bluuebunny/crossref_metadata_2025_split huggingface dataset:
The inclusion of high-dose therapy and autologous stem cell transplantation (ASCT) in the treatment of follicular lymphoma (FL) is associated with prolonged overall survival (OS) from diagnosis
Authors: Sweetenham J. W. , Rybicki L. , Pohlman B. , Sobecks R. , Kalaycio M. , Dean R. , Andresen S. , Brown S. , Bolwell B. 
Published: March 2020

8061 Background: Recent studies have suggested that OS for patients (pts) with FL is improving compared with older reports in which median OS was typically 8 to 10 years. We analyzed outcomes for pts with FL undergoing ASCT at any time in the course of the disease to determine whether this contributes to improved OS. Unlike previously reported transplant series, we calculated OS from the date of diagnosis to determine the potential effect of ASCT on the overall course of the disease. Methods: Between 1/79 and 10/05, 188 pts with FL underwent ASCT at our center. Male/female = 103/85. Median age = 47yrs (20–73). Other pt characteristics are summarized in the table . The International Prognostic Index (IPI) was used since data for the FLIPI were only available for a minority of pts. All pts received chemotherapy-only conditioning regimens, most commonly with busulfan, cyclophosphamide and etoposide (82%). OS was calculated from the date of diagnosis, and survival comparisons were made using the logrank test. Results: 120 pts (64%) are alive at a median follow-up of 8.2 years (0.8–23.7 years). Median follow-up from date of transplant is 5.2 years (0.1–15.3 years). The median OS from the date of diagnosis is 15.2 years. IPI at diagnosis was predictive of OS (low-risk median not reached, low-intermediate = 18.3 yrs, high-intermediate = 4.9yrs) (p = <0.001). Status at transplant (CR/PR1 vs CR/PR2 vs CR/PR3 vs relapsed/refractory) had no effect on OS (p = 0.36). Conclusions: The use of ASCT as part of the overall treatment strategy for pts with FL is associated with prolonged OS and may in part be responsible for the reported improvement in survival for FL reported in recent years. Further prospective evaluation of the role of ASCT in the context of treatment regimens which include monoclonal antibodies is required. No significant financial relationships to disclose. [Table: see text]
Alemtuzumab plus CHOP as front-line chemotherapy for patients with peripheral T-cell lymphomas
Authors: Moon J. , Kim J. , Sohn S. , Yang D. , Lee J. , Kim H. , Shin H. , Chung J. , Lee W. , Joo Y. , Oh S. 
Published: March 2020

8069 Background: The present study was conducted to evaluate the safety and efficacy of alemtuzumab plus CHOP chemotherapy for patients with peripheral T-cell lymphomas (PTCLs). Methods: Twenty patients with newly diagnosed PTCLs were enrolled. The treatment consisted of classical CHOP plus alemtuzumab (10 mg/m2 i.v on day 1 and 20 mg/m2 i.v on day 2 in the first cycle, then 30 mg/m2 i.v on day 1 in the subsequent cycles) based on 3-week intervals. Results: Thirteen complete responses (65.0%) and 3 partial responses (15.0%) were confirmed, giving an overall response rate of 80.0 %. The estimated event-free survival at 1 year was 43.3%. The most severe hematologic adverse event was neutropenia, which occurred with a grade 4 intensity in 18 patients (90.0%). Plus, febrile neutropenia was observed in 11 patients (55.0%). Five patients (25%) experienced CMV (cytomegalovirus) reactivation, while 3 patients developed CMV diseases, such as pneumonitis or retinitis. There were 2 treatment-related deaths. Conclusions: The alemtuzumab plus CHOP chemotherapy seemed to produce active antitumor activity in terms of the complete response rates in patients with PTCLs. However, since high infectious and hematologic toxicities were observed, careful monitoring and early treatment to prevent treatment-related mortality are needed. No significant financial relationships to disclose.
Association of CD20 positivity (+) with event free survival (EFS) in children with post-transplant lymphoproliferative disease (PTLD) following solid organ transplantation (SOT)
Authors: Orjuela M. , Alobeid B. , Kott E. R. , Addonizio L. J. , Lobritto S. J. , Siebert A. L. , Morris E. , Garvin J. H. , Cairo M. S. 
Published: March 2020

