Improving Patient Value Through Cross-Country Collaboration

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S126-S126
Author(s):  
Tameson Yip ◽  
Jennifer Ford ◽  
Colleen Ramsower ◽  
Betty Glinsmann-Gibson ◽  
Ryan Robetorye ◽  
...  
Keyword(s):  
Mayo Clinic ◽  
B Cell Lymphoma ◽  
Health Staff ◽  
Cell Of Origin ◽  
Improvement Project ◽  
Fda Approval ◽  
Time Period ◽  
Cross Country ◽  
The Impact ◽  
Local Laboratory

Abstract Introduction Lymph2Cx lymphoma cell-of-origin assay (LM2CX) was developed by the Lymphoma/Leukemia Molecular Profiling Project (LLMPP) to better categorize diffuse large B-cell lymphoma (DLBCL). NanoString has licensed the assay and is currently pursuing FDA approval. In the meantime, the test is offered exclusively as a lab-developed test (LDT) by the Mayo Clinic Molecular Diagnostics–Arizona Lab (MDAZL) to Mayo Clinic Enterprise patients. In order to comply with these restrictions, the normal workflow for Mayo Clinic Rochester has been modified as cases are sent to Arizona. Rochester consultants order LM2CX using their local laboratory information system (LIS). Slides are prepared by Rochester histology and then shipped to Arizona, where they are entered into the Arizona LIS and processed. In July 2018, we discovered numerous cases that were ordered but not shipped. Because this step took place at the LIS transition between Arizona and Rochester, it was not detected immediately. Methods Allied Health Staff (AHS) colleagues in Rochester and Arizona had the unique opportunity to collaborate. After Arizona AHS identified the problem, they reached out to the Rochester pathology reporting specialists (PRSs) and began a joint improvement project. Together, we were able to measure the impact of the problem, with Arizona auditing digitally, while Rochester audited physical cases. We found 29% of the cases were handled improperly over a 6-month time period. In order to eliminate the gap, Rochester implemented several improvements, including training, tagging all LM2CX cases, and huddle discussions, while Arizona AHS monitored the process digitally. Results Since implementation of improvements, we have had zero defects. Modifications to AHS/consultant training in Rochester will ensure continued success. Conclusions This intervention illustrates the importance of strong collaborations in order to quickly respond to testing issues and provide the greatest value to patients.

Differential Impact of Relative Dose-Intensity Reductions (DIR) in Diffuse Large B-Cell Lymphoma (DLBCL) Treated with R-CHOP21 or R-CHOP14

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3073-3073
Author(s):  
Leyre Bento ◽  
Francesc Garcia ◽  
Antonia Maria Bautista-Gili ◽  
Blanca Sanchez ◽  
Lucia Garcia ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Selection Bias ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Stage Iii ◽  
Prognostic Impact ◽  
Differential Impact ◽  
Bulky Disease ◽  
Time Period ◽  
The Impact

