bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of patients with myelofibrosis on ruxolitinib for three or more years.
Authors: Masarova Lucia , Bose Prithviraj , Pemmaraju Naveen , Chifotides Helen T. , Zhou Lingsha , Estrov Zeev , Kantarjian Hagop M. , Verstovsek Srdan 
Published: June 2022

e19082 Background: Ruxolitinib (RUX) was the first JAK1/2 inhibitor approved for patients with advanced phase of myelofibrosis (MF) with median therapy duration of about 3 years. We aimed to characterize clinical features of patients treated with RUX for ≥3 years who presented to our institution between January 2000 and January 2019. Methods: Retrospective review of medical records of 131 patients who received RUX for ≥3 years. Clinical characteristics, therapy details and overall survival (OS; Kaplan Meier method) were assessed at/from the time of RUX initiation. Cox proportional hazard model was used for univariate (known clinical variables) and multivariate analysis (p < 0.05 on previous analysis) of factors associated with OS. Results: Median age of patients was 67 years (range, 31-84), 56% were males (clinical characteristics in Table). Among 62 patients with ≥ 28 gene next generation sequencing; 19, 24 and 19 patients had none, 1 and ≥2 mutations beyond JAK2, MPL, CALR, respectively. Eighty four percent of patients received RUX as frontline therapy. Median time to RUX from presentation and from MF was 4 (range, 0.1-123) and 11 months (range, 0.1-228), respectively. Starting dose of RUX was ≥ 15 mg, 10 mg and 5 mg twice daily in 110 (84%), 17 (13%), and 4 (3%) patients, respectively. Median duration of RUX therapy was 76 months (95% CI, 56-88). At the time of last follow-up (median duration of 104 months; 95% CI, 93-115), 44 patients (35%) were on RUX. Reasons for discontinuation in the remaining patients included MF progression (n = 54; 62%), blastic phase (n = 7; 8%), cytopenias (n = 4; 5%) and unrelated causes (n = 22, 25%). Median OS since therapy start was 90 months (95% CI, 76-104) with 40% of patients being alive at 10 years. Patients ≥ 65 years had median OS of 76 months (95% CI, 67-85). Patients with intermediate 2 (n = 81) or high risk (n = 29) DIPSS at RUX start had median OS of 89 (95% CI, 71-107) and 72 (95% CI, 55-89) months, respectively. Factors affecting OS on univariate analysis (HR, 95% CI, p-value) were age > 65 years (2.56, 1.49-4.35, < 0.001), neutrophils % (0.97, 0.95-0.99, 0.006), blasts % (1.213, 1.035-1.421, 0.017), performance status of <2 (0.228, 0.069-0.752, 0.015). The only factors retaining significance on multivariate analysis were age > 65 years (2.7, 1.50-4.14, < 0.001) and neutrophils % (0.66, 0.29- 0.86, 0.012). Conclusions: Forty percent of patients who remained on RUX for ≥3 years were alive at 10 years since their therapy initiation. Age remains the major predictive factor of survival despite long RUX therapy.[Table: see text]
Erdheim-Chester disease: An orbital MRI study.
Authors: Haroche Julien , Gueniche Yoram , Galanaud Damien , Cohen-Aubart Fleur , Dormont Didier , Rousseau Théophile , Spano Jean-Philippe , Amoura Zahir , Touitou Valerie , Shor Natalia 
Published: June 2022

e19085 Background: Erdheim-Chester disease (ECD) is a rare L-group histiocytosis. Orbital involvement is found in a third of cases, but few data are available concerning the radiological features of ECD-related orbital disease (ECD-ROD). Our aim was to characterize the initial radiological phenotype and outcome of patients with ECD-ROD. Methods: Initial and follow-up orbital MRI from the patients with histologically proven ECD at a national reference center were reviewed. Results: Pathological orbital findings were recorded for 45(33%) of the 137 patients included, with bilateral involvement in 38/45 (84%) cases. The mean age of these patients was 62 years (24-81) and 78% were men. Intraconal fat infiltration around the optic nerve sheath adjacent to the eye globe (52%), with intense gadolinium uptake and fibrous component was the most frequent phenotype described. Optic nerve signal abnormalities were observed in 47% of cases. Two patients presented bilateral homogeneous extraocular muscle enlargement suggestive of the myositis type of ECD-ROD. None had isolated dacryoadenitis. Only seven patients (15%) had normal brain MRI findings. ECD-associated paranasal sinus involvement and post-pituitary involvement were detected in 56% and 53% of patients respectively. A decrease/disappearance of the lesions was observed in 17/24(71%) of the patients undergoing late follow-ups. Interestingly, ECD-ROD only rarely (7/45(16%)) revealed the disease, with exophthalmos being the most frequently identified feature in this subgroup (3/45 (6%)). Conclusions: Even though ECD-ROD can be clinically silent, it constitutes a broad array of lesions often resulting in optic nerve signal abnormalities, the functional outcome of which remains to be established. ECD-ROD should thus be assessed initially and subsequently monitored by orbital MRI and ophthalmological follow-up.
