bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amplification and overexpression of the PSMB5 gene contributes to bortezomib resistance in retreatment of patients with multiple myeloma
Authors: Altavilla G. , Arrigo C. , Marabello G. , Galletti G. , Santarpia M. , Sauta M. , Pitini V. 
Published: August 2020

e19500 Background: The proteasome inhibitor Bortezomib is a novel anticancer drug that targets primarily the beta5 subunit (PSMB5) of the 26 S proteasome which has also demonstrated efficacy in re-treatment of almost half of relapsed Multiple Myeloma (MM) pts. Recent studies have identified qualitative and quantitative alterations at the level of PSMB5 subunit, which is located at 14q11, and cells that carry these alterations displayed a marked resistance to proteasome inhibition. We investigated the relevance of amplification and PSMB5 overexpression in the clinical outcome of pts with MM during retreatment with bortezomib. Methods: Between January and June 2008 pts with secretory MM on relapse were elegible for bortezomib re-treatment (1.3 or 1.0 mg/mq on days 1,4,8 and 11 of a 21 day cycle) if they had at least a partial remission to a bortezomib based on most recent treatment and a free interval of at least 6 months since the last dose. Bone marrow samples for morphologic analysis, mRNA expression levels of PSMB5, classical cytogenetics, FISH and in situ hybridization using a fluorescein-labeled probe to detect the amplification of PSMB5 gene, were obtained from 26 pts (16 male, 10 female mean age 64 years) before and during re-treatment with Bortezomib. Results: At the time of analyses all pts who received at least two cycles were evaluable. We identified 12 pts refractory to retreatment and five of these pts (3 males, 2 females, mean age 65 years) had a detectable amplification and overexpression of PSMB5 which interestingly appears rapidly following exposure to bortezomib and wanes with time off-therapy, even if it curiously reappeared rapidly after re-exposure to bortezomib. Conclusions: Amplification and overexpression of PSMB5 contributes to bortezomib resistance in clinical practice. These findings do highlight the susceptibility of proteasome units to genetic modifications under constant selective pressure which occur with continued treatment, furthermore, the drug resistance remains dormant but it rapidly revives upon re-exposure to bortezomib. No significant financial relationships to disclose.
Efficacy and safety of lenalidomide oral monotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma: Results from an international study (NHL-003)
Authors: Czuczman M. S. , Vose J. , Zinzani P. , Reeder C. , Buckstein R. , Haioun C. , Bouabdallah R. , Polikoff J. , Ervin-Haynes A. , Witzig T. 
Published: August 2020

e19504 Background: Patients with diffuse large-B-cell lymphoma (DLBCL) who are not cured with R-CHOP or high-dose chemotherapy with autologous stem cell rescue have a dismal prognosis. A recent phase II trial (NHL-002) of lenalidomide in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) demonstrated a 19% overall response rate (ORR) with a 7-month median duration of response (DR) in the subset of patients with DLBCL. A supporting international phase II trial (NHL-003) of single-agent lenalidomide was initiated for patients with relapsed or refractory aggressive NHL that had received at least one prior treatment and had measurable disease. Herein, we report the data from the DLBCL patients enrolled in this trial. Methods: Patients received 25 mg oral lenalidomide once daily on days 1–21 of every 28-day cycle and continued therapy until disease progression or toxicity. The 1999 IWLRC methodology was used to assess response and progression. Results: One hundred-three DLBCL patients were enrolled and were evaluable for response assessment. The median age was 66 years (21–87) and 70 patients (68%) were male. Median time from diagnosis was 2 years (0.4–18.6), patients had received a median of 3 prior treatment regimens (1–10) and 46 of the patients (45%) had received a prior stem cell transplant (DLBCL-stem cell). Response rates are shown in the Table . Grade 3 or 4 adverse events occurring in more than 5% of patients were neutropenia (34%), thrombocytopenia (18%), asthenia (9%), anemia (8%), leucopenia (7%), back pain (6%) and dyspnea (6%). Conclusions: This international study demonstrates that lenalidomide is active in heavily pre-treated patients with relapsed or refractory DLBCL and has manageable side effects. [Table: see text] [Table: see text]
Age at diagnosis does not adversely affect outcome in patients with Hodgkin's Disease (HD) after autologous transplantation
Authors: Popat U. R. , Saliba R. , Hosing C. , Khouri I. , Alousi A. M. , Giralt S. A. , de Lima M. J. , Qazilbash M. H. , Champlin R. , Anderlini P. 
Published: August 2020