Abstract Introduction: DLBCL is the more common non Hodgkin lymphoma. This is an aggressive lymphoma that is treated with a standard chemotherapy regimen: R-CHOP. In the last years attempts have been done to improve the outcome both increasing dose-density (CHOP14) or intensity (CHOEP, ACVBP, autologous stem cell transplantation) without obtaining benefit in terms of survival. This has allowed setting R-CHOP administered every 21 days (R-CHOP21) as the standard treatment for DLBCL patients. RDI is an important issue to consider when treating malignancies. Although this a well-known prognostic factor in Hodgkin lymphoma, scarce information has been published in DLBCL. Objective: The purpose of this study is further analyzing the prognostic impact of RDI in two cohorts of DLBCL patients treated with R-CHOP21 or R-CHOP14, to evaluate its differential impact when increasing dose density. Material and methods: All patients diagnosed of DLBCL from January-1999 to June-2013 at University Hospital Son Espases were retrospectively identified from Pathology Department registry to avoid selection bias. Only patients treated with R-CHOP21 or R-CHOP14 +/- radiotherapy were included (N=115). To increase the R-CHOP14 cohort we added also all patients treated with R-CHOP14 in the same time period in two additional hospitals (Hospital Son Llatzer of Palma and Hospital del Mar of Barcelona) identified from their Pharmacy registries to avoid selection bias (N=42). Other regimes, consolidations or maintenance were excluded. Table 1 shows main characteristics of the global series (N=157). RDI represents the ratio of the amount of a drug actually administered to the amount planned for a fixed time period. RDI was calculated as previously described. Briefly, RDI of each drug was obtained followed by an average of RDI in CHOP consisting in the sume of RDI of the 3 drugs divided by 3. Main prognostic factors at diagnosis in DLBCL were obtained, including international prognostic index (IPI) factors. Evaluations were carried out following standard guidelines. Results: Overall response and complete response rates were similar in both groups:86% and 76% for R-CHOP21 and 94% and 74% for R-CHOP14(p=0.17 and p=0.85, respectively). Median follow-up for alive patients was 68 months (4-156). There were no differences between the two cohorts in terms of either OS or PFS (Figure 1). In the R-CHOP21, both a reduction higher than 15% in RDI [RR 7.41 (2.51-21.83); (p<0.001)] and an unfavorable R-IPI [RR 2.99 (1.1-8.16); (p=0.032) were independently associated with a worse OS. For PFS only a reduction higher than 15% in RDI [RR 4.41 (1.77-10.99) (p=0.001) was independently associated to worse PFS. By contrast, in the R-CHOP14 group an unfavourable NCCN-IPI [RR 8.74 (2.23-34.25); (p=0.002)] and the presence of B-symptoms [RR 5.13 (1.98-13.3); p=0.001)] was independently associated to worse OS and having a AA stage III-IV [RR 5.09 (1.14-22.62); p=0.032)] and bulky disease [RR 3.95 (1.46-10.7); p=0.007)] were independently related to worse PFS. RDI reductions did not show any significant impact in OS or PFS in patients treated with R-CHOP14 (Figure 2). Conclusions: Overall in our series there were no differences in terms of response or survival between patients treated with R-CHOP21 or R-CHOP14. A higher rate of RDI reduction was observed in the R-CHOP14 group. However, the impact of RDI reductions on response and survival was only observed in the R-CHOP21 group but not in patients treated with R-CHOP14. We can conclude that R-CHOP21 and R-CHOP14 are equivalent regimens in terms of response and survival only if RDI reductions are avoided. For patients receiving R-CHOP21 we recommend using clinical and support measures in order to avoid RDI reductions. Table 1. Main clinical characteristics of the patients. R-CHOP21 group(n=74) R-CHOP14 group(n=83) P Age (median & range) 65 (25-88) 55 (15-79) 0.005 Sex (M/F) 34 (46%) / 40 (54%) 51 (61%) / 32 (39%) 0.056 ECOG PS > 1 17 (23%) 18 (22%) 0.85 Ann Arbor stage III-IV 40 (54%) 48 (58%) 0.75 B-symptoms 25 (34%) 26 (31%) 0.86 Elevated LDH 33 (46%) 40 (49%) 0.75 > 1 extranodal site 8 (11%) 19 (23%) 0.057 Bulky disease 23 (31%) 34 (41%) 0.24 R-IPI unfavorable 24 (32%) 26 (32%) 1 NCCN-IPI: - Low - Low-intermediate - High-intermediate - High 9 (13%) 27 (39%) 26 (38%) 7 (10%) 17 (21%) 35 (44%) 24 (30%) 4 (5%) 0.31 Elevated Beta-2-microglobulin 32 (49%) 31 (39%) 0.24 Radiotherapy 27 (36%) 27 (32%) 0.62 Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals A multi-institutional analysis of diffuse large B-cell lymphoma (DLBCL) treated with consolidative radiotherapy and the impact of cell-of-origin on outcomes

2019 ◽  
Vol 53 (4) ◽  
pp. 473-479 ◽  
Author(s):  
Chrishanthi Rajasooriyar ◽  
Jeremy Tey ◽  
Lea Choung Wong ◽  
Michelle Poon ◽  
Rao Nandini ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Disease Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Cell Of Origin ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Abstract Background Patients with diffuse large B-cell lymphoma (DLBCL) with bulky disease and/or those who fail to achieve complete response benefit from the addition of radiotherapy (RT). We aim to review the outcome, as well as determine the impact of cell-of-origin, on patients undergoing consolidative RT. Patients and methods Patients with DLBCL treated with radical intent consolidative RT were included. Clinical, pathological and treatment characteristics were extracted from electronic medical records. Survival outcomes and factors that predict for disease-free survival (DFS) were analysed. Results Seventy-four patients were included in this analysis. The median follow up was 3 years (0.7–16 years). Fifty-eight percent of patients had stage I–II disease, and 61% received at least 6 cycles of chemotherapy. Cell-of-origin was discernible in 60% of patients, and approximately half were classified as Germinal centre origin. The 5-year overall survival (OS) of this group was excellent at 92% (median survival not reached). The 5-year DFS was 73% (95% CI 57–83%). Seven percent (n = 5) of patients experienced local recurrence at a median time of 6 months. Failure to achieve complete response post RT and/or initial bulky disease are significant predictors of inferior DFS. There was no association between cell-of-origin and DFS or OS. Conclusions The outcome of patients who received radiotherapy as consolidation is excellent. Patients who fail to achieve complete response after radiotherapy had poorer outcomes. Despite using radiotherapy, presence of bulky disease remains a significant predictor of disease recurrence. We did not find any association of poorer outcomes, with regards to cell-of-origin, in the use of consolidative RT.

