bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between the presence of lectin binding sites of pulmonary adenocarcinoma cells and their metastatic cells
Authors: Thöm I. , Schult-Kronefeld O. , Burkholder I. , Görn M. , Andritzky B. , Kugler C. , Edler L. , Schumacher U. , Laack E. , Bokemeyer C. 
Published: March 2020

7212 Background: During tumor progression to metastasis, the aberrant glycosylation of tumor cell membrane glycoconjugates plays a key role. These changes can be detected histochemically by the use of lectins. The aim of the present investigation was to analyze a possible association between the presence of lectin binding sites of pulmonary adenocarcinoma cells and their lymph node and hematogenous metastatic cells. Methods: For this purpose, the expression of HPA-, PHA-L- and UEA-I binding sites were assessed in primary tumors, lymph node metastases and hematogenous metastases of 96 patients with metastatic adenocarcinomas of the lung who underwent surgery between 1999 and 2002. Results: We found a significant positive correlation between the binding of the lectins HPA (p = 0.002), PHA-L (p < 0.00001) and UEA-I (p < 0.00001) to the cells of the primary tumor and to its lymph node metastases. There was positive correlation between the binding of HPA to the cells of the primary tumor and the hematogenous metastases as well. Conclusion: We are the first to demonstrate a positive correlation between the binding of the lectins HPA, PHA-L and UEA-I to the cells of the primary tumor and to its lymph node metastases. Expression of HPA bindig sites is also preserved in the hematogenous metastases in metastatic disease. Our results support the hypothesis that the aberrant glycolsylation of tumor cell membrane glycoconjugates is involved in the metastatic spread of tumors. No significant financial relationships to disclose.
Prognostic significance of clinical features and Akt activation in the survival of patients with bronchioloalveolar carcinoma (BAC)
Authors: Ballas M. S. , Tsurutani J. , Steinberg S. , Robertson M. , Egilsson V. , Dennis P. A. 
Published: March 2020

7217 Background: Lung cancer is the leading cause of cancer related mortality in the world. BAC is a subset of NSCLC that has recently gained attention because of enhanced efficacy of epidermal growth factor receptor (EGFR) inhibitors in this population. Prognostic features for BAC have not been well defined. Because activation of Akt is a poor prognostic factor for other types of NSCLC, and because changes in Akt may predict outcome for EGFR inhibitors, we assessed the prognostic significance of clinical features and Akt activation in patients with BAC. Methods: 46 cases of BAC were classified according to WHO 2001 criteria. Akt activation was assessed using immunohistochemistry. Associations between ordered Akt levels and other dichotomous parameters were evaluated using an exact Cochran-Armitage test for trend. Survival was analyzed by the Kaplan-Meier method, and hazard ratios (HR) were determined based on Cox proportional hazard models. Results: Tissues from 45 patients were analyzed. Age and histology (mucinous vs. non-mucinous) were not associated with survival. Akt activation was observed in 63% of cases, but was not associated with differences in survival. Complete clinical data (except smoking) were available for 43 patients, and smoking history was available for 31 patients (8 never-smokers, 23 smokers). Cox model analysis revealed that male gender (HR 2.24, 95% CI 1.07–4.71, p = 0.032) and advanced stage (III or IV) (HR 2.17, 95% CI 1.004–4.71, p = 0.049) were associated with a worse prognosis. A model limited only to the 31 patients with smoking data demonstrated that smoking alone (HR 6.89, 95% CI 1.49–31.88, p = 0.013) was associated with a worse prognosis. Conclusions: These studies identify gender, stage, and especially smoking status as potentially important prognostic features for BAC. Akt was not prognostic. Given that the recent NSCLC clinical trials with erlotinib and gefitinib that showed varying survival benefit did not stratify by smoking status and BAC, it is possible that these characteristics could have affected the clinical outcomes. Investigators studying EGFR inhibitors should consider stratifying by smoking status and BAC to determine if there are subsets of patients who could benefit most from these therapies. No significant financial relationships to disclose.