e19507 Background: Age at diagnosis is a poor prognostic factor for overall survival after standard therapy for HD. Whether older age is a prognostic factor for outcome after autologous transplantation is not known. We sought to evaluate the effect of older age at diagnosis on transplant outcome. Patients and Methods: All patients with HD undergoing autologous transplantation with BEAM conditioning (BCNU, Etoposide, Cytarabine, and Melphalan) between January 1996 and December 2007 were included in this study. During these 12 years, 248 patients (103 males) underwent autologous transplantation. Seventy two patients (29%) were older than 40 years of age at the time of initial diagnosis. Median age at transplantation was 31 years (range 11–74). At transplantation, 63 (25%) were in complete remission (CR); 148 (60%) were in partial remission (PR); and 37 (15%) had stable (SD) or progressive disease (PD). Forty-six patients (19%) had received more than 3 courses of chemotherapy prior to transplantation. LDH was elevated in 131 (53%). Peripheral blood stem cells were used as stem cell source in 241 (97%) patients. Results: With a median follow up of 48 months (range, 1–143 months), the 48-month overall (OS) and event-free survival (EFS) were 72% (95% CI; 65%-77%) and 57% (95% CI; 50%-63%), respectively. The cumulative incidence of non-relapse mortality at 1 year was 1.6%. The cumulative incidence of secondary MDS or AML was 8%. In univariate analysis, disease status (p<0.001) and number of prior chemotherapy regimens (p=0.007) were the only factors significantly predicting OS. Disease status was the only factor significant (p<0.01) in a multivariate analysis with a hazard ratio of 2.7 (1.1–6.9) and 9.2 (3.4–25) for patients in PR, and SD/PD respectively (CR reference group). Age at diagnosis was not a significant factor (see table ). Conclusions: High-dose chemotherapy and autologous transplantation abrogate the adverse impact of age at diagnosis in patients with HD. [Table: see text] No significant financial relationships to disclose.
Survival benefit of post induction consolidation therapy in MCL (mantle cell lymphoma): A Polish Lymphoma Research Group (PLRG) retrospective multicenter analysis
Authors: Jurczak W. , Giza A. , Krochmalczyk D. , Sobocinski M. , Zimowska-Curylo D. , Stella-Holowiecka B. , Boguradzki P. , Kisiel E. , Wróbel T. , Knopinska-Posluszny W. , Skotnicki A. B. 
Published: August 2020

e19510 Background: In MCL, early intensification and consolidation of the first line therapy by ASCT is the treatment of choice. Elderly age and co-existing co-morbidities makes it however feasible for less than a third of patients. Methods: All MCL cases consulted in 8 PLRG centers within the last 5 years (n=140) were included in a retrospective analysis. Only 23% (n=32) were consolidated with ASCT, further 28% (n=40) by radioimmunotherapy (Ibritumomab), while in 49% (n=68) neither consolidation was performed. Rituximab was used in 36/72 patients subjected to consolidation and 25/68 treated without consolidation. There were no statistically significant differences in IPI, CS (clinical stage), frequency of extranodal manifestations and B symptoms between analyzed subgroups ( Table ) although patients subjected to ASCT were younger (median age 54 vs 62) and tend to have higher LDH (556 IU vs 473), while those who were not consolidated more frequently had a large tumor burden (defined as a mass > 7 cm, 24 vs 15%). Results: There was a clear impact of consolidation on overall and progression-free survival (OS,PFS): at 5 years OS 65 vs 20 % (p= 0.0003 in Gehan Wilcoxon test); and PFS 40 vs 0 % (p= 0.0003 in Gehan Wilcoxon test). Rituximab used in the first line therapy further increased it's efficiency in terms of PFS, prolonging median time to progression from 15 to 26 months, however the OS benefit was seen only in consolidated patients (at 5 years 75% OS in those with Rituximab including induction followed by consolidation). Conclusions: With all limitations of retrospective analysis, it strongly supports the necessity of post induction therapy in MCL patients. The role of ASCT is established in younger patients, radioimmunotherapy may prove to be a feasible approach for the elderly and unfit ones. [Table: see text] No significant financial relationships to disclose.
Factors that determine survival among patients with multiple myeloma (MM) treated with zoledronic acid (ZOL)
Authors: Yellin O. , Crowley J. , Swift R. A. , Makary A. , Gravenor D. S. , Yang H. H. , Upadhyaya G. H. , Flinn I. W. , Staszewski H. , Tiffany N. M. , Berenson J. R. 
Published: August 2020