scholarly journals The Efficacy of Passive Valve Antimicrobial Swab Caps Against Existing Clabsi Prevention Bundle in an Adult Hematology Inpatient Population: A Quality Improvement Initiative

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-14
Author(s):  
Joseph F. Ferry ◽  
Neil Bailey ◽  
Vanessa Dunleavy ◽  
Joanna Fesler ◽  
Judson Hall ◽  
...  
Keyword(s):  
Quality Improvement ◽  
Vascular Access ◽  
Patient Population ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Central Line ◽  
Improvement Project ◽  
Common Diagnosis ◽  
The Cost ◽  
The Impact

Background : Central line associated blood stream infections (CLABSI) have been the costliest of all healthcare associated infections. The average CLABSI cost is approximately $46,000 (Haddadin & Regunath, 2019). Most cases may be preventable with utilization of aseptic techniques, surveillance, and management through local protocols. The majority of CLABSI occur more than five days after central vascular access (CVA); therefore, there has been a growing focus on central line handling and maintenance techniques. CLABSI prevention data has been largely focused on the intensive care unit (ICU) patient population where an average of about half of patients have CVA. There have been few studies exploring the rates of CLABSI in the adult hematology population, a population with unique risk factors due to their immunosuppressing treatments and prolonged immunocompromised states. There has been emerging data that suggests the use of new technology in addition to existing central line maintenance recommendations by the Center for Disease Control may further reduce the rate of CLABSI occurrences in high-risk patient populations. Aim: To determine the efficacy of passive valve antimicrobial swab caps on the reduction of CLABSI in an inpatient hematology patient population when compared to current existing local practices. Outcomes of reported incidents of CLABSI have been evaluated against pre-interventional data for this setting. Methods : Retrospective analysis of medical records from January 2016 - September 2019 identified the existing rate of CLABSI occurrence among inpatient hematology patients at a single institution. We utilized the intervention of antimicrobial swab caps for 10 months and tracked the rate of CLABSI during this time. The nursing staff were educated on the quality improvement project, the use of the new equipment, and expectations that existing standard practices per local policy for CLABSI prevention bundles would be adhered to prior to the start of the intervention. To evaluate the impact of the antimicrobial swab caps on the rate of CLABSI we compared the number of infections pre- and post-intervention. Randomized audits, including chart reviews for compliance with existing standard CLABSI bundle practices were performed during the initial 3 months of the intervention. Results : Prior to the introduction of the passive valve antimicrobial swab cap to the existing CLABSI prevention protocol, CLABSI rates on the hematology unit exceeded the standardized infection ratio 75th percentile on 9 of the previous 15 calendar quarters. The intervention was observed for 6,674 central line days. The CLABSI rate during the intervention was 0.4495 per 1,000 central line days. The CLABSIs identified were due to nosocomial opportunistic infection in setting of immunosuppressed status (66%) and gastrointestinal translocation (33%). The common diagnosis in setting of CLABSI was refractory/relapse diffuse large B-cell lymphoma (66%) and active acute myeloid leukemia (33%). The two patients who were diagnosed with CLABSI were neutropenic with an absolute neutrophil count of 0 at time of CLABSI diagnosis. The organisms identified at time of CLABSI diagnosis were Clostridium ramosom, Enterococcus faecium, Staphylococcus epidermisis, and Candida parapsilosis. When considering the cost of a CLABSI to be about $46,000 per event and the annual cost for the inpatient hematology unit's use of the caps of approximately $19,710, the implementation of the antimicrobial swab cap reduced the cost associated with CLASBI in the hematology unit by approximately $26,290 annually. Conclusions : The introduction of the passive valve antimicrobial swab caps appears to demonstrate potential for reduced costs due to CLABSI when implemented into current CLABSI prevention bundles. This resulted in a 25% reduction in rates of CLABSI in the adult hematology patient population when compared to the previous year. The prevention of CLABSI in hematology patients with central vascular access remains challenging, however, standardized protocols for CLABSI prevention and use of antimicrobial swab caps may help further reduce the rate of CLABSI in hematology patients. Disclosures: No relevant conflicts of interest to declare. Disclosures Glennie: Pharmacyclics: Speakers Bureau; Janssen: Speakers Bureau. Bensinger:BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Regeneron: Consultancy, Honoraria, Research Funding, Speakers Bureau. Patel:Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; BeiGene: Consultancy; Adaptive Biotechnologies: Consultancy; Genentech: Consultancy, Speakers Bureau; Kite: Consultancy; Pharmacyclics: Consultancy, Speakers Bureau.

