bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural history and clinical prognosis of in situ mantle cell lymphoma.
Authors: Kubal Timothy Edward , Peker Deniz , Sagatys Elizabeth , Zhang Ling , Naghashpour Mojdeh , Moscinski Lynn , Sotomayor Eduardo M. , Sokol Lubomir , Bello Celeste M. , Cultrera Jennifer L. , Chervenick Paul A. , Shah Bijal D. 
Published: March 2020

e18506 Background: In-Situ Mantle Cell Lymphoma is a rare clinical entity that presents with involvement limited to the mantle zone of secondary follicles. Its true incidence may be underestimated and its natural history and clinical behavior remains poorly characterized given the small number of representative cases available in the literature. Current guidelines for patients diagnosed with In-Situ Mantle Cell Lymphoma advocate staging studies and close follow-up with treatment based on the clinical behavior of the disease. Methods: Database review of 204 patients diagnosed with Mantle Cell Lymphoma at Moffitt Cancer Center between May 1992 and December 2010 Results: Three cases of In-Situ Mantle Cell Lymphoma were found and analyzed. Patients 1 & 2 had disease isolated to a single lymph node at diagnosis. In these cases, there were long latency periods of 5 and 9 years between initial resection of a single nodal site and later presentation with active, diffuse disease. Neither patient received therapy until progression with more advanced disease. Patient 2, who had a 9-year latency period was found to have complex cytogenetics suggesting evolution of the malignant clone during this prolonged latency period. Patient 3 presented with in situ disease in an inguinal node in conjunction with diffuse extranodal lung and forehead involvement, all noted at the time of diagnosis. Patient 1 obtained remission with Bendamustine & Rituxamab. Patient 2 obtained remission with HyperCVAD and Autologous HSCT consolidation. Patient 3 obtained remission after R-CHOP. Patients 1 & 2, both with long latency periods remain alive and free of disease, while patient 3 relapsed with extranodal disease 3 years after initial therapy. Conclusions: The natural history of In Situ-Mantle Cell Lymphoma varies with prolonged latency periods present in some patients. The genetic profile of the lymphoma may evolve during these latency periods portending a more aggressive clinical course at progression. Patients with newly diagnosed In-Situ Mantle Cell Lymphoma with no other evidence of active disease should be followed expectantly with therapy reserved for those patients whose disease progresses during followup.
Prognostic impact of immunohistochemically defined germinal center B-cell and nongerminal center B-cell subtypes of diffuse large B-cell lymphoma in rituximab era.
Authors: Cao Yabing , Huang Ying , Ye Sheng , Lin Tongyu 
Published: March 2020

e18517 Background: Diffuse large B-cell lymphoma (DLBCL) can be molecularly subtyped as either germinal center B-cell (GCB) or non-GCB. The role of rituximab(R) in these two groups remains unclear. Methods: We studied 204 patients with de novo DLBCL (107 treated with CHOP; 97 treated with R-CHOP); patients being stratified into GCB and non-GCB on the basis of BCL-6, CD10 and MUM1 protein expression. The relationships between clinical characteristics, survival data and immunophenotype were studied. Results: The median follow-up was 51months for CHOP group and 56 months for R-CHOP group. The 5-year overall survival (OS) in the CHOP and R-CHOP group was 50.4% and 66.6% (p=0.031), respectively. GCB patients had a better 5-year OS than non-GCB patients whether treated with CHOP (65.0% vs. 40.9%; p=0.011). In contrast, there’s no difference in the 5-year OS for the GCB and non-GCB with R-CHOP (76.5% vs. 61.3%; p=0.141). In non-GCB subtype, additional rituximab improved survival than CHOP (61.3% vs. 40.9%; p=0.0303). Conclusions: These results indicated that addition of rituximab to standard chemotherapy eliminate the prognostic value of immunohistochemically defined GCB and non-GCB phenotypes in DLBCL by improving the prognostic value of non-GCB subtype of DLBCL
Impact of lower chemotherapy dose on treatment outcome and survival of patients with advanced Hodgkin lymphoma: Single institution experience.
Authors: Tomasevic Zoran , Tomasevic Zorica 
Published: March 2020

