bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the oral chemotherapy pharmacist on direct cost avoidance and cost savings of oral oncolytics at an integrated health system.
Authors: Nguyen Analia 
Published: June 2022

e18839 Background: The impact of oncology pharmacists on patient care have been well-documented including enhanced medication safety and efficacy, increased medication adherence, improved provider and clinic burden, and increased patient and provider satisfaction. There is a scarcity of articles relating to pharmacists’ drug cost savings or cost avoidance of oncologic drugs in an oral chemotherapy management clinic within an integrated healthcare system. Cost savings and cost avoidance studies are needed to reinforce this practice and gain support and funding from hospital administration. Methods: This retrospective, observational study analyzed interventions made by oncology pharmacists in the Pharmacist-Managed Oral Chemotherapy Clinic at Kaiser Permanente San Diego and determine the direct drug cost savings and cost avoidance effects over one year. Cost savings and cost avoidance were calculated by comparing the costs of drug utilization if no interventions were implemented versus costs of drug saved from accepted interventions for dose reduction, dose delay, temporary dose hold, therapy discontinuation, therapy conversion, formulary alternative conversion, and brand to generic conversion. Secondary outcomes included the highest and average cost avoidance per intervention, intervention type, medication, medication class, and cancer type. Additionally, interventions that did not lead to direct drug cost savings such as adverse drug reaction management, drug interaction identification, and supportive care recommendation were also recorded. The secondary endpoint was oncologist satisfaction via a six-question satisfaction survey. All documented oncology pharmacist interventions that were made in the Oral Chemotherapy Clinic from January 1 to December 31, 2021 were reviewed for study inclusion. From a report generated monthly from the electronic health record (EHR), retrospective chart review was conducted to verify whether each cost-savings intervention was truly recommended by an oncology pharmacist and if the intervention was accepted by the treating oncologist. The Average Wholesale Price (AWP) of drugs listed on Lexicomp as of November 1, 2021 was used to calculate the drug cost savings and cost avoidance. During this period, there were no changes to practice and no increased efforts to identify interventions. Results: As of September 2021, 156 interventions were identified, with a total cost savings and cost avoidance of $2,245,856. Once all data have been collected for the remainder of 2021, descriptive statistics will be used to analyze and stratify the data as appropriate. Conclusions: Pharmacist interventions in the Oral Chemotherapy Clinic led to significant overall cost savings to the health care system. It is reasonable to expect that higher cost savings will be achieved as more oral chemotherapy agents are managed by pharmacists.
Mismatched donor transplantation with post-transplantation cyclophosphamide for advanced cutaneous T-cell lymphoma: A single-center experience.
Authors: Hughes Michael Sang , Sterling Cole Harris , Varadhan Ravi , Ambinder Richard F. , Jones Richard J. , Rozati Sima , Bolanos-Meade Javier , Luznik Leo , Ambinder Alexander Joseph , Wagner-Johnston Nina D. , Fuchs Ephraim Joseph 
Published: June 2022

e19045 Background: Mismatched blood or marrow transplantation (BMT) using post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GvHD) prophylaxis has not been well-studied in CTCL. Methods: We analyzed all patients above 18 years old with relapsed/refractory CTCL undergoing mismatched alloBMT. Primary endpoints included disease-free survival (DFS) and overall survival (OS). Secondary endpoints included time to neutrophil and platelet recovery, GvHD outcomes, and day +30 and day +60 donor chimerism. Results: From 2003-2020, 8 patients with relapsed CTCL underwent mismatched related (n=7) or mismatched unrelated (n=1) BMT. Mean age was 50 years (range 30-62); median time from diagnosis was 2 years (range 1.3-11.4). All had received prior treatment for their disease; two (25%) had received immune checkpoint inhibitors. Four (50%) were in partial response and 4 (50%) were in complete remission prior to BMT. Six received bone marrow grafts. Two received mobilized peripheral blood. Five (62.5%) achieved full donor chimerism by day 30 after BMT; 6 (75%) had achieved full donor chimerism by day 60 after BMT. One patient failed to engraft. Mean time to neutrophil recovery was 17.3 days (range 17-45); mean time to platelet recovery was 28.4 days (range 11-69). Median DFS was 11.3 months (95% confidence interval 2.6 months-not reached). Median OS was not reached. One patient developed grade 1 acute GvHD, and 2 patients developed mild chronic GvHD. There were no instances of transplantation-related mortality (TRM). At 1 year post-BMT, 4 patients had relapsed (50%), and no patients had died. At 3 years post-BMT, 7 patients had relapsed (87.5%), and 1 patient had died (12.5%). Conclusions: In our preliminary retrospective study, partially mismatched BMT with PTCy-based GVHD prophylaxis for advanced-stage CTCL was associated with minimal GvHD, no TRM, and good long-term survival. Investigation into relapse reduction is warranted.[Table: see text]
Expression of CD47 and CALR in myeloproliferative neoplasms: Potential new therapeutical targets.
Authors: Rinaldi Ciro Roberto , Boasman Kristian , Simmonds Matthew 
Published: June 2022

