bluuebunny/crossref_metadata_2025_split huggingface dataset:
The utility of serum lactate dehydrogenase (LDH) in the follow-up of patients with diffuse large B-cell lymphoma (DLBCL).
Authors: Bongu Navneeth Rao , William Basem M. , Bast Martin , Bociek Gregory , Bierman Philip Jay , Vose Julie , Armitage James O. 
Published: March 2020

8047 Background: The prognostic significance of high serum LDH is well established for both indolent and aggressive lymphomas at diagnosis. The performance characteristics of LDH in predicting relapse after treatment in patients (pts) with DLBCL has not been well studied. The determination of utility of LDH monitoring in pts with DLBCL would have widespread practice implications. Methods: We searched the Nebraska Lymphoma Study Group database to identify pts with DLBCL who were treated with a rituximab-based regimen, from 2000 to 2010, and sustained a complete response (CR). For the pts who relapsed (RP), after sustaining a CR, we collected the LDH level at relapse and the LDH level 3 months prior (considered baseline). For pts who never relapsed (NR), we collected the last 2 LDH levels at follow-up; levels had to be at least 3 months apart. The relative increase of LDH was compared, to baseline, among RP vs. NR. Results: We identified 129 pts, 15 pts were excluded from the analysis as their LDH results were not available, 27 relapsed and 87 didn’t. Median age of pts was 57 years. Only 9/27 RP (33%) had increase in LDH above upper limit of normal (ULN) at relapse. The mean increase in LDH at relapse was 1.2 fold above the ULN for RP vs. 0.83 for NR (p=0.59). The mean increase in LDH, from baseline, was 1.1 fold in NR vs. 1.3 in RP (p=0.3). The likelihood ratio (LR) of relapse was 4.65 for pts who had 1.5 fold increase in LDH above baseline (1.5xLDH) vs. those who didn’t (p=0.03). The sensitivity, specificity, positive and negative predictive values of 1.5xLDH for detecting relapse, compared to clinical and imaging findings were 0.18, 0.95, 0.55, and 0.79 respectively. Also, 1.5xLDH at relapse was significantly associated with the presence of fever (LR=5.74; p=0.03) but not with other symptoms including drenching night sweats, anemia, or new/progressive lymphadenopathy. Conclusions: A 1.5 fold increase in LDH, over a period of 3 months, is associated with increased likelihood of relapse from DLBCL. Modest elevations in LDH (<1.5 fold of baseline) doesn’t seem to be associated with relapse. LDH, when elevated at least 1.5 fold of baseline, is a specific (i.e. 56%), but not a sensitive (i.e. 19%) marker, for relapse of DLBCL.
Association of low expression of VEGF121 soluble isoform with prognostic impact and survival in patients with activated B-cell-like (ABC-like) diffuse large B-cell lymphoma (DLBCL) from the CORAL trial.
Authors: Thieblemont Catherine , Mounier Nicolas , Mourah Samia , Houlgatte Remi , Hirchaud Edouard , Cuccuini Wendy , Ysebeart Loic , Bron Dominique , Gaulard Philippe , Gisselbrecht Christian , Briere Josette 
Published: March 2020

8048 Background: Gene expression profiling (GEP) has demonstrated that survival of DLBCL is influenced by the origin of the tumor cells (COO), germinal center-like (GC-like) vs ABC-like (Alizadeh et al. 2000), but also by the tumor microenvironment, particularly the angiogenesis (Lenz et al., 2008). To further understand the prognostic impact of these tumoral characteristics, we analysed the prognostic impact of COO and the expression of biomarkers involved in angiogenesis, in a selected population of 36 patients with relapsed/refractory DLBCL included in CORAL (Gisselbrecht, ASCO 2011). Methods: Expression of 5 biomarkers including VEGF (isoforms 121, 165, and 189), and their receptors (VEGFR-1 and R-2) was assessed by quantitative qRT-PCR after total RNA extraction and cDNA synthesis of tumor samples. COO was determined by GEP, and progression free- (PFS) and overall- (OS) survivals were analysed. Results: In the study population, VEGF121 expression below the median was associated to a better outcome, with 4 year-PFS at 63% vs 33% (p=.053), and a 4-year-OS at 79% vs 37% (p = 0.032), respectively. VEGF-165 -189, VEGF-R1, -R2 did not have any significant impact. Eighteen patients were predicted as ABC-like DLBCL and 18 as GCB-like DLBCL. In patients with ABC-like DLBCL, low VEGF121 level was associated to a significantly better survival than in those with high VEGF121 level: 4-year OS at 100% vs 36% (p=.011). The type of induction treatment, R-ICE or R-DHAP, did not influence the outcome. The differences in outcome according to VEGF isoforms were not significant among CGB patients. Conclusions: Our data suggest that angiogenesis plays a central role in ABC-like DLBCL. VEGF121 seemed to be a key player in this context and should be proposed as a target in the treatment of patients with ABC-like DLBCL.