e19519 Background: Although the overall survival of MM patients has improved with new treatment options, few studies have evaluated prognostic factors since these new therapies have become available. Monthly ZOL has been incorporated into many of these regimens to reduce skeletal complications. Side effects from ZOL have been reported but their frequency and outcomes have not been well-defined. This retrospective study aimed to identify key baseline and on-treatment prognostic factors among MM patients treated with ZOL. Methods: Three hundred patient charts were consecutively reviewed. Data was collected from the date of MM diagnosis to the date of chart review. Patient chart inclusion criteria required a diagnosis of MM and having received at least one dose of ZOL. Results: The median survival of among patients in this study was 131 months. Significant early risk factors for overall survival included skeletal-related events (SRE), increased serum creatinine, elevated serum calcium, and ISS Stage II or III at diagnosis. Fourteen patients (4.7%) developed osteonecrosis of the jaw (ONJ) after 9–96 months of ZOL treatment. Notably, there was a trend toward an increased risk of ONJ among diabetic patients. Thirteen patients with ONJ remain alive and currently are in remission or with stable disease. One patient with ONJ died while in remission from a myocardial infarction. Among the patients with a follow up of 4–49 months from the diagnosis of ONJ, 2 showed some worsening of this complication, 5 remained stable, while 7 improved or resolved. Patients with ONJ showed an improved overall survival using both landmark and time-dependent analysis. In addition, the overall skeletal morbidity rate (SMR; SREs/year) was 0.16. Notably, patients who developed ONJ had a lower SMR than among patients who did not develop ONJ. Conclusions: These results suggest that skeletal complications are an important prognostic factor for MM. Although ONJ occurs in MM patients, most patients show improvement with proper management and this complication appears to be associated with a reduced risk of SREs and improved overall survival. [Table: see text]
A multivariate analysis for the survival of nodal peripheral T-cell lymphoma (PTCL)
Authors: Oki M. , Isozaki M. , Nakamura N. , Kikuchi A. , Tsuchiya T. , Arbogast P. , Ogawa Y. , Ando K. 
Published: August 2020

e19521 Background: Nodal peripheral T-cell lymphoma (PTCL) is uncommon lymphoma with various subtypes and poor prognosis. There is no definitive therapeutic improvement by conventional chemotherapy (CT) for decades. However, the superiority of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has remained inconclusive. The infrequency of PTCL is an obstacle to perform a large prospective study. We conducted a retrospective study of fifty six patients with three major nodal PTCL, histologically classified as PTCL-not specified (NOS, n=29), angioimmunoblastic T-cell lymphoma (AITL, n=19), and ALK-negative anaplastic large cell lymphoma (ALCL, n=8) who underwent ASCT (n=14) or not (n=42) after CT in Tokai University Hospital, Ebina General Hospital, and Hadano Red Cross Hospital, Kanagawa, Japan between 1997 and 2008. We determined whether international prognostic index (IPI), serum soluble IL-2 receptor level (sIL-2R) and ASCT were correlated with the survival. Methods: Retrospective, multicenter cohort study by time-dependent or non-time-dependent multivariate survival analysis with Cox proportional hazard regression. Results: Median age was 61 (18–81). The percentage of IPI more than 3 was 50. Median sIL-2R was 4120 ng/ml. (311–96,800). In non-time-dependent analysis, both ASCT and sIL-R were significant prognostic factors for overall survival (OS). Hazard ratio (HR) of ASCT, IPI, and sIL-2R were 0.24 (95%CI: 0.08–0.76, p=0.02), 0.77 (95%CI: 0.34–1.77, p=0.54), and 1.45 (95%CI: 1.129–1.857, p=0.035), respectively. But in time-dependent manner, the significant effect of ASCT was offset for OS. HR of ASCT was 0.82 (95%CI: 0.25–2.71, p=0.75). Only sIL-2R was still statistically significant, which HR was 1.31 (95%CI: 1.04–1.66, p=0.03). On the other hand, ASCT was only important effect on progression-free survival (PFS) by non-time-dependent analysis, which HR was 0.20 (95%CI: 0.07–0.55, p=0.02). After time-dependent analysis, no variates influenced PFS. Conclusions: The OS advantage of high-dose chemotherapy followed by ASCT is offset by time-dependent Cox proportional hazard analysis. The level of sIL-2R has impact on OS. Prospective multicenter randomized trial will be needed to show or not to show an advantage for ASCT. No significant financial relationships to disclose.
Clinical activity of rituximab with either CHOP or CVP in MALT lymphoma
Authors: Aguiar Bujanda D. , Bohn Sarmiento U. , Saura Grau S. , Rodriguez Franco C. , Aguiar Morales J. 
Published: August 2020

