bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastric MALT lymphoma (GML) after helicobacter pylori (Hp) eradication: Prognostic value of histological and molecular findings in 120 patients of a prospective multicenter trial
Authors: Wündisch T. , Neubauer A. , Gunther A. , Stolte M. 
Published: March 2020

8041 Background: Long lasting remissions occur in most patients with localized GML after Hp eradication. Ongoing B-cell clonality and the translocation t(11;18) have been described as factors associated with no response, relapse and histological residual disease (hRD). Systematic evaluation of histological findings associated with the clinical course and molecular data has not been described yet. Methods: Detailed analysis of long term follow up data of a prospective multicenter trial including 120 patients (median follow up > 5 years) with Hp-positive stage I1E GML was performed. Histological and molecular data of biopsies from 1187 endoscopies were analyzed using a large data base. Hp-status, granulocytic-, lymphocytic infiltration and intestinal metaplasia (IM) were histologically graduated according to the Updated Sydney system. The histological findings empty lamina propria (ELP), fibrosis, lymphoid follicles (LF) and lymphoepithelial lesions and lymphoid aggregates (LA) were evaluated. Prospective molecular data concerning B-cell clonality as well as retrospective data concerning the status of the translocation t(11;18) were also collected. Results: LA and LF were more present in patients not responding towards Hp eradication [P < 0.0001]. ELP in high frequency is a positive predictor for reaching complete remission (CR) [P= <0,0001]. Fibrosis was only found in CR patients. In patients reaching a histological CR presence of LA and LF were associated with hRD and relapse [P=0.04]. LA / LF were also more prevalent in t(11;18) positive and patients with ongoing B-cell clonality. An association between ongoing monoclonality and t (11;18) was also demonstrated [p=0,012]. In 66% of patients IM was detected, it does not disappear during long term follow up after successful Hp eradication. Conclusions: Simple histological findings can help to predict the clinical course of GML after Hp eradication and are associated with known molecular data. No significant financial relationships to disclose.
Oral combination chemotherapy for refractory/relapsed lymphoma with the PEP-C (C3) regimen (daily prednisone, etoposide, procarbazine, cyclophosphamide): Low-dose continuous metronomic multidrug therapy
Authors: Coleman M. , Ruan J. , Furman R. R. , Niesvizky R. , Martin P. , Leonard J. P. 
Published: March 2020

8064 Background: Oral daily low dose chemotherapy (metronomic therapy) may maintain continuous sequential drug levels to impact endothelial cell viability (anti-angiogenesis) or to overcome drug resistance. Methods: We retrospectively reviewed data on 97 patients with refractory/relapsed Hodgkin's and non-Hodgkin's lymphoma treated with the PEP-C (C3) regimen, which consists of oral prednisone (20 mg in am), cyclophosphamide (50 mg at noon), etoposide (50 mg at dinner) and procarbazine (50 mg at h.s.with an oral anti- emetic). Medications were administered daily until the white blood cell count fell to less than 3000/dl, when treatment was held until recovery from the nadir. Treatment was then reinstituted on a daily, alternate day, or fractionated weekly basis (e.g. 5 of 7 days) based on patient tolerance. Doses given per day were constant. Results: All patients had been previously treated, with 80% having received 2 or more prior therapies and 57% with 3 or more previous regimens. Overall, 69 patients (71%) achieved a response. Responses by histology were: follicular (n=26) 92%, mantle cell (n=22) 82%, marginal zone (n=14) 71%, small lymphocytic (n=12) 67%, Hodgkin's lymphoma (n=9) 44%, diffuse large B cell (n=9) 33%, and T cell (n=5) 40%. Time on therapy of responding patients ranged from 3 weeks to 48 months (median 9 months, mean 11 months). Toxicity was predominantly myelosuppression, with hospitalization for infection occurring in 10 patients. Five patients developed H. zoster. Gastrointestinal effects prompting cessation of therapy occurred in 6 subjects, and 2 patients developed hematuria. Conclusions: Low dose, continuous (metronomic) combination chemotherapy with PEP-C is an easily administered, generally well- tolerated and effective treatment for relapsed/refractory lymphoma, particularly in indolent and mantle cell histologies. No significant financial relationships to disclose.
High-dose carmustine (BCNU), etoposide (VP-16), cytarabine (Ara-C), and cyclophosphamide-BVAC with autologous transplant (ASCT) in relapsed and refractory Hodgkin disease (HD): Long-term follow-up of 89 patients
Authors: Iyengar T. , Hayashi M. , Leopold C. , Smith B. J. , Gingrich R. , Carter T. , de Magalhaes-Silverman M. 
Published: March 2020