Transformation of follicular lymphoma in the era of immunochemotherapy: A population-based study from British Columbia.
Authors: Al-Tourah Abdulwahab J. , Sehn Laurie Helen , Moccia Alden A , Gascoyne Randy D. , Connors Joseph M. 
Published: March 2020

8049 Background: Several published series have established that the risk of transformation of follicular lymphoma (FL) to aggressive lymphoma is approximately 3% /year (15%-20% at 5 years). The addition of rituximab (R) to chemotherapy (immuno-chemotherapy) has significantly improved the outcome of patients with FL. The impact of immuno-chemotherapy on the risk of transformation remains unknown. We assessed whether the introduction of immuno-chemotherapy has altered this risk. Methods: We examined the Lymphoid Cancer Database of the British Columbia Cancer Agency for FL patients treated with immuno-chemotherapy. Inclusion criteria: FL grades 1-3A by WHO criteria; only patients requiring treatment at diagnosis were included. Exclusion criteria: FL grade 3B or composite histology (FL and DLBCL) at diagnosis; pts who received anthracycline-based chemotherapy; and HIV positivity. The diagnosis of transformation was confirmed by biopsy when possible (n=19; 79%) but patients who were considered to have transformed based on pre-defined clinical assessment (n=5; 21%) were also included in the analysis. Results: We identified 261 pts with FL grade 1-3A requiring treatment at diagnosis, who received immuno-chemotherapy; median f/u 47 months (0.2-116), median age, 61 y (34-86). Treatment: 243 (93%), R-CVP of which 145 (59%) also received maintenance R; 9 (4%), R-Fludarabine combination. 24 pts developed transformed aggressive lymphoma. The risk of transformation for the entire group was approximately 2% per year or 10% at 5 years. However, pts treated with maintenance R (n=151) had a lower risk of transformation compared to pts who only received R-chemo at induction (n= 110), 8% vs 20% at 5 years respectively, (P= 0.003). The post-transformation outcome remains poor with a median survival of 6 months. Conclusions: We and other groups have demonstrated that the risk of transformation from FL to aggressive lymphoma is approximately 15% to 20% by 5 years. Our study suggests that the introduction of immuno-chemotherapy has reduced this risk to less than 10%. This effect is particularly apparent when patients receive maintenance R. The outcome for patients who develop transformation remains poor.
LR-CD: Lenalidomide combination therapy for untreated low-grade B-cell NHL.
Authors: Reeder Craig B. , Tiedemann Rodger Edwin , Gano Katherine , Dueck Amylou C. , Conley Christoher R , Ansell Stephen Maxted , Nowakowski Grzegorz S. , Curtis Kelly Kevelin , Camoriano John Kelly , Leis Jose Francisco , Slack James L. , Valdez Riccardo , Stewart A. Keith , Witzig Thomas E. 
