bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of patients treated with a single-fraction dose of radiation for lymphomatoid papulosis.
Authors: Gentile Michelle Sara , Thomas Tarita O. , Agrawal Priya , Guitart Joan , Rosen Steven T. , Kuzel Timothy , Mittal Bharat Bhushan 
Published: March 2020

e18523 Background: Lymphomatoid Papulosis (LYP) is a primary cutaneous CD30+ lymphoproliferative disorder and a radiosensitive tumor. Treatment with radiation is typically given in multiple fractions for patients presenting with symptomatic unilesional or multilesional disease. However, a single fraction of radiation is more convenient to the patient. The purpose of this retrospective review was to evaluate the clinical response to a single fraction of radiation for palliation of symptomatic LYP lesions. Methods: The records of 8 (5 female, 3 male) patients with LYP, treated with a single or multi-fractionated palliative radiation therapy between 10/2001 and 9/2011, were reviewed. All patients had received multiple previous treatments such as chemotherapy, PUVA, topical nitrogen mustard, and UVB. A total of 19 sites with disease were given the following single doses: 700 (n=3) and 800 (n=16). In the earlier years, a total of 6 sites with disease were given 250 cGy in 18 fractions for a total dose of 4500 cGy. Radiation therapy was administered with electrons to 20 sites and with photons to 5. A bolus was used in most cases to increase the radiation dosage to the skin. Results: Minimum and median follow-up were 1 and 43 months (range, 1 - 120), respectively. Median age of the patients was 65 (range, 24 - 83). For disease sites receiving a single fraction therapy, a complete response (CR) was seen in 17 of the 19 sites (89.5%), and a partial response (PR) was seen in an additional 2 of the 19 sites (10.5%). Therefore, the overall response rate was 100%. For the disease sites receiving multi-fractionated therapy, a CR was seen in 6 of the 6 sites (100%). Evaluation of patient characteristics and treatment did not reveal any differences between patients achieving a CR or PR. Conclusions: For previously treated, radiation-naıve LYP lesions, palliative radiation therapy with single fractions of 700 - 800 cGy is associated with an excellent CR and is a convenient and cost effective strategy.
Association of the reduced expression of NR4A1 and NR4A3 with poor survival in patients with aggressive lymphomas.
Authors: Deutsch Alexander Josef , Pichler Martin , Reitter Sonja , Troppan Katharina , Beham-Schmid Christine , Neumeister Peter 
Published: March 2020

e18525 Background: NR4A1 and NR4A3 belong to the orphan nuclear receptors. Their function as critical tumour suppressor genes was demonstrated by the rapid development of acute myeloid leukemia (AML) in NR4A1 and NR4A3 double knock-out mice and by their reduced expression in leukemic blasts from human AML patients. The aim of our study is to comprehensively study and functionally characterize NR4A1 and NR4A3 expression in Non-Hodgkin's Lymphomas (NHL). Methods: NR4A1 and NR4A3 expression were determined on mRNA- and protein levels in most lymphoid malignancies of B cell type. Additionally direct sequencing, methylation specific PCR and microRNA analyses of potential interacting NR4A partners were performed. For functional characterization NR4A1was over expressed in a Sc-1 lymphoma cell line by using an inducible lentiviral construct, and treated with Cytosporone-B (Csn-B), a non physiological NR4A1 ligand, followed by apoptotic assays (cleaved caspase 3, Sub-G1 peak determination, and the Annexin V staining). Results: We found a more than 50% reduction of both, NR4A1 and NR4A3, in B-CLL (71%) and Follicular Lymphoma (70%), and more pronounced in diffuse large B cell lymphoma (DLBCL) (74%) compared to normal controls. Mutational analyses in selected cases revealed four of 16 aggressive lymphoma samples mutated (one misssense- and three silent mutations (=25%)). Induction of NR4A1 expression in the transduced Sc-1 lymphoma cell line led to apoptosis in a significantly higher proportion of induced cells compared to their uninduced controls. Additionally, Csn-B treatment of an immortalized B cell line and three lymphoma cell lines caused NR4A1 mediated apoptosis. In a patient cohort of 83 DLBCL, NR4A1 and NR4A3 were more than 50% down-regulated in 88% and 74% of patients, respectively. A low expression of NR4A1 was significantly associated with non-germinal center B-cell like subtype (p<0.001) and with poor overall survival (p=0.042, HR=2.2, CI=1.01-4.9). Conclusions: Our data indicates that NR4A1 has pro-apoptotic functions and that Csn-B induces NR4A1 mediated apoptosis in lymphoma cells. Hence, regulation of NR4A1 by Csn-B is a promising target for the development of new therapeutic drugs.
