bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of parvovirus B19 (B19V) on the results of chemotherapy in adult patients with lymphoma.
Authors: Zykova Tatiana A. , Kit Oleg I. , Lysenko Irina B. , Guskova Nailya K. , Shevyakova Elena A. , Nikolaeva Nadezhda V. , Shatokhina Olga N. , Kapuza Elena A. , Pushkareva Tatiana F. , Velikorodnaya Lilia A. 
Published: March 2020

e19022 Background: The purpose of the study was to reveal the prevalence of B19V in adult patients with lymphomas and the influence of B19V on the on the results of chemotherapy (CT). Methods: The study included 41 patients aged 48.9±2.3 years: 12 with Hodgkin’s lymphoma (HL), 29 with Non-Hodgkin’s lymphoma (NHL) (21 aggressive, 8 indolent). Patients received CT according to the tumor immunophenotype. B19V DNA was determined in plasma and in bone marrow (BM) by qPCR, B19V IgМ and IgG in the serum by ELISA. Results: 78.0% of patients had B19V IgG, mean concentration was 158.1±12.9 U/mL. B19V DNA in plasma was detected in 7.3%, in BM in 48.8%. Viral load in plasma was 68.7±35.8 IU/mL, in BM – 438240.0±281316.8 IU/mL. Seroprevalence and the mean concentration of B19V IgG was higher in NHL than in HL (79.3% vs 75.0% and 161.4±16.3 vs 153.6±20.5, p > 0.05). In NHL, the number of seropositive patients and the mean level of B19V IgG were higher in aggressive than in indolent tumors (81% vs 75% and 177.9±19.3 U/mL vs 114.4±22.8 U/mL, p = 0.052). B19V IgМ were not found. B19V DNA in plasma was found only in NHL patients (10.3%). The frequency of B19V DNA detection in plasma was higher in indolent (12.5%) than in aggressive lymphomas (9.5%), while DNA concentration was higher in aggressive lymphomas (102.5±20.5 IU/mL vs 1.0±0.0 IU/mL, p > 0.05). B19V DNA detection frequency in BM was similar in HL (50.0%) and NHL (48.3%, p > 0.05), but the mean B19V DNA concentration was higher in NHL than in HL: 624496.9±395398.3 IU/mL vs 3640.5±1649.2 IU/mL, p > 0.05. In NHL, B19V DNA in BM was more frequent in indolent than in aggressive lymphomas (50.0% vs 47.6%), and the average concentration was higher in aggressive lymphomas (865689.2±541738.6 IU/mL vs 21516.3±19352.8 IU/mL, p > 0.05). Complete remission was observed in 68.3% of patients, partial remission 17.0%, stabilization 4.8%, progression 9.9%. CT results depended neither on serostatus and B19V IgG concentration nor on B19V DNA presence in BM or plasma (p > 0.05). Conclusions: All parameters of the viral infection (B19V IgG, DNA) were higher in NHL than in HL (p > 0.05). The mean concentration of B19V IgG was higher in aggressive NHLs than in indolent ones (p = 0.052). B19V infection did not influence results of antitumor CT (p > 0.05) in adult patients with lymphoma.
Treatment outcomes of HIV patients with non-Hodgkin’s lymphoma treated with standard dose CHOP compared with dose-modified CHOP chemotherapy at the Uganda Cancer Institute.
Authors: Bakenga Alex 
Published: March 2020