8070 Background: The roles of CD20 and EBV as prognostic features for development and survival of pediatric PTLD after SOT are poorly understood. We previously demonstrated the safety and efficacy of cyclophosphamide, prednisone and rituximab (CPR) in CD20+ PTLD (Orjuela/Cairo, CCR 2005) Methods: All patients (pts), =25 yrs with PTLD in the past 15 yrs were analyzed and classified according to presence of detectable EBV or CD20 by IHC or ISH. Overall survival (OS) and EFS were estimated using Kaplan-Meier, significance was assessed by t-test comparison and Mantel-Cox. Results: 41 SOT pts (28 heart, 8 liver, 4 kidney) had PTLD (53.6% female) at a median of 38.8 months (mo) post SOT (4–43); Age 14–263 mo. Of 35 evaluable tumors, 29 (82.9%) had detectable EBV, while 22 (62.9%) expressed CD20 antigen. All pts had immunosuppression reduced, followed by chemo- and immunotherapy as needed. In pts with =9 mo follow-up after PTLD (n = 38) (median 49 mo, 10–184) OS is 73.2% and PTLD related EFS is 63%. Pts with EBV+ tumors had a shorter time to onset than those with EBV- tumors (median 18 vs 44 mo, p = 0.002). Pts with CD20+ PTLD were diagnosed earlier than those with CD20- PTLD (median 19 vs 62 mo, p= 0.006). PTLD-related 5 yr EFS showed significantly increased survival for CD20+ over CD20- pts (90 ± 6.5% vs 25 ± 11.2%, respectively [95% CI], p = 0.001). EBV status did not have a significant effect on OS (p=0.7) or EFS (p=0.7). Conclusions: CD20 and EBV are important predictors of time to PTLD development and presence of CD20 predicts for significantly improved EFS for SOT PTLD. CD20- PTLD pts appear to have lower EFS suggesting a need for alternative treatment strategies. No significant financial relationships to disclose.
VEBEP regimen and highly active antiretroviral terapy (HAART) in patients (pts) with HD and HIV infection (HD-HIV)
Authors: Spina M. , Rossi G. , Antinori A. , Allione B. , Fasan M. , Rizzardini G. , Tirelli U. 
Published: March 2020

8083 Background: The outcome of pts with HD-HIV is still poor, mainly because the duration of complete remission (CR) is short. To improve the prognosis of HD-HIV, a feasibility study with the third generation VEBEP regimen (developed at the NCI, Milan) and radiotherapy and concomitant HAART was started in previously untreated HD-HIV pts within the GICAT (Italian Cooperative Group on AIDS and Tumors). Methods: CT included epirubicin 30 mg/m2/day (days 1–3), cyclophosphamide 1,000 mg/m2 (day 1), vinorelbine 25 mg/m2 (day 1), bleomycin 10 mg/m2 (day 3) and prednisone 100 mg/m2/day (days 1–3), every 3 weeks. Results: Between September 2001 and June 2006, 43 pts have been enrolled. The median age was 39 yrs. The median CD4+ cell count at entry was 269/mm3 (range 44–887) and 24 pts had a detectable HIV viral load (median 12780 copies/mm3, range 89->500,000). Stage III and IV disease was present in 30/43 (70%) pts. Histologic subtypes were: MC 72%, NS 16%, LD 5%, LP 2%, and unknown 5%. One toxic death, due to hepatic failure in a HCV positive pt was observed. An absolute neutrophil count <500 was noted in 21/43 pts (49%). Grade 3–4 anemia was observed in 12/43 pts (28%) and severe thrombocytopenia in 6/43 pts (12%). Thirteen pts (30%) had febrile neutropenia with 10 documented infections in 8 pts (2 bacterial pneumonia, 2 bacterial sepsis, 2 varicella, one PCP, one cerebral toxoplasmosis, one salmonellosis, one prostatitis). A grade 2–3 mucositis was observed in 9/43 pts (21%). CR was obtained in 33/43 pts (76%) and PR in 5/43 pts (12%). With a median follow up of 30 months, only 3 pts have relapsed (9%). OS and TTF at 30 months are 80% and 66%, respectively. Conclusions: Our preliminary data demonstrate that VEBEP regimen in combination with HAART is less toxic and as active as Stanford V regimen in pts with HD-HIV. This study was supported by ISS grants. No significant financial relationships to disclose.
Utility of PET imaging in predicting the aggressiveness and histopathology of lymphoma
Authors: Chandana S. R. , Movva S. , Arora M. , Singh T. 
Published: March 2020

