Diffuse large B-cell lymphoma (DLBCL) in African American patients: A retrospective study of clinical, molecular, and therapeutic differences in a sample population treated at UAB Comprehensive Cancer Center (UAB CCC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21035-21035
Author(s):  
A. S. The ◽  
V. Reddy ◽  
Y. Li ◽  
R. Davis ◽  
M. Baird ◽  
...  

21035 Background: SEER registry data indicate African Americans (AA) have a lower incidence of non-Hodgkin's lymphoma (NHL) but face higher lymphoma-specific mortality rates than Caucasians (C). To investigate this we compared outcomes between AA & C patients (pts) with DLBCL treated at UAB CCC. Correlative histologic & molecular studies of established prognostic features were performed to investigate differences. Methods: After IRB approval, DLBCL pts diagnosed '95-'06 were identified from pathology & referral databases. Baseline demographic & clinical data were extracted, including treatment (Rx), response & survival. Expression patterns of CD10, bcl-6, & MUM-1 were used to identify germinal center B-cell-like (GCB) vs non-GCB molecular subtype of DLBCL based on algorithm of Hans et al (2004). HLA-DR, bcl-2, & CD138 expression was determined. A 2:1 age- & gender-matched comparison of C to A pts was performed to evaluate differences. Descriptive analysis with X2 & Wilcoxon nonparametric tests & Kaplan Meier survival analysis were performed to determine differences. Results: 188 DLBCL patients were identified. Race was noted in 129, including 18 AA pts (14%). In comparison to 36 C pts (2:1 match), no differences were seen in LDH or stage at presentation. AA pts achieved better response to 1st-line Rx (p=0.01) & received fewer regimens (1 vs >1, p=0.05), however they were more likely to receive rituximab with 1st-line Rx (p=0.02), likely reflecting presentation in the post-rituximab era. Median survival, not yet reached for AA's, was 23 months for C pts (p=0.0509). Univariate & parametric survival analyses demonstrated LDH (p=0.0217) & 1st-line rituximab (p=0.0048) independently affected survival. In a separate cohort, no significant difference between races was seen in frequency of GCB vs non-GCB subtype or in expression of bcl-2, CD-138, or HLA-DR. Conclusions: Contrary to SEER observations, the outcome of AA DLBCL pts was superior to C pts in this single center study. No molecular or clinical prognostic feature dominated in either race. The fact that more AA than C patients received rituximab upfront confirms the benefit of adding this agent to 1st-line Rx. No significant financial relationships to disclose.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19034-e19034
Author(s):  
Poorvi Kirit Desai ◽  
Magali Van den Bergh ◽  
Xiaohui Zhang ◽  
Hailing Zhang ◽  
Braydon Schaible ◽  
...  

e19034 Background: PCBCL is a group of rare lymphoproliferative disorders, with an estimated annual incidence of 2.5 per 1,000,000 persons. Indolent subtypes include Primary Cutaneous Marginal Zone Lymphoma (PCMZL) and Primary Cutaneous Follicular Center Lymphoma (PCFCL). Primary Cutaneous Diffuse Large B-cell Lymphoma (PCDLBCL) is an aggressive subtype with a fatality rate of 50%. The Cutaneous Lymphoma International Prognostic Index (CLIPI) can risk-stratify indolent subtypes, but age is not considered. Here we present our single-institutional analysis of clinicopathologic features and outcomes of patients with PCBCL. Methods: This is a retrospective study of patients evaluated at Moffitt Cancer Center between 01/1990 and 12/2016. Patients were identified using our PCBCL database and diagnosis was verified by independent hematopathologists and dermatopathologists. Staging was determined by ISCL/EORTC criteria. Demographics, subtype, stage, disease course, and CLIPI scores were collected. Continuous and categorical values were tested using Kruskal-Wallis ANOVA method and Fisher’s Exact Test, respectively. Kaplan-Meier curves were produced to determine PFS. Results: We identified 37 patients who met diagnostic criteria for PCBCL (35% PCFCL, 40.5% PCMZL, 13.5% PCDLBCL, and 11% indolent, unspecified). Male:female ratio was 2.4:1. 51% of patients were ≥ 60 years old (yo), and 49% were < 60 yo. 54% had stage T1 disease, 27% T2, and 19% T3. Median PFS for patients <60 was 1.1 years, but was not reached for those ≥60. Mean follow-up time was 2.6 years for all patients. Log-rank test showed a statistically significant difference in PFS between the two age groups (p=0.01). PFS for stage of indolent subtypes showed marginal significance (p <0.06). CLIPI for indolent subtypes did not show a significant difference in PFS. Conclusions: We found that age is a highly statistically significant prognostic parameter in PCBCL, as patients ≥ 60 yo had a longer PFS compared to younger patients, even after adjusting for stage and CLIPI. These results are promising for age as a possible prognostic indicator for PCBCL, but validation is needed with a larger sample size.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1646-1646
Author(s):  
Sumana Devata ◽  
Nicholas Herrman ◽  
Robert Briski ◽  
Farahk Keyoumarsi ◽  
Daniel F Boyer ◽  
...  