A phase II, multicenter study of bendamustine HCl plus rituximab in relapsed indolent B-cell and mantle-cell non-Hodgkin’s lymphoma (NHL)
Authors: Williams M. E. , Cohen P. , Tulpule A. , Van der Jagt R. H. , Herst J. A. , Bessudo A. , Lemieux B. , Schwartzberg L. S. , Oliver J. W. , Robinson K. S. 
Published: March 2020

7528 Background: Bendamustine HCl, a novel alkylating hybrid agent, has single-agent activity in multiple hematologic and solid tumors. In vitro data have demonstrated the multifunctional mechanisms of bendamustine by which cell death occurs via both apoptosis and mitotic catastrophe. Bendamustine has shown activity in NHL cell lines that are refractory to conventional alkylator chemotherapies. The combination of bendamustine and rituximab has shown a synergistic effect on NHL cells. The efficacy and safety of bendamustine in combination with rituximab in patients with relapsed NHL were evaluated. Methods: This phase II, multicenter study enrolled adult patients with relapsed, indolent, rituximab-sensitive B-cell or mantle-cell NHL. Patients received rituximab 375 mg/m2 IV on day 1 and bendamustine 90 mg/m2 IV on days 2 and 3 of a 28-day cycle for 4 to 6 cycles. An additional dose of rituximab 375 mg/m2 IV was given 1 week prior to the first cycle of bendamustine and 4 weeks after the last cycle. Results: The intent-to-treat population included 67 patients (57% males; median age, 60 years) with indolent NHL (81%) or mantle-cell NHL (16%) (data not available [3%]). A total of 81% of patients had stage III/IV disease. Patients had relapsed from a median of 1 prior therapy; 37% had prior treatment with rituximab. In the 57 evaluable patients, the overall objective response rate (ORR) was 87% (complete response [CR], 33%). The ORR for the 9 evaluable mantle-cell NHL patients was 89% (CR, 33%). For all patients, the median duration of response and progression-free survival had not been reached after a median follow-up of 3.7 months (range, 0–14.2 months). This therapy was well tolerated. Most commonly reported nonhematologic toxicities were grade 1/2 gastrointestinal events, with nausea being the greatest (38%). The primary grade 3/4 hematologic toxicity was neutropenia (29%), with 1 event of sepsis. Conclusions: Bendamustine in combination with rituximab was well tolerated and produced high response rates in patients with relapsed indolent and mantle-cell NHL. These results suggest bendamustine in combination with rituximab provides a potential benefit over single-agent rituximab therapy. [Table: see text]
A humanized antibody against CD40 (SGN-40) is well tolerated and active in non-Hodgkin’s lymphoma (NHL): Results of a phase I study
Authors: Forero-Torres A. , Furman R. R. , Rosenblatt J. D. , Younes A. , Harrop K. , Drachman J. G. , Advani R. 