e18531 Background: Combined chemotherapy regimen, although highly effective, still fail to cure about one third of patients with advanced Hodgkin lymphoma (aHL). On the other hand, similar proportions of patients are probably over treated and cure might be obtained with less intensive doses. The aim of this retrospective analysis is to evaluate chemotherapy dose intensity and cumulative dose in aHL, in the context of treatment outcome and survival. Methods: At the Institute for Oncology and Radiology of Serbia, during 1991-1993 all consecutive aHL patients have been treated with MOPP (M; 41 pts) and afterwards (1994-1996) with MOPP/ABVD (M/A; 40 pts). In accordance to previous local practice, chemotherapy was given in projected, absolute doses, calculated on average body surface area of 1.7 m2. Characteristics of patients in both regimens were well balanced for age, gender, PS, B symptoms, histology, stage, laboratory prognostic parameters (International Prognostic Score- IPS). Approximately 50% pts in both groups were in high/intermediate risk IPS. Relative dose intensity (RDI), defined as given/scheduled dose ratio per week and relative cumulative dose (RCD), defined as given/projected dose ratio, were retrospectively analyzed whether there is potential negative impact on response, time to relapse and survival. Results: The average RCD and RDI for both regimens were 85% and 58%. Complete remission (CR) was achieved in 60% (M/A 67% vs. M 54%) (p=NS); 90% of pts with CR in both groups had no relapse during follow up. Different cumulative doses and dose intensity had no significant impact on time to relapse and overall survival. However, trend for better overall survival for patients receiving RDI over 60% was observed (p=0.09). Hemoglobin level ≤10.5 g/dl had significant adverse effect on outcome regardless of treatment dosage (p=0.02). No second malignancy has been registered during follow up. Conclusions: Although this retrospective analysis does not pretend to recommend lower chemotherapy dose regimen for routine treatment, it seems that selected aHL patients could still be effectively treated with less chemotherapy dose intensity, because 90% of pts with CR are cured.
Expression of mTOR in diffuse large B-cell lymphoma.
Authors: Gopaluni Srivalli , Vajpayee Neerja , Newman Nancy , Thakral Charu , Husain Juhi , Gajra Ajeet 
Published: March 2020

e18535 Background: The mammalian target of rapamycin (mTOR) pathway mediates protein synthesis, cell growth and survival of normal and malignant cells. This pathway is constitutively activated in several B-cell lymphomas. We studied immunohistochemical expression of mTOR, phosphorylated mTOR (pmTOR) and bcl-2 in 55 cases of diffuse large B-cell lymphomas (DLBCL) and their association with established prognostic factors as well as treatment outcomes in a retrospective single instituition study. Methods: After IRB review, 55 cases of DLBCL were identified. Immunostains for mTOR, pmTOR and bcl-2 were performed and their expression correlated with clinical and survival data. Associations of demographic (age and gender), clinical (stage, IPI score) and chemotherapy (RCHOP or other) with marker expression as well as association with recurrence and survival were studied using chi square and t-test for univariate analysis and logistic regression for multivariate evaluation. Results: Of the 55 patients, 44% were > age 65, 65% were males and 65% had advanced stage (III or IV) disease. High IPI scores were noted in 42% and 87% received the RCHOP regimen.On univariate analysis, high mTOR expression was associated with male gender (85% vs. 46%, p<0.01), high IPI score (67% vs. 18%, p, 0.001) and higher mean age (66 vs. 53 years, p < 0.001). With high mTOR expression a trend towards higher stage ( 78% vs 54% p=0.08) and likelihood of poor overall survival (defined as survival <3 years; 41% vs 18% p =0.08) was noted. Further, on univariate analysis bcl-2 expression was associated with higher risk of recurrence (35% vs.11%, p 0.05) whereas no association with clinical factors or outcomes was noted with pMTOR expression. On multivariate analysis the only parameter found to be significant was IPI [0R 11.6 95% CI 1.4-100]. Conclusions: High mTOR expression is associated with gender, age, IPI and showed a trend towards advanced stage and shorter survival. This target needs to be investigated prospectively in DLBCL as a prognostic factor and predictive marker. Given the availability of several mTOR inhibitors, the natural history of patients with poor risk DLBCL(high IPI) with high expression of mTOR may be favorably altered.
A phase II study of PXD101 (belinostat) in relapsed and refractory aggressive B-cell lymphomas (rel/ref ABCL): SWOG S0520.
Authors: Persky Daniel Oscar , Bernstein Steven H. , Goldman Bryan H. , Rimsza Lisa M. , Fisher Richard I. , Miller Thomas P. 
Published: March 2020