e19075 Background: Myeloproliferative neoplasms (MPN) are myeloid malignancies characterized by overproduction of mature blood cells, hyperplastic bone marrow and tendency to evolve into acute myeloid leukaemia. In solid tumours, calreticulin (CALR) overexpression produces a pro-phagocytic signal and is counteracted by concomitant expression of anti-phagocytic CD47, reflecting an apoptosis vs survival mechanism. Increases of both CALR and CD47 on the cell membrane have been observed in response to chemotherapy, however their role in myeloid malignancies is poorly understood. Methods: Investigate the expression and cellular localisation of CALR and CD47 in untreated and treated patients with essential thrombocythemia (ET), polycythemia vera (PV) myelofibrosis (MF), in comparison with healthy controls. Mononuclear cells were collected by Ficoll separation, from peripheral blood of 30 MPN (8 PV, 16 ET, 6 MF); 18 MPN patients received cyto-reductive therapies (Hydroxyurea, Anagrelide or Ruxolitinib); and 4 controls. Cells were fractionised into 4 compartments: membrane, cytoplasm, cytosol and nucleus. Proteins were extracted using TRIzol, with CALR and CD47 protein expression analysed by western blotting. Results: Total CALR and CD47 protein expression increased in MPN samples compared with controls (CALR- 7.9 vs 5.1; CD47- 2.7 vs 2.2 fold, respectively). CD47 showed higher expression of its overall protein on MPN cell membranes when compared with CALR (22% vs 13.9%). We observed a significant reduction of CALR expression in all MPN subtypes when patients were treated with cyto-reductive agents (ET- untreated 43.3% vs treated 2%, PV- 3.6% vs 2.2%, ET- 21% vs 11%). Interestingly we have observed a significant increase in CD47 cell membrane expression after treatment in MF and PV (CD47 in MF- untreated 11.8% vs treated 34.3%, PV-11.4% vs 35.9%), suggesting an anti-phagocytic effect induced by cytotoxic drugs. In ET cell membranes however, CD47 expression is reduced after cyto-reductive treatment (22% vs 16.6%), suggesting instead a prophagocytic effect. Conclusions: CD47, but not CALR, is overexpressed on the membrane of patients with MPN, suggesting a role for CD47 as a strong antiphagocytic signal responsible for immune survival in MPN. We observed a significant difference in CD47 expression across different MPN subtypes with a significant increase in CD47 expression in PV and MF but not ET. The use of anti-CD47 antibodies could represent a new strategy to enhance the treatment response in particular in PV and MF.
Characteristics of patients with hematologic malignancies without seroconversion post-COVID19 third vaccine dosing (3V): Real-world data from large midwestern healthcare system.
Authors: Hallmeyer Sigrun , Thompson Michael A. , Fitzpatrick Veronica , Liao Yunqi , Mullane Michael P. , Medlin Stephen Charles , Cleland Katherine , Rodriguez Tulio , Citronberg Robert , Weese James L. 
Published: June 2022