The Impact of Immunophenotypic Subtypes and Treatment Regimens on Patient Outcomes in Monomorphic Post-Transplant Lymphoproliferative Disorders (Diffuse Large B-Cell Lymphoma)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4449-4449 ◽  
Author(s):  
Dejan Radeski ◽  
Daniela Hoehn ◽  
Francesca Montanari ◽  
Bachir Alobeid ◽  
Yuan Zhang ◽  
...  
Keyword(s):  
B Cell ◽  
B Cell Lymphoma ◽  
Refractory Disease ◽  
Cell Of Origin ◽  
Post Transplant ◽  
Treatment Regimens ◽  
Large B Cell Lymphoma ◽  
Stage Disease ◽  
Germinal Center B Cell ◽  
The Impact

Abstract Introduction : Post-Transplant Lymphoproliferative Disorders (PTLD) are a group of heterogeneous disorders that arise as a consequence of iatrogenic immunosuppression for solid organ or allogeneic bone marrow/stem cell transplantation. Though they all arise in a common clinical context, different types of PTLD differ with respect to their underlying biology, clinical presentation and treatment. The aims of this study were to: (1) Define the cell of origin (COO) of monomorphic Diffuse Large B-cell Lymphoma (DLBCL) PTLD and evaluate their impact on clinical presentation and survival and (2) assess the impact of different Rituximab containing treatment regimens on survival outcomes in monomorphic DLBCL PTLD patients. Methods : We conducted a retrospective review of our institutional databases to identify all the cases of monomorphic PTLD (DLBCL) diagnosed and treated at our medical center from 2000-2013. COO classification into germinal center B-cell like (GCB) and non-germinal center B-cell like (non-GCB) type was performed by immunohistochemistry using the Hans algorithm. Results : Cell of origin: 40 cases of monomorphic PTLD (DLBCL) were diagnosed during the study interval. Tissue material for COO subtyping was available for 25 patients. By immunohistochemistry 16/25 (64%) were non-GCB and 9/25 (36%) were GCB subtype, median age of presentation being 46 years (range 3-75) and 48 years (range 3-64), respectively. A trend towards EBV positivity (by in situ hybridization for EBV encoded RNA) was noted in the non-GCB group (75% vs. 33%) [p=0.09]. Non-GCB DLBCL PTLD presented earlier post-transplant at a median 1.5 years (range 0.2-15) vs. 3.9 years (range 0.7-17) for GCB cases. When comparing immunosuppressive therapy at the time of PTLD presentation, an association between Tacrolimus therapy and non-GCB phenotype was identified [p=0.03]. Non-GCB DLBCL PTLD demonstrated a trend towards higher rates of extra nodal involvement (88% vs. 44%) [p=0.06] and advanced stage disease (Stage III/IV 75% vs. 33%) [p=0.09]. No significant differences in organ transplanted, LDH, ECOG performance and IPI were observed. While acknowledging the heterogeneity of therapies administered, no significant differences in Progression Free Survival (PFS) (median PFS non-GCB = 17 months vs. GCB = 15 months [p=0.36]) and Overall Survival (OS) (median OS non-GCB = 33 months vs. GCB = 27 months [p=0.22]) were identified. Impact of Treatment: 35 adults (age≥18) were treated at our center. The four most common first line therapies administered were R-CHOP (14), R-EPOCH (7), Palliative Care (5) and Rituximab monotherapy (4). Five patients were given 4 other different therapies. In patients given Rituximab monotherapy, two patients presenting with stage I disease responded while two with stage IV disease progressed. When focusing on patients who commenced R-CHOP or R-EPOCH as their initial therapy, no significant differences in age, stage, LDH, extra nodal disease, ECOG performance status, IPI and immunosuppression therapy was identified between the groups. The complete response (CR) rate for R-CHOP was 50% vs. 71% for R-EPOCH. Primary refractory disease was present in 29% of patients receiving R-CHOP vs. 14% with R-EPOCH. Death during first line therapy occurred equally in both groups (14%). All four primary refractory disease patients in the R-CHOP arm died, while the one patient who was primary refractory to R-EPOCH is alive 3 years post autologous stem cell transplant. R-EPOCH demonstrated prolonged PFS (median PFS R-CHOP = 15 months vs. R-EPOCH not reached [p=0.049]) and prolonged OS (Figure 1) [p=0.036]. Conclusions : (1) In monomorphic PTLD (DLBCL), the non-GCB subtype predominates and is associated with the use of Tacrolimus. It commonly presents with advanced stage disease and extra nodal involvement however, no difference in PFS and OS was noted when compared to GCB DLBCL PTLD. (2) R-EPOCH demonstrated prolonged PFS and OS when compared to R-CHOP. The survival differences reflect the higher rates of primary refractory disease in the R-CHOP group and the inability to salvage patients once they become relapse/refractory. Given the retrospective nature of our analysis, further studies in a larger cohort of patients are ongoing to validate these results. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Comparison of protein-based cell-of-origin classification to the Lymph2Cx RNA assay in a cohort of diffuse large B-cell lymphomas in Malaysia