e19025 Background: Despite the increased access to effective combination ART, there is still significant mortality associated with malignancies in HIV-positive patients. Because majority of patients present late especially with advanced disease, some of whom may not be able to tolerate standard dose chemotherapy, the Uganda Cancer Institute utilizes both standard dose and dose-modified CHOP chemotherapy for HIV-related NHL. We evaluated HIV patients with NHL treated with standard dose or dose-modified CHOP with the aim of accessing treatment outcomes. Methods: A retrospective cohort study was conducted among patients who received chemotherapy at the UCI between January 2004 to December 2014. 410 eligible patients were reviewed and information on clinical characteristics, chemotherapy regimens, treatment outcomes and vital status at 6-months after completion of chemotherapy. Results: Overall 450 patients were available for screening, 12 did not receive chemotherapy and 37 received other chemotherapy regimens. 410 patients with HIV-related NHL were analyzed with 291 receiving standard dose and 119 patients received dose-modified CHOP chemotherapy. Most patients were male 59.8% and 50.4% in standard dose and dose-modified group respectively. 83.2% in the standard dose and 79.8% in the dose-modified group had advanced disease. A complete response was achieved in 67 of the 291 (23%) patients who received 6 standard dose chemotherapy cycles and 32 of the 119 (27%) patients who received 6 cycles dose-modified chemotherapy. The overall mortality was (18/202) 8.9%; 13/143 (9.1%) in the standard dose group and 5/59 (8.5%) in the dose-modified group. On multivariate analysis, female gender (OR 1.71, 95% CI 1.02-2.85, at least 6 cycles of chemotherapy (OR 0.31, 95% CI 0.11-0.87), chemotherapy received on schedule (OR 0.52, 95% CI 0.30-0.90) and disease progression (OR 3.58, 95% CI 1.01-12.63) were significantly associated with mortality. Conclusions: The complete response rates and mortality were not different; thus, recommendation is to consider dose-modified therapy because of the fewer associated side effects and lesser chemotherapy associated toxicities. Although, this was not statistically significant.
Single-center analysis of post-transplant lymphoproliferative disorder (PTLD) outcomes with Epstein Barr virus (EBV) assessments.
Authors: Moyers Justin , Liu Lawrence , Kim Matthew , Mo Huan , Kamal Muhammad Omair , Villacana Rafael , Chen Chien-Shing , Cao Huynh Le 
Published: March 2020

e19029 Background: EBV is associated with the majority of cases of PTLD, a serious complication after solid organ and hematopoietic stem cell transplantation. EBV serum viral loads have been used to identify those at risk of this disease in EBV-positive cases. We aimed to characterize the clinical presentation, pathologic diagnosis andprognostic implications of EBV viral load and its response to treatment. Methods: This is a retrospective observational study approved by IRB including all organ transplant patients with histologic diagnosis of PTLD between 2000 and 2018 at Loma Linda University Medical Center. Data was collected by chart review. Kaplan-Meier survival estimates were used to determine primary outcomes of overall survival and progression free survival. Results: 68 patients (41 male, 27 female) were identified who developed PTLD following solid organ transplantation (22 kidney, 37 heart, 6 liver, 3 multi-organ). Median time from transplant to PTLD diagnosis was longest among neonatal transplants 12.0 years versus 3.76 in pediatric and 6.43 in adult transplantations. EBER positive histology was observed in 93% (39/42) of pediatric population versus 52% (12/23) of the adult population. During treatment 16 (23%) experienced acute rejection with 5 (7%) graft losses. The largest subset, monomorphic diffuse large B-cell lymphoma (n = 34), had a median overall survival of 15.1 years. M-DLBCL with high levels of EBV copy load > 10,000 IU/mL had a trend toward worse overall survival of 9.0 versus 15.1 years in < 10,000 IU/mL (HR 2.74, p = 0.14). Treatment resulted in complete serologic EBV copy load response in 15/19 and a trend toward improved overall survival with a median OS not yet reached versus 13.7 years in incomplete responders (HR 0.76, p = 0.76). Conclusions: Our study introduces the hypothesis that initial EBV viral loads and treatment response may have prognostic importance. The characteristics, pathologic diagnosis and treatment response for this cohort of patients will be presented. [Table: see text]
Are double-hit lymphoma patients being adequately evaluated for CNS disease?
Authors: Hancock Christie , Bitran Jacob D. , Almanaseer Imad , Green Angel 
Published: March 2020

e19036 Background: Double hit lymphoma (DHL) is a high-grade lymphoma with a propensity to involve the central nervous system (CNS) compared to the typically less aggressive diffuse large B cell lymphoma (DLBCL). Guidelines recommend considering cerebrospinal fluid (CSF) evaluation and prophylaxis per institution guidelines in DHL patients (pts). It is not clear when this evaluation should occur and what prophylaxis should be delivered. Methods: We performed an IRB granted retrospective analysis of pts with de novo DHL based on assessing high-grade lymphoma FISH panels treated within the Advocate Health Care System. The pt’s age, IPI score, CNS-IPI score, systemic treatment, CSF evaluation, CNS prophylaxis or treatment, CNS event (yes/no), progression free survival and overall survival were recorded. Results: Thirty-one pts were evaluated. Seventeen were male. Median age was 72 years (range: 40 to 89). Fifteen were stage IV. Median IPI score was 3 and CNS IPI was 3. Fifteen pts had CSF evaluated within their disease course. Fifteen pts received CNS prophylaxis or treatment including intrathecal (IT) methotrexate (n = 10), IT methotrexate plus hydrocortisone (n = 2), IT cytarabine (n = 1), IT methotrexate and systemic methotrexate (n = 1), or only systemic methotrexate (n = 1). The number of patients with a CNS event during their disease course was 3 with all 3 having leptomeningeal involvement. These 3 pts had CNS IPI scores > 4. Two had CSF involvement at diagnosis. One died at 2 months; the other is alive and disease free at 44 months. The third pt developed CSF disease at relapse and ultimately died at 12 months. This pt had previously received IT methotrexate. For all pts, the median disease free survival (DFS) was 8.1 months; median survival was 11 months and 3-year DFS was 45%. Conclusions: Our small, but extensive review of community oncologists treating DHL patients showed there was a lack of CSF evaluation in these high-risk patients with a rate of less than 50%. For the patients evaluated, there was significant heterogeneity in CNS prophylaxis. The rate of 10% of patients having CNS disease is consistent with other reports of high-risk lymphoma and CNS relapse suggesting all DHL patients should have CNS prophylaxis.
Elevated serum lactate in lymphoma: Not always infection.
Authors: Gandhi Sangeetha , Pophali Priyanka Avinash , Witzig Thomas E. 
Published: March 2020