Abstract Background: Diffuse large B-cell Lymphoma (DLCBL) is a heterogeneous disease. Current prognostic models have limitations, but emerging research utilizing the cell of origin and host immune factors, such as the absolute monocyte count (AMC) and absolute lymphocyte count (ALC), may improve risk stratification in these patients. In the rituximab era, the majority of relapses are observed within the first 24 months following treatment. Therefore, event free survival at 24 months (EFS24) is a reliable surrogate for overall survival in DLBCL [Maurer et. al., J Clin Oncol, 2014 Apr 1; 32(10): 1066-73]. The primary objective of this study was to determine if the ALC/AMC ratio predicts EFS24 in DLBCL risk-stratified by the cell of origin (COO). Methods: Patients with de novo DLBCL who were evaluated at the University of Michigan Comprehensive Cancer Center between 1997 and 2011 and had archived diagnostic tissue available were eligible for participation in this retrospective study. We identified 243 eligible patients. The ALC and AMC were obtained from a complete blood count with differential at the time of diagnosis. Immunohistochemical staining for CD10, Bcl-6 and IRF4/MUM1 was performed and cases independently scored in a blinded fashion by up to three hematopathologists. A consensus opinion was obtained in order to determine the cell of origin (COO) using the Hans algorithm. Results: The median age at diagnosis was 61 years with a median follow-up of 3.1 years. Among the 218 patients for whom the revised IPI could be calculated, 46% were high risk (IPI 3-5). Most patients received rituximab based chemoimmunotherapy (88%), largely R-CHOP (81%). The median ALC/AMC ratio for the entire cohort was 2 (interquartile range: 1-3). The ALC/AMC ratio was analyzed as a continuous variable on univariate analysis and was associated with inferior EFS (hazard ratio (HR) =0.81, 95% confidence interval (CI) 0.68-0.93, p=0.003). A receiver operating characteristic curve (ROC) was generated utilizing EFS24 to establish the optimal cut-off point for the ALC/AMC ratio. An ALC/AMC ratio of 1.6 was best able to risk-stratify patients for EFS24. The 24-month EFS for patients with an ALC/AMC ≥1.6 was 73% and for ALC/AMC <1.6 was 47% (p<0.001), and the 5-year OS was 68% vs 51% (p=0.004), respectively. On multivariate analysis the ALC/AMC ratio and R-IPI were both independently significant for EFS (HR 1.5, 95% CI 1.0-2.4, p= 0.036 and HR 1.88, 95% CI 1.2-2.9, p=0.003, respectively). Tissue exhaustion precluded determination of the COO for many patients. Among the remaining 112 patients, 63% were GCB and 37% non-GCB. Mean ALC/AMC ratios for the GCB and non-GCB subtypes were not significantly different at 2.2 and 2.4, respectively. Among GCB DLBCL the EFS24 and 5-year OS for ALC/AMC ≥1.6 vs ALC/AMC <1.6 was 77% vs 46% (p = <0.0001) and 71% vs 50% (p = 0.0007), respectively. Among non-GCB DLBCL, the EFS24 was 70% for ALC/AMC ≥1.6 and 49% for ALC/AMC <1.6 (p=0.025). No significant difference in 5-year OS was observed when non-GCB DLBCL were stratified by the ALC/AMC ratio. Conclusions: The ALC/AMC ratio is an independent prognostic factor for EFS24 in both GCB and non-GCB DLBCL. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
pp. 107815522096708
Author(s):  
Wenhui Li ◽  
Katherine A Richter ◽  
Katherine A Tobon ◽  
Kevin T McCarthy ◽  
Timothy E Kubal