2017 ◽  
Vol 71 (3) ◽  
pp. 215-220 ◽  
Author(s):  
Kean-Chang Phang ◽  
Ariz Akhter ◽  
Nur Maya Sabrina Tizen ◽  
Faridah Abd Rahman ◽  
Raja Zahratul Azma ◽  
...  
Keyword(s):  
B Cell ◽  
B Cell Lymphoma ◽  
Rank Test ◽  
Cell Of Origin ◽  
Log Rank Test ◽  
Assay Performance ◽  
The Impact ◽  
Digital Quantification ◽  
Large B Cell

AimsThe cell of origin (COO) based molecular characterisation into germinal centre B-cell-like (GCB) and activated B-cell-like (ABC) subtypes are central to the pathogenesis and clinical course in diffuse large B-cell lymphoma (DLBCL). Globally, clinical laboratories employ pragmatic but less than ideal immunohistochemical (IHC) assay for COO classification. Novel RNA-based platforms using routine pathology samples are emerging as new gold standard and offer unique opportunities for assay standardisation for laboratories across the world. We evaluated our IHC protocols against RNA-based technologies to determine concordance; additionally, we gauged the impact of preanalytical variation on the performance of Lymph2Cx assay.MethodsDiagnostic biopsies (n=104) were examined for COO classification, employing automated RNA digital quantification assay (Lymph2Cx). Results were equated against IHC-based COO categorisation. Assay performance was assessed through its impact on overall survival (OS).Results96 (92%) informative samples were labelled as GCB (38/96; 40%) and non-GCB (58/96; 60%) by IHC evaluation. Lymph2Cx catalogued 36/96 (37%) samples as GCB, 45/96 (47%) as ABC and 15/96 (16%) as unclassified. Lymph2Cx being reference, IHC protocol revealed sensitivity of 81% for ABC and 75% for GCB categorisation and positive predictive value of 81% versus 82%, respectively. Lymph2Cx-based COO classification performed superior to Hans algorithm in predicting OS (log rank test, p=0.017 vs p=0.212).ConclusionsOur report show that current IHC-based protocols for COO classification of DLBCL at UKM Malaysia are in line with previously reported results and marked variation in preanalytical factors do not critically impact Lymph2Cx assay quality.

Outcomes Following Allogeneic Stem Cell Transplantation (AlloSCT) in Patients with Primary Mediastinal (PMBL), Germinal Center B (GCB) and Non-GCB Cell-like Diffuse Large B Cell Lymphomas (DLBCL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2563-2563 ◽  
Author(s):  
Issa F. Khouri ◽  
Rima M Saliba ◽  
Zijun Y. Xu-Monette ◽  
Martin Korbling ◽  
Gabriela Rondon ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Bulky Disease ◽  
Stem Cell Source ◽  
The Impact