e19039 Background: In patients with lymphoma, lactate dehydrogenase (LDH) is an important prognostic marker. Serum lactate can also be elevated due to hypermetabolism from aggressive lymphoma. We have observed critically ill lymphoma patients with elevated serum lactate who had a delay in the diagnosis and treatment of their underlying lymphoma because the cause of the elevated lactate was presumed to be infection. This clinical observation led us to perform a study to evaluate the relationship between serum lactate and LDH levels in lymphoma patients. Methods: We used the Mayo Clinic Lymphoma Database to search for patients with lymphoma and elevated lactate during a recent two year time period, January 2014 through December 2015. Fifty patients met these initial criteria and underwent medical chart review. The patients were divided into two groups – those with documented infection (SepsisLA group) and those without infection (all cultures negative) where the elevated lactate was due to lymphoma hypermetabolism (LymLA group). The Wilcoxon/Kruskal-Wallis test was used to compare the SepsisLA and LymLA groups. Kaplan-Meier analysis was used to estimate survival. Results: The mean age of the 66 patients was 65 ± 14.8 years and 60% were male. At the time of presentation, the mean lactate and LDH values were 4.5 ± 2.81mmol/L (UNL < 2 mmol/L) and 835.1 ± 1741.4 U/L (UNL < 222 U/L), respectively. 64% (32/50) of patients had elevated LDH values. After review, 32 (64%) patients were in the SepsisLA group; 18 (36%) were in the LymLA group. DLBCL was the most common disease type in both the SepsisLA (50%; 16/32) and LymLA (88%; 16/18). The sepsisLA and LymLA groups were not significantly different in terms of age, sex, lactate levels, or maxSUV on PET scan (N = 13). However, patients in the LymLA group did have higher LDH values (p = 0.02) compared to those with SepsisLA. Patients with LymLA had a reduced overall survival (OS) (1.45 median months) compared to those with SepsisLA (7.83 median months) p = 0.02. Conclusions: This study demonstrates that the level of lactate elevation is not helpful indiscriminating SepsisLA vs LymLA; however an elevated LDH with elevated lactate is more likely LymLA. Lymphoma pts with LymLA had an inferior survival compared to SepsisLA. We are unable to define the true incidence and prognostic value of elevated serum lactate in lymphoma; this will require a prospective study with fresh samples. In summary, lymphoma activity can masquerade as infection with elevated lactate. Once sepsis is ruled out, treatment for the lymphoma should not be delayed as this presentation portends poor prognosis.
An objective based model of published treatment options for relapsed or refractory (R/R) peripheral t-cell lymphoma (PTCL): An evidence-based decision-making approach.
Authors: Marchi Enrica , Tobinai Kensei , Maruyama Dai , Nagai Hirokazu , O'Connor Owen A. 
Published: March 2020

