bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 2 study of suberoylanilide hydroxamic acid (SAHA) in relapsed or refractory indolent non-Hodgkin lymphoma: A California Cancer Consortium study
Authors: Kirschbaum M. , Zain J. , Popplewell L. , Pullarkat V. , Obadike N. , Frankel P. , Zwiebel J. , Forman S. , Newman E. , Gandara D. 
Published: March 2020

18515 Background: The indolent (follicular, marginal zone and mantle cell) lymphomas tend to recur with decreasing intervals of remission post standard chemotherapy. Vorinostat (SAHA, Zolinza), an orally administered hydroxamic acid histone deacetylase inhibitor with activity against class I and II deactylases, with preclinical and clinical activity against various forms of lymphoma, is being studied in patients with relapsed or refractory indolent lymphoma. Methods: Patients with relapsed or refractory follicular, marginal zone, or mantle cell lymphoma are eligible. Vorinostat is dosed at 200 mg po twice daily for 14 consecutive days on a 21 day cycle. CT scanning and marrow biopsy is performed after every three cycles. Patients may have received up to four prior chemotherapy regimens including Zevalin or Bexxar; previous transplant is allowed. Results: 15 patients (9 female, 6 male) have been enrolled thus far. Median age is 64 (40- 78) years One patient was found to have coexisting DLBCL and was removed from study. Four patients were taken off study due to progression, three stopped due to toxicity (fatigue in a 73 yo woman who had stable to improved marginal zone lymphoma after 10 cycles, fatigue and atrial fibrillation in a 65 yo man after 7 cycles, diarrhea in a 78 year old woman after 2 cycles). Complete Response (CR) in a patient with follicular lymphoma was attained after 9 cycles, this CR persists now for eight months at the time of abstract submission off therapy. A partial response (PR) was seen in a 40 yo man with lymphoma progression despite multiple rounds of therapy, with rapidly expanding masses just prior to starting vorinostat, the largest of which was 16x12.3 cm. This lesion currently measures 7.2x4.6 cm, with disappearance of many other sites; patient continues on vorinostat. Three of the patients with continued stable disease beyond 9 cycles have marginal zone lymphoma, while the two responders (CR or PR) have follicular lymphoma. A patient with PET resolution and decreases in two of the involved sites stopping after 10 cycles due to fatigue, developed rapid progression three months after stopping vorinostat. Conclusions: Vorinostat demonstrates preliminary activity against follicular and marginal zone lymphoma. No significant financial relationships to disclose.
A large multicentric study of gemcitabine-based regimen in relapsed or refractory Hodgkin lymphoma (HL) patients (pts)
Authors: Validire P. , Fermé C. , Brice P. , Diviné M. , Gabarre J. , Bouabdallah K. , Fitoussi O. , Chaoui D. , Soussain C. , Carde P. , Decaudin D. 
Published: March 2020