8068 Background: High dose chemotherapy followed by ASCT has been established as the therapy for refractory and relapsed HD. Relapse remains the primary contributor to an unsuccessful outcome after ASCT. Intensification of the conditioning regimen is one means of decreasing relapse and improving results. We report our experience with an augmented preparative regimen in patients (pts) with relapsed or refractory HD undergoing ASCT. Methods: Retrospective analysis of 89 consecutive pts from October 1984 to October 2004. All pts received high-dose chemotherapy with BCNU 600mg/m2 IV day -8, Etoposide 400mg/m2/day days -7, -6, -5, and -4, Ara-C 3gm/m2 IV every 12 hours for 8 doses starting day -7, and Cyclophosphamide 90mg/kg IV on day-2 followed by bone marrow (40 pts), peripheral blood (43 pts) or both (6 pts) rescue. Ten pts received planned XRT post-transplant. Survival data were estimated using Kaplan-Meier curves. Cox proportional hazards regression was used to assess the impact of variables on disease-free survival (DFS) and overall survival (OS). Results: A total of 89 pts were identified. Median age was 31 (range 16–62); 51 pts (57.3%) had received one prior therapy at the time of transplant. At transplant only 28 pts (34.6%) were in CR; 79.8% had sensitive disease (CR plus PR).Time to transplant was < 1 year for 17% of pts. With a median follow-up of 811 days, the 5 and 10-year DFS rates were 63.3% and 60.4%, respectively. The estimated 5 and 10- year OS rates were 47.3% and 33.7%. The rate of secondary malignancies at 10 years was 7.8%. Lack of B symptoms and stage at transplant were associated with improved DFS (p= 0.01 and p= 0.0005, respectively) and OS (p=0.002 and p=0.02, respectively). Patients with primary induction failure and resistant relapse did as well as patients with sensitive disease. Conclusions: Though ASCT has been beneficial in prolonging DFS and OS in pts with chemosensitive HD, there has been conflicting data regarding refractory disease. We propose that an intensified regimen, i.e. BVAC, may be of benefit in that setting. Only a large randomized trial can determine whether intensification of the preparative regimen can improve OS for such a population. No significant financial relationships to disclose.
A multi-center, open-label study to evaluate the safety and efficacy of pentostatin, cytoxan, and rituxan (PCR) in the treatment of previously untreated or treated, stage III or IV, low-grade B-cell non-Hodgkin lymphoma (NHL) or bulky stage II lymphoma
Authors: Christiansen N. P. , Mena R. , Markan Y. , Pandit L. 
Published: March 2020

8071 Background: The decision to treat indolent B-cell NHL is often based on progressive disease, worsening symptoms, and increasing hematological variations. When treatment is indicated, these lymphoproliferative disorders are very sensitive to combination chemotherapies. Combination therapy with these agents, pentostatin (P), a purine analog, cyclophosphamide (C), a DNA alkylator, and rituximab (R), an anti-CD20 monoclonal antibody, represents a promising approach in the treatment of these patients. Most regimens have utilized fludarabine (F) as the purine analog but the myelosuppression and immunosuppression of (F) combinations frequently results in severe infections. Methods: Eligibility criteria allow previously treated and treatment-naïve patients diagnosed with bulky stage II or low-grade stage III/IV NHL (REAL classification) to be enrolled. Treatment consisted of intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for a total of up to 10 cycles. Clinical evaluation was performed after cycles 2, 4, 6 and 8 and 10 (if necessary). Results: The intent-to-treat (ITT) population consisted of 87 NHL patients (median age 62.5, range 29–84) who received a total of 476 cycles (median 6 per patient). The ECOG status was 0 (62.4%), 1 (37.6%) and 2 (0%). The overall response rate of the 80 evaluable patients was 72.5% (CR 11.3%, Cru 12.5%, PR 48.8%). 14 cases of grade 4 and 17 cases of grade 3 neutropenia were documented. There were a total of 4 deaths due to acute myocardial infarction, NSCLC, a suspected cardiac event and 1 unknown cause of death. Conclusions: This immunochemotherapeutic regimen is active in indolent Grade III/IV NHL and the incidence of significant toxicities was low. Future trials evaluating the use of rituximab as maintenance therapy following this PCR regimen may also be warranted with a future goal towards possibly increasing the overall survival of patients with NHL. The presented results are preliminary and the study is currently on-going. No significant financial relationships to disclose.
Clinical characteristics and course of chronic lymphocytic leukemia patients with the combination favorable and unfavorable cytogenetics
Authors: Harting R. R. , Venugopal P. , Hsu W. , Catchatourian R. , Ogundipe O. 
Published: March 2020

