bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial therapeutic strategy in follicular lymphoma (FL): An analysis from the National LymphoCare Study (NLCS)
Authors: Friedberg J. W. , Huang J. , Dillon H. , Farber C. , Feliciano S. , Hainsworth J. , Link B. , Steis R. , Vose J. , Zelenetz A. 
Published: March 2020

7527 Background: Initial treatment strategies in FL include observation (obs), rituximab (R), chemotherapy ± R, and XRT. A recent study suggests initial therapy may impact FL survival (JCO 23:8447). NLCS is the first prospective observational study in the US designed to assess FL presentation, prognosis, treatment, and clinical outcomes. We describe initial therapeutic strategy in NLCS FL pts. Methods: FL pts diagnosed within 6 months with no prior lymphomas were recruited in this ongoing study. Data collected includes histology, stage, therapy, response, relapse and death. There is no specified treatment regimen. Results: From 3/04 to 11/05 1493 pts enrolled at 237 sites in the United States. Demographics have been initially reported at ASH 2005 (Blood 106:293a) and are comparable to SEER. Initial therapeutic strategy was: obs, 19%; R-monotherapy, 13%; chemo+R, 51%; XRT, 5%; chemo only, 4%. Chemo+R regimens were: R-CHOP, 59%; R-CVP, 19%; R-fludarabine based,11%; other, 11%. Choice to initiate therapy was associated with FLIPI, stage, and grade (p < 0.0001). Significant regional differences (p < 0.0001) were noted: obs was used in 13% of pts in Southeast and 31% in Northeast (NE); fludarabine-based R-chemo was used in 18% of pts in Southwest and only 3% in NE. Academic sites were more likely than community sites to treat pts on clinical trials (12% vs 4%). In pts treated with R or chemo+R, a higher FLIPI was not associated with decision to utilize chemotherapy. 26% of initially observed pts have switched to active therapy after a median of 2.8 months on obs since diagnosis; this was associated with baseline grade (III>II>I), but not stage or FLIPI. Conclusions: Diverse regimens are used for initial management of FL in the United States. Few pts are treated on clinical trials. Significant differences among regions and between center types suggest physician preference may drive initial therapy. Studies such as NLCS are needed to better understand the impact of initial therapy on short- and long-term outcomes. [Table: see text]
Serum levels and pharmacokinetic of rituximab in Bi-weekly R-CHOP in elderly patients with DLBCL treated in the RICOVER-60 trial:
Authors: Reiser M. , Wenger M. , Nickenig C. , Peter N. , Metzner B. , Pfreundschuh M. 
Published: March 2020

7537 Background: The combination of Rituximab (R) and CHOP is considered the standard of treatment for DLBCL in elderly patients (pts) but there is hardly any data on the pharmacokinetic of Rituximab in aggressive lymphoma pts. The RICOVER-60 trial using Rituximab + bi-weekly CHOP-14 resulted in improved TTF in 828 elderly DLBCL pts (Blood 106:9a, 2005). Objective: To study serum levels and pharmacokinetic properties of Rituximab when combined with CHOP-14 in elderly DLBCL pts. Methods: Blood samples of 20 pts were taken before and after Rituximab infusion at each chemotherapy cycle. Additional samples were taken after the end of treatment and at the following time points: after 1 week, 1 month, 2 months, 3 months, 6 months and 9 months, respectively. Peak serum samples were taken within a maximum of 30 min, all samples were centrifuged at 1000 g for 10 min (room temperature) and stored at −20 degrees C. Batch samples were shipped to Xendo Laboratories, Groningen, The Netherlands, and analysed. Results: Samples from 20 pts were evaluable for this analysis with 16/20 pts having completed all 8 cycles of treatment, yet. The median (range) of serum Rituximab levels (μg/ml) before each cycle were: #1 0 (0–0); #2 39 (13–62); #3 74 (47–109); #4 95 (40–136); #5 111 (55–157); #6 114 (12–518); #7 125 (72–207);#8 116 (75–304). After therapy median (range) of serum Rituximab levels were: 163 (67–248) at 1 week; 101 (44–163) at 1 month; 55 (1–123) at 2 months; 34 (1–577) at 3 months; 5 (0–103) at 6 months; 1 (0–128) at 9 months. At 9 months samples from 7 pts were evaluable with detectable serum Rituximab levels in 4/7 pts. Conclusion: In the dose dense regimen R+CHOP-14 Rituximab levels increased after each subsequent cycle for the first 4 cycles. During cycle 5- 8 the serum Rituximab levels reached a plateau and decreased constantly after the end of treatment with detectable levels even after 9 months. Based on this data the German High Grade NHL Study Group (DSHNHL) further investigates a densification of Rituximab in the first cycles in order to improve treatment outcome. A final analysis of all 20 pts and a pharmacokinetic model of Rituximab distribution and elimination phase will be presented at the meeting. [Table: see text]
Clarithromycin, lenalidomide and dexamethasone combination therapy as primary treatment of multiple myeloma
Authors: Niesvizky R. , Jayabalan D. S. , Furst J. R. , Cho H. J. , Pearse R. N. , Zafar F. , Lent R. W. , Tepler J. , Schuster M. W. , Leonard J. P. , Coleman M. 
Published: March 2020