Published: March 2020

8053 Background: Lenalidomide (LEN) is an immunomodulatory agent that has shown significant single-agent anti-lymphoma activity in patients with relapsed disease and in combination may enhance the efficacy of rituximab by various mechanisms. There is limited data on the role of LEN in combination regimens for treatment-naïve patients. This phase II single arm trial was designed to evaluate tumor response, toxicity (AE) and survival with a combination of LEN, rituximab, cyclophosphamide (CTX) and dexamethasone (DEX) (LR-CD) in symptomatic untreated patients with low grade B-cell non-Hodgkin lymphoma. Methods: Eligibility required age ≥18, ECOG PS ≤2, confirmed diagnosis of low-grade B-cell lymphoma (FL1-2, SLL, MZL or LPL/WM), measurable nodes ≥2cm or IgM ≥400mg/dL(LPL/WM), ANC ≥1400/mm3, platelets ≥100,000/mm3, creatinine ≤2mg/dL, signed informed consent and in need of therapy. Treatment consisted of IV rituximab 375mg/m2 D1, oral LEN 20mg D1-21, CTX 250mg/m2 D1, 8, 15, DEX 40mg D1, 8, 15, 22 and ASA 325 mg daily in a 28 day cycle. Treatment continued 2 cycles beyond best response (max 12). Toxicity was assessed by NCI CTCAE v3.0. Results: 28 patients have enrolled at Mayo Clinic with 25 evaluable for toxicity and 21 for response: Median age 65(43-83), 72% male, FL 24%, MZL 28%, LPL/WM 38%, and SLL 4%. Median number of cycles given was 5. Overall response in 21 patients with response data is 95% (95% CI 76-100%) with 19% CR (95% CI 5-42%), and 76% PR (confirmed and unconfirmed, 95% CI 53-92%). The ORR in 8 patients with LPL/WM with response data was 88%, all PR (95% CI 47-100%). At a median f/u of 14.7 months 96% are alive without progression. 1 death (unrelated) occurred 7.7 months after completing 12 cycles of treatment. The most common grade ≥3 AEs were neutropenia (37.5%), leukopenia (16.7%), anemia (12.5%) and fatigue (12.5%). Conclusions: The combination LR-CD with the novel agent LEN is feasible, well tolerated and produces high response rates in symptomatic patients with low grade B-cell NHL. Toxicities are manageable and similar to reported data of single agent LEN.
MLN9708, an investigational proteasome inhibitor, in patients (pts) with relapsed/refractory lymphoma: Emerging data from a phase I dose-escalation study.
Authors: Martin Peter , Chang Julie E. , Rifkin Robert M. , Hui Ai-Min , Berg Deborah , Gupta Neeraj , Liu Guohui , Di Bacco Alessandra , Assouline Sarit E. 
Published: March 2020

8064 Background: MLN9708 is a reversible, orally bioavailable, specific 20S proteasome inhibitor. This study (NCT00893464) studied the safety and determined the MTD of IV MLN9708 in pts with relapsed/refractory lymphoma, and characterized pharmacokinetics (PK) and pharmacodynamics (PD). Methods: Pts aged ≥18 yrs who had failed ≥2 chemotherapeutic regimens received IV MLN9708 on days 1, 8, and 15 of 28-day cycles until disease progression or unacceptable toxicity. One pt was enrolled at the 0.125 mg/m2 starting dose; dose doubling proceeded with 1 pt at each dose up to 1.0 mg/m2. Dose escalation occurred in ≤40% increments using a standard 3+3 scheme based on DLT occurrence in cycle 1. Blood samples were collected at multiple time points after dosing on days 1 and 15 of cycle 1 for PK/PD analyses. Results: At data cut-off (Dec 1 2011), 21 pts had been enrolled and treated: 1 each at 0.125, 0.25, 0.5 and 1 mg/m2, 4 at 1.4 mg/m2, 7 at 1.76 mg/m2, and 6 at 2.34 mg/m2. Median age was 57 yrs (range 23–78); 57% were male. Median number of prior therapies was 5; 29% had prior radiation, 24% prior stem cell transplant. Histologies included T-cell lymphoma (n=5), Hodgkin lymphoma (n=3), follicular lymphoma (n=2), DLBCL (n=1) and other indolent B-cell lymphoma (n=7). Pts had received a median of 2 cycles (range 1–22); 2 DLTs were seen (neutropenia at 1.76 and 2.34 mg/m2). All pts experienced drug-related AEs, including fatigue (48%), nausea (29%), diarrhea (29%), pyrexia, thrombocytopenia, and vomiting (each 24%). 43% had drug-related grade ≥3 AEs, 1 pt discontinued due to drug-related grade 3 neutropenia (2.34 mg/m2). Three pts had drug-related peripheral neuropathy (1 grade 1, 2 grade 2). There were no on-study deaths. Of 18 response-evaluable pts, 3 achieved PR (including 2 who remain in response and on-study for >1 yr) and 4 SD. PK analyses showed linear PK (0.5–2.34 mg/m2) and a terminal half-life of ~6–9 days. There was a dose-dependent increase in maximal whole blood 20S proteasome inhibition. Conclusions: These data suggest IV MLN9708 is generally well tolerated, with infrequent PN, and is clinically active in pretreated lymphoma pts. The trial is ongoing and updated data will be presented.