18518 Background: The aim of this study was to assess the efficacy and safety of gemcitabine-based regimen in heavily pretreated HL pts. Methods: Relapsed or refractory HL pts treated with gemcitabine were retrospectively reviewed. Gemcitabine was used as a single agent or administered in combination with vinorelbine, oxaliplatine, doxorubicine, vinblastine, rituximab, and/or corticosteroids. Results: Fifty-five pts treated in 9 departments of clinical hematology between January 1999 and August 2006 were included in the study. Initial characteristics before gemcitabine administration were: nodular sclerosis in 84%; sex ratio M/F 1.1; median age 29 years (range: 15–85 years); advanced stage 84%; extranodal sites were lung, bone, liver, soft tissues, and bone marrow in 68%, 31%, 13%, 21%, and 4%, respectively; Hasenclever index lower than 3 in 20/43 cases (47%). At the end of the first front-line therapy (chemotherapy ± radiotherapy), 19 pts (35%) were in complete response (CR) in whom 13 relapsed within one year, 5 were in partial response (PR), and 31 pts were primary refractory (56%). Median number of previous chemotherapeutic regimen was 3 (range 1–8), 39 pts (71%) have received radiotherapy (RT), and 34 pts (62%) one or two autologous/allogenic stem cell transplantations (A/ASCT). Twenty-nine pts received gemcitabine alone with a median initial dose per injection of 750 mg/m2 (range: 180–1250 mg/m2); Gemcitabine was administered at an initial dose per injection of 1000 mg/m2 (range: 500–1250) in combination with vinorelbine in 10 pts, oxaliplatine in 13 pts in whom 4 with rituximab, and with others drugs in 3 pts. In both cases, the median number of combined gemcitabine regimen injections was 6 (range: 1–27). Toxicity was mainly hematological (75% of pts developed bi- or pancytopenia) or infectious (13%). Among all included pts, 6 were in CR (11%) and 5 in PR with an overall response rate of 20%. Among the 6 CR, 5 pts received thereafter A/ASCT and 2 pts RT, with 2 persistent CR at 16 and 44 months. In univariate analysis, none prognostic factor for response to gemcitabine was identified. Conclusions: This study, which constitutes one of the most important series, showed a mild efficacy of gemcitabine-based regimen in heavily pretreated HL patients. No significant financial relationships to disclose.
Absence of chlamydial infection in Japanese patients with orbital adnexal MALT lymphoma
Authors: Yakushijin Y. , Kodama T. , Tanimoto K. , Yamanouchi J. , Azuma T. , Narumi H. , Hato T. , Hasegawa H. , Yasukawa M. 
Published: March 2020

18523 Background: The extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a distinct B-cell lymphoma that develops in extranodal sites and usually has an indolent clinical course as a localized disease. Recent clinicopathological studies suggest a strong relation between MALT lymphoma and inflammatory diseases of the epithelium such as autoimmune diseases and infections (Sjogren’s syndrome, Hashimoto’s thyroiditis, Helicobacter pylori infection, and etc.), because chronic antigen stimulation has been causally linked to the development of B-cells lymphoproliferative diseases. MALT lymphoma grows in extranodal lymphoid tissue and exists in epithelium tissues, and it is often difficult to distinguish malignant lymphoid tissue from benign inflammation. This is one cause since recent positive or negative correlations between ocular adnexal MALT lymphomas and chlamydial infections have been reported from different researchers, indicate several possible explanations. Methods: Twenty-three cases of ocular adnexal MALT lymphoma in southern regions of Japan, whose monoclonality was confirmed by immunoglobulin heavy chain gene rearrangement and/or cell surface antigens, were analyzed for evidence of several causative factors using ELISA analysis to detect antibodies and Southern blot analysis followed by specific PCR gene amplification. Results: Our series of patients did not show any serological relations to Epstein-Barr virus, Hepatitis C virus, and Chlamydophila psittaci. Two cases had positive serum antibodies for autoimmunity, and another two cases had positive antibodies against Chlamydia trachomatis. None of our cases showed the presence of chlamydial 16S rRNA and 16S-23S spacer rRNA genes (C. psittac, C trachomatis, C. pneumoniae, and C. felis) after Southern blot analysis followed by PCR amplification. Conclusions: Inflammatory agents are still unknown in our series of orbital adnexal MALT lymphomas, and some types of chlamydial infections are not associated with orbital adnexal MALT lymphoma in southern regions of Japan. No significant financial relationships to disclose.
Restrospective analysis of non-Hodgkin lymphoma (NHL) patients (p) treated with 90Y ibritumomab tiuxetan (90Y- IT): Iberia RIT database
Authors: Giraldo P. , Gómez Codina J. , Provencio M. , Hernando T. , Tisaire J. L. 
Published: March 2020