e18536 Background: The mechanism of action of histone deacetylase inhibitors (HDACI) in lymphomas is unknown. Loss of major histocompatibility Class II antigens (MHC II) in diffuse large B-cell lymphomas (DLBCL) is associated with decreased tumor infiltrating T lymphocytes (TIL) and poor survival. Transcription of MHC II is controlled by CIITA, which is itself regulated by histone acetylation, We hypothesized that PXD101 (belinostat), an HDACI, would increase MHC II expression in tumor cells, enhance immunosurveillance and improve outcome. Methods: Theprimary objective was to evaluate response rate and toxicity of PXD101 in patients (pts) with rel/ref ABCL with up to 5 prior chemotherapy regimens. Secondary objectives were to estimate the 6-month progression-free survival (PFS) and to assess MHC II and TIL. In a two-stage design, if at least 1 response was observed in the first 20 pts, another 20 pts would be accrued. PXD101 was administered at 1000 mg/m2 IV days 1-5 of 21-day cycle for up to 2 years. Results: The study was closed due to lack of response in the first stage. Of 22 pts enrolled, 19 were evaluable. Median age was 69, and median number of prior treatments was 3 (range 1-4). 18 pts had DLBCL and 1 had B-cell lymphoma, unclassifiable. Grade 4 toxicities were fatigue and muscle weakness (1) and lymphopenia (1). Despite initially finding no responses, 2 partial responses (PR) were observed at 5 and 13 months after registration, for an overall response rate (95% CI) of 10.5% (1.3-33.1%); 3 pts had stable disease (SD), lasting 4.7, 30.4+, and 40.7+ months. With a minimum follow-up of 2.0 yrs, median and 6-month PFS are 2.1 months (1.3-3.8) and 21.1% (6.6-41.0%); median and 6-month overall survival are 13.4 months (95% CI not yet estimable) and 57.9% (33.2-76.3%), respectively. Conclusions: Despite early closure, delayed PR was seen in 2 of 19 pts, and 2 pts had SD lasting 30.4+ and 40.7+ months. Therefore 4 pts (21%) who did not achieve complete response, very unusually, have not progressed for ≥2.0 yrs. Standard chemotherapy response assessment may not be appropriate for HDACI, which may require development of new biomarkers of response. Further work focuses on combining HDACI with standard chemotherapy.
CHOP chemotherapy plus rituximab compared with CHOP alone in patients with diffuse large B-cell lymphoma, from Indian subcontinent.
Authors: Linga Vijay Gandhi , Digumarti Raghunadharao , Maddi Rahul Narayan , Goteke Vamshi Krishna Reddy , Gundeti Sadashivudu , Thota Narender Kumar , Coca Pragnya 
Published: March 2020

e18545 Background: Outside the setting of the clinical trials there is very little data of CHOP chemotherapy plus Rituximab (CHOP-R) compared with standard CHOP in Indian population. We analyzed our cohort of patients diagnosed with Diffuse Large B cell Lymphoma (DLBCL). Primary objective was to compare CHOP with CHOP-R in term of PFS and OS. Methods: All the patients aged more than 21 years diagnosed with DLBCL (CD 20+) were retrospectively analyzed from Jan 2000 to June 2011. According to institute guideline staging and International Prognostic Index (IPI) risk grouping were done. Patients were started on standard cyclophoshomide 750mg/m2, doxorubicin 50mg/m2, vincristine 1.5mg/m2 on day 1 and prednisolone 60mg/m2 day 1-5 (CHOP). Rituximab 375 mg/m2 was given on day 1 depending on the affordability/Insurance. Clinical evaluation was done after each cycle and response assessment with CT scan was done after third and sixth cycle. Progression free survival (PFS) was defined as progression during therapy, relapse, death and lost to follow up. Overall survival was defined as time till death and lost to follow up. Statistical analysis was done using Graph pad software and p value less than 0.05 was taken significant. Results: There were 67 patients in CHOP-R and 206 patients in CHOP arm. Basic characteristics and survival data are described in table 1, which are not distributed equally in two arms. The PFS in R-CHOP and CHOP arms were 40 and 9 months respectively (p=0.0008). The OS in R-CHOP and CHOP arms were 47 and 13 months respectively (p=0.007). Conclusions: There was statistical difference between the PFS and OS between the two arms. [Table: see text]
Effect of berubicin, the 4'-o-benzylated doxorubicin analog, on growth inhibition and apoptosis in multiple myeloma.
Authors: Wang Michael , Sun Luhong , Fokt Izabela , Zhang Liang , Jayakumar Arumugam , Priebe Waldemar 
Published: March 2020