Phase I/II study of MEDI-551, a humanized monoclonal antibody targeting CD19, in subjects with relapsed or refractory advanced B-cell malignancies.
Authors: Goswami Trishna , Forero Andres , Hamadani Mehdi , Sonet Anne , Verhoef Gregor , Fanale Michelle A. , Bello Celeste M. , Huang Wenmei , Cheson Bruce D. 
Published: March 2020

8065 Background: Novel B-cell targeting agents, including monoclonal antibodies such as rituximab, are among recent advances in treatment of B-cell malignancies. New approaches are needed for patients progressing after rituximab-based therapies. MEDI-551 is an afucosylated monoclonal antibody targeting CD-19, a B-cell restricted transmembrane protein with enhanced affinity and antibody-dependent cellular cytotoxicity. Methods: Pts with relapsed or refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia, or multiple myeloma received single agent MEDI-551 at dosages ranging from 0.5 mg/kg to 12 mg/kg via intravenous infusion over 28-day cycles; cohorts 1-6 received 0.5, 1, 2, 4, 8, and 12 mg/kg, respectively. Results: 25 pts were enrolled in the phase I portion Jun 2010–Aug 2011. No maximum tolerated dose (MTD) was achieved. Most AEs were grade 1/2 with dose-independent frequency and severity (Table). Six pts had grade 3 toxicities including tumor lysis syndrome, infusion reaction, thrombocytopenia, and neutropenia, or grade 4 neutropenia. No grade 5 AEs were seen. All pts recovered. Three partial responses (PR) and 2 complete responses (CR) were seen in DLBCL and FL pts at 0.5, 4, and 8 mg/kg. Activity included a CR lasting 9 mo. in a FL pt in cohort 1, who is currently being retreated with MEDI-551 on relapse. Conclusions: MEDI-551 demonstrated a safety profile warranting further study and showed no MTD reached at the highest dose studied. Anti-tumor activity is suggested by the responses achieved across dose levels. Phase II is currently enrolling subjects. This study is funded by MedImmune, LLC. [Table: see text]
Comparison of the international prognostic factors index (IPI) with the absolute monocyte and lymphocyte prognostic index (AMLPI) for patients (Pts) with diffuse large b-cell lymphoma (DLBCL) receiving R-CHOP.
Authors: Batty Nicolas , Ghonimi Elham , Feng Lei , Fayad Luis , Younes Anas , Rodriguez Maria Alma , Romaguera Jorge Enrique , McLaughlin Peter , Samaniego Felipe , Kwak Larry W. , Hagemeister Fredrick B. 