18526 Background: 90Y-IT is approved for the treatment of refractory NHL. The aim of this study was to collect data of NHL p treated with 90Y-IT within the clinical practice setting, to retrospectively analyze treatment effectiveness and tolerability, in order to provide a pragmatic approach to experimental data. Methods: Multicenter, retrospective study. NHL p treated during last year with 90Y-IT, were registered. Effectiveness endpoints retrospectively studied were: objective response rate (ORR), time to progression (TTP) and overall survival (OS). Clinical prognostic factors were collected to asses their possible influence upon treatment effectiveness, by multivariate analyses. Results: 65 p were registered: M/F, 58.5%/41.5%; median age, 59 years (22–83); ECOG 0–1, 73.3%. Median time since lymphoma diagnosis was 3.6 years. At diagnosis, 84.6% had follicular lymphoma (grade 1, 44.9%; grade 2, 40.8%) and 15.4% non- follicular lymphoma. Most of the cases were refractory to previous treatments (78.1%). Median number of previous treatments was 3 (range 1–8) Median administered dose of 90Y-IT was 0.4 mCi/Kg. ORR was 70.8% (95% CI: 59.8, 81.9). With a median follow-up time of 6 months, median TTP was 16.1 months (95% CI: 11.2, 21.1) and median OS has not been achieved. Within the group of follicular lymphoma, ORR was 74.6% (95% CI: 63.1–86.1) and TTP 17.7 months (95% CI: 14.3, 21.1). Bone marrow involvement and high FLIPI score were significantly associated with higher risk of progression disease: hazard ratio 3.71 (95% CI: 1.00, 13.68) and 21.12 (95% CI: 2.37, 187.91), respectively. Median time to G3–4 haematological toxicity ranged between 27–38.5 days, being the most frequent thrombocitopenia (46.2%) and neutropenia (33.8%). 17 p required red blood cell transfusions (median, 4 U) and 19 required platelet transfusions (median, 7 U). The most frequent G3–4 non haematological toxicity was asthenia (10.8%). Updated survival data will be presented at the meeting. Conclusions: These results obtained with 90Y-IT for NHL treatment within the clinical practice setting are concordant with published experimental data, despite the limitations of the retrospective design. [Table: see text]
CD44 standard isoform expression is associated with diffuse large B cell lymphoma of non-germinal center B cell-like types
Authors: Kim W. , Oh Y. , Park C. 
Published: March 2020

18531 Background: Diffuse large B cell lymphoma (DLBCL) can be subdivided into germinal center B cell-like (GCB) and non- germinal center B cell-like (Non-GC) types by immunohistochemical profiling. Previous studies showed better survival rate for the GCB groups. CD44 is necessary for tumor spread and metastasis and its expression is generally associated with unfavorable prognosis. We analyzed the expression and prognostic significance of standard isoform CD44s and its variant isoform CD44v6 in DLBCL types. Methods: Tissue microarray blocks were created from 52 nodal DLBCL with control tissue. Immunohistochemical staining for CD10, Bcl-6, MUM-1, CD44s, and CD44v6 were performed. The median follow-up period was 44 months. Results: Nodal DLBCLs were subclassified into GCB [CD10+ or CD10-/Bcl6+/MUM1+, n=17 (33%)] and non-GC subgroups [CD10-/Bcl6- or CD10-/Bcl6+/MUM1+, n=35 (67%)]. CD44s expression appeared more on non-GC cases of DLBCL (p=0.04). CD44s and CD44v6 did not result in any difference according to tumor stage, IPI scores, LDH levels. Upon survival analysis, CD44s and CD44v6 expression did not show any statistical correlation. Conclusions: CD44s expression may play a role during lymphomatogenesis of non-GC type DLBCL. No significant financial relationships to disclose.
Clinical implication of distinction from clinical features and treatment outcome of malignant lymphoma in Korean childhood and young adult
Authors: Hwang I. , Yoo K. , Lee S. , Park S. , Park B. , Ko Y. , Kim K. , Park K. , Koo H. , Kim W. 
Published: March 2020