e18557 Background: Doxorubicin (DOX), an anthracycline, topoisomerase II inhibitor, is routinely used for hematologic malignancies including multiple myeloma (MM); however, its efficacy is limited by drug resistance and cardiotoxcity. To overcome these limitations, we designed, synthesized and tested Berubicin (BRN). BRN has been evaluated in clinical trials in neuroblastoma multiforme. It is a representative of a novel class of mechanistically altered anthracycline analogs. The data obtained from this study will serve as the basis for the rapid translation of BRN from the bench to the clinic in a phase I clinical trial for patients with MM at MD Anderson Cancer Center. Methods: We investigated the effects of BRN, DOX and Bortezomib (BTZ) in 3 human MM cell lines, MM1S, ARP-1, U266, and freshly isolated primary samples from patients with MM. MM cells were treated with BRN, DOX, and BTZ. The effects of these compounds on cell proliferation, apoptosis, and the cell cycle were analyzed using MTS assay and flow cytometry analysis. Results: BRN potently inhibited the growth of the established MM cell lines, as well as the freshly isolated primary MM cells in a dose-dependent manner. It showed growth inhibition at IC50 of 5.99 nM (U266), 5.21 nM (MM1S) and 3.99 nM (ARP-1), and was more potent than doxorubicin (IC50 14.63 nM, 7.24 nM and 11.06 nM) and bortezomib (IC50 304.9 nM, 15.47 nM and 53.19 nM). In contrast, BRN did not affect the proliferation of patient-derived normal bone marrow cells (CD138- cells) at the concentrations that were lethal to MM cells. Conclusions: Berubicin not only induced apoptosis in 3 cell lines in dose-dependent manners but also induced G2/M cell cycle arrest in 3 cell lines. In conclusion, BRN was effective against MM cells in vitro and will be applied to our planned clinical trial.
Effect of 13q deletion on IL-6 production in patients with multiple myeloma.
Authors: Azim Hamdy A. , Kassem Neemat , Khalifa Rania H , Mohamed Tarek Yakout 
Published: March 2020

e18570 Background: Numerous studies have shown a correlation between 13q deletion and poor prognosis in multiple myeloma (MM), but the mechanisms are not fully understood. Earlier studies suggest that this lesion involves large segments or the entire long arm involving the retinoblastoma (Rb) gene. In myeloma, Rb gene is believed to down regulate interleukin -6 (IL-6) which plays a central role in the pathogenesis of MM. Therefore, it has been hypothesized that loss of Rb gene might be associated with very high expression of IL-6 and subsequent bad prognosis. Methods: Forty MM patients and 20 matched controls were included in this study. Interphase fluorescence in situ hybridization (FISH) analysis was performed using LSI 13q14-specific probe. Serum levels of IL-6 were determined by ELISA. All patients received conventional chemotherapy. Refractory patients received other therapeutic regimen of thalidomide or bortezomib. Results: Significant increase (p < 0.001) of IL-6 production was recorded in patients with 13q deletion compared to patients with normal chromosome 13q status. These patients were also refractory to conventional chemotherapy but showed striking response to thalidomide or bortezomib. Conclusions: This study suggests that 13q deletions are associated with increased production of IL-6 in MM and this could be a possible cause of the associated bad prognosis. In addition, the results also show the potential to improve responses inpatients with refractory MM with the introduction of novel therapies.
Plasmacytoma: 10 years experience at a tertiary care center in India.
Authors: Baghmar Saphalta , Raina Vinod , Sharma Atul , Kumar Lalit 
Published: March 2020