Adolescents and young adults versus adults’ patients with large B-cell lymphoma: A matched-control analysis on 55 patients.
Authors: Bouabdallah Reda , Coso Diane , Esterni Benjamin , Vey Norbert , Chetaille Bruno , Blaise Didier 
Published: March 2020

e18526 Background: Among non-Hodgkin’s lymphomas, large B-cell lymphoma (LBCL) accounts for 60% in adolescents and young adults (AYA). There are no so many reports in the literature on LBCL in AYA patients. Moreover, there are no data available to suggest whether AYA patients with LBCL would benefit more from pediatric-chemotherapy regimen or from adult rituximab-chemotherapy treatment. In order to clarify this point, we conducted a matched-control analysis comparing AYA patients and adult’s patients with LBCL. Methods: We performed a clinical and pathological review of LBCL cases referred to our institution over a 15-year period from 1996 to 2010. Fifty-five AYA (16-30 years) were fully matched to 165 adult’s patients aged between 31 years and 65 years (ratio 1/3) for each of the following factors: international prognostic index (IPI), chemotherapy regimen, and rituximab delivery. Results: When compared to LBCL adults’ patients, pathological features in AYA showed a high incidence of primary mediastinal thymic LBCL subtype (33% vs. 5%, P= 0, 0001), while histological transformation was rare (2% vs. 14%, P= 0, 01). LBCL in AYA also presented with a bulky mediastinal mass (51% vs. 21%, P= 0, 0001), gastrointestinal tract involvement was less frequent (2% vs. 13%, P=0, 03), and LDH value was significantly higher (73% vs. 54%, P= 0, 01). The complete response rate to chemotherapy combination regimen was at 82% in AYA, with no difference with that observed in adult patients (82%, P=0, 8). With a median follow-up of 80 months, the 5-year overall survival (OS) and event-free survival (EFS) of AYA patients were at 73% ± 12% and 68% ± 12%, respectively. The matched-control analysis showed no difference either for OS (P = 0.8) or EFS (P = 0.9). Conclusions: LBCL in AYA should be considered as a true clinical and pathological entity. However, age does not confer a prognostic value different from that observed in LBCL in patients older than 30 years.
Outcomes of advanced HL with ABVD: The University of Pennsylvania experience.