Introduction Dose-adjusted (DA-) EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) is a front-line treatment option for aggressive B-cell lymphomas. Due to regimen complexity, inpatient administration of DA-EPOCH has been historically required. Moffitt Cancer Center (MCC) developed an Inpatient/Outpatient (IPOP) program to facilitate administration of complicated regimens in the outpatient setting. We hypothesized that outpatient administration of DA-EPOCH at a comprehensive cancer center is both safe and cost-effective. Methods We conducted a single-center, retrospective chart review including B-cell lymphoma patients who were 18 years or older and who had received DA-EPOCH at MCC from April 26, 2017 through August 10, 2019. The primary endpoint was hospital admissions during outpatient chemotherapy administration. Additional safety endpoints included hospitalizations between cycles, infectious complications, extravasations, drug spills, pump-malfunctions, and drug-related adverse events. Financial analysis included drug cost, resource utilization, and impact of hospital bed backfill. Results 56 patients received 219 cycles of DA-EPOCH with 193 cycles administered outpatient. Zero patients required hospitalization during outpatient administration of DA-EPOCH, resulting in 965 saved hospital days. 23 patients (41%) were hospitalized between cycles, most commonly due to neutropenic fever (52%). No extravasations were documented throughout the study period. There were few incidences of drug spills or pump malfunctions. Based on current regimen utilization, the annual transition of 84 cycles of DA-EPOCH to the outpatient setting has a positive impact on margin of $1,444,548. Conclusions Routine outpatient administration of DA-EPOCH is both safe and feasible with a positive annual impact on margin of $1,444,548 at a comprehensive cancer center.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 444-444
Author(s):  
Andrea Rinaldi ◽  
Daniela Capello ◽  
Marta Scandurra ◽  
Timothy C. Greiner ◽  
Wing C. Chan ◽  
...  