Abstract Background: Primary mediastinal (PMBL), GCB and non-GCB B-cell lymphoma are three major subtypes of DLBCL with distinct clinical outcomes. PMBL and DLBCL of GCB immunophenotype have a higher chance of cure than patients with non-GCB DLBCL when treated with conventional chemotherapy. In the relapsed/refractory setting, there is paucity of data regarding the impact of histological classification of DLBCL on survival following alloSCT in patients who were not eligible for or who have failed a prior autologous SCT (ASCT). Herein, we compare outcomes of alloSCT in these patients. Methods and Patients: We identified 101 de novo DLBCL patients who were treated at our center from January 1, 1998 to December 31, 2011. Seventeen (17%) tumors were PMBL. We determined the cell-of-origin in the remaining patients, based upon the Visco/Young and Choi immunohistochemical algorithms, and classified 62 (61%) as GCB and 22 (22%) as non-GCB tumors. GCB patients were older than non-GCB [median (range): 54 (21-70) vs 48(24-58) years, p=0.003)] and PMBL [26(19-48), P <0.001)]. Patients with PMBL, however, were more likely to have bulky disease at study entry (SE) than other subtypes [24% (PMBL) vs 5% (GCB) and 5% (non-GCB); P= 0.04]. Stage III-IV at SE in GCB, non-GCB and PMBL was present in 42%, 45% (P=0.8) and 35% (P=0.6), respectively; the number of prior chemotherapies received was 4 in both GCB and non-GCB and 5 in PMBL (P=0.3). The proportion of patients who have failed a prior ASCT was comparable in all three groups (32%, 32% and 47%, P=0.2). Refractory disease was present in 35% of GCB and PMBL patients at SE compared to 14% in non-GCB patients (P=0.03). Distribution of IPI, LDH, and proportion of PET+ patients (47%, 45% and 47%) were not statistically different in all 3 groups. A larger proportion of GCB patients (44%, reference) received non-myeloablative conditioning than non-GCB (23%, P=0.07), or PMBL (12%, P=0.3); the remaining patients received reduced-intensity conditioning (RIC). The proportion of patients who received a matched sibling donor in GCB, non-GCB and PML were 69% (reference), 64% (P=0.6) and 41% (P=0.03), respectively. The remaining patients received matched unrelated donors. More GCB patients received peripheral blood as stem cell source than non-GCB (89% vs 73%, P=0.08) or PMBL (47%, P=0.001) patients. Median year of transplant was 2006 in both GCB and non-GCB and 2004 in PMBL. Results: Median (range) follow-up months in surviving GCB, non-GCB and PML patients were 63 (5-157), 29 (7-117) and 52 (10-133) months respectively. The 3-year cumulative OS were 52% (reference), 18% (P=0.09) and 46% (P=0.6). The 3-year cumulative PFS were 39%, 12% (P=0.1) and 41% (P=0.9) (Figure). When we restricted the comparison to patients who had chemosensitive disease and received RIC, the 3-year OS rates for GCB, non-GCB and PMBL were 47%, 25% (HR=0.6, P=0.3) and 44% (HR=0.9, P=0.9), respectively. The 3-year PFS rates were 37%, 10% (HR=0.6, P=0.2) and 44% (HR=0.7, P=0.8). Non-relapse mortality at 3-years was 29% (reference), 47% (P=0.1), and 35% (P=0.6). The incidence of acute II-IV GVHD was 24%, 27% and 29%. The incidence of extensive chronic GVHD was 34%, 54% (P=0.07) and 41% (P=0.5). The major cause of death in all 3 subgroups was disease progression (38%, 38%, and 33%), followed by acute GVHD 14%, 13%, and 33%. Conclusions: Our results suggest a tendency for inferior survival after alloSCT in non-GCB when compared to GCB and PMBL subtypes of DLBCL. This occurred despite the younger age in the non-GCB versus GCB group. Innovative approaches are needed to improve outcomes in non-GCB patients after alloSCT. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Impact of Cell-of-Origin on Outcome of Patients With Diffuse Large B-Cell Lymphoma Treated With Uniform R-CHOP Protocol: A Single-Center Retrospective Analysis From North India

2021 ◽  
Vol 11 ◽  
Author(s):  
Ajay Gogia ◽  
Sukesh Nair ◽  
Shalabh Arora ◽  
Lalit Kumar ◽  
Atul Sharma ◽  
...  
Keyword(s):  
B Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Ecog Performance Status ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
The Impact