7545 Background: Lenalidomide (Revlamid [R]) is the leading clinical compound in a new group of drugs called IMiDs. Our group demonstrated that clarithromycin (Biaxin [Bi]) augments tumor mass reduction and improves responses in patients (pts) receiving low-dose thalidomide and/or dexamethasone (D). We report the results of the combination of Bi plus R plus D (BiRD) in newly diagnosed MM. Methods: A phase II trial designed to accrue 50 pts. A 2-stage design rejects a CR rate of < 10% (alt >30%). Between Nov. 2004 and Jan. 2006, 46 pts have been accrued of which 40 pts are eligible for evaluation. R is given po at 25 mg daily on days 1–21 of a 28-day cycle. D is given po at 40 mg once weekly. Bi is given po at 500 mg bid. Pts receive low dose aspirin (ASA)(81mg) qd as thrombosis (TE) prophylaxis. Responses are defined according to modified EBMTR criteria. Analysis is by intent-to-treat. Patient Selection: Median age: 62.5 years (36–80), Male/Female 25/15, Hgb: 10.6 g/dL (7.2–15.1), Plt 234 k/uL (51–526), β2m: 3 mg/L (0.8–12.8), CRP: 0.6 mg/dL (0.12–14.2), creat: 1.1 mg/dL (0.6–3.1), albumin 3.5 g/dL (2.3–4.9). SD stage IIIa: 48%, stage IIIb: 10% and IIa: 42%. ISS stage I: 50%, stage II: 25% and stage III: 25%. Cytogenetics and FISH: trisomy 11 (10 pts), tetrasomy 11 (3 pts), del13q14 (14 pts), t (4,14) (1pt), t (11,14) (3 pts). Results: Of the 40 evaluable pts, 38 (95%) have achieved an objective response (>PR) within 3–4 months of Rx with the remaining pts continuing to respond. Seventeen pts (43%) had a >90% reduction of the initial paraprotein. Nearly one third of pts have achieved either a CR (10/40) or a nCR (2/40-continuing on Rx). CR has been confirmed in all pts by normalization of free light chain levels and ratio. The remaining 26 pts (65%) achieved a PR. Of those pts who achieved a PR, 5/26 pts (19%) had >90% reduction in the initial paraprotein. Nineteen pts have experienced grade ≥3 adverse events. Heme toxicities: anemia (11%), neutropenia (9%) and thrombocytopenia (9%). Non-heme toxicities (NHT) include TE in 7 patients (15%) 2 of them fatal. Four of the TE events were while off ASA. Other NHT include myopathy (6%), GI (4%), and mood (4%). Conclusions: BiRD therapy is a safe and highly effective primary therapy for symptomatic, treatment-naïve MM. [Table: see text]
Salvage chemotherapy with rituximab DHAP (RDHAP) for relapsed non-hodgkin lymphoma (NHL): A phase II trial in the North Central Cancer Treatment Group
Authors: Witzig T. E. , Geyer S. M. , Kurtin P. J. , Colgan J. P. , Inwards D. J. , Micallef I. N. , Michalak J. C. , Salim M. , Nikcevich D. A. , Dakhil S. R. , Fitch T. R. 
Published: March 2020