Published: March 2020

8067 Background: We studied the value of a proposed prognostic index (PI) generated by baseline absolute monocyte (AMC) and lymphocyte (ALC) counts for pts with DLBCL, using values as previously reported (Leukemia 25:1502-9, 2011). Methods: From 03/07 to 01/09, 245 consecutive pts with untreated DLBCL receiving standard R-CHOP from the MDACC database were evaluated. Baseline AMC and ALC were retrospectively recorded. High AMC (≥610/uL) and a low ALC (≤1000/uL) were examined as dichotomized variables for progression-free (PFS) and overall survival (OS). An AMLPI was generated, stratifying pts into 3 risk groups (RGs): low-(AMC <610/uL and ALC >1000/uL), intermediate-(AMC ≥610/uL or ALC ≤1000/uL), and high-risk(AMC ≥610/uL and ALC ≤1000/uL). The prognostic effect of the AMLPI and the IPI were examined by multivariate analysis (MVA). Results: Ninety (37%) had high AMC and 71 (29%) had low ALC. By univariate analysis, a high AMC was associated with inferior PFS (p=0.01) and OS (p=0.03). The frequencies of AMLPI RGs were: low-105 pts (43%), intermediate-119 (48%), and high risk-21 (9%). With a median follow-up of 22 months (range <1-42), 3-year PFS and OS rates for these RGs were 80%, 61%, and 46% (p=0.007) and 92%, 76%, and 60% (p=0.006), respectively. Three-year PFS rates for IPI 0-2 and 3-5 RGs were 73% and 58%, respectively (p=0.0004); comparable OS rates were 88% and 68%(p<0.0001). For pts with IPI 0-2, 1-year PFS rates for AMLPI low, intermediate, and high RGs were 92%, 89% and 80% (p=0.022); comparable 1-year OS rates were 96%, 95% and 80% (p=0.049). By MVA, AMLPI effect (low vs. high RGs) on PFS was significant (p=0.046) as was IPI effect (0-2 vs 3-5, p=0.005); similar results were observed for OS (p=0.052 and p=0.003, respectively). Conclusions: Baseline AMC and AMLPI are significant variables for PFS and OS for pts with DLBCL receiving R-CHOP. AMLPI can identify pts with low, intermediate, and high-risk disease for PFS and OS, particularly for those with IPI 0-2. AMLPI may also add prognostic value beyond that of the IPI.
Prognostic value of etoposide area under the curve (AUC) in lymphoma patients treated with BEAM regimen and ASCT: Multicenter study of Groupe d’Etudes des Lymphomes de l’Adulte (GELA).
Authors: Bally Olivia , Freyer Gilles , Salles Gilles A. , Michallet Anne-Sophie , Casasnovas Olivier , Tilly Herve , Ribrag Vincent , Sebban Catherine , Falandry Claire , You Benoit 
Published: March 2020

8068 Background: The prospective LYMPK study primary objective was to assess the impact of etoposide pharmacokinetic (PK) parameters on toxicity and efficacy in lymphoma patients receiving the BEAM regimen (carmustine, cytarabine, etoposide and melphalan) followed by autologous stem cell transplant (ASCT). We previously showed the high inter-individual variability in etoposide PKs, defined by area under the curve (AUC) and trough concentration (Cmin), among study patients treated with the same doses /m2 (You B et al, Proc. ASCO 2008). Methods: Ninety-six patients with malignant lymphoma at 1st line (n=52) or relapse (n=44) were enrolled in 5 centers. All received BEAM regimen, including high-dose etoposide (100 to 200 mg/m2 bid for 4 days), followed by ASCT. Individual etoposide AUC and Cmin were estimated by population PK approach using NONMEM program. The impact of PK parameters on toxicity and survival was assessed using linear regression and univariate/multivariate analyses. Results: Data from 90 patients were assessable after a 4.2-year median follow-up. The bi-compartment model previously reported was used to characterize PK parameters (You B et al, Proc. ASCO 2008). Etoposide AUC and Cmin correlated with mucositis duration, especially for grade 3-4 toxicity (p< 0.05), but not with other toxicities. Cmin had significant prognostic value regarding 5 year progression free survival (p=0.03). Five year overall survival (OS) was longer in patients with higher AUC (76% vs 56%, if AUC > median, p=0.04) as it was in patients with higher Cmin (78% vs 54%, if Cmin > median, p=0.02). When assessed with available IPI prognostic factors (age; performance status; LDH and stage) using Cox analysis, the only independent prognostic factors of OS and disease specific survival were etoposide AUC (HR= 0.39, 95% CI = 0.16-0.94) and Cmin (HR = 0.32, 95% CI = 0.12-0.80). Conclusions: LYMPK study results suggest that individual etoposide systemic exposure has a strong impact on survival in lymphoma patient receiving BEAM regimen and ASCT. Given the high variability in patient AUCs, plasma concentration-based adjustment of etoposide dose may be considered in future studies.
Ocular adnexal lymphoma (OAL)-outcomes for 82 patients (pts) treated at a single center.
Authors: Portell Craig Anthony , Aronow Mary E , Rybicki Lisa A. , Singh Arun D , Sweetenham John W. 