Authors: Trivedi Meghna S. , Bajor David , Ahmadi Tahamtan , Svoboda Jakub , Loren Alison W. , Schuster Stephen J. , Nasta Sunita 
Published: March 2020

e18529 Background: Hodgkin Lymphoma (HL) is considered a curable malignancy with standard therapy using the doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) regimen. Even with standard therapy, the relapse rate for patients with advanced HL (stage IIB and higher) remains significant. The International Prognostic Score (IPS) uses 7 adverse prognostic factors (serum albumin, hemoglobin, male sex, age, stage IV disease, leukocytosis, and lymphopenia) to predict outcomes in advanced HL. Methods: We performed a retrospective chart review of all patients evaluated at the University of Pennsylvania for primary HL from July 2006 to June 2011. Of 257 patients, 26 were identified as those with advanced HL who initiated ABVD treatment at the University of Pennsylvania. The study outcomes were defined by RECIST criteria. The 26 patients were stratified by IPS and outcomes were evaluated. Results: 22 of 26 patients (85%) achieved lasting complete response (CR) after receiving treatment with ABVD with a median length of follow-up of 2.93 years. Three patients had primary refractory disease. Of these patients, two (IPS 1-2) achieved CR with salvage therapy. The third patient (IPS 5) had initial partial response (PR) to ABVD then continued to have relapsed disease after 4.50 years of follow-up. One patient (IPS 5) relapsed 2.74 years after receiving ABVD and at best had PR with salvage chemotherapy. Conclusions: ABVD was effective in achieving CR; however, 4 patients were unable to achieve lasting CR from ABVD alone. Two patients with IPS of 1 and 2 eventually achieved CR from salvage therapy. Two patients with IPS of 5 were unable to achieve lasting CR. Based on this data, IPS of 5 was associated with worse outcome. Use of IPS may be helpful to identify patients needing more intensive initial therapies. [Table: see text]
Preclinical activity of ofatumumab (OFA) in mantle cell lymphoma (MCL) in vitro, ex vivo, and in vivo models.
Authors: Barth Matthew John , Pendurti Gopichand , Mavis Cory , Czuczman Natalie , Skitzki Jospeh J. , Hernandez-Ilizaliturri Francisco J. , Czuczman Myron Stefan 
Published: March 2020

e18537 Background: MCL is characterized by an aggressive clinical course and inevitable development of refractory disease despite early intervention that often includes: immunotherapy (e.g., rituximab), multi-agent induction chemotherapy and consolidation with high dose chemotherapy and autologous stem cell transplant in first remission. OFA is a fully human anti-CD20 mAb targeting a novel membrane-proximal epitope on CD20. To characterize the activity of ofatumumab in MCL, we conducted pre-clinical studies in cell lines, primary tumor cells derived from MCL patients and a MCL bearing severe combined immunodeficiency (SCID) mouse model. Methods: Antibody-dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) assays were performed in 51Cr labeled Mino, Jeko, Rec-1 and Z-138 cells comparing RTX or OFA. Primary tumor cells were exposed ex vivo to OFA or RTX with human serum, differences in cell viability were determined by Cell Titer Glo assay. Expression of CD20 and complement inhibitory proteins (CIPs) CD55 and CD59 was determined by Imagestream analysis and Western blot. SCID mice were inoculated SQ with 10x106 Z-138 cells. Once tumors were established, mice were assigned to observation versus 4 doses of either OFA or RTX, and anti-tumor activity was measured by changes in tumor volume. Results: OFA induced higher CDC than RTX in all MCL cell lines tested (Mino: 65.9% vs. 0.5% ; Jeko 43.9% vs. 13.3% ; Rec-1 25.4% vs. 4.7% ; Z-138: 56.4% vs. 0.65%). No differences in ADCC were noted between OFA and RTX. In primary tumor cells, OFA and RTX demonstrated similar activity. CD20 levels were similar in all MCL cell lines tested. Of interest, CIP expression in MCL cell lines was higher when compared to other NHL cell lines, explaining differences observed between OFA and RTX. In vivo OFA was more effective in slowing tumor progression than RTX. Conclusions: Our data suggest OFA is more potent than RTX against MCL pre-clinical models. In addition and as expected, OFA exhibits potent CDC despite high expression of CIP. Our results support the evaluation of ofatumumab in future prospective clinical trials for patients with MCL.
Evaluation of MLN4924, an investigational NEDD8-activating enzyme (NAE) inhibitor, as a novel targeted agent with single-agent antitumor activity in mantle cell lymphoma (MCL) and Hodgkin lymphoma preclinical models.
Authors: Dawar Richa , Barth Matthew John , Mavis Cory , Skitzki Jospeh J. , Czuczman Myron Stefan , Klener Pavel , Hernandez-Ilizaliturri Francisco J. 