7574 Background: Patients (pts) with relapsed aggressive NHL are usually treated with intensive platinum-based chemotherapy regimens prior to stem cell transplant (SCT). This study was designed to learn the toxicity and efficacy of adding 4 doses of rituximab to the standard DHAP salvage chemotherapy regimen. Methods: Eligible pts had biopsy-proven relapsed CD20+ NHL and were eligible for platinum-based chemotherapy. Pts were treated with rituximab 375 mg/m2 d1,8,15, and 22 as well as cis-platinum 100 mg/m2 d3, cytosine arabinoside 2 g/m2 IV q 12 hours x two doses d4, dexamethasone 40 mg PO/IV d3–6, and G-CSF d5–14. Pts were restaged after 1 and 2 cycles; responding pts could proceed to SCT or further cycles of DHAP at MD discretion. There was no provision for rituximab maintenance. The goal was to achieve an overall response rate (ORR) of ≥ 75%. Results: Fifty-eight pts were enrolled between 10/29/00 and 6/20/03. The median age was 63 years (range, 43–83). One pt was ineligible because the tumor was CD20-. All 57 eligible pts completed one cycle; 48 pts completed 2 cycles. The ORR was 70% (40/57) with 16 (28%) CR/CRu and 24 (42%) PR. For all 57 pts, the median TTP was 13.1 months (mos) (95% CI: 7.3–18.2) and the median OS 30.5 mos (95% CI: 17.8–52.5). Seventeen pts (30%) proceeded to SCT. The median duration of response (DR), time to progression (TTP) and overall survival (OS) for the SCT pts were 41.6, 42.3, and 43.6 mos, respectively. The median DR, TTP, and OS for the 25 pts who responded to RDHAP but did not proceed to SCT were 12.4, 13.1, and 38.8 mos, respectively. The incidence of grade 3 and 4 thrombocytopenia was 53% and 39%, respectively. The incidence of grade 3 and 4 neutropenia was 11% and 68%, respectively. Six pts (11%) had nephrotoxicity–five grade 3 and two grade 4 (one pt had both) and one pt required dialysis. Conclusions: The addition of rituximab to standard DHAP is safe with similar toxicity profile to DHAP alone. Despite a high ORR, the CR rate and the % pts proceeding to SCT in this cooperative group setting remain low. New agents are needed that can be added to these regimens to increase the effectiveness and reduce toxicity to allow more pts to proceed to SCT. No significant financial relationships to disclose.
A phase I trial of PS-341 and fludarabine for relapsed and refractory indolent non-Hodgkin’s lymphoma and chronic lymphocytic leukemia
Authors: Snell M. , Koc O. N. , Bahlis N. J. , Liu L. , Lazarus H. M. , Gerson S. L. , Laughlin M. J. , Jacobberger J. , Horvath N. , Remick S. , Cooper B. W. 
Published: March 2020

7580 Background: The safety and efficacy of PS-341 (bortezomib) as a single agent in relapsed and refractory hematologic malignancies has been well documented. Fludarabine is known to be active in indolent non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL). PS-341 may potentiate fludarabine activity by inhibiting DNA repair and inducing apoptosis in Bcl-2 over-expressing cells. The safety of this combination was evaluated in an ongoing phase I study. An additional dose level including rituxumab has been added to potentially improve efficacy without significant additional toxicity. Methods: Dose levels were as outlined in the table below. Each cycle was 21 days. Results: To date, 13 patients have received at least one cycle of treatment and are evaluable for toxicity. Diagnoses of patients included CLL, Waldenstom’s macroglobulinemia and MALT, lymphoplasmacytoid, mantle cell and follicular lymphomas. Patients received a median of 3 prior treatments (range 1–6). DLT’s were not observed in the first 4 dose levels, however the first patient on dose level 5 experienced grade 4 neutropenia. Three patients had doses of PS-341 held due to toxicity (2 due to neuropathy and one leukopenia; doses were held during cycles 3, 4 and 2 respectively) and two required dose reductions for grade 2 neuropathy (on cycles 2 and 3). One CRu has been documented (follicular lymphoma), 1 PR (mantle cell) and 6 patients with SD for 1.5 to 3 months. One patient was taken off the study with disease progression after 1 cycle (CLL) and two discontinued treatment due to prolonged cytopenias (MCL) and patient decision. The most 2 most recent patients are not yet evaluable for response. Conclusions: Combination PS-341 and fludarabine appears to be well-tolerated and active in relapsed and refractory NHL and CLL. Enrollment and follow-up of patients on level 5 (addition of rituxan) continues. Initiation of a phase II study of this regimen is anticipated shortly. [Table: see text] No significant financial relationships to disclose.
High expression of nucleoside transporter hENT1 predicts a worse event-free survival in relapsed/refractory Hodgkin lymphoma patients treated with gemcitabine, vinorelbine, and liposomal doxorubicin—A CALGB 59804 correlative study
Authors: Lai R. , Hsi E. D. , Mackey J. , Jung S. , Johnson J. L. , Cook J. R. , Jones D. , Said J. W. , Cheson B. D. , Bartlett N. L. 
Published: March 2020

