bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allogeneic stem cell transplantation improves cerebro-vascular disease in two sickle cell anemia patients
Authors: Kraut L. , Al-Momen A. , Nürnberger W. , Boguth L. , Erken E. , Fauser A. A. 
Published: March 2020

16524 Background: Sickle cell anemia (SCA) patients are at high risk for vaso-occlusion with cerebral vascular complications like strokes being one of the most devastating clinical events. Prophylactic transfusions might prevent strokes resp. improve cerebro-vascular status in SCA patients. Allogeneic stem cell transplantation (SCT) is considered a therapeutic option with curative intention of SCA, and thus also to improve cerebro-vascular complications by preventing further strokes, as demonstrated by two cases in our center. Methods: Transcranial Doppler sonography (TCD) and cerebral magnetic resonance angiography (MRA) were used to assess cerebro-vascular disease status prior, during and post related SCT of 2 SCA patients. Results: Two sibling SCA patients (male resp. female, aged 13 and 11 years resp.) both suffered from multiple cerebral microinfarcts during the course of their disease, the boy additionally suffered from two strokes. Prior to related SCT in 2004 with unaffected siblings, both patients were assessed by MRA and TCD. The diagnostic data revealed a hypoplastic ACI (right side) in both children as prominent pathological feature, in combination with different grades of stenosises of ACM, AV and ACI (left side), for example. The evaluation of cerebro-vascular status 3–4 months post SCT showed a persisting stenosis of right ACI in both patients, whereas circulation in the cerebrum resp. flow velocity profiles in other intracranial arteries significantly improved or turned to normal. The course of SCT was rather uncomplicated in the immediate post-transplant period except clinically controlled acute GvHD grade III in one patient. Currently, i.e. 18 resp. 21 months after transplant, the children are in good clinical condition. Conclusions: The results of allogeneic SCT in 2 SCA patients suggest that cerebro-vascular disease does not progress after SCT resp. shows major improvement by SCT. Regular follow up is necessary to assess long term results of cerebro-vascular status in these patients. No significant financial relationships to disclose.
Hematopoietic stem cell transplantation (HSCT) in patients with primary granulocytic sarcoma (GS)
Authors: Hentrich M. , Ledderose G. , Lutz L. , Tischer J. , Gerl A. , Hartenstein R. C. , Kolb H. J. 
Published: March 2020

16529 Background: GS preceding acute myeloid leukemia (AML) is extremely rare and the prognosis is poor. Patients usually undergo systemic chemotherapy (CT) but the role of HSCT is not sufficiently defined. Methods: We report on 3 cases of non-leukemic GS, all of those treated with inductive CT followed by either autologous or allogeneic SCT. Furthermore, the literature on the role of HSCT in GS is reviewed. Results: Case 1: A 55-year-old man presented with a mediastinal mass and right pleural effusion. Fluid cytology revealed hematopoietic cells. Mediastinoscopy showed GS but peripheral blood and bone marrow were free of blasts. He underwent 2 cycles of anthracyline-cytarabine (AC) containing induction CT followed by myeloablative conditioning and autologous SCT in 1st remission. Radiotherapy to the mediastinum was applied afterwards. He remained in CR for 6 months when a leukemic relapse was diagnosed. He is currently undergoing reinduction CT and will proceed to receive an unrelated donor (URD) SCT. Case 2: A 51-year old man was diagnosed with GS of the right testicle. After orchiectomy he was followed by observation only. 8 months later a leukemic relapse [karyotype 46 XY, del (9)(q22), der(13) t(8;13)] occurred. The patient received 2 courses of AC-based induction CT followed by myeloablative conditioning and an HLA-matched URD transplant in 1st CR. However, 27 months after HSCT another leukemic relapse was diagnosed. He received a 2nd URD transplant but died of severe graft versus host disease (GvHD) and veno-occlusive disease 10 weeks later. Case 3: A 37 year-old woman was diagnosed with non-leukemic GS located at multiple bone sites. She underwent 4 courses of AC-containing CT resulting in a CR. 6 months later she presented with multiple recurrent GS confined to the skeleton. She received myeloablative conditioning followed by an allogeneic SCT from her HLA-mismatched brother. Another CR was attained. However, she suffered from severe GvHD and died of severe sepsis 3 months after HSCT. Conclusions: The outcome of patients with primary GS appears to be poor even after treatment with HSCT. However, allogeneic SCT has curative potential as indicated by some cases of successful transplants reported in the literature. No significant financial relationships to disclose.
Prognostic value of baseline inflammatory markers in inoperable non-small cell lung cancer (NSCLC)
Authors: MacDonald N. , Kasymjanova G. , Dobson S. , Kreisman H. , Cohen V. , Agulnik J. S. , Small D. 
Published: March 2020