18534 Background: The Clinicopathologic features of malignant lymphomas vary to geography and differ to age. The goal of this study was to find the implication of distinction from biology, clinical features and treatment outcome of malignant lymphoma in childhood and young adult. Methods: We analysed the clinical features including age, gender, histologic type, and treatment outcome of 294 children and young adults during 13-year period (from May 1993 to November 2005) in Samsung medical center and compared our study to all age group and western childhood and adolescence group on clinical features or treatment outcome in malignant lymphoma. Results: Median age at diagnosis was 20.7 years (range: 0.1–30.1 years). Male to female ratio was 1.37:1, Of 294 cases, there were 248 cases of non-hodgkin’s lymphoma (NHL) (84.3%) and 44 cases of hodgkin’s disease (HD) (15%). This rate was significantly different to rate of all age group (HD= 5.3%) (p=0.001). Of 248 cases of non-hodgkin’s lymphoma, 134 cases (54.0%) were B-lineage and 113 cases (45.6%) were T- or NK-cell lineage. Our study group had higher rates of T- or NK-cell NHL compared to all age group (p=0.001) and western group (p=0.001). Among 248 cases of NHL, the most common histologic type was diffuse large cell lymphoma (DLBL) in our study group. Burkitt’s lymphoma (BL) was the most common histologic types in Western study group. 5-year survival rate (5YSR) was 80.4% and was superior for BL and was inferior for NK/T cell lymphoma. However male T-LBL patients had better outcome in western study group. NHL and T-cell NHL had significantly worse outcomes than HD and B-cell NHL (p=0.049, 0.001, respectively). Comparing age-groups 0–10, 10–20 and 20–30, 5YSR was inferior for the oldest patients only in NHL-, T-cell NHL- and T-cell LBL-groups. Conclusions: Our study suggested environmental and genetic factor was associated with the development of malignant lymphoma. No significant financial relationships to disclose.
Avascular necrosis of the jaw in multiple myeloma (MM) patients (pts) treated with bisphosphonates (BP)
Authors: Curreli L. , Palmas A. D. , Latte G. , Murgia A. , Gabbas A. 
Published: March 2020

18538 Background: Oral cavity avascular bone necrosis (ABN) has been recently reported as an emerging serious complication in pts receiving BP for the treatment of hypercalcemia related to MM or metastatic solid tumors. Methods: We report the cases of 6 pts with MM treated initially with pamidronate and later with zoledronic acid (ZA). Results: Pts characteristics : M/F 3/3; mean age 58.4 (46–78); 4 IgG κ,1 γ and 1 κ MM; 5 St IIIA and 1 IIIB; mean history of disease 61.3 mo. (23–103); 5 pts had a relapsing MM refractory to several lines of therapy but 1 pt had received only high dose dexametazone (D); 2 pts had received autologous stem cell transplantation and 1 pt allogenic bone marrow transplantation; mean n.° of BP doses was 41.3 (17–81). At the time of ABN onset all pts were receiving ZA along with, respectively: D (2 pts); cyclophosphamide plus D (1 pt), bortezomib plus D (2 pts) and oral melphalan (1 pt). ABN was localized in 2 pts at alveolar bone of the right maxilla and presented as an inflammation of the gum, followed by a painful bone exposure. In the other 4 pts ABN was localized at mandible and presented as dental abscesses followed in 2/4 pts by cutaneous fistulization. Treatment has included in all pts discontinuation of ZA, antibiotics, chlorhexidine mouthwashes, pain control, minor regional débridement, and bone trimming. In 1 pt a more aggressive surgical approach was attempted at an other Institution and postoperative course was complicated by massive haemorrhage and complete loss of chewing. Four pts dead with progressive disease with a mean overall survival after ABN presentation of 6 mo.; 2 pts are alive after 3 and 4 mo. after ABN presentation; however in all pts ABN significantly worsened quality of life. Conclusions: Oral cavity ABN is a severe complication in refractory MM pts receiving BP. Mechanisms of action of BP that determine a reduction in osteoclastic activity and an accumulation of nonvital osteocytes with microfractures of old mineral matrix appear to play an important role. However other causes may be involved as a long history of disease; an uncontrolled progressive disease; type and doses of previous and present therapies, primarily steroids; status of oral cavity and teeth of pts and possibly the n.° of doses of BP. No significant financial relationships to disclose.
Effect of combined treatment of bortezomib and valproic acid on multiple myeloma cells
Authors: Kim B. , Ahn K. , Kim I. , Park S. , Kim B. , Yoon S. 
Published: March 2020