8086 Background: Patients with CLL have a highly variable clinical course. Genomic aberrations detected by FISH have been shown to correlate with survival and treatment free interval (TFI). Patients with the presence of 17p or 11q deletions (del) either alone or in combination with other cytogenetic abnormalities have the worst prognosis while patients with 13q del as a sole abnormality have the best prognosis. Our objective was to further investigate poor prognosis CLL patients with either del 17p or 11q to determine if the addition of the favorable 13q del influences the predicted clinical course and survival. Methods: We performed a retrospective chart review on 22 patients (pts) who had been identified by FISH as having either the combination of del 17p and 13q or del 11q and 13q. Results: 128 CLL FISH panels were performed from April of 2003 through October of 2006. Twenty-two pts (17%) had either del 17p and 13q (9%) or del 11q and 13q (9%). Historical data notes a frequency of 7% and 8% for deletions 17p and 11q, respectively, and 55% for 13q as a sole aberration. The median age was 66 yrs, the majority of whom were male (73%). Two of 22 pts (9%) presented with advanced stage disease. Splenomegaly was seen more often in the 17p/13q pts (36%) vs 11q/13q pts (9%). With a median follow up of 46 months since diagnosis, the median TFI for all patients (20 known) was 56 months. TFI was 13 months for patients with 17p/13q del; whereas TFI was not reached for patients with 11q/13q. Historical data noted a TFI for patients with deletions 17p, 11q, and 13q (as a sole aberration) as 9, 13, and 92 months respectively. The median survival from diagnosis was not reached for the group overall or for either combination of genetic abnormalities. Historical data noted, with 70 months follow up, a median survival of 108 months overall and 32, 79, and 133 months for 17p, 11q, and 13q (as a sole aberration) respectively. Conclusions: The addition of favorable cytogenetics, del 13q, in a CLL patient with an unfavorable cytogenetic pattern (either del 17p or del 11q) appears to improve the predicted clinical outcome and survival. Additional follow up and prospective studies are needed to further define which genetic subgroups help to prognosticate CLL patients. No significant financial relationships to disclose.
Do patients with MGUS require a bone marrow biopsy?
Authors: Singh J. , Malani A. K. , Huang C. H. , Hashmi M. , Mathur S. C. , Stasik C. , Van Veldhuizen P. 
Published: March 2020

8117 Monoclonal gammopathy of undetermined significance (MGUS) increase in prevalence with age and it is associated with risk of progression to plasma cell disorder. According to ASH guidelines, patients (pts) should have a complete blood count (CBC), creatinine, calcium, and a complete bone survey and periodic follow up. There has been no clear-cut guideline regarding the role of bone marrow biopsy in these patients. There is suggestion in the literature that bone marrow aspiration and biopsy is indicated if the M protein is 1.5 g/dL. Hypothesis We hypothesize that the increase in serum immunoglobulin is correlated with an increase in plasma cell in the bone marrow biopsy. Methods: We performed a retrospective chart review of 327 MGUS veteran patients seen from 2002 to 2005. Diagnostic criteria for MGUS were defined as <3 g/dL serum monoclonal protein, <10 % plasma cells in the bone marrow and absence of radiographic or laboratory abnormality related to the plasma cell proliferative process. Patients with smoldering myeloma were excluded. Bone marrow biopsies were available on 97/327 patients. Bone marrow biopsy with plasma cell percentage, serum protein electrophoresis (SPEP) and immunofixation (SFE), and immunoglobulin levels of these patients were retrieved and statistical analysis was performed by using Pearson correlation coefficient and linear regression analysis to detect the correlation between plasma cell percentage and immunoglobulin levels. Results: Of the 97 patients whom the bone marrow biopsy was available, 66 patients had IgG, 15 had IgA and 16 had IgM monoclonal paraprotein. There was linear correlation between serum IgG and IgA levels with the percentage of plasma cells in the bone marrow. (p< 0.001 and < 0.02 respectively. By regression analysis, using a cut off value of 10% plasma cells in the bone marrow, the predicted level of IgG and IgA immunoglobulin was 2124 mg /dl and 1564 mg/dl respectively. There was no correlation between IgM immunoglobulin and plasma cell percentage in the marrow. Conclusion: There is a linear correlation between serum IgG and IgA immunoglobulin with plasma cell percentage in the bone marrow. Bone marrow biopsy with plasma cell percentage of 10% or higher may be predicted in patients with MGUS with IgG or IGA above 2g/dl and 1.5g/dl respectively. No significant financial relationships to disclose.
Use of autologous bone marrow cells following high-dose chemotherapy (HDCT) for patients (pts) with recurrent lymphoma in whom stem cell harvesting from the peripheral blood was inadequate
Authors: Kumaran G. , Murray J. , Sweeney D. , Liakopoulou E. , Radford J. A. 
Published: March 2020