Published: March 2020

7534 Background: CD40 is a member of the TNF receptor family and is widely expressed on hematologic malignancies of B-cell origin. SGN-40 is a humanized antibody against CD40 with effector cell function and mild agonistic activity. Preclinical toxicity studies and efficacy data supported initiation of a multi-institutional phase I study to test the safety, pharmacokinetics, immunogenicity, and efficacy of SGN-40 in patients with relapsed NHL. Methods: Cohorts of 3–6 pts were treated weekly with a maximum dose of 2, 3, or 4 mg/kg/wk SGN-40. A dose escalation schedule is used such that patients receive 1 mg/kg on D1 and D4, 2 mg/kg on D8, and higher doses on weeks 3–5. Responding patients may receive a second cycle. Further dose escalation up to 8 mg/kg is planned. Results: 16 pts have been treated with multiple histologic subtypes: follicular (1), marginal zone (MZL; 1), mantle cell (4), and diffuse large B-cell (DLBCL; 10). One patient (2 mg/kg) developed a reversible Grade 3 unilateral conjunctivitis and ipsilateral loss of visual acuity. No other dose limiting toxicity has been observed up to 4 mg/kg. Preliminary pharmacokinetic data suggest that the antibody has a relatively short half-life, perhaps reflecting a route of elimination or binding that is not saturated at current doses. Two partial responses have been observed at 3 mg/kg (1 MZL, 1 DLBCL) and one partial response has been observed at 4 mg/kg dose (DLBCL relapsed after autologous stem cell transplant with small volume tumor). Conclusions: Using an intra-patient dose escalation schedule, SGN-40 has been well-tolerated at doses up to 4 mg/kg/wk. Further dose-escalation is ongoing to determine the maximum tolerated dose. Three objective responses have been seen, including two in patients with extensively treated aggressive disease. Correlative studies are underway measuring soluble CD40, cytokine release, effect of FcR polymorphisms, and SGN-40-induced immunogenicity. Given the favorable tolerability and activity, phase II studies in NHL are planned. [Table: see text]
CHOP/CHOEP-14 followed by consolidation with alemtuzumab in untreated aggressive T-cell lymphomas (DSHNHL 2003–1): Feasibility and toxicity of a phase II trial of the German High Grade Non-Hodgkin’s Lymphoma Group DSHNHL
Authors: Trumper L. H. , Hohloch K. , Kloess M. , Dührsen U. , Eimermacher H. , Haas A. , Aldaoud A. , Loeffler M. , Schmitz N. , Pfreundschuh M. , Binder C. 
Published: March 2020

7538 Background: The clinical course of peripheral T-cell lymphomas (PTCL) is unfavourable. Treatment protocols developed for aggressive B-NHL are employed, with significantly worse outcomes. The MoAb alemtuzumab (CAM) has shown promising activity in T-NHL, although its use may be complicated by severe infections. Methods: In 2003, the DSHNHL group initiated a prospective multicenter phase II trial for previously untreated PTCL. Six cycles of either CHOEP-14 (< 60 y) or CHOP-14 (> 60 y) with G-CSF support are followed by a short consolidation course with CAM, when either a CR or a good PR has been achieved. Inclusion criteria: PTCL-NOS, AILD, intestinal T-NHL, anaplastic large cell T-NHL (ALK negative); age 18–70 y; all IPIs; ECOG PS 0–3. The primary endpoint is feasibility, measured by occurrence SAE and protocol adherence. Secondary endpoints are remission rate, TTF, OS, DFS, tumor control and TRM. CAM is given at a total dose of 133 mg over 4 weeks. Prophylaxis against PCP and herpes infections is mandatory during CAM therapy and is continued until CD 4 cells are > 200/μl. CMV-positive patients are monitored weekly. Results: 35 (of the planned 37) pts have been enrolled, 31 are evaluable. 5/31 pts are still undergoing chemotherapy. 7/31 pts had progressive disease or NC under/after chemotherapy and did not receive CAM. 18 of the 19 pts who achieved a CR/PR (15/4) received CAM. 12 of the CAM pts are in continuous CR, 7 had progressive disease or relapsed. There was no treatment-related death. Of 7 registered SAEs, 3 were related to chemotherapy, 4 to CAM (1 fungal pneumonia, 2 CMV pneumonias, 1 bacterial sepsis after dental procedure). Other CAM side effects were: Herpes Zoster (1), CMV-reactivation (1), grade III-IV neutropenias (2). All pts recovered with appropriate treatment. Conclusion: Preliminary analysis demonstrates that the combination of CHO/E/P-14 followed by a short course of CAM consolidation therapy is feasible without TRM. The adverse effects related to infections can be severe but manageable upon careful monitoring and close follow-up. The phase II trial will close in 4/2006, to be followed by a randomized phase III trial of A-CHOP-14 vs CHOP-14. No significant financial relationships to disclose.
Adenovirus-interferon γ (TG1042) demonstrates good tolerance and efficacy in relapsing primary cutaneous lymphoma (PCL): Final results of a phase I/II multicentric trial
Authors: Urosevic M. , Gellrich S. , Dreno B. , Schiller M. , Dereure O. , Baudard M. , Bagot M. , Khammari A. , Bleuzen P. , Dummer R. 