8085 Background: F (18)-fluorodeoxyglucose positron emission tomography (FDG-PET) is widely used in the staging and restaging of non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). Few studies have investigated whether the intensity of tumor FDG uptake, measured by standard uptake value (SUV), a semiquantitative measure, could differentiate between indolent and aggressive disease. The clinical utility of SUV in determining the aggressiveness of NHL and HD and in differentiating histopathological subtypes was investigated in the present study. Methods: FDG-PET studies and histopathology of patients with NHL and HD were evaluated retrospectively. Inclusion criteria include PET before any therapy or on relapse of the disease, no diagnosis of diabetes mellitus or other types of cancer and time interval of < 90 days between PET and biopsy. After reviewing the PET scans, the SUV of biopsy site were measured by drawing regions of interest. Mean ± SD of SUV was calculated for HD and various histopathological subgroups of NHL. Results: Fifty-five patients (mean age 58.1 ± 17.2 years, 30 males, 25 females, 13 patients with HD, 42 with NHL, among which 24 with aggressive and 18 with indolent NHL) were included. The mean SUV was 9.9 ± 7.8 for aggressive NHL, 4.1 ± 2.6 for indolent NHL and 11.5 ± 7.3 for HD. Mean SUV was statistically different between aggressive and indolent NHL (p < 0.001) and HD and indolent NHL (p < 0.001), but not between aggressive NHL and HD (p = 0.4). The SUV for the aggressive NHL can be subdivided further as follows: anaplastic (n =3, 15.1 ± 1.7), diffuse large cell (n=19, 9.6 ± 5.3) and follicular grade III (n=2, 8.1 ± 2.2). Indolent NHL included: mantle cell (n=1, 4.3), marginal zone (n=1, 6.3), small cleaved (n=12, 4.2 ± 3.5), low grade follicular (n=4, 3.2 ± 1.4) and small lymphocytic NHL (n=1, 2.3). Conclusions: Our study suggests that FDG- PET can distinguish aggressive from indolent lymphomas. There was a considerable overlap between HD and aggressive NHL.A SUV of seven or less indicates indolent lymphoma. PET could potentially differentiate between different histopathological subgroups of lymphomas. Future studies with greater sample size are warranted. No significant financial relationships to disclose.
Meta-analyses of the association between Chlamydia psittaci and ocular adnexal lymphoma and the response of ocular adnexal lymphoma to antibiotics
Authors: Husain A. , Roberts D. , Pro B. , McLaughlin P. , Esmaeli B. 
Published: March 2020

8090 Background: There are conflicting reports regarding the association between Chlamydia psittaci (Cps) and ocular adnexal lymphoma (OAL) and the efficacy of antibiotics for OAL. We sought to clarify the association between Cps and OAL and the efficacy of antibiotics for OAL. Methods: We conducted 2 meta-analyses. One focused on Cps association with OAL across geographic regions and among different studies. The other was a meta-analysis of responses to antibiotic treatment. Results: We identified 10 studies of Cps prevalence which included 430 cases of OAL from 10 different countries. We found 4 studies on the efficacy of oral antibiotics to treat OAL. Ninety-six (22%) of the 430 OAL specimens and 78 (26%) of the 305 MALT lymphoma specimens were positive for Cps. Ninety-four (98%) of the 96 Cps-positive OAL specimens came from 3 of the 10 studies. There was wide variation between geographic regions and even between studies from the same geographic region in the rate of Cps positivity. The 4 studies on the efficacy of antibiotics for OAL were from Italy, Austria, Taiwan, and the United States and included 24 patients. Eleven patients (46%) had some response (complete response in 4, partial response in 3, minimal response in 4). Twelve patients had stable disease, and 1 patient progressed during antibiotic therapy. Objective documentation of response (radiographs or clinical slit-lamp photographs) was available for only 2 out of 24 patients. Conclusions: Our findings suggest a striking variability in the association of Cps and OAL across geographic regions and even between studies from the same geographic regions. The overall rate of Cps positivity in our meta- analysis (22%) was much lower than that reported in the original report by Ferrari et al. Our findings also suggest that antibiotics have low efficacy against OAL. Future prospective trials with standard objective response criteria and a longer follow-up time would be necessary to further evaluate the role of antibiotics in the treatment of OAL. No significant financial relationships to disclose.
The characteristics and clinical course of MALT lymphoma: A 10-year single center analysis
Authors: Raderer M. , Troch M. , Woehrer S. , Streubel B. , Puespoek A. , Formanek M. , Turetschek K. , Jaeger U. , Drach J. , Chott A. 
Published: March 2020