17035 Background: Markers of chronic inflammation are not commonly included in standard NSCLC staging, which remains anatomically based. Several studies have reported that an increased C-reactive protein (CRP), a marker of chronic inflammation, presages short survival for NSCLC patients (pts). A cohort of 68 pts with advanced NSCLC (stages 3A, 3B and 4) was studied in order to evaluate the prognostic value for survival of various pretreatment inflammatory parameters. Methods: The following factors were collected at the time of diagnosis prior to treatment: sex, age, stage, performance status, CRP, LDH, hemoglobin, platelets, albumin, and white blood cells (WBC). Statistical evaluation employed univariate and multivariate analyses. Survival was calculated using the Kaplan-Meier method and compared using the log-rank test. Results: Median survival for the entire cohort was ten months (mo) (95% CI 7, 15). Those with stages 3A, 3B (18 pts) had a survival of 11 mo (95% CI 6,15), whereas those with 3B (effusion)/4 (50 pts) had a survival of 8 mo (95% CI 3,13). Univariate analysis identified CRP and WBC as the only significant prognostic factors for survival (p < 0.01). Multivariate analysis also demonstrated that CRP (p = 0.005), and WBC (p=0.009) displayed independent correlation with prognosis. CRP and WBC were then combined into a prognostic index (PI) ranging from 0–2. The total score demonstrated a better stratification value for survival. Both parameters were normal [WBC ≤ 11, CRP ≤ 10] (PI 0) in 26 (38%) pts; one parameter was elevated (PI 1) in 27 (40%) pts; and both parameters were elevated (PI 2) in 15 (22%) others. Pts with PI 0 had a median survival of 14 mo (95% CI 12, 21); those with PI 1 had a median survival of 7 mo (95% CI 5, 10); and pts with PI 2 had a median survival of 5 mo (95% CI 3, 7). Conclusions: Systemic inflammatory markers predicted survival in our cohort with NSCLC. These data need to be confirmed in a larger validation study. Studies on staging systems that include inflammatory markers are indicated. Clinical trials linking anti-inflammatory therapies with chemotherapy should be prioritized. No significant financial relationships to disclose.
Total blockade of the epidermal growth factor receptor with the combination of cetuximab and gefitinib: A phase I study for patients with recurrent non-small cell lung cancer (NSCLC)
Authors: Naret C. L. , Ramalingam S. , Beattie L. , Mayfield S. D. , Lu H. , Langer C. , Belani C. P. 
Published: March 2020

17045 Background: Cetuximab and gefitinib inhibit the epidermal growth factor receptor (EGFR) through different mechanisms. Preclinical evidence suggests that the combination of cetuximab and Gefitinib is synergistic and has shown antitumor activity in vitro and in xenografts (Matar et al, Clin Cancer Res, 2004). We are conducting a phase I study to determine the doses of the two agents that can be administered in combination. Methods: Patients (pts) with advanced NSCLC were eligible upon progression following 1 or 2 prior chemotherapy regimens. Gefitinib was administered at a dose of 250 mg/day for all cohorts. The dose of cetuximab was escalated in sequential cohorts of patients ( table ) and there will be no dose escalation above the approved doses for both agents (dose level 3). Paraffin-embedded tissue samples of the primary cancer were collected from all patients for analysis of EGFR mutations, gene amplification and protein expression. Results: From March to December 2005, 11 patients have been entered to the 3 planned cohorts. Patient characteristics include: 3 women and 8 men, with a median age of 63 years (range 51–77) and ECOG performance status (PS) of: 0 = 50%, 1 = 50%. A total of 26 treatment cycles were administered to the 11 pts with a median of 2 cycles per pt (range 1–8). Other observed adverse events include grade 1/2 skin rash and diarrhea. Of 8 evaluable patients, 4 had stable disease. No DLT has been experienced so far at the projected recommended phase 2 dose (dose level 3). The results of correlative studies will be presented at the meeting. Conclusions: The novel combination of cetuximab and gefitinib is safe and is associated with promising anti-cancer activity in recurrent NSCLC. [Table: see text] [Table: see text]
The role of methylation leading to capecitabine resistant malignant mesothelioma
Authors: Kosuri K. V. , Wu X. , Otterson G. 
Published: March 2020