Published: March 2020

e18539 Background: MLN4924 is a novel, potent, and selective inhibitor of NAE, an essential component of the ubiquitin-proteosome system (UPS). We have previously demonstrated that the UPS plays a pivotal role in the development of rituximab and chemotherapy resistance in B-cell lymphomas. There is a scientific need to target the UPS more efficiently in an attempt to reverse acquired resistance to biological and chemotherapeutic agents in relapsed/refractory aggressive lymphoma. To this end, we studied the anti-tumor activity of MLN4924 in rituximab-chemotherapy sensitive and resistant pre-clinical models. Methods: A panel of Burkitt (BL), diffuse large B-cell (DLBCL), MCL and HL lymphoma cell lines and primary tumor cells isolated from patients with non-Hodgkin lymphoma (NHL) (N=10) were exposed to escalating doses of MLN4924 alone or in combination with a panel of chemotherapeutic agents for up to 72 hrs. Cell viability was determined by alamar Blue reduction or CellTiter-glo assay. Apoptosis was determined by Western blotting. Cell cycle analysis was performed by flow cytometry. Results: MLN4924 demonstrated activity in all cell lines in a time-and dose-dependent manner, including the rituximab/chemotherapy-resistant cell lines. The most potent activity was noted in MCL and HL cell lines (IC50 doses were tenfold lower as compared to DLBCL or BL cell lines). A variable degree of anti-tumor activity was observed in primary tumor cells isolated from NHL patients. Induction of apoptosis was observed in rituximab-resistant cell lines. MLN4924 exhibited synergistic anti-tumor activity when combined with bortezomib, bendamustine, and cytarabine in MCL cell lines. Conclusions: MLN4924 exhibits potent in vitro cytotoxic activity against a variety of human B-cell lymphoma cell lines and primary tumor cells isolated from NHL patients. Significant activity was observed in MCL cell lines. Experiments investigating the in vivo activity of MLN4924 are ongoing. MLN4924 is a highly promising agent for the treatment of relapsed/refractory MCL or HL.
AIDS-related lymphoma (ARL) in Asians in the era of HAART and rituximab.
Authors: Tan Wu Meng , Tan Soo Yong , Ng Tat Ming , Pan Summer , Quek Richard Hong Hui , Tao Miriam , Tai Wai Meng David , Koh Yin Ling , Tan Thuan Tong , Tan Daryl C.L. , Ha Tam Cam , Chan Alexandre , Tay Kevin , Lim Soon Thye 
Published: March 2020

e18546 Background: We described EBV & HHV8 co-infection rates, histology subtypes (particularly T-cell), prognosticators and outcomes of Asian ARL and compared them to Western series. Methods: We studied clinicopathologic features of 46 HAART-era ARL diagnosed from 1998-2011 in an Asian Tertiary Cancer Centre. To study HIV effect on survival, we applied multivariate analysis to HIV-DLBCL matched against 453 de novo DLBCL from 2000-2008. Results: The 46 patients’ characteristics are presented in the table below. Of note, germinal centre B-cell (GCB) subtype predominated in HIV-DLBCL with evaluable tissue. In multivariate analysis of HIV-DLBCL and matched de novo DLBCL, HIV status did not predict survival (HR1.33, p=0.63); CR was the only significant prognosticator (HR0.30, p=0.048). Conclusions: 1. EBV+ rates appeared to surpass prior Western ARL series. Although concomitant EBV infection appeared to correlate with inferior survival (HR34.5), it was not statistically significant. 2. Alb<30 (p=0.02) & Hb<10 (p=0.003) significantly predicted worse OS, but not CD4 or concurrent HIV&ARL diagnosis. 3. In this predominantly EPOCH-treated population, BL (HR 2.27) non-significantly trended to worse OS than DLBCL. 4. T-cell ARL (2/46, 4%) was rarer than the expected Asian de novo rate. 5. In multivariate analysis, HIV-DLBCL OS was similar to matched de novo DLBCL, suggesting they should be similarly treated with curative intent. CR rates and 5yr OS were comparable to de novo DLBCL. [Table: see text]
Evaluation of serum B-cell maturation antigen in multiple myeloma.