e19513 Background: Patients (Pts) with hematologic malignancies (HM) are at greater risk of severe morbidity and mortality caused by COVID19 and show a lower response to the two-dose COVID19 mRNA vaccine series. The primary vaccine series now includes a third dose of the COVID19 vaccine (3V) for immunocompromised Pts. The objective of this study was to explore the characteristics of HM patients who had no change in SARS-CoV-2 spike protein titer levels post 3V (-/-) to gain a better understanding of the drivers of serostatus. Methods: This retrospective cohort study analyzed Pt data on SARS-CoV-2 spike IgG antibody titers pre- and post- 3V across the healthcare system. This study included 268 fully vaccinated HM Pts diagnosed with HM between October 31, 2019 and January 31, 2022 and had a negative serostatus prior to 3V. Post 3V titers were obtained 21 days after 3V. Demographics, association between characteristics and seroconversion status, and odds ratios were all assessed (table). Results: Pts with Non-Hodgkin lymphoma (NHL) had 6 times the odds of not seroconverting compared to multiple myeloma (MM) (CI 1.88 – 19.12, P = .0010). NHL also have about 14 times the odds of not seroconverting compared to Pts diagnosed with other HM conditions, which included: neoplasms of uncertain behavior and disorders of white blood cells (CI 1.72 – 112.44, P = .0021). 90% of seronegative Pts showed no spike IgG antibody reaction to 3V as indicated by pre- and post- 3V index values. Demographics, previous COVID19 infection, and vaccine type were not significantly associated with seroconversion. Conclusions: HM patients who are not seroconverting after 3V, suggest a prioritized population for continued increased behavioral precautions, additional vaccination efforts, including a fourth dose of an mRNA COVID19 vaccine, as well as passive immunity boosting through monoclonal and polyclonal antibodies.[Table: see text]
Safety and efficacy of allogeneic CAR-T cells in B-cell malignancies: A systematic review and meta-analysis.
Authors: Chattaraj Asmi , Rehman Mohammad Ebad Ur , Khan Israr , Franco Diana , Ibrahim Atif , Khanam Razwana , Tahir Nayha , Iqbal Qamar , Waqar Syed Hamza Bin , Pachika Pranali Santhoshini , Khan Rafiullah , Anwer Faiz 
Published: June 2022

e19530 Background: Immunotherapy with chimeric antigen receptor T (CAR-T) cells has proven effective in recent trials for patients with B cell malignancies, who relapsed after stem cell transplantation. Genetically modified allogeneic CAR T-cells used in advanced B cell malignancy engage with multiple target allo-antigens along with CD19 and/or CD20, leading to elimination of malignant B cells resulting in a potent graft versus malignancy effect with avoidance of tumor escape. Some concerns regarding their use exist like life-threatening graft-versus-host disease (GVHD) and rapid clearance by the host immune system. This study summarises the efficacy and safety of allogeneic CAR-T therapy in B cell malignancies. Methods: A systematic literature search was conducted on PubMed, Embase, Cochrane and Clinicaltrials.gov from inception to Jan 26, 2022, using MeSH terms and keywords for B cell malignancies and CAR-T therapy. We also screened the data presented in various conferences and handpicked references from previous systematic reviews. Outcomes of interest were complete remission (CR), 1-year overall survival (OS), GVHD, cytokine release syndrome (CRS), and immune effector cell associated neurotoxicity (ICANS). Proportional outcomes were pooled using a random effects model (Freeman-Tukey double arcsine transformation) in OpenMetaAnalyst software. Results: The initial search retrieved 1247 articles. After excluding reviews, duplicates and non-relevant articles, we included data from 9 clinical trials (n = 146 patients). The most common malignancy was acute lymphoblastic leukemia (125 patients, 86%). The median age of patients ranged from 19 to 49 years. All patients received CD19 targeting therapy and the cell dose administered ranged from 0.4×10^6 to 5×10^8 cells/kg. CR was reported in 93 of 146 patients, with a pooled rate of 63% (95% CI 47.4 - 78.6%; I2 78.5%). The pooled 1-year OS was 57.3% (95% CI 30.8 - 82%; I2 79.2%). The pooled proportion of GVHD was 9.4% (95% CI 3.1- 15.6%; I2 47.6%). The pooled CRS and ICANS rates were 59.3% (95% CI 30.5 - 88.1%; I2 95.2%) and 15.4% (95% CI 4.6 - 26.3%; I2 72.7%), respectively. Conclusions: Allogeneic CAR-T therapy has demonstrated acceptable efficacy and safety in B cell malignancies, with CR being reported in about 60% of patients and GVHD in < 10% of patients. Although allogeneic CAR-T cells are showing promise, several trials are ongoing and we need longer follow up.[Table: see text]
Prognostic role of neutrophil-to-lymphocyte ratio in patients with diffuse large B-cell lymphoma.
Authors: Kushtova Luiza B. , Frantsiyants Elena M. , Bandovkina Valeria A. , Kozel Yuliya Yu. , Dmitrieva Viktoria V. , Kozyuk Olga V. , Snezhko Aleksandr V. , Malinin Sergey A. , Chalkhakhyan Lusegen Kh. , Kaminskiy Gennadiy V. , Duritskiy Maksim N. , Gabrichidze Petr N. , Vladimirova Liubov Yu , Lysenko Irina B. , Nikolaeva Nadezhda V. , Kit Oleg I. 
Published: June 2022