Published: March 2020

8071 Background: OALs comprise 1-2% of NHL and are extranodal marginal zone (EMZL) in 80% of cases. We present a retrospective review of 82 pts with OAL managed at the Cleveland Clinic between January 2004 and November 2011. Methods: 82 pts with NHL of the OA were identified. All biopsies were performed/reviewed at the Cleveland Clinic. Survival and relapse were estimated using the Kaplan-Meier method. Risk factors for relapse and survival were identified using Cox proportional hazards analysis. Risk factors included age at diagnosis (dx), gender, prior autoimmune disease, prior lymphoma history (hx), hx of other malignancy, bilateral disease, and ocular disease site. Results: The table lists pt characteristics. Median follow-up was 25.8 months (range 0.3-307.4). Age at dx (HR=1.45, CI 1.04-2.02) and prior lymphoma hx (HR=3.35, CI 1.33-8.46) were predictive of relapse in a multivariate analysis. There was no difference in relapse rates between pts with EMZL and other lymphoma types (p=0.82). Relapse occurred in 26 (31.7%) pts with most common sites being ipsilateral eye (n=8), contralateral eye (n=3), distant lymph node (n=11), and other organs (n=11). Most common organ was breast (n=4). Of the 10 pts who had eye-only relapses, 8 received rituximab (R) and 2 were observed. Of the 16 with extraocular relapse, 9 received radiation (RT), 2 received R, 3 received other therapies, and 2 were observed. 7 deaths were recorded with a 5 year overall survival of 84.2%. Survival was similar to a matched healthy population (p=0.69). Causes of death were lymphoma in 4, another cancer in 1, and unknown in 2. Conclusions: OAL relapse patterns differ depending on initial treatment. Initial RT was more likely to relapse at distant sites; where as initial R was more likely to relapse in the OA. RT should be used for localized OAL. With bilateral ocular or systemic disease, R results in a high rate of long-term disease control. [Table: see text]
The impact of race, age, and sex in follicular lymphoma (FL): A comprehensive SEER analysis in the pre- and post-rituximab (R) eras.
Authors: Nabhan Chadi , Aschebrook-Kilfoy Briseis , Chiu Brian C-H , Kruczek Kimberly R. , Clemenzi-allen Angelo , Patel Anand , Smith Sonali M. , Evens Andrew M. 
Published: March 2020

8072 Background: While racial disparity has been well documented in a number of cancers, the impact of race in FL outcomes is not well defined. Further, the importance of gender in FL has not been fully explored. Methods: We examined population-based FL overall survival (OS) data from SEER 13 (1993-2008) regarding race, sex, age, and socioeconomic status (SES) over two consecutive 8-year (yr) periods: Era 1 (1993-2000, n=7,409) and Era 2 (2001–2008, n=9,083). Results: We identified16,492 FL patients (pts) (white (W): n=13,441; Hispanic (H): n=1,417; Asian/Pacific Islander (A/PI): n=887; and Black (B): n=747). Median ages at diagnosis differed significantly according to: (in yrs, W: 62.1, H: 57.3, A/PI: 60.5, B: 56.6; P<0.01 for each race vs. W). For all pts, OS was superior in Era 2 vs. Era 1 (5-yr OS: 77% vs. 68%, respectively, P<0.0001). Further, OS was significantly improved for all age groups (<50, 50-59, 60-69, and 70-79 yrs) as well as for males (P=0.0019) and females (P<0.0001) across eras. Interestingly, females had superior OS compared with males in Era 1 (P=0.004), but not in Era 2 (P=0.83). We subsequently compared OS within and across races (Table). All races, except A/PI, had improved 5-yr OS rates (age adjusted) from Era 1 to Era 2 (W: <0.001, H: 0.049, A/PI: 0.15, B: 0.003). Notably, A/PIs had the highest OS in Era 1, while H had the poorest OS in Era 2. These differences were more evident in males compared with females within each race. Finally, pts with higher SES had better OS in both eras, although OS was improved across eras for lower and higher SES populations. Conclusions: Collectively, we identified improved OS across eras, which was apparent for all ages, both sexes, and all races. We did not find superior outcome for females in the modern era as has been recently noted. However, several racial disparities persist, including inferior OS for H and superior OS A/PIs in the contemporary era. The disproportionate improvement in outcomes for some, but not all races, warrants continued study of racial disparities in FL. [Table: see text]