Authors: Sanchez Eric , Li Mingjie , Kitto Alex , Li Jennifer , Wang Cathy , Kirk Dylan T , Robinson Austin , Madden Erik , Okhovat Jean-Phillip , Waterman Gabriel N. , Swift Regina A. , Bonavida Benjamin , Chen Haiming , Berenson James R. 
Published: March 2020

e18549 Background: B cell maturation antigen (BCMA) is a receptor whose expression increases during B-cell development and is found on malignant cells from multiple myeloma (MM) patients; however, it has not been identified in human serum. Methods: Bone marrow (BM) aspirates and peripheral blood were obtained from patients with MM, monoclonal gammopathy of undetermined significance (MGUS) and healthy control subjects following informed consent (Western IRB BIO 001). Serum was isolated and analyzed with a BCMA enzyme‑linked immunosorbent assay. Values represent the mean of triplicate experiments. BM mononuclear cells (MCs) were isolated using density‑gradient centrifugation and cultured for 72 h in RPMI1640 supplemented with 10% fetal bovine serum. Our human MM xenograft (LAGκ-2)was grown in SCID mice and treated with bortezomib (BORT) with cyclophosphamide (CY); tumor volume and BCMA levels were determined. Statistical significance of differences observed was determined using a Student’s t test and analysis was determined using GraphPad prism software. Results: We showed that the supernatants of cultured BMMCs from MM patients had high concentrations of BCMA (median = 2,250 pg/ml) whereas normal subjects showed minimal amounts (56 ng/ml; P < 0.0001). The serum BCMA levels from newly diagnosed MM patients (n = 51) had much higher levels (13.74 ng/ml) than among controls (n = 40; median 2.58 ng/ml; P < 0.0001) and MGUS subjects (n = 26; median 5.40 ng/ml; P = 0.005). Notably, protein levels were much higher among patients with relapsed or refractory (R/R) disease (n = 79; median 20.02 ng/ml) compared to those with responsive (> partial response) disease (n = 80; median 4.14 ng/ml; P = 0.0038). Following treatment, patients with responsive disease showed decreases in BCMA levels whereas those with R/R disease showed increases. Following treatment with BORT and CY, we also showed a marked decrease in tumor volume and serum human BCMA levels in mice bearing the LAGκ-2 xenograft whereas untreated animals showed marked increases in tumor size and serum BCMA. Conclusions: This is the first report identifying serum BCMA in any human disease and suggests that these levels may be a novel biomarker for monitoring disease status and therapeutic response of MM patients.
An evaluation of efficiency, safety, tolerability, patient satisfaction, and preference of subcutaneous (SQ) versus intravenous (IV) bortezomib (BTZ) administration in patients with multiple myeloma (MM).