e19530 Background: Optimal management of MALT lymphoma remains undeffined. Rituximab has been proven to be an active agent in the treatment of MALT lymphoma. Several reports suggest that the activity of rituximab can be improved when added to chemotherapy. We aimed to evaluate safety and activity of rituximab combined with chemotherapy (CHOP or CVP) in first-line therapy for MALT lymphoma. Methods: Retrospective review of patients with MALT lymphoma treated in first-line with R-CHOP or R-CVP. Patients with gastric MALT lymphoma were included if resistant to or not eligible for anti-Helicobacter pylori therapy. Results: There were 22 patients (8 male, 14 female) with a median age 60 years (range 34 to 77 years). Primary origin: 14 stomach (64%), 3 skin, and 5 others (nodal, parotid gland, orbital, colon, and lung). Stage of disease wa I in 13 patients (59%), II in 2 patients (9%), and IV in 7 patients (32%). Bone marrow infiltration was present in 5 patients (23%). Chemo-immunotherapy was R-CVP in 13 patients and R-CHOP in 9 patients. The median number of cycles for patient was 6. The treatment was well tolerated with mild toxicity. Patients with gastric lymphoma did not have bleeding or perforation during therapy. One patient had to stop rituximab after second cycle because severe infusion reaction. In three patients the vincristine was reduced or removed because sensitive neuropathy. The overall response rate (ORR) in 21 evaluable patients was 95% (CR 81%, PR 14%). None of the patients progressed during therapy. Patients with gastric lymphoma (n=14) showed an ORR of 93% (CR 86%, PR 7%, SD 7%). Radiation therapy was given as consolidation after chemotherapy to 3 patients with extra-gastric origin. With a median follow-up of 28 months, two patients (gastric lymphoma) have relapsed at 4 and 12 months respectively. All patients are alive and 19 (86%) in complete response. Conclusions: Combination of rituximab with either CHOP or CVP is very active with acceptable toxicity in the treatment of MALT lymphoma. Further studies are needed to elucidate the optimal combination of rituximab and chemotherapy in this patient population. No significant financial relationships to disclose.
Soluble CD44 in patients with aggressive non-Hodgkin's lymphoma: Prognostic and clinical value
Authors: Gharib A. F. , Eltarhony S. A. , Elsawy W. H. 
Published: August 2020

e19539 Background: CD44 is a cell surface glycoprotein expressed by a large variety of tissues. In addition to their expression on the cell membrane, CD44 proteins are also released from cells, and soluble CD44 proteins are detectable in the normal human circulation. The observation that several human tumors show an overexpression of CD44 and the presence of soluble CD44 in the circulation makes CD44 a potential serum marker for tumor detection. In this prospective study, we investigated the prognostic and clinical value of s-CD44 in patients with aggressive non-Hodgkin's lymphomas. Methods: s-CD44 concentration was measured in the sera of 64 patients with aggressive non-Hodgkin's lymphomas treated with standard CHOP by using chemiluminescence-enzyme immunoassay (EIA). Results: Circulating serum CD44 (s-CD44) levels have been found to change in parallel with response to therapy, but little is known about the predictive or prognostic significance of s-CD44. The median pretreatment s-CD44 level was 510 ng/mL(range, 90 to 2,120 ng/mL). Only 10 (31%) of the 32 patients with an International Prognostic Index (IPI) score 0 or 1 had s-CD44 concentration higher than the median level, whereas 11 (52%) of 21 patients with an IPI score ≥2 had a concentration higher than the median before initiation of treatment (P < .0001). Patients with lower than the median s-CD44 achieved more often a complete response to therapy (P = .0002) and had better survival (P = .007) than those with higher s-CD44 levels. However, in a multivariate analysis, only the IPI score had independent prognostic value (P < .001). Conclusions: Our results showed that a high s-CD44 level before treatment is associated with a high IPI score, poor response to treatment, and unfavorable prognosis in aggressive non-Hodgkin's lymphoma. No significant financial relationships to disclose.
Are comorbidities present in non-Hodgkin's lymphoma (NHL) patients (pts) enrolled in recent clinical trials different from those observed in previous clinical trials?
Authors: Noga S. J. , Mo M. , Dreiling L. , Ozer H. 
Published: August 2020