Anti-CD19 chimeric antigenic receptor T cell as a second-line therapy for patients with relapsed/refractory diffuse large B-cell lymphoma.
Authors: Naqvi Syed Arsalan Ahmed , Asghar Noureen , Sipra Qurat Ul Ain Riaz , Paludo Jonas , Riaz Irbaz Bin , Husnain Muhammad 
Published: June 2022

e19502 Background: Inconsistent results observed in recent trials (ZUMA-7, TRANSFORM, BELINDA) assessing chimeric antigenic receptor T (CAR-T) cell therapy in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) prompted a meta-analysis to assess the available evidence and to compare the effectiveness of different CAR-T products. Methods: MEDLINE and EMBASE were searched to identify full-text or abstract publications of phase 3 randomized controlled trials (RCTs) assessing CAR-T in patients with R/R DLBCL compared to standard of care (SOC). Efficacy outcomes included event-free survival (EFS), progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and complete response (CR). CR rates were also compared between CAR-T and patients in SOC arm who received autologous stem-cell transplantation (ASCT). Safety outcomes included grade > 3 any adverse events (AE), cytokine release syndrome (CRS) and neurological toxicity (NT). A DerSimonian-Laird random-effects meta-analysis was conducted to pool effect estimates. Freeman-Tukey transformation method was used to estimate pooled proportion (PP) of safety events specific to CAR-T. Mixed treatment comparisons were computed using a frequentist network meta-analysis approach. Results: Of 1803 studies identified, three RCTs with 865 patients were included. Meta-analysis showed significant improvement in EFS (HR: 0.51; 95% CI: 0.27-0.97; I2: 92%), PFS (HR: 0.47; 95% CI: 0.37-0.60; I2: 0%) with CAR-T compared to SOC. OS was not significantly different between the two groups (HR 0.76; 95% CI: 0.56 to 1.03; I2: 29%). Higher objective response (RR: 1.49; 95% CI: 1.13-1.97; I2: 81%), and CR rates (RR: 1.55; 95% CI: 1.07-2.24; I2: 79%) were observed with CAR-T compared to SOC. However, CAR-T was associated with lower CR when compared to patients who underwent ASCT (RR: 0.65; 95% CI: 0.46-0.90; I2: 89%). The safety profile was not different between CAR-T and SOC. The incidences of grade ≥3 CRS (PP: 4.19; 95% CI: 1.60-7.80; I2: 57%) and grade ≥3 NT (PP: 7.57; 95% CI: 0.20-22.6; I2: 95%) were low. Mixed treatment comparisons showed significant EFS benefit with liso-cel (rank 1: HR: 0.37; 95% CI: 0.22-0.61) and axi-cel (rank 2: HR: 0.42; 95% CI: 0.29-0.61) compared to tisa-cel (rank 3). No significant differences were observed among different CAR-T products for PFS or OS improvement. The safety profile of CAR-T products was comparable with tisa-cel (rank 1) being the safest. Conclusions: CAR-T therapy, as a second line treatment, appears to be effective in achieving higher response rates and delaying the disease progression compared to SOC in R/R DLBCL. However, given lack of OS benefit coupled with lower response rates when compared to patients who received ASCT, we should exercise caution in adopting CAR-T as second line therapy for all patients with R/R DLBCL.
Role of anakinra in the management of icans after CAR T-cell therapy for lymphoma.