Abstract Abstract 444 Post transplant lymphoproliferative disorders (PTLD) are important complications of solid organ transplantation associated with severe morbidity and mortality. DLBCL represents the most common form of monomorphic PTLD. Since knowledge of the pathogenesis of monoclonal PTLD is limited, we studied a series 44 cases of PT-DLBCL with high-density genome wide SNP-based arrays, and compared them with 105 cases immunocompetent DLBCL (IC-DLBCL) and 28 cases of HIV-DLBCL. Methods. DNA was extracted from frozen biopsies. All 177 DNA profiles were obtained using the Affymetrix GeneChip Human Mapping 250K NspI arrays. Recurrent minimal common regions (MCR) were defined using the algorithm by Lenz et al. (PNAS, 2008). Differences in frequencies between subgroups were evaluated using Fisher's exact test followed by multiple test correction. Results. The most common MCR were losses at 2p16.1 (29%) and 17p11.2-p13.3 (22%, TP53), and gains at 11q14.2-q24.2 (22%) and 7q (22%). Amplifications occurred in 7% at 9p23-p24 (PTPRD, JAK2, JMJD2C). MCRs more frequently deleted in PT-DLBCL when compared to IC-DLBCL included a series of small interstitial deletions at 1p32.2, 2p16.1, 3p14.2, 4p14, 14q13.2, 20p12.3, 20q13.32. Some of these aberrations targeted known fragile sites (FRA3B, FRA1B and FRA2E). FRA2E deletion showed the most significant difference with IC-DLBCL (PT-DLBCL 30% vs IC-DLBCL 4%, p<0.0001, adj.p<0.0005) and contained two genes, Vaccinia Related Kinase 2 (VRK2) and Fanconi anemia, complementation group L (FANCL). VRK2 is a negative regulator of MAPK pathway. FANCL is an E3 ubiquitin ligase, that is part of the FA nuclear protein complex, mainly involved in DNA repair, but also in telomere stability, chromatin remodelling, cell cycle regulation and apoptosis. No deletions of WW domain-containing Oxidoreductase (WWOX) were observed in PT-DLBCL, as opposed to HIV-DLBCL. Aside from the small interstitial deletions, PT-DLBCL overall showed a profile similar to IC-DLBCL, but PT-DLBCL contained no 13q14.3 deletions (0% vs 15%; p=0.003, adj.p = 0.04), which among other genes contains MIR15 and MIR16, and had fewer copy neutral LOH at 6p21.32-p21.33 (HLA-DR locus; 4% vs 24%; p=0.005, adj.p = 0.04). By immunophenotype, PT-DLBCL resembles most closely activated B cell like (ABC) / non germinal center (GC) B-cells. However, when compared with gene expression-classified ABC DLBCL, the MCRs characteristic of this subtype were under-represented in PT-DLBCL: gains of 18q (BCL2; 5% vs 32%; p=0.007, adj.p=0.07) and 3q (0% vs 32%; p=0.02; p=0.006, adj.p=0.07) and 6q losses (PRDM1 and TNFAIP3; 9% vs 23%; p=0.06, adj.p=0.3). Also, MCRs in GC such as 2p14-p16.1 (REL) gains were less common in PT-DLBCL compared to GC-DLBCL (11% vs 37%, p=0.019, adj.p = 0.13). In conclusion, PT-DLBCL shared similarities with IC-DLBCL, but presented unique features, such as the lack of copy neutral LOH at 6p (HLA-DR locus) and frequent breakage at fragile sites. The latter appeared partially different from what observed in HIV-DLBCL, suggesting different pathogenetic mechanisms in the context of the two conditions of immunodeficiency. The comparison with IC GC- and ABC-DLBCL subtypes indicated discrepancies between the PT-DLBCL phenotype and their genomic profile. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii361-iii361
Author(s):  
Brandon Brown ◽  
Paolo Tambaro ◽  
Kris Mahadeo ◽  
Sajad Khazal ◽  
Priti Tewari ◽  
...  

Abstract INTRODUCTION Immune effector cell associated neurotoxicity (ICANS) and cytokine release syndrome (CRS) are potentially life-threatening complications associated with immune effector cell (IEC) therapies. We characterize ICANS in pediatric and adult young adolescent (AYA) patients receiving IEC therapy at our institution. METHODS We reviewed clinical characteristics and severity (based on ASTCT Consensus Criteria) in pediatric and AYA patients with IEC products from 2018–2019 at MDACC. RESULTS Nine patients, median age 15.5 (range: 3–25) years received chimeric antigen receptor (CART) IEC therapy. Four (44%) developed ICANS within median of 8 (range: 3–27) days of CAR T cell infusion and median 6 (range: 2–7) days after CRS. Primary diagnoses were pre-B cell acute lymphoblastic leukemia (8) and mediastinal large B-cell lymphoma (1). Median CRS and ICANS severity grade was 2 (range 1–4). Symptoms included altered mental status (AMS) (5), seizure (1), aphasia (2), impaired ability to write a standard sentence (4). Neuroimaging did not correlate to ICANS symptoms or severity. EEG was performed in 3 and 1 had background slowing correlating with aphasia. CSF was obtained in two revealing lymphocytosis. All received prophylactic anti-epileptic medication and tocilizumab for concomitant CRS. Three received steroids. CONCLUSION ICANS may present in almost half of pediatric patients within one week of receiving CART products associated with CRS. CAR-T trafficking into the CSF may explain pleocytosis in the CSF. Prospective studies may clarify. Impaired ability to write a standard sentence and the Cornell Assessment of Pediatric Delirium (CAPD) may be early indicators of ICANS in pediatric/AYA patients.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13056-e13056
Author(s):  
Michael Grimm ◽  
Bhuvaneswari Ramaswamy ◽  
Maryam B. Lustberg ◽  
Robert Wesolowski ◽  
Sagar D. Sardesai ◽  
...  