e19540 Introduction: Co-morbidities are often more prevalent in community practice than in clinical studies due to an increased mortality risk (Kuderer 2006; Noga 2007). As NHL treatments have changed and NHL rates in the US have increased 81% from 1973 to 1997 (Garber 2001), pt characteristics of NHL practice-changing studies may have changed to reflect the general NHL population. Here we summarize major co-morbid conditions present in pts from 4 key NHL trials published from 1976 to 2007. Methods: Intermediate/high-grade NHLs are sensitive to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; McKelvey 1974; Fisher 1993), especially when combined with rituximab (RCHOP; Coiffier 2002). Entry criteria and demographics were tabulated from 4 interventional NHL trials published from 1976 to 2007: McKelvey 1976, a randomized study of 420 pts comparing CHOP and HOP; Fisher 1993, a phase 3, randomized study of 899 pts comparing CHOP, m-BACOD, ProMACE-CytaBOM, and MACOP-B; Coiffier 2002, a randomized study of 399 pts comparing CHOP with RCHOP; Noga 2007, an open-label study that included 325 NHL pts in community practice. Results: More recent NHL trials enrolled older pts compared with earlier trials ( Table ). Further, in the community-practice study by Noga et al (2007), nearly 1/3 of treated pts had at least 1 major co-morbidity. Such co-morbidities may have been formally or informally excluded in earlier clinical trials. Conclusions: More recent clinical trials tend to enroll older pts compared with earlier trials and tend to include pts with the major co-morbidities often seen in the general NHL population. Physicians may be more aware that cancer pts often have a significant prevalence of co-morbid conditions and that supportive care may allow these pts to benefit from study treatment. Clinical practice may also be changing to allow more elderly pts with co-morbidities to receive aggressive chemotherapy. [Table: see text] [Table: see text]
Outcomes in patients with primary gastric diffuse large B-cell lymphoma after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy
Authors: Sohn B. , Yoon D. , Kim S. , Lee D. , Kim S. , Huh J. , Lee J. , Suh C. 
Published: August 2020

e19543 Background: The optimal therapy for primary gastric diffuse large B- cell lymphoma (DLBCL) still needs to be defined. The aim of this study was to investigate the patient's outcomes after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) treatment in primary gastric DLBCL in a single institution. Methods: We searched AMC Registry for Non-Hodgkin's Lymphoma and found 26 patients with primary gastric DLBCL, who received R-CHOP as first-line chemotherapy. Ten of 26 patients had localized disease. Remaining patients had disseminated disease. R-CHOP was repeated every 21 days in all patients. Results: Overall, complete response (CR) was observed in 20 of 26 patients (76.9%). Three-year event free survival (EFS) and overall survival (OS) was 76.5% and 75.0%, respectively. After analyses of 10 patients with localized disease, we found that these patients had received a total 38 cycles, with a median of 3 cycles per patient. Of 10 patients, one patient had 2 cycles of R-CHOP, 4 had 3 cycles, and one had 4 cycles, all 6 patients above followed by consolidation radiotherapy. Remaining one patient and 4 patients had 5 cycles and 6 cycles of R-CHOP, respectively. In patients with localized disease, CR was observed in 10 of 10 patients (100%), and both 3-year EFS and OS was 100% (10 of 10 patients). In analyses with 16 patients with disseminated disease, all patients had received a total 91 cycles, with a median of 6 cycles per patient. In these patients, two patients had radiation therapy after R-CHOP, one patient had CR before consolidation radiation therapy, and another had partial response before radiation therapy. CR after R-CHOP treatment was observed in 10 of 16 patients (62.5%), partial response in 3 patients, stable disease in 1 patient, and progressive disease in 1 patient. Three-year EFS and OS was 61.1% and 57.8% in patients with disseminated disease. Conclusions: R-CHOP regimen showed a promising result in primary gastric DLBCL. Combination with rituximab in CHOP regimen showed excellent prognosis especially in patients with localized disease. In localized disease, CR was 100%, 3-year EFS and OS was 100%. In disseminated disease, CR was 62.5%, 3-year EFS and OS was 61.1% and 57.8%. No significant financial relationships to disclose.