e19560 Background: Diffuse large B-cell lymphoma (DLBCL) represents about 30-40% of all cases of non-Hodgkin lymphoma. The addition of rituximab to standard chemotherapy significantly improves survival, yet 30% of advanced-stage patients relapse. The International Prognostic Index (IPI) is used to evaluate the prognosis, but it cannot always accurately predict the outcome of therapy. The neutrophil-to-lymphocyte ratio (NLR) has recently been recognized as a prognostic factor in various types of solid tumors. The purpose of this study was to assess the prognostic value of NLR in DLBCL patients. Methods: Patients with DLBCL (n = 47) were recruited, including 31 patients in remission and 16 patients with relapsed DLBCL. All patients received 6-8 cycles of R-CHOP. Clinical parameters were studied, including IPI and complete blood count before treatment and after each chemotherapy cycle. Results: IPI predicted unfavorable outcome in 3 (18.75%) patients with relapses, and favorable outcome and high treatment efficacy in 13 (81.25%) patients. Among patients in remission, IPI predicted unfavorable outcome in 2 (6.5%) patients and favorable outcome in 29 (93.5%) patients. NLR calculation showed 100% low treatment efficacy for patients with relapses (NLR =4.1±0.51). At the same time, NLR predicted favorable outcome in 22 (70.96%) patients in remission (NLR =1.9±0.20), and relapses in 9 (29.04%) patients (NLR =4.83±0.55). 7 (22.6%) of the patients at risk developed relapses within 6-10 months after good treatment effects. Conclusions: Thus, NLR can be used as a prognostic factor in patients with DLBCL.
Tisagenlecleucel in the treatment of aggressive large B-cell lymphoma: A review of literature.
Authors: Devarkonda Vishal , Balmuri Shravya , Ponna Pramod Kumar , Devarashetty Sindhu Priya 
Published: June 2022

e19563 Background: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor T-cell therapy approved for refractory diffuse large B-cell lymphoma(DLBCL) in May 2018. However, a recently concluded phase 3 international trial showed that Tisagenlecleucel was not superior to standard salvage therapy with aggressive lymphoma that was refractory to or progressing within 12 months after first-line treatment. Also, recently the availability of long-term outcomes from earlier trials makes it an excellent time to evaluate the Sustained response(SR) and Adverse effects associated with it. Methods: A comprehensive literature search was done of Pubmed, Embase, and Cochrane. Results: We included three trials which included two multicenter trials and one case series. Schuster et al. in their single-center case series demonstrated that Tisagenlecleucel infusion in patients with refractory diffuse large B-cell lymphoma on median follow-up at 28.6 months showed Complete remission(CR): 43%; 95% CI(18-71) Sustained remission(SR): 86%; 95% CI(13 to 98), Severe cytokine-release syndrome(CRS): 18%. On further median follow-up at 60.7 months showed a CR: 46%, overall response rate(ORR): 58%, Progression-free survival(PFS): 31% (95% CI:14-51). Good recovery in humoral and cellular response. The limitation of the trial was a relatively small number of enrolled patients. JULIET trial, a more extensive multicenter phase 2 trial involving 93 patients, demonstrated that Tisagenlecleucel infusion in patients with refractory diffuse large B-cell lymphoma on 14 months median follow-up showed an ORR: 52% (95% CI, 41 to 62), CR: 40%, Partial response(PR): 12%. On further median follow-up at 40.3 months showed CR: 39%, ORR: 53·0% (95% CI 43·5–62·4). Grade 3-4 CRS: 23%. BELINDA Trial also an extensive multicenter phase 3 trial involving 322 patients which involved patients with aggressive B cell lymphoma that was refractory to or progressing within 12 months after first-line therapy showed infusion of Tisagenlecleucel with optional bridging treatment or salvage chemotherapy and autologous HSCT Showed similar Medial event-free survival(MEFS) at three months for both groups. Progression at six weeks was 25.9% in Tisagenlecleucel vs. 13.8% in the control group. Conclusions: Tisagenlecleucel infusion is shown to have a high rate of durable response in relapsed or refractory diffuse large B-cell lymphoma in adults. Long-term follow-up showing satisfactory ORR with good recovery in cellular and humoral function. However, infusion of Tisagenlecleucel with optional bridging therapy or salvage chemotherapy and autologous HSCT inpatient with aggressive B cell lymphoma that was refractory to or progressing within 12 months after first-line therapy showed Tisagenlecleucel is not superior to standard salvage therapy needing additional studies to evaluate the benefits when used as a second-line agent.
Factors associated with death from lymphoma in a single center study.
Authors: Ma Helen , Ricks-Oddie Joni , Streja Elani , Eapen Ann , Gupta Pankaj 
Published: June 2022