Authors: Munugala Nishant , Dashkevych Ulyana , Husnain Muhammad 
Published: June 2022

e19506 Background: Chimeric antigen receptor (CAR) T-cell immunotherapy is a revolutionary treatment modality which has gained attention for its potential in treating multiple refractory hematological malignancies. Significant toxicities associated with CAR T- cell therapy remain a major concern. Cytokine release syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS) are seen early on post CAR-T cell therapy. To date, the treatment of ICANS has largely been limited to supportive care and corticosteroids. More recently, some early clinical data investigated the use of Anakinra as a promising agent in prevention and treatment of severe ICANS. Methods: We analyze three cases in which Anakinra was used to treat high-grade ICANS concurrently with high dose steroids. Results: A 51-year-old woman with high grade DLBCL and secondary CNS involvement was treated with Tisagenlecleucel CAR-T therapy. On day 2, patient became altered and was diagnosed with ICANS Grade II. High dose steroids were started leading to resolution of ICANS. However, patient’s mentation worsened by day 7, progressing to ICANS Grade IV by day 8, and Anakinra 100 mg IV was added to the steroid regimen. By day 11, after 4 doses of Anakinra, patient’s neurotoxicity completely resolved. Patient achieved a PR by day 30 after CAR-T cell infusion. In the second case, a 65-year-old man with DLBCL and leptomeningeal involvement developed ICANS Grade II on day 1 after Tisagenlecleucel CAR-T therapy and was started on high dose steroids. By day 4, neurotoxicity worsened and progressed to ICANS Grade IV. On day 5 patient was transferred to ICU for a mechanical ventilation, and Anakinra 100 mg IV was added and continued daily for 7 days. By day 12, neurotoxicity improved to ICANS grade II and patient was extubated. Meanwhile, high dose steroids were tapered. His condition acutely worsened by day 19, prompting transfer to the ICU and re-initiation of Anakinra concurrently with steroids. His family decided against further escalation of care on day 22. Patient was transitioned to comfort care and died 23 days post CAR-T cell infusion. In the third case, a 65-year-old man with mantle cell lymphoma was treated with Brexucabtagene autoleucel CAR-T therapy. On day 8, patient developed ICANS Grade I which rapidly progressed to Grade IV. High dose steroids were started and ICANS improved to Grade II on Day 9. However, on Day 10 patient’s mentation again worsened and one dose of Anakinra 100mg IV was added to the steroid regimen. By day 11, ICANS completely resolved, and patient was ultimately discharged home on day 15. Patient was able to achieve interval CR by day 30 after CAR-T cell infusion. Conclusions: In the reported cases, ICANS improved following administration of Anakinra, adding support to the idea that Anakinra may be beneficial in treatment of high-grade ICANS. Future studies are needed to better understand the overall efficacy and the ideal timeline for administration.
Outcomes of Richter’s syndrome in patients with chronic lymphocytic leukemia (CLL) treated with platinum or anthracycline based chemotherapy with or without a BTK inhibitor (BTKi).
Authors: Alasfour Maryam , Pongas Georgios , Jones Sandra , Alawadi Salman , Plate Thomas 
Published: June 2022

e19511 Background: Richter’s syndrome (RS) is a rare complication of chronic lymphocytic leukemia (CLL) and the median survival is generally poor. Evidence is limited regarding the biology of the disease, treatment and outcomes. Methods: We retrospectively reviewed pts diagnosed (dx) with pathologically confirmed RS who presented at the University of Miami Sylvester Cancer Center between 2011 and 2020. Informed consent was provided through IRB-approved protocols. Descriptive statistics were utilized and overall survival (OS) was calculated from RS diagnosis to death or last follow-up by Kaplan-Meier. Results: 33 patients with RS, including 87.9% diffuse large B-cell lymphoma-type RS and 12.1% Hodgkin lymphoma-type RS were identified. Median time from CLL dx to RS transformation was 37months (m). Most patients presented with elevated LDH 75%, bulky lymphadenopathy 66%, and adverse genetic features, such as TP53 disruption 52% or complex karyotype 81%. FISH at RS dx: del(17p) 37%, del(11q) 17%, trisomy 12 58%. ORR to first line therapy was 75.8% (55% CR, 27% PR), but of those who achieved CR, 44% relapsed. Median PFS (mPFS) was 10m for the anthracycline-based chemotherapy group (ABC) with a CR of 50%, compared to 15.5 m for the platinum-based chemotherapy group (PBC) and a CR of 60%. Similar OS were observed regardless of the chemotherapy regimen with median OS (mOS) of 60 m in the ABC group vs 59.5 m in the PBC group. Notably, the addition of a BTKi to chemoimmunotherapy lead to a mOS of more than 10 years in BTKi-naïve pts compared to 5.1 years in BTKi-exposed pts and 1.8 years in pts who did not receive a BTKi for RS treatment. Conclusions: Patients who develop RS often have high risk CLL, especially complex cytogenetics. Although a large proportion of pts with RS respond to frontline therapy, almost half relapse. While mOS is similar for anthracycline and platinum-based chemotherapies, platinum-based chemotherapy can lead to superior CR and PFS. BTKi-naïve pts who receive a BTKi with chemotherapy for RS treatment have superior mOS.