e19048 Background: PTCL are rare diseases with a poor prognosis. Front line therapy achieves CR in 30% to 60% and OS of 25%. Patients with R/R disease have an even worse prognosis. There is no consensus on the management of R/R disease because evidence supporting most treatment approaches is modest. Many approaches are often not supported by literature, and categorizations regarding efficacy and toxicity without attention to details are ignored. Treatments that have achieved regulatory approval with stringent independent assessment of pathology and response are viewed as less established, or equivalent to smaller published experiences. In the effort to take a critical and comprehensive evidence-based approach to available standards in R/R PTCL we developed an objective scoring system for all types of studies published in the literature (eg randomized phase 3, case match control, phase 2, phase 1, case reports and small series) to aid decision-making based on an assessment of all the available data. Methods: An extensive review on PubMed of clinical trials published in literature for R/R PTCL was performed. A rigorous scoring system based on a survey from 100 authorities in the field to quantitate scientific impact of each study based was developed. These include: type of study (randomized phase 3, case match control analysis, phase 2 weighted based on number of PTCL patients [ > 100 vs < 100 patients], phase 1 with > 5 or < 5 PTCL patients enrolled, and retrospective); weighting for use of central pathology or response review; weighting for detailed study metrics (ORR, CR, DoR, PFS). The scoring system included a penalty for omission detail. The proposed scoring system was evaluated by a panel of experts. The scoring system was modified based on recommendations made by 2 or more panel members. Results: We identified 58 publications between 2004 and 2018. The scoring system spanned from 0 to 9. Only 12 of the 58 studies had a score above 5; 15 of 58 had a score between 1 - 5; remaining publications scored 0 - 1. Conclusions: Our analysis suggests practice patterns are based on studies with low priority scores, and underweight robust clinical experiences. This analysis aims to produce an evidenced based approach for R/R PTCL.
Real-world treatment patterns among patients (pts) diagnosed with primary mediastinal large B-cell lymphoma (PMBCL) in the United States (US).
Authors: Yang Xiaoqin , Laliberté François , Germain Guillaume , Raut Monika Kumar , Duh Mei Sheng , Sen Shuvayu , Lejeune Dominique , Desai Kaushal , Armand Phillippe 
Published: March 2020

e19050 Background: PMBCL is a rare mature B-cell neoplasm (2-4% of non-Hodgkin lymphomas) for which there is only limited data on treatment patterns in clinical practice. In October 2015, PMBCL was differentiated from diffuse large B-cell lymphoma (DLBCL) with the advent of ICD-10-CM PMBCL-specific codes. This study aims to describe real-world treatment patterns among pts diagnosed with PMBCL in the US. Methods: A retrospective database analysis was conducted using the Optum Clinformatics DataMart database (01/2013-03/2018). Pts with a first PMBCL ICD-10-CM diagnosis (with or without an antecedent ICD-10-CM diagnosis of DLBCL/other lymphoma, which may have been assigned before PMBCL confirmation) after October 1st, 2015 (index date) and no ICD-9-CM diagnosis code for unspecified PMBCL/DLBCL, were identified as incident pts. Those with PMBCL ICD-10-CM and unspecified ICD-9-CM diagnosis for PMBCL/DLBCL before October 2015 (index date) were identified as prevalent pts. PMBCL diagnoses on ≥2 medical visits and ≥12 months of continuous enrollment pre-index date were required. An adapted algorithm developed from previously published studies was used to identify lines of therapy (LOT). Duration of therapy spanned from LOT initiation up to discontinuation of all agents in the LOT, a switch to another LOT, or the addition of a new agent. Results: Among 148 PMBCL pts (118 incident; 30 prevalent), median (interquartile range) age was 66 (42-77) years. In incident pts, 48.3% were treated with ≥1 LOT (mean ± standard deviation [SD] duration of therapy: 86.0 ± 69.8 days) and 14.4% were treated with ≥2 LOT. The most frequently used first-line (1L) therapy (54.4% of pts) was R-CHOP (rituximab, cyclophosphamide, doxorubicin and vincristine). In prevalent pts, 63.3% were treated with ≥1 LOT (mean ± SD duration of therapy: 88.3 ± 44.6 days) and 20.0% were treated with ≥2 LOT. The most frequently used 1L therapy was R-CHOP (68.4%). Conclusions: This study demonstrated that a large portion of pts require additional therapy after 1L treatment to manage PMBCL, underscoring the significant unmet need in this population.
Bispecific ligand-directed toxin targeting CD22 and CD19 (DT2219) for refractory B-cell malignancies: Results of phase I-II trial.
Authors: Bachanova Veronika , Cao Qing , Weisdorf Daniel Jordan , Curtsinger Julie M , Cooley Sarah A. , Miller Jeffrey , Vallera Daniel 
Published: March 2020

