin ◽  
High Dose ◽  
Line Therapy ◽  
Grade 3 ◽  
One Year

Abstract Introduction: 30% of Hodgkin Lymphoma (HL) patients are refractory or relapse (RR) after first line therapy. Salvage chemotherapy followed by high-dose chemotherapy and with Autologous Peripheral Blood Stem Cell Transplantation (APBSCT) can cure many patients, but those who are transplanted with active disease detectable by PET-CT have a very poor prognosis. Therefore, the current challenge in HL is to improve the results of the pre-transplant chemotherapy. We and others have demonstrated that the addition of Brentuximab Vedotin (BV) to chemotherapy can produce very good results. Objectives: We conducted a phase II trial to assess response rate with combined Brentuximab vedotin and ESHAP chemotherapy [BRESHAP] as 2nd line therapy for RRHL prior to APBSCT (ClinicalTrials.gov #NCT02243436). Methods: Primary efficacy endpoint was the proportion of complete responses (CR) pre-APBSCT. A prior phase I step was carried out to establish the appropriate dosis. Final treatment consisted of Brentuximab Vedotin (1.8 mg/m2/day IV, D1), Etoposide (40 mg/m2/day IV, D1-4), Solumedrol (250 mg/day IV, D1-4), High dose AraC (2 g/m2 IV, D5) and cisPlatin (25 mg/m2/day IV, D1-4). Results: Patients with relapsed or refractory classical HL (cHL) after one prior line of therapy were eligible. 66 patients were included in the trial. There were 35 females and 31 males, with a median age of 36 years (18-66). At inclusion, 40 patients were considered primary refractory, 16 as early relapses (complete remission -CR- shorter than 1 year) and 10 as late relapses. Currently, all patients have completed the pre-transplant therapy. During that period, there were 22 Severe Adverse Events (SAEs) reported in 15 patients: Fever in 13 occasions (neutropenic in seven, and non-neutropenic in six), hypomagnesemia and gastrointestinal alterations (n=2) and pneumothorax, skin lesions, left ventricular function reduction and pulmonary embolism [PE](n=1). There were 2 deaths: non-neutropenic abdominal sepsis and PE. Grade 3-4 hematologic toxicity presented in 22 cases: neutropenia (n=18), thrombocytopenia (n=12), and anemia (n=5). Grade 3-4 extrahematologic adverse events present in ≥5% of cases were non-neutropenic fever (n=8) and hypomagnesemia (n=3). All patients except three underwent stem cell mobilization after the 1st (n=15), 2nd (n=36) or 3rd (n=12) cycle using subcutaneous G-CSF 5 mcg/Kg/12 h. for 5 days. All patients collected >2·10e6/Kg peripheral blood CD34+ cells in all cases (median 5.75, range 2.12-33.4). The number of harvesting procedures was one in 47 patients, two in 13, three in 2 and four in 1. The transplant has been done in 61 patients, with data are available from 47: all engrafted with a median of 9&10 days for neutrophil and platelet recovery, respectively. No major events were registered during transplant period, except for one patient who died at day +110 due to pneumonia. Overall pre-transplant response was 96%, including a 70% and 26% complete and partial remission rates, respectively. Of these forty-seven patients, 37 (80%) were in metabolic CR after transplant and 3 (7%) in PR; six patients were considered as non-responders (13%) and went out of the trial. At a mean follow-up of 11 months, 7 patients have progressed, rendering a projected progression free survival of 87% at one year. Six patients have already died: three due to progression, and the three already mentioned above (PE, abdominal sepsis and pneumonia). With a mean follow-up of 11 months, the projected overall survival was 90% at one year (cause specific, 96%). Conclusions: BRESHAP is a highly effective regimen for remission induction prior to transplant in patients with refractory or relapsed Hodgkin lymphoma. The addition of BV to the conventional chemotherapy did not resulted in a higher toxicity for the pre- and post-transplant periods and it did not hamper the collection of PBSC. Disclosures No relevant conflicts of interest to declare.

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