17105 Background: Malignant mesothelioma is a deadly malignancy whose global incidence continues to be on the rise. Established therapies have been less than optimal. The current therapeutic standard is intravenous pemetrexed, an antifolate medication. Yet, another folate antimetabolite, capecitabine, is significantly less effective than pemetrexed. The enzymes thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidylate phosphatase (TP) are critical to the efficacy of antifolates. Specifically, for capecitabine to be converted into a potent cytotoxic agent, the enzyme TP must be present and active. In one of four mesothelioma cell lines examined, the gene that encodes for TP, extracellular growth factor-1 (ECGF-1), is methylated. Methylation of this gene and the subsequent downregualtion of the TP enzyme confer a diminished cytotoxic effect by a capecitabine prodrug, dioxyfluridine (DFUR). Methods: Cells were cultured treated with and without 1uM decitabine (DAC) under identical conditions. DNA, RNA, and protein lysates were collected after 72 hours. Bisulfite-treated DNA was examined by MS-PCR for evidence of methylation of TS, DPD, and TP. RNA was collected and cDNA was synthesized. Real time PCR was utilized to detect the relative difference in RNA quantity. Western blots were done to evaluate the differences in protein expression between DAC treated and untreated cells. MTT assay was performed with DAC pretreated and untreated cell lines subsequently treated with DFUR and 5-fluorouracil. Results: One of the four mesothelioma cell lines showed consistent evidence of TP methylation by MS-PCR. The addition of 1uM DAC to the cell lines conferred a six-fold difference in expression of the methylated gene by both real time PCR as well as by Western blot. The prodrug DFUR subsequently shows increased cytotoxicity in the methylated cell line by MTT assay when pretreated with DAC compared when not exposed to the DAC. Conclusion: By demethylating the ECGF-1 gene with DAC, the now upregulated TP enzyme has an increased ability to convert DFUR to 5-FU; thus enhancing the cytotoxicity of a drug thought to be ineffective in malignant mesothelioma. No significant financial relationships to disclose.
Sleeve lobectomy an affidable lung sparing procedure
Authors: Cavallesco G. , Maniscalco P. , Quarantotto F. , Acerbis F. , Santini M. , Brombin C. , Valieri L. , Azzena G. 
Published: March 2020

17159 Background: Sleeve Lobectomy (Sl) is generally considered a surgical alternative of choice to Pneumonectomy (Pn) for the treatment of central NSCLC. The aim of this study is to value if the Sl could be really a Lung saving procedure that warrants right survivals, according to stage of disease, with acceptable perioperative risks. Methods: In 165 patients (67 Sl and 98 Pn) operated from 1995 to 2003 for NSCLC of main bronchus we have analyzed the hospital stay, morbidity and mortality within 30 days, long term survival. In 39 Sl and 46 Pn we compared spyrometric volume’s changes at a distance of 6–24 months from operation. Sl was performed where it was technically possible. Long term survivals had been separated and comparated according to pathologic stadium (TNM 1997) and lymphonodal involvement: all these data were estimated by Kaplan-Meier method and log rank test. All statistical data underwent SPSS elaboration and significant assumption for p < 0.05. Results: In our population of study we didn’t check any statistically significant’s differences comparing age, sex or preoperative Fev1. Complications occurred in 28% of cases where Sl was performed and in 36.7% after Pn with a mortality rate of 2.9% vs 5.1%. Average hospital staying was longer in patients underwent to Pneumonectomy. Long term survival (5 years) in Sl group is 36% and 24% in Pn group with a statistically significant difference P = 0.016, but this difference is not evident from the comparison between the two group’s survivals based on pathological stadium or lymphonodal involvement. Spyrometric values showed a global Fev1 reduction of 245 ml (−10%) after Sl procedure and 884ml (36.3%) after Pn with a significant difference of p = 0.0042. Conclusions: In this study Sl got similar survival results if not better, with those obtained after Pn. Moreover, Sl showed to be a lung sparing procedure with an acceptable operative risk. These data confirmed that SL is the gold standard surgical procedure in the treatment of central tumors where if technically possible. [Table: see text] No significant financial relationships to disclose.
Clinical and biological implication of defective p53 pathway in multiple myeloma (MM)
Authors: Chng W. J. , Price-Troska T. , Van Wier S. , Jacobus S. , Blood E. , Henderson K. , Oken M. M. , Van Ness B. , Greipp P. , Fonseca R. 
Published: March 2020