8124 Background: HDCT with autologous stem cell rescue (ASCR) is an established treatment for recurrent Hodgkin and non- Hodgkin lymphoma (HL, NHL) but some of these pts fail to mobilise adequate numbers of CD34+ cells from the peripheral blood (PB). Harvest of bone marrow (BM) stem cells and use of these alone or in combination with PB derived cells is an option but there are concerns about feasibility and outcome. Methods: 29 pts who had HDCT after failed PB stem cell harvest between July 1999 and December 2005 were studied in terms of CD34+ cell yield (PB and BM), transfusion dependence, engraftment and survival. Results: There were 17 males and 12 females (median age 49yrs, range 19–66) with recurrent HL (n=16) or NHL (n=13). All had received at least 2 lines of chemotherapy (10 pts =3) and 7 had received radiotherapy (5 mediastinal, one neck and one abdominal field). Mobilisation of CD34+ cells from PB was attempted using chemotherapy followed by filgrastim. 22 pts proceeded to leukapheresis on the basis of predictive CD34+ counts (median collects 2; range 0–4) with a median total collect of 0.98×106 CD34+cells/kg (range 0.03–1.84). Subsequently, all pts had a BM harvest producing a median collect of 1.63x106 CD34+cells/kg (range 0.45–4.75). 29 pts then received BEAM/CBV followed by re-infusion of PB+BM cells except in 7 pts where only BM cells were available. In 26/29 pts surviving to day 100; total CD34+ cells infused, 2.37×106/kg (range 1.73- 5.0), time to neutrophils >0.5×109/L, 12 days (range 9–23), platelet units transfused, 6 (range 0–24), red cells units transfused 6 (range 0–18) (all medians). 2 pts continued to have red cell transfusions beyond day 100. 3/29 pts died due to severe neutropenia/septicaemia at days 23–25 (treatment related mortality 10.3%); the CD34+ dose received by these pts was 1.97×106/kg in 2 and 1.84×106/kg in 1. Beyond day 100, 9 pts have died from HL/NHL and 2 are lost to follow-up. Conclusions: In patients with HL/NHL who fail to mobilise adequate numbers of CD34+ cells from PB, a BM harvest can produce a combined BM/PB collect capable of producing haemopoeitic reconstitution following HDCT without excessive toxicity. No significant financial relationships to disclose.
Association between use of non-steroidal anti-inflammatory drugs (NSAIDs) and statins and the risk of cutaneous melanoma (CM): A case-control study
Authors: Curiel C. , Gomez M. L. , Atkins M. B. , Nijsten T. , Stern R. S. 
Published: March 2020