e19066 Background: The novel bispecific toxin DT2219 consists of a fusion between the catalytic domain of diphtheria toxin (DT) and single-chain variable fragments (scFV) of antibodies targeting human CD19 and CD22. Methods: The primary objective of Phase I Dose was to determine DT2219 dose which is well tolerated on an 8 dose schedule (days 1, 3, 5, 8 and day 15, 17, 19 and 22). Phase II Extension aimed to establish a preliminary estimate of overall response at day 29 in patients stratified to Arm A (relapsed/refractory B-cell lymphoma) and Arm B (B-cell leukemia). Baseline serum level of neutralizing antibody (NA) against diphteria toxin below 50% was required for eligibility. Results: Eighteen patients (NHL n = 12; ALL n = 6) at median age 65 years (range 50-83 yrs) with relapse/refractory disease and confirmed expression of CD19 and/or CD22 were enrolled. Treatment was well tolerated at 60 mcg/kg x 8 doses and the most common adverse events included capillary leak sy, elevated AST/ALT, low albumin, weight gain and leukopenia. All were Gr 1-2 and resolved after 3-5 days allowing day 15 DT2219 administration. There were no neutropenic fever or immune mediated adverse events. Four patients experienced dose limiting toxicity at dose 80 μg/kg/day: Gr 4 capillary leak syndrome (n = 1), Gr 3 LFTs abnormalities (n = 2) and Gr 4 thrombocytopenia > 7 days duration (n = 1). Thirteen patients were evaluable for response and 3 experienced objective clinical benefit. One patient with primary refractory pre-B acute lymphoblastic leukemia achieved complete remission after 1st cycle. Two patients with transformed lymphoma demonstrated transient tumor shrinkage, however, DT2219 therapy was discontinued due to DLT and increased NA titer after 1st cycle (pre C1 28%, pre C2 108%). Correlative studies showed a low incidence of neutralizing antibody in NHL patients recently exposed to Rituximab. Conclusions: We have established the biologically active dose of DT2219 at 60 μg/kg/day ×8 doses. Further development of DT2219 includes combination with rituximab (to reduce NA formation) and synergistic combinations against B-cell malignancies. Clinical trial information: NCT02370160.
A mixed method analysis of toxicities of anti-CD19-CAR T cell therapy in hematological malignancies.
Authors: Jindal Vishal , Akella Padmastuti , Piranavan Paramarajan , Siddiqui Ahmad Daniyal 
Published: March 2020

e19068 Background: CAR (Chimeric Antigen Receptor) T cell therapy is a promising therapy with significant benefits. But cytokine release syndrome (CRS) and neurological toxicities (NT) are major obstacles in its success. In this study we did mixed method analysis of literature to explore side effect profile of Anti CD19-CAR T cell therapy in hematological malignancies. Methods: A review of literature was done to find appropriate studies on Medline database. Total 11 studies were selected on the basis of 1) Anti CD19-CAR T cell therapy 2) Lymphodepletion 3) Sample size equal to or more than 15, 4) Hematological Malignancies 5) Detailed toxicities mentioned. Data was extremely heterogenous for metanalysis therefore results were descriptively formatted using summary texts and tables. Results: Total patient count was 452, out of them 59% had ALL, 35.61% had NHL and 5.30% had CLL. Majority of studies used second generation CAR T cells (n = 10, 90.1). CAR T cell dosage protocol was variable among studies and it range from 1 X 105 to 1 X 107 cells. CRS occurred in 82.7%, with grade 1-2 CRS in 58.4% and grade 3-4 CRS in 24.3%. CRS presented early (range of median = 2.5 – 4 days) and recovers completely generally with in 1st week (range of median = 4.8 - 8 days). NT are seen in 45.6%, with grade 1-2 NT in 20.6% and grade 3-4 NT in 25.0%. NT have variable presentations, encephalopathy was seen in 22.65% of patients and 3.22% had seizures. For management of side effects 28.6% patients required ICU level of care and 21.86% required pressor support. Tocilizumab was used in 30.7%. Total 10 patients (2.2%) died due to side effects and out of them 6 (1.32%) due to CRS and 4 (0.88%) due to NT. Clinically significant associations were shown between tumor grade and CRS (n = 6, 54.5%), IL-6 and CRS (n = 8, 72.7%), CRP (C reactive Protein) and CRS (n =6, 54.5%), and CRS and NT (n = 7, 63.6%) (Table). Conclusions: This study concludes that CRS and NT are most common side effects of CAR T cell therapy. Most of the time they are completely reversible and manageable with tocilizumab and steroid therapy. Levels of IL6, Interferon gamma, CRP and ferritin are elevated in CRS patients. Therefore, can be used as biomarkers. NT and CRS are also associated with each other and likely share the pathological pathway. [Table: see text]