8099 Background: An evaluation of clinical characteristics and potential risk factors affecting outcome in patients with MALT lymphoma was performed at our institution. Patients and Methods: As of 1997, a total of 170 consecutive patients with histologically verified MALT lymphoma (99 female/71 male) underwent uniform staging and assessment of clinical characteristics including assessment of genetic changes, presence of autoimmune disease (AD), Helicobacter pylori (HP)-status, monoclonal immunoglobulins (MG) and plasmacytic differentiation (PD). All patients with follow-up at our institution were analysed, and influence of various parameters on dissemination and outcome were evaluated. Sixty-four patients (38%) had gastric MALT-lymphoma (GML) and 106 (62%) extragastric MALT-lymphoma (EGML). Results: 66/170 patients (39%) had multiorgan-involvement upon presentation, while only 3 patients had bone marrow involvement. Patients with EGML (49/106, 46%) were at significantly higher risk for multiorgan-disease than patients with GML (17/64, 27%, p = 0.013). 58 patients had genetic aberrations, with t(11;18) being more common in GML (p = 0.002) and trisomy 3 (p = 0.03) and trisomy 18 (p = 0.02) in EGML. Among GML, translocation t(11;18) was significantly associated with multiorgan-disease, as was trisomy18 in EGML (p = 0.038). After a median follow-up time of 40 months, 139 patients (86%) are alive. 58 patients (39%) have relapsed, with the median to relapse being 60 months. Overall, multifocality and extragastric origin (p < 0.001) were significantly associcated with relapse, while patients with t(11;18) had a significantly longer time to relapse (131 vs 49 months). Survival and relapse were not affected by the form of therapy applied (i.e. local vs systemic). An underlying AD was found in 65 patients (38%), and was significantly associated with EGML (p = 0.007) and multifocality (p = 0.04), but did not influence relapse and survival. HP-positivity was significantly associated with GML (p = 0.001), and patients with EGML did not respond to HP-eradication. Conslusion: Our data suggest dissemination and (late) relapse to be relatively common in MALT-lymphoma. Based on our findings, however, an individualized staging approach and risk-assessment is possible. No significant financial relationships to disclose.
Novel therapy with 2-methoxyestradiol (2ME2) for the treatment of relapsed and plateau phase multiple myeloma
Authors: Lacy M. , Richardson P. , Gertz M. , Dispenzieri A. , Greipp P. , Witzig T. , Schlossman R. , Sidor C. , Anderson K. , Rajkumar S. 
Published: March 2020

8108 Background: 2-methoxyestradiol (2ME2) is a natural endogenous product of estradiol metabolism with anti-angiogenic and anti-neoplastic properties that has demonstrated activity against multiple myeloma cell lines and xenografts in immunocompromised mice. We report results of the first phase II clinical trial of 2ME2 in pts with relapsed and plateau phase myeloma. Methods: This trial was designed with a one-stage design to accrue 60 pts in the setting of relapsed and plateau phase myeloma. 2ME2 was administered orally at a dose of 1000 mg daily. After the first 39 pts were accrued, based on the results of ongoing phase I trials, the dose of 2ME2 was increased to 800 mg twice daily for the remaining patients. Pts who were already on study at that point were also allowed to escalate their dose to 800 mg twice daily. The primary endpoint was overall response rate. Responses were assessed using Eastern Cooperative Oncology Group criteria. Results: Sixty patients were treated at Mayo Clinic and Dana Farber Cancer Institute. Median age was 60 years (range, 28–99). Thirty-one patients had relapsed/refractory myeloma and 29 patients had plateau phase myeloma. Median number of prior therapies was 4 including stem cell transplant (48%), thalidomide (62%), bortezomib (6%) and lenalidomide (3%). Therapy was well tolerated. Adverse events were anemia (35%), fatigue (35%), nausea (25%), diarrhea (20%), hot flashes (20%), headache (17%), muscle cramps (15%), and upper respiratory tract infection (15%). Most toxicities were mild (grade 1–2). Estimated progression-free survival rates for all pts at one, two, and three years are 24%, 16%, and 9% respectively. Three pts with plateau phase disease, have been on study for over 4 years without progression at 50, 60, and 63 months. Response assessment is ongoing; so far, whilst no partial responses have been seen, prolonged stable disease has been observed in 3 pts (5%). Conclusions: 2ME2 is a novel agent that appears to be safe and well tolerated. Although no responses have been seen, prolonged stable disease in some pts is promising. Preliminary pharmacokinetic data indicate that the dose of 2ME2 used in this study may be inadequate, and a new formulation with significantly better bioavailability will be tested soon in this patient population. No significant financial relationships to disclose.
Inhibition of cell proliferation by lenalidomide is associated with stimulation of Egr1 transcriptional activity in a chromosome 5 deleted Burkitt’s lymphoma and multiple myeloma cell line
Authors: Gandhi A. K. , Kang J. , Verhelle D. , Stirling D. I. , Schafer P. H. 
Published: March 2020