e13056 Background: Invasive lobular carcinoma (ILC) accounts for only 10-15% of all invasive breast cancers but has distinct clinicopathologic characteristics and genomic profiles. In particular, metastatic lobular cancers (mILC) have unique sites of metastasis and it is unclear if the response to initial endocrine therapy differs from metastatic ductal cancers (mIDC). Therefore we have undertaken a single-institution, retrospective analysis to compare overall outcomes and response to initial endocrine therapy (ET) in patients (pts) with metastatic ILC and IDC. Methods: An IRB approved retrospective review of medical records was conducted evaluating pts treated for metastatic IDC and ILC at The Ohio State University Comprehensive Cancer Center from January 1, 2004 to December 31, 2014. Pts diagnosed with mIDC were matched on age, year of diagnosis, estrogen receptor/progesterone receptor and HER2 status and site of metastasis 2:1 to patients diagnosed with mILC. Overall survival (OS) was defined as the time from metastasis to death or last known follow-up. Progression-free survival (PFS) was defined as time from metastasis to progression on first-line ET. Time to chemotherapy (TTC) was defined as time from starting ET for metastasis to initiation of chemotherapy. Kaplan Meier (KM) methods were used to calculate median OS, PFS and TTC. Results: A total of one hundred sixty one pts with metastatic breast cancer were included in this analysis. The demographic features between the two groups were well balanced and included in the table below. The median OS was 2.6 yrs (95% CI: 1.55, 3.22) for mILC and 2.2 yrs (95% CI: 1.95, 2.62) for mIDC. A subset of 111 patients who started on endocrine therapy were used in the PFS and TTC analyses. The median PFS following first-line ET was 2.2 yrs (95% CI: 0.1.0, 2.7) for mILC and 1.4 yrs (95% CI: 0.91, 1.90) for mIDC. Median TTC was 2.1 yrs (95% CI: 1.71, 4.92) for mILC and 2.4 yrs (95% CI: 1.90, 4.77) for mIDC. There was no statistically significant difference in outcomes between the two groups. Conclusions: Outcomes in patients with ILC and IDC have been varied, with several studies reporting that patients with ILC have worse outcomes and response to chemotherapy. Our retrospective study examining outcomes in mILC in comparison with mIDC showed no difference in OS. Given the concern of resistance to conventional therapies in patients with lobular cancers, it is reassuring to see that the median PFS on first line ET and TTC was similar to metastatic ductal cancers.[Table: see text]


2018 ◽  
Vol 25 (7) ◽  
pp. 1645-1650 ◽  
Author(s):  
Stefanie K Clark ◽  
Lisa M Anselmo