Real-world data of lebanese patients with chronic lymphocytic leukemia.
Authors: Nasr Lewis , Yehia Intissar , Diab Saada , Ghoche Ahmad , Nasr Fadi louis 
Published: June 2022

e19512 Background: Many advances in the treatment of chronic lymphocytic leukemia (CLL) has been made in the 6 past years aiming at attaining durable complete responses and even cure. The choice of upfront therapy is driven by several factors including presence of 17p deletion or TP53 mutation, IGHV mutation status, patient fitness, comorbidities, drug availability and affordability etc.. The aim of the current study was to describe aspects of CLL in real world data setting in Lebanon regarding patients’ characteristics, diagnostic studies, indications for therapy and implication of new treatments including small molecule inhibitors including Bruton Tyrosine Kinase BTK and BCL2 inhibitors. Methods: This was an observational prospective study (2004-2021) of consecutively diagnosed patients with CLL at a single center in Lebanon. The characteristics, indication for treatment, types of treatment used were recorded progression free survival (PFS) was defined as the time from treatment initiation at first line until progression from any cause. Results: The registry covered 128 patients, 82 males and 46 females (ratio 1.78:1). Median age at diagnosis was 66 years. 23.6% were younger than 55 years. 73% of patients were asymptomatic at diagnosis, and 25% had lymphadenopathies. RAI stage 0 (BINET stage A) was observed in 73%. Median absolute lymphocytic count was 15,340 (unit), median hemoglobin was13.2. and median platelet count was 188,000. FISH panel was done in 56 patients (43%) and IGHV in 13%. 17p deletion was detected in 14.3%, and 13q deletion as a sole abnormality in 46.6%. 15.7% of patients required treatment at diagnosis; 52.6 % of them due to anemia/thrombocytopenia, and 15.8% due to presence of constitutional symptoms; other treatment indications included massive splenomegaly, and massive or symptomatic lymphadenopathy. 71 patients (55.4%) fell into the watch and wait category; 37 of which required treatment at some point during follow up with a median duration from diagnosis till starting treatment of 34 months.FCR Fludarabine + cyclophosphamide + rituximab (38.5%), BR bendamustine + Rituximab (23%), and Ibrutinib (19.2%) were the most common regimens used upfront. PFS was not reached. and correlation between genetic features and survival couldn’t be done, due to the relatively small number of patients whom showed progression. Conclusions: Epidemiologic characteristics of Lebanese patients with CLL is comparable to the international data.Molecular studies are being more implicated in the diagnostic workup. FCR and BR were mostly used upfront during the previous decade. We noticed a trend toward using Ibrutinib after 2016 in frontline and relapsed setting (after its approval and availability).
Population-wide patterns of care in chronic lymphocytic leukemia in Australia: An analysis of the pharmaceutical benefits scheme dataset.