Authors: Barbee Meagan Spencer , Wilson Nicole Maire , Harvey R. Donald , McKibbin Trevor , Lonial Sagar , Kaufman Jonathan L. , Shah Katherine Sanvidge 
Published: March 2020

e18553 Background: SQ BTZ is approved for use in patients (pts) with MM; however, there is no data assessing the effect of SQ BTZ administration on practice variables (e.g., chair time, total time in clinic) or patient preferences. Furthermore, few studies have evaluated the incidence of PN with SQ BTZ, especially in treatment naïve patients. Methods: This study is divided into three components. Eligible pts for the retrospective efficiency study received ≥ 6 doses of either IV or SQ BTZ in the clinic in 2011 with no concurrent infusions/transfusions other than IV fluids, premedications, or concurrent chemotherapy during their visit. Individual clinic encounters of eligible pts were assessed for chair time and overall clinic visit time, and the average times were compared between the IV and SQ groups. Eligible pts for the preference/satisfaction survey study received ≥ 1 dose of each IV and SQ BTZ in 2011 and spoke English. Percent response to answer choices are reported. De novo SQ BTZ pts who received ≥ 6 doses were eligible for the retrospective safety/tolerability study. Patient chart notes were reviewed to identify the incidence and grade of PN. Results: 92 pts representing 1458 encounters were included in the efficiency study. Average chair time was 54 min less with SQ BTZ than IV BTZ (95% CI, 48 to 59 min; n = 1077 encounters; 89 vs 143 min). Average overall clinic visit time was 46 min less with SQ BTZ than IV BTZ (95% CI, 40 to 52 min; n = 1102 encounters; 123 vs 169 min). 28 of 47 eligible pts completed the survey. 19/28 (67.8%) preferred and 19/28 (67.8%) were more satisfied with SQ BTZ than IV BTZ. 11/28 (39%) experienced an injection site reaction, and 14/28 (50%) agreed they would feel comfortable with self-administration at home. Of the 14 pts receiving SQ BTZ who were BTZ naïve, 11 were newly diagnosed. One of these pts had new PN and 3 had worsened PN from baseline. SQ BTZ was dose reduced in 2 patients and discontinued in 2 pts due to PN. Conclusions: A complete transition in the practice of administration of BTZ from IV to SQ could improve clinic efficiency and provide a more preferable/satisfactory experience for pts.
Race- and health-related quality of life among patients newly diagnosed with multiple myeloma.
Authors: Pashos Chris L , Durie Brian G. , Rifkin Robert M. , Abonour Rafat , Fonseca Rafael , Gasparetto Cristina , Mehta Jayesh , Narang Mohit , Shah Jatin J. , Terebelo Howard R. , Thomas Sachdev P. , Toomey Kathleen , Swern Arlene S , Harding Gale , Sullivan Kristen , Street Thomas , Khan Zeba M. 
Published: March 2020

e18556 Background: Studies in the United States (US) have identified variation in incidence and survival of multiple myeloma (MM) patients of different races, and noted that MM is the most common hematologic cancer among African Americans. This analysis evaluated whether health-related quality of life (HRQOL) of patients in the US varies by race as they initiate treatment having been newly diagnosed with active, symptomatic MM. Methods: Data were collected in Connect MM, a prospective US observational registry begun in September 2009. Data on patient demographics and clinical characteristics were provided by clinicians. HRQOL was reported by patients at enrollment within 2 months of diagnosis. Patients completed the Brief Pain Inventory (BPI), EQ-5D, and Functional Assessment of Cancer Therapy-Multiple Myeloma (FACT-MM). Mean reported scores for BPI, EQ-5D and FACT-MM were analyzed by patient race. Statistical significance was ascertained by ANOVA using SAS 9.1. Results: Baseline HRQOL data were reported by 1144 patients (enrolled in 228 centers) of whom 82% were White, 13% Black, and 6% Other race. The cohorts did not differ statistically by ECOG status or by multiple myeloma stage (assessed by either the International Staging System or the Durie and Salmon system). Compared to non-Blacks, Black patients reported less anxiety/depression on the EQ-5D (p=0.030) and better emotional well-being on the FACT-MM (p=0.003). No other statistically significant differences were noted between cohorts on the BPI, other EQ-5D domains (mobility, self care, usual activities, pain/discomfort), or other FACT-MM domains (physical, social/family, functional, and MM-specific considerations). Conclusions: Initial results from the Connect MM Registry indicate that baseline HRQOL prior to initiation of treatment may vary by patient race with respect to emotional well-being, and specifically anxiety/depression. These results serve as a baseline reference for future analyses. As patients in the Connect MM Registry proceed through therapy, analyses should be conducted of patients by race, among other characteristics and factors, to determine whether it may be associated with subsequent clinical outcomes and HRQOL over time.