Published: March 2020

7539 Background: Interferons (IFNs), which can offset the Th2 dominance associated with PCL have been successfully used to treat these PCL. Intratumoral (i.t.) injection of TG1042 (a non-replicating recombinant adenovirus with a human IFNγ cDNA insert) induces high local production of IFNγ without severe toxicity associated with systemic delivery. Methods: We undertook a phase I/II multicentric trial of repeated, i.t. injections of TG1042 in patients with advanced primary T cell (CTCL) or B cell (CBCL) CL. One to 3 lesions were injected on day 1, 8, and 15 (a 4-week cycle) and thereafter up to 12 cycles. Immunohistochemistry and quantitative PCR were performed on injected lesions biopsied at baseline and after the 1st cycle. In the phase I, 18 patients were enrolled in 3 successive cohorts at the doses of 3 × 109 viral particles (vp) (n = 3), 3 × 1010 vp (n = 3) and 3 × 1011 vp (n = 12). In the phase II, 18 evaluable patients were planned to be treated at 3 × 1011 vp. Results: To date, enrollment is complete, 39 patients (32 CTCL and 7 CBCL) have been included, 9 of them are still on treatment. Patients received a median of 4 lines of prior therapy. 11 patients were at stage Ib and 16 patients at higher stage. Altogether, 245 injections of TG1042 have been administered. Treatment was well tolerated with 8 grade 3 related adverse events. Injection site reaction and flu like syndrome are the most common adverse events. Histology demonstrates pronounced changes in infiltrate patterns with signs of vasculitis, increased numbers of eosinophils, neutrophils, CD8 and TIA-1+ve cells. CD4/CD8 ratio decreased in most tumors. Transgene-IFNγ mRNA was detected in injected lesions. Gene expression analysis of biopsies and PBMC shows up-regulation of IFNγ genes. Local clinical response has been observed in 17 (including 9 complete responses [CR]) out of 31 evaluable patients. 13 global responses (7 CR) out of 30 evaluable patients have been observed. All 5 evaluable CBCL responded (3 CR). Conclusions: These results demonstrate that TG1042 is well tolerated and presents a potential significant benefit for the treatment of both CTCL and CBCL. A phase II is planned in patients with CBCL to confirm those encouraging results. [Table: see text]
Prospective, randomized, multicentre clinical trial on the use of interferon a 2a plus PUVA versus PUVA monotherapy in patients with cutaneous T-cell lymphoma, stages I and II
Authors: Stadler R. , Kremer A. , Luger T. , Sterry W. 
Published: March 2020

7541 To further define the role of IFN in combination with PUVA we conducted this prospective, randomized, multicentre clinical trial, in cooperation with 26 departments of dermatology in Germany and Switzerland, comparing the efficacy and tolerability of the combination of IFN alfa plus PUVA versus PUVA alone. IFN alfa 2a was administered at 9 Mill units three times a week s.c. in the combination arm, photochemotherapy was applied after oral intake of 8-methoxypsoralen (0.6 mg/kg body weight) five times a week during the first weeks, three times a week from weeks 5 to 23, and twice a week from weeks 24 to 48, with escalating doses, beginning with 0.25J/cm2. Of 124 patients randomized in this trial stages I and II, 50 were evaluable in the PUVA arm and 43 in the IFN plus PUVA arm in total 93 patients. Overall 75% of all patients showed a complete remission, 79% in the combination arm and 72% in the PUVA arm. The primary response criteria of this randomized trial protocol as a rate of complete remissions was therefore statistically non significant. However, the total dose of meladinine to reach best response was significantly lower in the combination arm, in the IFN arm only 74% of the meladinine dose and 57% of the UVA dose was necessary to reach a complete remission in comparison to the PUVA arm. The follow-up period was defined was defined on time to progression and documentation maximal 12 months after best response. The medium follow-up duration is 101 weeks, the medium value 123.7 weeks. The Kaplan-Meyer graph analysis showed a significant difference towards the progression-free interval of the IFN PUVA arm (log-rank test; p = 0.0398, 2-sided, Wilcoxen test p = 0.0465). The results are based on 55 documented progressions of 93 patients. The medium progression-free time for the whole group is 63 weeks, for the PUVA arm 53 weeks, and in the combination arm 113 weeks. Based on these findings, we conclude that IFN alfa 2a plus oral photochemotherapy induces a high remission rate with less UVA dose compared to PUVA alone and doubles the progression-free time of CTCL, stages I and II. IFN and PUVA will be the first-line treatment in early CTCL of the EORTC treatment guidelines. No significant financial relationships to disclose.