IntroductionThere is a scarcity of data from India on the impact of cell of origin (COO) on outcomes of diffuse large B-cell lymphoma (DLBCL). This study was conducted to evaluate the impact of COO on outcomes of DLBCL patients treated with uniform rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (RCHOP) protocol.Materials and MethodsThis retrospective analysis included patients who received uniform RCHOP chemoimmunotherapy during the study period (2014–2020) at the Department of Medical Oncology at All India Institute of Medical Sciences (AIIMS), New Delhi, India. The patients were classified as germinal center B-cell like (GCB) or activated B-cell (ABC) type using the Hans classification.ResultsFour hundred seventeen patients with median age of 48 years (range, 18–76) and a male-female ratio of 2:1 were included in the analysis. B symptoms and bulky disease were seen in 42.9% and 35.5%. Extranodal involvement was seen in 50.8% of cases. ECOG performance status (0-2) was present in 65%, and 51% presented with advanced disease. GCB subtype was seen in 43%, and 47% were ABC type. Low- and intermediate-risk international prognostic index (IPI) score was seen in 76% of cases. The overall response rate to RCHOP was 85.8%, including a complete response rate of 74.8%. After a median follow-up of 30 months, the 3-year event-free survival (EFS) and overall survival (OS) were 80% and 88%, respectively. The presence of B symptoms and poor ECOG performance status (3-4) was associated with inferior CR rate. Low albumin (p &lt; 0.001), age &gt;60 years (p = 0.001), bulky disease (p &lt; 0.001), and extranodal involvement (p = 0.001) were associated with inferior EFS, whereas a high IPI risk score was associated with an inferior OS (p &lt; 0.001). EFS and OS were not significantly different between the GCB and ABC subtypes. Grade III/IV anemia, neutropenia, and thrombocytopenia were seen in 7.6%, 13.6%, and 2.7% of patients, respectively. Febrile neutropenia was seen in 8.9% of patients, and there were four treatment-related deaths.ConclusionsCell of origin for DLBCL has no impact on CR, EFS, and OS if patients are appropriately treated with standard doses and frequency of RCHOP. RCHOP is well tolerated in our patients, and results are comparable with the Western data.

Combinatorial Targeting of BCL6 and Anti-Apoptotic Proteins in Diffuse Large B-Cell Lymphoma (DLBCL) and Follicular Lymphoma (FL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 64-64
Author(s):  
Thibault Dupont ◽  
Zhenghong Dong ◽  
ShaoNing Yang ◽  
Ari Melnick ◽  
Leandro Cerchietti
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Conflicts Of Interest ◽  
Constitutive Expression ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Mutational Status ◽  
Apoptotic Genes ◽  
Apoptotic Proteins ◽  
The Impact