7581 Background: CALGB 59804 was a phase I/II trial of gemcitabine, vinorelbine, and liposomal doxorubicin (GVD) for pts with relapsed Hodgkin lymphoma (HL). Overall response rate (RR) was 70% (manuscript in review). Plasma membrane nucleoside transporters such as hENT1 are important in transporting nucleoside analogs into cells to exert their pharmacologic effects. We hypothesized high hENT1 expression would predict better RR and outcome in pts treated with GVD. Methods: 58 of 91 pts enrolled in CALGB 59804 had sufficient tissue for study; 31 relapse biopsies and 27 initial diagnosis biopsies. Expression of hENT1 was evaluated by immunohistochemistry in formalin fixed tissue and scored independently by two hematopathologists (RL and EH) blinded to the clinical outcomes. Positivity for hENT1 was defined as >25% of Reed-Sternberg (RS) cells expressing hENT1. Expression was correlated with clinical factors, including IPS at relapse, as well as the overall (OS) and event-free survival (EFS). Results: Expression of hENT1 in RS cells was heterogeneous among cases. 28/58 cases (48%) were hENT1-positive. hENT1-expression was not associated with age, gender, stage, IPS (≤2 or >2), or maximum toxicity grade (≤2 or >2). Compared to hENT1-negative pts, hENT1-positive pts were less likely to have complete or partial response (19/30, 63% versus 22/28, 76%, P=0.20, chi square). hENT1 expression was not significantly associated with OS (P=0.18). Univariate log-rank analysis showed hENT1 positivity and IPS >2 correlated significantly with a lower EFS (P=0.05, and P=0.03, respectively). Multivariate Cox regression analysis confirmed that IPS >2 and hENT1 positivity were independent predictors of EFS (Hazard ratio 2.16, 95%CI 1.08–4.35, P=0.03; and Hazard ratio 2.10, 95% CI 1.06–4.19, P=0.03, respectively). P-values are two-sided. Conclusions: Contrary to our hypothesis, there is an inverse relationship between EFS and hENT1 expression in relapsed HL pts treated with GVD. High expression of hENT1 did not identify gemcitabine-sensitive disease, but may identify a biologically aggressive and/or treatment refractory subtype of HL. No significant financial relationships to disclose.
Novel model to evaluate changes in gene expression profile of myeloma cells in vivo following interaction with human BM microenvironment
Authors: Neri E. P. , Tassone P. , Shammas M. , Tai Y. , Blotta S. , Prabhala R. , Catley L. , Tagliaferri P. , Venuta S. , Anderson K. C. , Munshi N. C. 
Published: March 2020

7613 Background: Interaction between multiple myeloma (MM) cells and the bone marrow (BM) microenvironment plays a critical role in promoting MM cell growth, survival, migration and development of drug resistance. This interaction within the bone marrow milieu is unique and its understanding is important in evaluating effects of novel agents in vitro and in vivo. We here describe a novel murine model that allows us to study the in vivo expression changes in MM cells within the human BM milieu. Methods: In our model, BM stromal and IL-6-dependent human MM cell line, INA-6, tranduced with green fluorescent protein (INA-6 GFP+) was injected in human fetal bone chip implanted into SCID mice. At different time points the bone chip was retrieved, cells flushed out and GFP+ MM cells were separated by flow cytometry or purified by CD138 MACS microbeads. Similar isolation process was used on INA-6 GFP+ cells cultured in vitro and used as control. Total RNA was isolated from these cells and gene expression profile analyzed using the HG-U133 array chip (Affymetrix). Results: We report that interaction between INA-6 cells and the BM microenvironment in vivo induced significant changes in expression profile; specifically, we observed up-regulation of genes implicated in cell growth; DNA transcription; chromosome structure; cell-cell signaling and adhesion. We also observed down-regulation of genes involved in apoptosis and cell death. To determine which biological pathways are modulated by interaction between MM cells and human stroma, all genes were subjected to Ingenuity Pathway Analysis. Our results indicate that the most relevant pathways modulated by the interaction between MM cells with BMSCs are involved in cell-cycle regulation, apoptosis and integrin signaling, as well as with IL-6, IGF1 and PI3K/AKT, p38-MAPK and ERK/MAPK-mediated pathways. These results are consistent with previously observed in vitro cell signaling studies. Conclusions: Taken together these results highlight the ability of BM microenvironment to modulate the gene expression profile of the MM cells in vivo. This model now provides us with an opportunity to study in vivo effects of novel agents on MM cells expression profile, to pre-clinically characterize their activity. No significant financial relationships to disclose.
Autologous stem cell transplant for primary CNS lymphoma results in prolonged progression free and overall survival
Authors: Johnston P. B. , O’Neill B. P. , Ansell S. M. , Inwards D. J. , Porrata L. F. , Micallef I. N. 
Published: March 2020