e19566 Background: It is well known that age, stage, and performance status are important prognostic factors in predicting survival of patients diagnosed with lymphoid malignancies. At the VA Healthcare System, many patients have comorbidities and poor performance status. We evaluated the association of clinical outcomes with lymphoma stage, subtype and performance status in US Veterans. Methods: This retrospective study included patients diagnosed with a lymphoid malignancy including diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and peripheral T-cell lymphoma (PTCL) from January 2008 - December 2021 at the VA Long Beach Healthcare System (n = 221). Endpoints included clinically relevant hematological and non-hematological adverse events (AE), and death from lymphoma (with death from other causes as competing events). Variables of interest included aggressive lymphomas (DLBCL and PTCL, n = 85) vs indolent lymphomas (CLL, FL, MZL and MCL, n = 149), stage (early [0-2] vs advanced [3-4]), age at diagnosis (continuous variable), and performance status (Eastern Cooperative Oncology Group [ECOG] scale: good [0-2] vs poor [3-4]). Logistic regression and Cox models with Fine and Gray competing risk were performed. Results: In patients receiving first line therapy, performance status, disease type, stage, and age at diagnosis did not predict development of clinically relevant AEs with an odds ratio [OR] of 4.1 (p = 0.12, 95% CI 0.70-24), 0.36 (p = 0.06, 95% CI 0.12-1.0), 1.5 (p = 0.39, 95% CI 0.58-4.0), and 1.0 (p = 0.12, 95% 0.99-1.1), respectively. Patients with worse performance status (ECOG 3-4) and advancing age did not have a statistically higher risk of dying from lymphoma vs other causes: performance status: HR 1.7, p = 0.26, 95% CI 0.67-4.3 and age: HR 1.02, p = 0.11, 95% CI 1.0-1.1. In a multivariate analysis, patients with more advanced stage and aggressive subtype were more likely to die from lymphoma vs other causes (hazard ratio [HR] 4.1; p < 0.001, 95% CI 2.2-7.8 and 3.1; p = < 0.0001, 95% CI 1.7-5.5), respectively. Conclusions: The fact that performance status may not predict the development of AEs with first line therapy for lymphoid malignancies is relevant to clinical decision making. However, our findings need confirmation in larger prospective studies.
Treatment of patients with hematological malignancies and left-ventricular assisted device (LVAD) managed cardiomyopathy.
Authors: Cervoni-Curet Frances Natalia , Rios Adan , Yohannan Binoy 
Published: June 2022

e19581 Background: An estimated 2-3% of individuals who undergo advanced heart failure therapies, such as left ventricular assist devices (LVAD) or orthotopic heart transplantation (OHT), have an antineoplastic-related cardiomyopathy. We investigated the incidence and clinical outcomes of non-ischemic or dilated cardiomyopathies on LVAD patients who have been diagnosed with lymphomas or leukemias in our institution between years 2015 - 2022. Methods: We found four cases of patients with newly diagnosed hematological malignancy who had existing underlying LVAD-dependent cardiomyopathy in our center. One patient was excluded due to loss to follow up. The other three patients were treated in the heart failure unit while concurrently managed by LVAD specialists. One patient required administration of continuous 72hr-infusion of doxorubicin to minimize the risk of right-sided ventricular failure. The response to treatment was assessed with use of PET-CT scans, bone marrow biopsies and serological markers per standard of care guidelines. Results: The median age was 54.6 years. Two were African Americans, one Caucasian and one Hispanic (lost to follow up). All patients were males. Of these four individuals, two were diagnosed with Non-Hodgkin Lymphomas (one Peripheral T-cell lymphoma, one Diffuse Large B-cell lymphoma), one with Chronic Lymphocytic Leukemia (CLL) and one with Acute Promyelocytic Leukemia (APL). Three patients completed or have ongoing chemotherapeutic treatment. All have achieved complete remission (CR 3/3) of their diseases. Conclusions: To date, there is no significant volume of data showing the administration of chemotherapy on patients with concurrent LVAD-dependent cardiomyopathies. The Peripheral T-cell lymphoma patient received anthracycline therapy via a continuous 72-hour infusion with close LVAD monitoring at the heart failure unit. After completion of total 6 cycles in 2021, he still is in complete remission. Our CLL patient, has also completed 5 cycles of rituximab and venetoclax while also maintaining disease remission. The APL patient has completed 5 cycles of arsenic trioxide and ATRA with also a complete remission of his leukemia. LVAD-dependent cardiomyopathy patients concurrently diagnosed with malignant hematological diseases, can be considered for treatment with antineoplastic therapies. Durable remission rates can be achieved while undergoing aggressive cardiovascular care.