Abstract Abstract 64 BCL6 represents a survival factor in DLBCL and FL since specific BCL6 inhibitors (i.e: the peptidomimetic RI-BPI and the small molecule 79-6) kill DLBCL and transformed FL (tFL) cell lines. Our group showed that BCL2 and other anti-apoptotic genes are transcriptionally repressed by BCL6 and could be reactivated upon treatment with RI-BPI or 79-6. We also showed that BCL6 and BCL2 control distinct and non-overlapping survival pathways in these lymphomas. This suggests that blocking the function of anti-apoptotic proteins might overcome any resistance that these proteins might mediate in response to BCL6 inhibition. In addition, constitutive expression of BCL2 has been observed in DLBCL and FL cases. We therefore hypothesized that targeting both BCL6 and BCL2 would eliminate two of the most potent survival mechanisms and would translate in synergistic killing of these lymphomas. In order to test this hypothesis, we examined the proteome-wide consequence of BCL6 inhibition in a DLBCL cell line (SU-DHL6) transfected with siBCL6 by phospho-protein arrays. We found that 280 unique proteins changed their abundance after siBCL6, 40 of them related to (pro and anti) apoptosis signaling (p<0.001). By means of pathway analysis bioinformatic tools, we then identified anti-apoptotic proteins with increased abundance after siBCL6 that could be therapeutically targeted. Among these druggable proteins we found BCL2, BCL-XL, MCL-1, NEDD8, PARP1 and several ubiquitin ligases. We confirmed in independent experiments that BCL6 knockdown induced mRNA (by qPCR) and protein up-regulation (by immunobloting) of these genes in 2 additional DLBCL and 2 tFL cell lines. Treatment of these siBCL6-transfected cell lines with small molecules inhibitors of BCL2 family members (ABT-737 and oblatoclax), NEDD8 activating enzyme (MLN4924), PARP (olaparib) and proteasome (bortezomib) showed increased killing compared to each treatment alone. In order to identify rational combinatorial therapies that could be potentially translated for use in clinical trials, we performed additional studies with the BCL6 inhibitor RI-BPI that is being developed for clinical use. We first analyzed the impact of RI-BPI on the apoptosome in a panel of 6 DLBCL (SU-DHL6, Ly1, Ly7, Ly3, Ly10, SU-DHL4) and 4 tFL (DoHH2, WSU-DLCL2, Granta452, SC-1) cell lines. RI-BPI induced a profile of up-regulated pro and anti-apoptotic proteins similar to siBCL6. Because ABT-737 and obatoclax are active in DLBCL cells where apoptotic BH3 activators are neutralized by BCL2 or BCL-XL and RI-BPI treatment changes the stoichiometry of pro and anti-apoptotic proteins, we determined the post-RI-BPI BH3 profiling accordingly to the amount of BIM sequestration (by co-immunoprecipitation). Accordingly, sequential treatment of DLBCL and tFL cell lines with RI-BPI and ABT-737 or obatoclax synergistically killed BCL2/BCL-XL dependent cells (but not MCL-1 dependent cells). This effect was independent of the mutational status of BCL2, MCL1, BCL6, MYC and TP53. Olaparib was not tested in combination since most cell lines were resistant to clinically achievable concentrations of this drug. Bortezomib and MLN4924 were synergistic in most cell lines when combined with RI-BPI (as determined by isobologram analysis). The synergistic killing was associated with increase in caspase 7/3 activation (by a plate-based assay) and NFkB inhibition (by p65 DNA binding assay). This effect was independent of the cell of origin classification of the cell line (i.e. ABC vs. GCB). We then tested the combination of RI-BPI with ABT-737, MLN4924 or bortezomib in Ly1 xenograft models (n=10 mice per combination). Ly1 represents a DLBCL with 3q27 and t(14,18). We found that after 10 days of treatment, each combinatorial treatment was more effective than their individual components (p=0.02, p=0.01 and p<0.01 for RI-BPI with ABT-737, MLN4924 and bortezomib, respectively; T-test, day 10). Detailed toxicity studies revealed no toxicity excess with these combinations. In sum, our work shows that pharmacologic targeting of anti-apoptotic pathways induced by inhibition of BCL6 activity successfully sensitized DLBCL and tFL cells to apoptosis. This effect was evident in cells in which the apoptosis resistant mechanism evolved as response to BCL6 inhibition and gene de-repression as well as those with constitutive overexpression of anti-apoptotic genes. Disclosures: No relevant conflicts of interest to declare.

Use of Tailored Feedback Improves Accuracy of Delirium Documentation in the Burn ICU: Results of a Performance Improvement Initiative

2019 ◽  
Author(s):  
Amy N Gloger ◽  
Paul A Nakonezny ◽  
Herb A Phelan
Keyword(s):  
Intensive Care ◽  
Performance Improvement ◽  
Assessment Tool ◽  
Corrective Feedback ◽  
Assessment Method ◽  
Delirium Assessment ◽  
Improvement Project ◽  
Time Period ◽  
The Impact ◽  
Feedback Time

Abstract One of the most widely used tools for delirium assessment in burn intensive care units is the Confusion Assessment Method for the Intensive Care Unit delirium assessment tool. However, some nurses struggle with inaccurate delirium documentation. This performance improvement project was undertaken to assess the impact that routine chart audits with tailored feedback would have on documentation accuracy. An a priori goal of at least 90% documentation accuracy was set by burn leadership at our academic, American Burn Association-verified burn center. For the precorrectional feedback time period, nursing delirium documentation was reviewed for accuracy by the nurse educator. In the postcorrectional feedback time period, an intervention was started, in which the educator sent tailored feedback to nurses with inaccurate delirium documentation. A Poisson regression with robust standard errors was used to compare the proportions of correct delirium documentation for the precorrectional feedback and postcorrectional feedback time periods. The overall rates of correct delirium documentation in the precorrectional feedback time period were 49.15% (SD = 31.86), 95% CI: 36.43 to 66.31. A significant increase was seen in the rates of correct delirium documentation for the postcorrectional feedback time period (91.47% [SD = 8.28], 95% CI: 87.45 to 95.67), P = .0001. In the 4 months prior to starting corrective feedback, zero out of five (0%) audits reached the 90% goal of accurate delirium documentation. In the 8 months in which corrective feedback was being given, 9 out of 15 (60%) audits reached the compliance goal set by leadership. Using corrective feedback improves the accuracy of nursing delirium documentation.

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