7623 Background: Survival for patient with primary CNS lymphoma (PCNSL), in general, is poor with patients requiring frequent chemotherapy treatments or receiving whole-brain radiation therapy, which can potentially result in significant neurologic decline and dementia. Because of the improved survival of high risk patients with aggressive lymphoma undergoing autologous stem cell transplant (ASCT), we began ASCT for patients with PCNSL in first or later remission with chemotherapy sensitive disease. We now report on outcomes of patients who have had at least 1 year follow up post ASCT. Methods: Between June, 2000 and September, 2004, 11 patients underwent ASCT for PCNSL. The medical records of consenting patients were abstracted for the following information. Median age at transplant was 47 years old (range 30–67). Median number of prior treatments 1 (range 1–3). Median time from diagnosis to transplant was 7.5 months (range 2.9 to 75.8). Median International Extranodal Working Study Group Prognostic Score: 2 (range 0–3). Disease status at transplant: First CR 5 patients, later CR or PR 6 patients. Results: Eleven patients underwent ASCT for PCNSL and have a minimum of 1 year follow-up. All patients received BEAM conditioning. Median follow up was 28.3 months. Four patients have relapsed at a median of 200 days (range 40–523). Of the patients who relapsed, one has died of disease progression and the remaining three are alive after additional therapy. Median overall survival and progression free survival from transplant have not been reached. Two year overall and event free survival are 89% and 61%, respectively. Conclusions: Although limited by patient selection and retrospective biases, this review suggests that ASCT for PCNSL demonstrates improved overall survival when compared to historical controls with similar PCNSL Prognostic Scores (2 year survival for patients from diagnosis with PS 2–3 was 48% in a prior published study). ASCT in first remission in patients with PCNSL appears promising and may limit the need for additional therapy which can be myelosuppressive or result in neurologic decline. No significant financial relationships to disclose.
Genomewide single nucleotide polymorphism microarray mapping for prediction of outcome of neuroblastoma patients
Authors: Hiyama E. , Yamaoka H. , Kamimatsuse A. , Onitake M. , Sueda T. , Nishiyama M. , Hiyama K. 
Published: March 2020

9010 Background: Neuroblastoma is a biologically and genetically heterogeneous tumor and demonstrates favorable or unfavorable outcomes. However, the number of subgroups in neuroblastoma and natural history of each subgroup remain unclear. In Japan, nation-wide neuroblasotma mass-screening (MS) project had been performed on 6-month-old babies for 20 years that might have detected almost all neuroblastomas including regressing/ maturing tumors developed in this period. We surveyed more than 3,600 neuroblasotma cases including approximately 2,000 MS detecting cases. In this study, we examined genetic alterations in the representative cases using genome-wide SNP array and compared with the clinical courses. Methods: Genomic DNA was extracted from 198 neuroblastoma samples. SNP array (Affimetrix GeneChip Human mapping Array100K) was used to determine genome-wide aberrations. Chromosome aberrations were confirmed by BAC array and FISH examination. Expression profiles of these tumors were also examined using whole genome microarray (Codelink and Affimetrix Array U133 plus2). Results: SNP arrays could frequently identify chromosomal aberrations and allelic imbalances including 1p and 11q loss and MYCN amplification in unfavorable tumors. Then, we broadly classified the chromosome aberrations in neuroblastoma into four types: whole gain/loss type, partial gain/loss type, MYCN amplified type, and silent type with no large alterations. Almost all tumors with whole gain/loss type showed favorable prognosis, while MYCN amplified type and partial gain/loss type showed unfavorable outcome. In 32 tumors with silent type, 18 unfavorable tumors had small deletions and/or gains in 1p, 2p, 3p, 11q, and/or 17q but the remaining 16 favorable cases did not. The expression analysis of the unfavorable tumors showed high expression of several genes (DDX1, NAG, NME1, MAC30) in these loci. Conclusions: Genome-wide genetic analysis classified neuroblastoma into four types, which are useful to predict the outcome of patients. In the silent type, unfavorable tumors revealed several genes to predict the outcome of the patients. These data provided important candidates of indicators for risk assessment and of therapeutic targets for unfavorable neuroblastoma. No significant financial relationships to disclose.