Impact of prior autologous stem cell transplant (ASCT) in patients receiving bortezomib or dexamethasone for relapsed/refractory multiple myeloma in the APEX trial
Authors: Vogl D. T. , Stadtmauer E. A. , Richardson P. G. , Sonneveld P. , Schuster M. W. , Irwin D. , Facon T. , Harousseau J. M. , Boral A. , Anderson K. C. 
Published: March 2020

7546 Background: The phase 3 international APEX trial demonstrated significantly superior overall survival (OS), time to progression (TTP), and overall response rate (ORR: CR+PR, EBMT criteria) with bortezomib (VELCADE [Vc]) therapy for relapsed myeloma compared with dexamethasone (Dex). ASCT is a common component of initial therapy and may affect the outcome of salvage therapies. Methods: This analysis aimed to evaluate the impact of prior ASCT on the APEX results. TTP, OS, and ORR were analyzed by prior ASCT treatment. Results: Of 669 randomized patients, 451 (67%) had received prior ASCT (median follow-up in survivors was 21.9 months); in this group, Vc led to higher ORR compared with Dex (41% vs 18%, p < 0.001), higher CR rate (8% vs 0.5%, p < 0.001), and longer TTP and OS (see table), the latter despite crossover to Vc of >62% of patients originally assigned to Dex. A subset of 156 (23%) patients had ASCT as their only prior line of therapy (median follow-up in survivors was 20.0 months), with similar superiority of Vc compared with Dex in ORR (48% vs 29%, p = 0.004), CR rate (6% vs 2%, p > 0.05), and TTP. Among 218 (33%) patients with no prior ASCT (median follow-up in survivors was 21.7 months), Vc was also superior to Dex in ORR (32% vs 18%, p = 0.025), CR rate (4% vs 1%, p > 0.05), and TTP. Conclusions: Vc is consistently superior to Dex in ORR, CR rate, and TTP, regardless of prior ASCT status, and OS is superior in patients who had received prior ASCT. Vc is an effective therapy for myeloma relapsing after ASCT. NE = not estimable. [Table: see text] [Table: see text]
Polymorphisms in genes of folate metabolism and effects of high-dose methotrexate in patients with primary central nervous system lymphoma
Authors: Knop S. , Guenther M. , Loeffler J. , Meisner C. , Korfel A. , Weller M. , Hebart H. , Herrlinger U. 