18539 Background: Valproic acid (VPA) has an activity of histone deacetylase inhibitor that is known to have in vitro cytotoxic effect on multiple myeloma (MM) cells. It was investigated that VPA could synergize with bortezomib for human MM cell lines. Methods: U266 cell lines were treated with bortezomib 50nM and/or VPA 0.6mM and then MTT assay, cell cycle analysis using FACS, immunoblot analysis, caspase-3 activity assay, and IL-6 ELISA assay were performed. Results: Bortezomib activated caspase-3 and induced G1 cell cycle arrest. In MTT assay, VPA suppressed the U266 cell proliferation with IC50 of 0.6mM and combined treatment of bortezomib and VPA had more inhibitory effect than bortezomib alone. This combination caused further G1 cell cycle arrest, caspase-3 activation, and lowered IL-6 secretion from U266 cells than bortezomib, respectively. In immunoblot analysis, this combination further decreased the expression of cyclin A, cyclin D1, cyclin E, CDK2, CDK4, and CDK6, whereas up-regulated p21 and p27 expression than bortezomib alone. Conclusions: The combined treatment of bortezomib and VPA has a more significant anti-myeloma effect than bortezomib alone. No significant financial relationships to disclose.
The value of combined modality therapy in elderly patients with stage III non-small cell lung cancer (NSCLC)
Authors: Schild S. E. , Mandrekar S. J. , Jatoi A. , McGinnis W. L. , Stella P. J. , Deming R. L. , Jett J. R. , Garces Y. I. , Allen K. L. , Adjei A. A. 
Published: March 2020

19503 Background: This study was performed to assess the value of combined modality therapy in elderly patients by comparing the differences in outcome of those who received radiotherapy (RT) alone or RT plus chemotherapy for stage III NSCLC. Methods: North Central Cancer Treatment Group (NCCTG) performed 2 recent phase III trials for stage III NSCLC. The first trial, 90–24–51, included 3 arms: once-daily radiotherapy (QDRT) alone, twice daily RT (BIDRT) alone, and concurrent chemotherapy plus BIDRT. The second trial, 94–24- 52 included 2 arms and compared concurrent chemotherapy with either QDRT or BIDRT. The chemotherapy arms of both trials included etoposide and cisplatin administered concurrently with RT. Only the patients ≥65 years of age (elderly) who participated in these trials were included in this analysis. Results: Of the 166 elderly patients included in this analysis, 37 received RT alone and 129 received concurrent chemotherapy plus RT. The median and 5-year survival rates were 10.5 months and 5.4% for the RT alone group compared to 13.7 months and 14.7% for the RT plus chemotherapy group (log-rank p=0.05). Patients who received RT plus chemotherapy experienced significantly greater severe (grade ≥3) toxicity than those who received RT alone (89.9% versus 32.4%, p < 0.01). Conclusions: Elderly patients who participated in these trials appear to gain a survival advantage from RT and chemotherapy compared to RT alone. As is the case with younger patients, this benefit comes at the cost of additional toxicity. No significant financial relationships to disclose.
A novel xenograft model to test the ovarian toxicity of chemotherapy agents in women
Authors: Oktay K. H. , Oktem O. 
Published: March 2020