Pemetrexed is a multitargeted antifolate indicated for locally advanced or metastatic non-squamous non-small-cell lung cancer and malignant pleural mesothelioma. Cutaneous reactions are associated with pemetrexed use. Pemetrexed prescribing information recommends oral dexamethasone 4 mg twice daily for three days starting the day before pemetrexed infusion to prevent cutaneous reactions. Patients receive intravenous dexamethasone before pemetrexed infusion at the University of New Mexico Comprehensive Cancer Center, but the oral dexamethasone recommendation is not always followed. The objective of this study was to determine if there is a difference between patients who received three days of oral dexamethasone starting the day before pemetrexed infusion and patients who did not by determining incidence of cutaneous reactions, delay in therapy, and therapy change due to adverse reactions. Eighty-five patients received at least one dose of pemetrexed between August 1, 2012 and August 31, 2017. Twenty-nine patients did not receive three days of oral dexamethasone 4 mg twice daily and 56 patients did (34.1% vs. 65.9%). There was no statistically significant difference in the incidence of cutaneous reactions between the intervention group and the control group (13.8% vs. 25.0%; p = 0.384), delay in pemetrexed therapy between groups (44.8% vs. 32.1%; p = 0.2), or therapy change due to adverse events (34.5% vs. 23.2%; p = 0.654). Results suggest three days of oral dexamethasone 4 mg twice daily did not significantly affect incidence rates of cutaneous reactions, delay in therapy, or therapy change in patients who received intravenous dexamethasone before pemetrexed infusion at University of New Mexico Comprehensive Cancer Center.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Di Wang ◽  
Peng Liu ◽  
Yue Zhang ◽  
Hui-Ying Liu ◽  
Di Shen ◽  
...  

Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is a common subtype of non-Hodgkin’s lymphoma and is very likely to infiltrate the bone marrow. Over 30% of patients are converted to relapsed/refractory DLBCL after first-line rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, with a poor prognosis. Our aim was to identify molecular markers that might be utilized to predict relapsed/refractory ABC-DLBCL patients. Hence, we collected bone marrow aspirate smears from 202 patients with ABC-DLBCL and detected expression of bone marrow molecular marker proteins by immunocytochemistry. Signal transducer and activator of transcription (Stat)3, nuclear factor (NF)-κB p65, Syk, Bruton’s tyrosine kinase (BTK), and Bcl2 proteins were strongly expressed in bone marrow aspirate smears of ABC-DLBCL patients. The same smear could present positive expression of multiple proteins simultaneously. Positive combinations of protein expression were associated with resistance. The most significant finding was that the Stat3+NF-κB+ group developed resistance, which was significantly higher than that of the Stat3-NF-κB-group (80 vs. 14%). There was a significant difference in two-year relapse-free survival between protein-positive and protein-negative combinations of Stat3-NF-κB (P = 0.005), Bcl2-Stat3 (P = 0.009), Bcl2-Pax5 (P = 0.003), and BTK-Syk (P < 0.001). Thus, we detected key molecules in multiple signaling pathways in bone marrow aspirate smears. At the same time, the results provide further clinical evidence of ABC-DLBCL drug-resistant molecules and provide a theoretical basis for rational second-line treatment after drug resistance.


2020 ◽  
Author(s):  
Kyu Hye Choi ◽  
Han Hee Lee ◽  
Seung-Eun Jung ◽  
Kyung-Sin Park ◽  
Joo-Hyun O ◽  
...  

Abstract Background Early-stage primary gastrointestinal (GI) low-grade B-cell lymphoma shows good therapeutic response to primary radiotherapy. However, there is no clear guideline for the evaluation of response to radiation therapy currently. The aim of this study was to analyze the relationship between the best response time and the clinical course after radiotherapy. Methods Patients who underwent radiotherapy for treatment of primary GI low-grade B-cell lymphoma from September 2007 to December 2018 at Seoul St. Mary's Hospital were included. Early responders were defined by best response within 6 months after radiotherapy, and delayed responders after 6 months. Clinical and pathological factors associated with delayed response and survival analyses were performed to investigate the recurrence and survival during follow-up. Results A total of 43 patients were evaluated and the number of gastric mucosa-associated lymphoid tissue and duodenal follicular lymphoma was 36 and 7, respectively. All of 43 patients showed complete remission to radiotherapy and the best response time after radiotherapy was a median of 3 months. There were 8 delayed responders with a median duration of 8.9 months. Early and delayed responders were characterized by a significant difference in depth of invasion beyond the mucosal layer. Conclusions Delayed responders did not show differences in oncological outcomes compared with early responders. They were allowed to watch and wait for an additional 6 to 12 months without further treatment.


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