8500 Background: CM accounts for more than 77% of skin cancer deaths. Chemoprevention strategies have been hampered by the lack of supporting epidemiological data. Methods: A case control study examined the association between statins and NSAIDs use and CM in people over 40 years of age. A total of 400 histologically confirmed CM cases were recruited within 3 months from diagnosis between 3/04 and 12/06. Controls included 600 individuals without history of CM matched for age, gender and neighborhood in a ratio of 1:1.5. All completed a standardized telephone questionnaire that captured demographic characteristics, CM risk factors, and drug exposure history (length and frequency of use). Odds ratios were calculated with testing for statistical significance based on Chi square analysis. Results: To date, all 400 CM cases and 547 controls have been recruited. Interview results out of 387 cases (192 F/195 M) and 505 controls (254 F/251 M) were included for data analysis. Mean age was 58.4 and 58.5 years. The most significant CM risk factors included: red hair phenotype OR: 2.29, history of non-CM skin cancer OR: 2.28, family history of CM OR: 1.76, light complexion OR: 2.7, and history of more than 4 sunburns in childhood OR: 4.06. 100 cases vs. 190 of the controls had been exposed to statins OR 0.58 (CI:0.43–0.78); no greater protective effect was detected with increased duration of statin use (p=0.87 for heterogeneity of ORs for =5 vs. <5 yrs). 238 cases vs. 397 controls reported the use of NSAIDs, OR 0.44 (CI 0.32–0.59). 43 cases reported the use of aspirin-ASA for = 5 years vs. 92 controls OR: 0.37 (CI: 0.20–0.68). Similar results were observed with exposure to other NSAIDs with 38 cases reporting the use for = 5 years vs.109 controls, OR: 0.35 (CI: 0.24- 0.50). Conclusions: This study suggests that extended use of NSAIDs decreases the risk of CM development. Although any statin use demonstrated a decreased risk, the lack of an association between duration of use and protective effect raises questions about a true causal relation. Further analysis with respect to the CM subtype and specific exposure (by dose, and frequency of use) to these groups of drugs may lead to the design of CM chemopreventive clinical trials. Final analysis will be presented at ASCO. No significant financial relationships to disclose.
Randomized phase III study of paclitaxel plus carboplatin with or without sorafenib as second-line treatment in patients with advanced melanoma
Authors: Agarwala S. S. , Keilholz U. , Hogg D. , Robert C. , Hersey P. , Eggermont A. , Grabbe S. , Gonzalez R. , Patel K. , Hauschild A. 
Published: March 2020

8510 Background: Sorafenib (SOR), a potent and selective multi-kinase inhibitor, exerts its anti-tumor and anti-angiogenic effects via inhibition of VEGFR-1, -2, -3, PDGFR-a, -β, and Raf. Promising results from a single-arm study of paclitaxel and carboplatin plus sorafenib (PC+SOR) in advanced melanoma warranted further investigation in a randomized phase III trial. Methods: Eligibility criteria: measurable disease by RECIST, progressive disease (PD) on dacarbazine or temozolomide-containing regimen. Prior adjuvant immunotherapy was allowed; pts with active brain metastases were excluded. Pts stratified by stage (unresectable III vs IV, M1a/M1b vs M1c) and ECOG PS (0 vs 1) were randomized to receive P 225 mg/m2 and C AUC=6 on day 1 every 3 wks + oral placebo (PL) or oral SOR 400 mg bid on Days 2–19 every 3 wks until the occurrence of PD or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Using a two-sided test with a = 0.01, 173 PFS events were needed to detect a hazard ratio (HR) of 0.56 (SOR/PL) with 90% power. The secondary endpoints were overall survival, objective response rate (ORR) and time to progression. Results: 270 pts randomized over 12 mos in equally balanced groups had: median age 57 yrs, male 63%, ECOG PS 1 46%, Stage IV M1c 69% and elevated LDH 46%. At the time of analysis by independent assessment, the median PFS of PC+PL vs PC+SOR was 17.9 wks (99% CI: 11.3, 22.9) vs 17.4 wks (99% CI: 11.9, 23.1), HR 0.906 [p=0.492]; PFS rate at Day 180 was 29% vs 32%, ORR was 11% vs 12%. Both regimens were well-tolerated with the following selected = Grade 3 toxicities in PC+PL vs PC+SOR: neutropenia (46% vs 49%), febrile neutropenia (7% vs 9%), thrombocytopenia (12% vs 28%), sensory neuropathy (13% vs. 20%), thrombosis/embolism (6% vs 4%), rash/desquamation (0 vs 7%), hand-foot skin reaction (0 vs 7%), fatigue (10% vs 16%), diarrhea (3% vs 8%) and hemorrhage (3% vs 2%). There were 2 deaths, possibly related to treatment with PC+SOR. Conclusions: The addition of SOR to PC did not improve PFS or ORR in this second-line patient population. Toxicity of PC+SOR is tolerable. The utility of PC+SOR in chemotherapy-naïve advanced melanoma pts remains an important question and a phase III trial is currently in progress (E2603). [Table: see text]