8110 Background: The mechanism by which lenalidomide exerts its anti-proliferative effects in deletion 5q MDS clones or MM cells is not yet fully elucidated. Early growth response (Egr1) gene is a tumor suppressor gene located on chromosome 5q31.1 that encodes a transcription factor involved in the regulation of cell proliferation and apoptosis. We hypothesized that lenalidomide may act by enhancing the expression or activity of Egr1 in sensitive hematopoietic tumor cells, especially those with only a single copy of the Egr1 gene. Methods: Transcriptional activity was measured using luciferase reporter plasmids. Gene knockdown and expression studies used siRNA technology and qRT-PCR, respectively. Cell proliferation was measured by 3H-thymidine incorporation. Results: Lenalidomide stimulated the transcriptional activity of Egr1 in the lenalidomide-sensitive chromosome 5 deleted Burkitt's lymphoma Namalwa CSN.70 and in the MM cell line LP-1. Egr1 siRNA Namalwa cells proliferated more than mock controls, indicating that Egr1 functions as a tumor suppressor in Namalwa cells. Lenalidomide had no effect on expression of Egr1, but augmented Egr1 nuclear transport in a dose-dependent manner. Lenalidomide did not affect expression of the Egr1 downstream effector genes ATF3, fibronectin, p53, PTEN, and TGF-β1, while p21 levels increased. However, lenalidomide-induced p21 expression was not affected in Egr1 siRNA Namalwa cells. Interestingly, lenalidomide’s anti-proliferative potency was greater in Egr1 siRNA Namalwa but not in Egr1 siRNA LP-1 cells. Conclusions: Lenalidomide induces nuclear transport and transcriptional activation of the tumor suppressor Egr1, which may contribute to lenalidomide’s anti-proliferative activity in a non-p21 dependent manner. This activity may be related to the levels of Egr1 expression, explaining why del 5q31 myelodysplastic clones are especially sensitive to the cytotoxic effects of lenalidomide. No significant financial relationships to disclose.
Effect of the green tea polyphenol epigallocatechin gallate (EGCG) on growth and IL-6 signalling pathways in malignant plasma cells
Authors: Burger R. , Czekalla H. , Richter K. , Ahrens T. , Guenther A. , Gramatzki M. 
Published: March 2020

8114 Background: Epigallocatechin gallate (EGCG) is the predominant polyphenolic constituent of green tea leaves that possesses antitumor, antiinflammatory, and antioxidant activity. EGCG exerts its effects through potentially multiple mechanisms including inhibition of growth factor receptor signalling. The compound is currently under investigation in a phase I/II clinical trial for treatment of patients with early stage chronic lymphocytic leukemia at Mayo Clinic. The goal of our study was to examine the in vitro effects of EGCG in multiple myeloma (MM). Methods: A panel of human myeloma cell lines (n=6) including the IL-6 dependent INA-6 cell line was used to evaluate the sensitivity to EGCG. Cells were cultured for three days in the absence or presence of EGCG at concentrations between 6.25 μM and 100 μM. Cell viability was determined in a colorimetric tetrazolium (MTS) based assay and by trypanblue exclusion. For signalling experiments, INA-6 cells were IL-6 and serum starved and then treated with EGCG for two hours before IL-6 was added. Whole cell lysates were prepared and subjected to SDS-PAGE and Western blot analysis. Results: EGCG inhibited the in vitro growth of human myeloma cell lines by inducing cell death in a time and dose-dependent manner. IC50 concentrations were between 12,5 μM and 50 μM. IL-6 mediated growth of INA-6 cells was inhibited at similar doses. The addition of excess amounts of IL-6 could not protect from EGCG induced cytotoxicity. Pretreatment of INA-6 cells with EGCG resulted in a dose-dependent inhibition of IL-6 induced STAT3 tyrosine phosphorylation. In these cells, stimulation with IL-6 leads to upregulation of Mcl-1 expression. In contrast, phosphorylation of p44/p42 MAPK, which is constitutively activated in INA-6 cells, was not affected. Conclusion: EGCG has growth inhibitory activity on myeloma cells. Specific inhibition of signalling pathways that regulate expression of anti-apoptotic proteins could be one mechanism how EGCG exerts its activity. Our work provides the rationale for further studies to evaluate the effect of EGCG not only in B-CLL, but also in plasma cell tumors. No significant financial relationships to disclose.