19504 Background: Many chemotherapeutic agents, especially of alkylating family, alter fertility in premenopausal females (1). While the impact of well-established agents such as cyclophosphamide (Cy) on fertility is well known (2), data are not available for newer agents. Moreover it is not practically possible to determine the individual ovarian-toxicity of each drug and the cellular mechanism of this damage from clinical trials.Thus our specific aim was to develop a xenograft model to characterize the impact of chemotherapy agents on human ovary. Methods: Ovarian pieces of 2x2 mm from 24 wk old abortuses were xenografted subcutaneously to immunodeficient mice (SCID) (n=52). At this gestational age ovarian histology is simiar to young females. Half of the animals received a single dose of 200 mg/kg of Cy intraperitoneally 14 days after the xenografting, while the other half received saline. Grafts were recovered from the control and treated mice 12, 24, 48, and 72h after the Cy injection (n=6–7 per time point), and serially sectioned for primordial follicle counts. Apoptosis was assessed with TUNEL assay. PECAM-1 staining, as well as intra-vital fluorescein conjugated lectin and Evans blue labeling were performed to assess microvasculature by confocal microscopy. All experiments were performed in triplicate. Results: While there was only 12 % loss 12h following the treatment compared to controls (p>0.05), the follicle loss significantly increased at 24h (53%, p<0.01) and peaked at 48h (93 %, p<0.0001), and reduced at 72h (70 %, p<0.001). TUNEL staining peaked at 12h, earlier than the follicle loss; then decreased at 24h and 48h, and faded at 72h. Less than 1% of follicles were TUNEL positive in controls. Xenograft vasculature was similar to non-xenografted tissue indicating that the ex vivo tissue drug delivery was similar to the in vivo delivery. Conclusions: A single injection of a typical dose of Cy can result in the loss of up to 93 % of ovarian reserve in a human ovarian xenograft model, consistent with the data from clinical trials. Fetal ovarian xenografting is a promising model to characterize the gonadotoxic effects of current and emerging cancer drugs without a need for lengthy clinical studies. 1. J Clin Oncol. 2006;24:2917–31 2. Hum Reprod Update. 2004;10:251–66. No significant financial relationships to disclose.
Comparison of bedside estimates of renal function and measured glomerular filtration rate (GFR) in 510 adult oncology patients
Authors: Dooley M. J. , Poole S. G. , Rischin D. 
Published: March 2020

19512 Background: Various bedside formulae have been used in practice to estimate renal function to predict drug dosing. Recently the ‘4-variable Modification of Diet in Renal Disease’ (4-v MDRD) equation1 was derived in patients with chronic renal disease and has been advocated for application in oncology. The aim of this study was to compare measured GFR with estimates from formula based equations in adult oncology patients. Methods: GFR was determined using technetium-99m diethyl triamine penta-acetic acid (Tc99mDTPA) clearance, serum creatinine (Jaffe method) was measured and renal function estimates calculated using 4-v MDRD, Cockcroft and Gault (CGF), Wright, Martin, and Jelliffe (JF) formulae. Accuracy, bias (mean % error (MPE)) and precision were assessed for varying levels of GFR, body mass index (BMI), age and gender. Results: In 510 adult oncology patients (323 male, 187 female, mean age 63years, range 17–87years) GFR was determined using Tc99mDTPA clearance (mean 84mL/min, range 16–205mL/min). The mean (range) calculated GFR was 72mL/min/1.73m2(9–162mL/min/1.73m2), 71ml/min (11–267mL/min), 78mL/min (12- 195mL/min), 81mL/min (12–279mL/min), 64mL/min/1.73m2 (10–165mL/min/1.73m2) for 4-v MDRD, CGF, Wright, Martin, and JF formula respectively. Bias, precision and accuracy (%within 30% and 50% of true GFR) of estimates are shown in the table . The Wright and Martin formulae had greater bias relating to degree of renal function and gender respectively. The 4-v MDRD equation provided a less biased estimate compared to the CGF across all levels of renal function and BMI. Conclusions: When compared to measured GFR, the 4-v MDRD equation provides a less biased estimate compared to the other formulae evaluated across a range of variables including degree of renal function and BMI. The limitations of all the bedside estimates must be understood to allow appropriate clinical utility. 1. Levey AS, et al. Ann Intern Med 2006; 145: 247–254. [Table: see text] No significant financial relationships to disclose.