17516 Background: The p53 tumor suppressor is commonly inactivated by mutations. Even in tumors without mutations, there are defects in the response to p53 activation. In MM, the prognostic significance of p53 mutation is unknown, while there has been no systematic study of p53 function. We seek to address these issues in this study. Methods: p53 mutation was studied by conformation sensitive gel electrophoresis with primers encompassing exons 1 to 10 followed by sequencing of DNA fragments with altered electrophoretic pattern in newly diagnosed MM patients entered into ECOG E9486 trial where patients were randomized to receive variations of melphalan-based conventional chemotherapy (VBMCP). Fisher’s exact tests were used to compare variables between patients. Kaplan-Meier survival curves were compared using the log-rank test. To investigate p53 function, we analyzed the expression of p53, and 3 of its transcriptional targets, APAF1, p21 and MDM2, in a separate cohort of 15 normal plasma cells (PC), 14 MGUS, 13 smoldering myeloma (SMM) and 101 MM (73 new and 28 relapsed) from the Mayo Clinic who had gene expression profiling performed on the Affymetrix U133A chip (Santa Clara, Ca). Results: Two hundred and sixty-eight patients had enough materials for study and were included in the analysis. The prevalence of p53 mutation was 3% (n = 9). Five of the 9 patients (56%, p = 0.001) with mutations also had p53 deletion (studied by fluorescent in-situ hybridization) resulting in bi-allelic loss of p53. Soft tissue plasmacytomas (37% v 7%, p = 0.018), and among the common translocations, t(4;14) and t(14;16) (50% v 18%) were more common in patients with p53 mutations. Despite similar response to treatment, those with p53 mutation had very short OS (16.7 v 41.4 months, p < 0.001). There was induction of p53 expression in MGUS and SMM with concurrent induction of APAF1, p21 and MDM2 whereas loss of this pattern was frequent in MM (45% in new MM and 60% in relapse MM compared to 15% in MGUS/SMM (p = 0.03)). Conclusions: p53 mutations are relatively rare in newly diagnosed MM patients but portend a short survival. However, functional abnormalities of p53 are prevalent and may be important in progression from MGUS/SMM to MM. [Table: see text]
Bronchial-associated lymphoid tissue (BALT) lymphoma: a retrospective analysis
Authors: Steffanoni S. , Pruneri G. , Spaggiari L. , Preda L. , Laszlo D. , Calabrese L. , Zucca E. , Bassi S. , Martinelli G. 
Published: March 2020

17547 Background: Systemic CT in BALT lymphoma is the accepted therapy for those pts where surgery isn’t radical or possible. There is not a standard systemic treatment for this uncommon lymphoma however its indolent behavior and the relative asymptomatic outcome, allows on systemic therapy delay and may justify the use of less toxic CT agents. Methods: Here we reported our experience on 19 pts (10 men and 9 women) with biopsy-proven BALT lymphoma, median age was 61 yrs; 8 pts presented a symptomatic disease at diagnosis. 15 pts had a localized pulmonary disease (stage IE); 4 pts had stage IVE disease for peripheral blood and bone marrow involvement (3 pts) and gastric involvement (1 pt). Of 16 pts valuable for response, 3 pts received radical surgery (1 wedge resection and 2 lobectomy) as definitive treatment and 13 pts received systemic treatment (Chl containing regimen in 6, Rituximab ± Chl in 6; CVP regimen in 1) because of symptomatic disease or relapse after major surgery. Results: 6/13 pts achieved CR: 5/6 are still alive and disease free: 1 pt in CR died for other causes. 3 pts in asymptomatic PR don’t need further therapy while the additional 4 pts in PR need subsequent treatment because of symptomatic progression after a median TTP of 40 months. With a median follow up of 39 months, the OS and RFS observed are 85% and 63% respectively. Hematology and non-hematology toxicity was in general mild: transient G3 neutropenia occurred in only two pts; no pt discontinued the treatment because of treatment-related toxicity and no toxic death was recorded. Conclusions: Our analysis seem to confirm that surgery could be considered as unique treatment only for minority of pts with BALT lymphoma. Systemic chemotherapy with Chl containing regimen may achieve a clinical control of disease with about 50% of CR as well as other reported with more aggressive CT regimen. A larger retrospective analysis on pathological figure and clinical outcome is planned on behalf of IELSG. No significant financial relationships to disclose.
A phase I/IIa clinical trial of CLAOP21 and CLAOP14 in patients with high grade non-Hodgkins lymphoma and cardiac risk factors
Authors: Busse A. , Huetter G. , Siehl J. M. , Schmittel A. , Keilholz U. 
Published: March 2020