Authors: Chuen Li Shu , Zhao Fei-Li , Gauba Raj , Yang Keri , Azmi Soraya , Tam Constantine Si Lun 
Published: June 2022

e19518 Background: The treatment landscape in patients with chronic lymphocytic leukemia (CLL) is changing with the approvals of Bruton’s tyrosine kinase inhibitors (BTKis) in Australia. We sought to understand the practice impact of the introduction of publicly funded novel agents for the treatment of CLL. The objective of this study was to describe the evolving treatment patterns of Australian patients with CLL over the last 10 years using population-wide prescription records. Methods: Patients who initiated a treatment for CLL between 01/01/2011 and 07/31/2021 were extracted from the Services Australia 10% Pharmaceuticals Benefits Scheme (PBS) dataset. This dataset includes the dispensing records for 10% of the Australian population and captures all publicly funded treatments in Australia. The index date was defined as the commencement of any drug for the treatment of CLL. First-line (1L) therapy was defined as the first treatments prescribed for CLL. A patient was defined as relapsed/refractory (R/R) if they had commenced a drug which was in a different therapeutic category, or if they re-started the same regimen after a gap of more than 180 days. Descriptive analyses were conducted to examine the use of treatment regimens for the overall 10-year population by line of therapy. Analyses by calendar year were also performed to assess changes in treatment patterns. Results: Overall, 803 patients with CLL were identified. The majority of patients were male (65%) and age > 60 years (77%), with most being aged 70-79 years (33% of total). Many patients were receiving comedications at baseline, including antihypertensives (47%), antipsychotics or antidepressants (17%), and/or anticoagulants (13%). In the overall population (2011-2021), the majority of patients had received 1L treatment with fludarabine-cyclophosphamide-rituximab (FCR, 49%), chlorambucil ± CD20 (27%), or CD20 monotherapy (17%). The most commonly used regimens in R/R patients at any subsequent episode of treatment included CD20 monotherapy (56%), BTKi (41%) or FCR (33%). A trend in adoption of novel agents was observed throughout the years following their PBS listing. Analysis by calendar year showed that from 2011 to 2020 use of FCR in 1L decreased from 78% to 10%; and use of BTKis in R/R increased from 0% to 62%. Conclusions: CLL treatment patterns have significantly changed in Australia since the introduction of the BTKis (e.g., ibrutinib, acalabrutinib). The use of FCR in 1L CLL has decreased and use of BTKis in R/R patients has increased.
Incidence, predictors and outcomes of cardiovascular events in patients with chronic lymphocytic leukemia.
Authors: Ghous Ghulam , Gvazava Nanuli , Egwom Peter , Saleh Mohammad , Franco Diana , Shoukat Hafiz Muhammad Hassan , Au Pak Ho , Nwabara Kelechi , Tarar Zahid 
Published: June 2022

e19524 Background: CLL accounts for about one-quarter of the new cases of leukemia and affects mainly elderly population. Recent literature highlights increased cardiovascular events in patients with CLL, notably those being treated with targeted therapy such as Bruton tyrosine kinase inhibitors. Here we examine data obtained from the National Inpatient Sample to find out incidence, predictors and outcomes of cardiovascular events in patients with CLL. Methods: We analyzed the National inpatient database from year 2019 and extracted the data of all patients with CLL. Multivariate regression analysis was performed to determine the aforementioned outcomes in CLL patients. Results: CLL patients showed increased odds of all cause in-hospital mortality (Adjusted Odds ratio (AOR) 1.28, 95% CI 1.19-1.38, P<0.001) in comparison to general adult population. CLL patients had higher odds of developing Atrial fibrillation (AOR 1.11, 95% CI 1.06-1.15 P <0.001) compared to patients without CLL. CLL patients had significantly higher odds of cardiac tamponade and pericardial effusion (AOR 1.64, 95% CI 1.10-2.42, P<0.001, 1.65 95% CI 1.43-1.92, P<0.001) respectively. Odds of congestive heart failure (AOR 0.97, 95% CI 0.93-1.01, P0.10) and atrial flutter (AOR 1.03, 95% CI 0.93-1.17, P 0.55) were similar between CLL patients and general adult populations. Patients with CLL have Increased mean hospital length of stay (adjusted mean LOS 0.51, 95% CI 0.42-0.61, p<0.001) and mean total hospital charges (adjusted mean charges 2006$, 95% CI 173$-3840$, P 0.03). [Table] We investigated the predictors of inpatient mortality in CLL patients and found that increase in age, black race, acute kidney injury, alcohol use, malnutrition and weekend admissions were associated with higher odds of mortality, whereas smoking, obesity, and female gender showed lower odds of mortality. Conclusions: CLL patients are at increased risk of developing atrial fibrillation, pericardial effusion, pericardial tamponade and all-cause in hospital mortality compared to their non-CLL counterparts, even after accounting for variables such as age, gender etc. Moreover, CLL patients have higher inpatient mortality associated with certain factors such as age progression, AKI, black race, alcohol abuse and malnutrition. Patients should be referred to cardiologist early and cardiovascular status should be optimized especially before initiating targeted therapy.[Table: see text]