Published: March 2020

7558 Background: The antifolate methotrexate (MTX) is the single most effective agent in primary central nervous system lymphoma (PCNSL) when given intravenously in high doses. MTX inhibits 5,10-methylentetrahydrofolate reductase (MTHFR) as well as thymidylate synthase (TYMS) in target cells what eventually results in decreased DNA synthesis. Intracellular uptake of folates is mediated by the reduced folate carrier (RFC). Two common MTHFR single nucleotide polymorphisms (SNPs) affect enzyme activity: 677 C→T and 1298A→C. A 28 base pair (bp) tandemly repeated sequence in the TYMS enhancer region (5’-UTR) containing either 2 or 3 repeats alters enzyme activity as does a 6 bp deletion (del) polymorphism in the 3’-UTR of TYMS. An RFC SNP (80G→A) is known to influence folate and MTX transport. We hypothesized that these polymorphisms may be directly linked to toxicity in PCNSL patients receiving high-dose MTX. Methods: Genomic DNA was prospectively collected from patients (pts) who received high-dose (HD) MTX 4 g/m2 every 2 weeks after enrolment onto the German multicenter G-PCNSL-SG1 trial. Genotyping of the two MTHFR and the RFC SNPs was performed by melting point analysis using the Light Cycler technology. Genotyping of the TYMS 28bp polymorphism was performed by conventional PCR followed by agarose gel electrophoresis. The TYMS 6bp del polymorphism was analyzed by PCR, restriction enzyme digest and agarose gel electrophoresis. Response, hematologic (Hb, WBC, ANC, platelets) as well as cumulative incidence of non-hematologic toxicity (renal, pulmonary, mucositis) were assessed prospectively. Results: 123 pts are evaluvable for clinical parameters. Relative risk of any °III/IV toxicity was 26-fold higher for pts with 677TT when compared to CT or CC genotype (p = 0.009). °III/IV non-hematologic toxicity for TT was 10-fold higher than with CT or CC (p = 0.02). Significant differences for hematologic values were restricted to WBC and ANC and found to be associated with RFC 80 GG vs. AG/AA (p = 0.047). Conclusions: Pharmacogenetic studies may identify PCNSL pts who are at risk for severe hematologic and non-hematologic toxicity when treated with HD-MTX. No significant financial relationships to disclose.
FDG PET for the routine follow-up in NHL: First prospective evaluation
Authors: Jerusalem G. , Silvestre R. , Beguin Y. , Hustinx R. , Fassotte M. , Fillet G. 
Published: March 2020

7569 Background: We have shown that FDG PET is able to detect preclinical relapses in patients with Hodgkin’s disease but the high rate of false-positivity (55%) was a problem (Jerusalem et al, Ann Oncol, 2003; 14 : 123–130). The aim of this study was to determine the accuracy of PET during follow-up after treatment in non-Hodgkin’s lymphoma (NHL). Methods: Patients were eligible if they had a positive baseline FDG PET and a negative end of treatment work-up including a negative PET study. They underwent FDG PET every 4–6 months until 3 years after diagnosis. Forty-five aggressive NHL (diffuse large B-cell lymphoma : 34, other : 11) and eighteen low grade NHL (follicular lymphoma : 16, other : 2) were recruited prospectively between 5/94 and 12/01. Results: A total of 197 FDG PET studies were realized. Six patients relapsed (aggressive NHL : 4, low grade NHL : 2) and 3 patients died (aggressive NHL : 2, pancreatic cancer : 1) during the time interval of the study protocol. Four asymptomatic relapses (aggressive NHL : 2, low grade NHL : 2) and one symptomatic relapse (aggressive NHL) was detected by FDG PET. Disease recurrence became symptomatic or clinically detectable a week, 3 months (both aggressive NHL), 12 and 17 months (both low grade NHL) after the first positive PET study. The latter had 4 positive FDG PET studies before biopsy-proven relapse. The time interval between the only false-negative PET and clinical relapse was 5 months in a patient with aggressive NHL. We observed for the whole study population a sensitivity of 89% (8/9), a specificity of 93% (174/188), a positive predictive value of 36% (8/22), a negative predictive value (NPV) of 99% (174/175) and an accuracy of 92% (182/197). In low grade NHL PET had a sensitivity of 100% (5/5), a specificity of 93% (50/54), a PPV of 56% (5/9), a NPV of 100% (50/50) and an accuracy of 93% (55/59). In aggressive NHL, PET had a sensitivity of 75% (3/4), a specificity of 93% (124/134), a PPV 23% (3/13), a NPV of 99% (124/125) and an accuracy of 92% (127/138). Conclusions: In aggressive NHL, routine follow-up by FDG PET is not very useful and we stopped it now in unselected aggressive NHL. In contrast, FDG PET can detect a relapse several months before the development of clinical symptoms in low grade NHL suggesting further evaluation of the role of PET in the routine follow-up of these patients. No significant financial relationships to disclose.