17548 Background: CHOP combination chemotherapy is the most effective and least toxic regimen for high-grade Non-Hodgkin’s-lymphoma (NHL). Doxorubicin, however, presents a problem in patients at risk for cardiotoxicity. Pegliposomal doxorubicin is a liposomal preparation of doxorubicin with minimal cardiotoxicity. In the CLAOP regimen reported here, we substituted conventional doxorubicin in the CHOP regimen by pegliposomal doxorubicin. Methods: An open-label phase I/IIa study was performed evaluating CLAOP21/20 with 20 mg/m2 of pegliposomal doxorubicin every 21 days, and a dose-dense CLAOP14 regimen supported by G-CSF or pegylated G-CSF every 14 days with escalating doses of pegliposomal doxorubicin in elderly high-grade lymphoma patients. Results: A total of 12 patients were enrolled for CLAOP 21/20, and 24 patients for CLAOP 14/20. CLAOP21/20 was well tolerated with a degree of hematotoxicity similar to that reported with regular CHOP. In the CLAOP14 cohort, a trend towards cumulative hematotoxicity. Palmar plantar erythema (PPE) exceeding grade II and other non-hematological toxicities exceeding grade I, except of alopecia, were not observed. A pegliposomal doxorubicin dose of 25 mg/m2 (CLAOP14/25) was associated with dose-limiting haematotoxicity, febrile episodes, and PPE. Both, the 3-weekly and the 2-weekly regimens were active with an overall response rate of 60% and 77%, respectively. Cardiotoxicity attributable to doxorubicin was not observed in any patient. Conclusions: The recommended dose of pegliposomal doxorubicin in the biweekly CLAOP regimen for Phase II/III testing is 20 mg/m2, a regimen that can safely be administered to old patients without apparent cardiotoxicity. [Table: see text]
Level of circulating endothelial cells as new biomarker in patients with multiple myeloma, treated with bortezomib-pegylated liposomal doxorubicin-dexamethasone combination
Authors: Gevorgyan A. , Pitini V. , Arrigo C. , Altavilla G. , Naro C. , Alu M. , Procopio G. , Verzoni E. , Platania M. , Bajetta E. 
Published: March 2020

17551 Background: Bortezomib is a proteasome inhibitor and has effects on both multiple myeloma (MM) tumor cells and stromal cells. Recent data suggests that relative levels of circulating endothelial cells (CECs) may serve as surrogate markers of myeloma activity. Hence, we assay the number of CECs by cell phenotype, to explore the activity and response to treatment with BMD (Bortezomib, Myocet, Dexametasone) in previously untreated MM patients. Methods: Twelve pts. with newly diagnosed multiple myeloma were enrolled in this study. Panel of monoclonal antibodies and appropriate analysis gates were used to enumerate CECs. Patients received Bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11, pegylated liposomal doxorubicin (30 mg/m2-Myocet) on day 1 and dexamethasone (40 mg/daily for 4days) for four cycles (q21) before Cyclophosphamide (5 g/m2) and G-CSF mobilization, followed by peripheral blood stem cell collection. The pts received high-dose Melphalan (MEL200) with PBSC transplantation. Samples of healthy controls were used to compare CECs levels. Results: After the treatment with BMD 4 patients had a complete remission, 2 nCR, 5 VGPR and 1 PD. All pts. underwent PBSC mobilization and 11 out of 12 were mobilized, with a median of 3.50 × 106 CD34+ cells/Kg collected with a median of 2 (range 1–4) collection procedures. Responding pts. (11) received high-dose Melphalan with stem cell transplantation. The median time to reach neutrophil and platelet regeneration was 13.5 days and 13 days respectively. In healthy controls (N° 18) mean values of CECs were 0.05% (0.1–0.62). Before treatment with BMD mean CECs level in study patients was 0.79% (0.54–1.53). After BMD treatment CECs in responding pts. was 0.07% (0.1–0.70; p < 0.01). Conclusion: BMD combination therapy in newly diagnosed MM pts. has a high response rate, it does not influence on subsequent stem cell collection, is associated with modest toxicity, furthermore, CECs value can serve as new biomarker for myeloma activity. No significant financial relationships to disclose.