e18573 Background: To evaluate the clinical features, diagnoses, prognostic factors, progression to MM of the patients of solitary plasmacytoma (SP) treated at AIIMS in last 10 years(2001-2010). Methods: From 2001-2010, we identified 57 patients with SP. OS, EFS, progression to myeloma were calculated using the Kaplan-Meier method and log rank test. Results: Out of 57 patients; 48 patients were evaluable. The M:F ratio was 3.5:1 with the median age of 49 years. The primary site was osseous(SBP) in 49 patients, extramedullary(EMP) in 8; 5 lesions were located in the upper respiratory passages, ie nasal cavity and maxillary sinus and rest of the 3 were one each in bronchus, gluteal region and intracranial. 43.8% of the lesions involved the vertebral column. The thoracic spine was the single most commonly involved site (12/57 patients). Out of 25 patients with lesions in vertebral column, 12 presented with paraparesis. Monoclonal protein was present in 48% patients and Urine M- Band in additional 2 patients. Treatment consisted of RT [45 Gy (8-50 Gy)] alone in 27, excision in 2 and excision and RT(n=9) and combined modality(n=10). The median follow-up was 28 months(range 3-160 months). Local control was achieved in 41(85%) while progressive disease was seen in 4. Serum M protein became undetectable after treatment in 60% patients. 17(41%) patients progressed to MM after initial response. The median duration of progression to MM was 21 months. Even though there was a trend towards a better EFS and OS for EMP than SBP, in univariate analysis this was not statistically significant. Patients having vertebral lesion showed trend towards progression to MM (p=.057). 5 yr EFS & OS were 44.4% and 89 % respectively. Median EFS and OS were 38 and 122 months respectively. 5 yr survival rate in patients who developed MM and those who did not were 81% and 100% respectively. None of the baseline characteristics were predictive of survival. Conclusions: Out of 1129 patients of plasma cell dyscrasias registered between 2001-2010; 5% were of SP. Bone was the most common site. Attainment of local control is the predictor of significant EFS (p<0.0001) and OS (p<0.05). Progression to MM is the commonest pattern of failure. Vertebrae involvement was predictor for disease progression to MM.
Spanish experience with the ipilimumab Expanded Access Program.
Authors: Berrocal Alfonso , Lopez-Martin Jose A. , Arance Ana Maria , Soriano V. , Espinosa Enrique , Lopez Criado M Pilar , Muñoz Eva , Berros Jose Pablo , Soria A , Marquez I , Sancho P , Gil I ,   Grupo Español Multidisciclinar de Melanoma GEM
Published: March 2020

e19023 Background: Second line ipilimumab has proven efficacy in clinical trial but few is known outside this setting. Methods: We have retrospectively reviewed experience with the Expanded Access Program for Ipilimumab in Spain. We have collected data on demographics, response survival and toxicity. Ipilimumab was administered at a 3 mg/kg dose for four induction courses. Results: We have retrieved 99 expanded access ipilimumab applications that represent 40% of all possible applications. Five patients are not evaluable because they never received ipilimumab 4 due to progression and 1 declined consent. Median age is 58.5 years (30-81) and 54.3% of the patients are males. 59.6% have 3 or more metastatic locations, 50% have liver metastases, 16% have CNS metastasis and 74.6% have elevated LDH. ECOG performance status was 0 to 1 in 91.9%. Previous adyuvant treatment was received by 43.6% of the patients and consisted in high dose interferon in 85.4%. All except one patient have received previous first line chemotherapy and 34.2% have received 2 or more chemotherapy lines. Medium time from the start of metastatic disease to the start of ipilimumab was 11.2 months. 58.5% of the patients completed 4 doses of ipilimumab main reason for not completion was death or progression in 84.6% and toxicity in 5.1%. 8 patients are not evaluable for response, 5 have just completed the treatment and 3 are still on treatment. Responses are 1 (1.1%) CR, 6 (6.4%) PR, 6 (6.4%) PR with previous progression or new lesions, 13 (13.8%) SD, and 60 (63.8%) progressive disease. Reinduction treatment was offered to 5 patients 2 PR patients achieved a new PR, one PR patients a SD and 2 SD patients progressed after reinduction. Kaplan and Meier median survival is 150 days (95% CI 110,5-189.4). One year survival is 32.4% and 18 months survival 21.6%. Toxicity has been mild, skin, 20.2% grade I and 5.3% grade II, liver 7.4% grade I, 2.1% grade II, 3.2 grade III, and diarrhea 19.1% gI, 3.2% grade II and 1.1% grade IV. Only 7 patients experienced toxicity grade III to IV. Conclusions: Ipilimumab efficacy when it is used outside clinical trial is similar to the reported. There is room for improvement in patient selection as 40% of them did not completed treatment. Toxicity of the 3 mg/kg schedule is mild.