Diagnosis Of Diffuse Large B-cell Research Articles

Demyelination as a harbinger of lymphoma: a case report and review of primary central nervous system lymphoma preceded by multifocal sentinel demyelination

BackgroundPrimary central nervous system lymphoma (PCNSL) may rarely be preceded by “sentinel demyelination,” a pathologic entity characterized by histologically confirmed demyelinating inflammatory brain lesions that mimic multiple sclerosis (MS) or acute disseminated encephalomyelitis (ADEM). Interpreting the overlapping radiologic and clinical characteristics associated with each of these conditions—contrast-enhancing demyelination of white matter and relapsing and remitting steroid-responsive symptoms respectively—can be a significant diagnostic challenge.Case presentationWe describe a 57-year-old woman with an unusual clinical course who presented with multi-focal enhancing white matter lesions demonstrated to be inflammatory demyelination by brain biopsy. Despite a good initial response to steroids and rituximab for treatment of presumed tumefactive multiple sclerosis, the patient’s condition rapidly deteriorated, and a repeat brain biopsy six months later was consistent with a diagnosis of diffuse large B-cell lymphoma.ConclusionsEarly clinical suspicion for PCNSL and awareness that biopsied lesions may initially show sentinel demyelination suggestive of alternate diagnoses may be essential for early initiation of appropriate therapies and mitigation of disease progression. Clinical, pathophysiological, and diagnostic aspects of sentinel demyelination and PCNSL are discussed.

The Burden Of Illness and Prevalence In Diffuse Large B-Cell (DLBCL) and Follicular (FL) Lymphomas

IntroductionIn non-Hodgkin lymphoma (NHL), particularly diffuse large B-cell (DLBCL) and follicular (FL) lymphomas, the prevalence, burden of disease, including that of relapse/recurrence, and quality of life (QoL) play a role in how novel treatment strategies are evaluated. We conducted a literature review to identify whether the current understanding of the prevalence, burden of illness (BOI) including QoL in these two predominant NHL histologies is sufficient to support novel treatment and resource allocation decisions. MethodsUsing EMBASE, PubMed, Cochrane, conference abstracts, treatment guidelines, and government, business and industry literature such as data from the WHO, we identified estimates for prevalence and BOI, defined as disease-related costs and QoL, for DLBCL and FL, from 2005 to 2013 in the US and EU5 (France, Germany, Italy, Spain, UK). In addition to appropriate MeSH (Medical Subject Headings) terms, search terms included, but were not limited to, burden of illness, quality of life, QoL, HRQoL, cost, direct cost, resource use, resource utilization, economic, incidence, prevalence, epidemiology, and mortality. FindingsBOI-related information within DLBCL and FL are very limited and antiquated DLBCLOnly one health economic study was identified – a US study using data from 1999-2000 in patients with aggressive NHL, including DLBCL (Kutikova et al. Leuk Lymphoma. 2006). Among the patients receiving initial treatment, which did not include the current standard of care R-CHOP, 68% of patients experienced treatment failure. The incremental cost of treatment failure was $14,174 per month, driven by higher initial treatment costs ($13,866 vs $4,754) and the need for secondary and/or palliative care ($5,062). However, these data may not accurately depict relapse rates and costs associated with more current standards of care. For QoL, one study was identified in DLBCL, a US based study in the elderly. The NCI sponsored Surveillance, Epidemiology, and End Results-Medical Health Outcomes Survey database was used to evaluate QoL in elderly DLBCL patients using the Short Form (SF-36) Health Survey. Patients surveyed 0–1 year after the diagnosis of DLBCL had poor QoL scores (physical component [PCS] median=33.6, mental component [MCS] median=40.8, poor self-rated health: 51.6%) (Kelly et al. Blood. 2012). FLOnly one health economic study was identified – a US study using data from 2006-2009 which estimated the cost of disease progression. Results showed that mean overall per patient per month (PPPM) costs over the 6-month follow-up were significantly higher for patients with progressive disease (PD) vs non-PD ($3527 vs. $860; difference=$ 2667; p<0.001) (Beveridge et al. Leuk Lymphoma. 2011). One QoL study was identified, a UK study that reported statistically significant differences by disease state using multiple QoL instruments. The total scores derived from the Functional Assessment of Cancer Therapy – Lymphoma (FACT-Lym) questionnaire showed that relapsed patients have lower QoL scores (109.7) than newly diagnosed patients (136.4), those achieving partial (128.81) or complete response (133.28), or when disease free (135.26) (p = 0.001) (Pettengell et al. Ann of Oncol. 2008).Regarding prevalence data, in the EU5, prevalence of DLBCL ranges from 30 – 58% of NHL cases and in the US estimates range from 25 – 35%. Prevalence of FL is lower, ranging from 11 – 19% in the EU5 and 20 – 25% in the US. Regarding the prevalence of relapse/recurrent disease, one-third of DLBCL patients are either relapsed or refractory after standard therapy (Friedberg. Clin Cancer Res. 2011; Abramson et al. Blood. 2005). ConclusionsCurrently available data related to BOI and prevalence are limited and dated making it difficult to accurately assess the impact of DLBCL and FL on patients and healthcare systems. In the absence of renewed information it may be challenging to quantify the incremental impact that novel regimens may have on clinical outcomes, BOI, and QoL. While NHL mortality has steadily decreased over the past few decades as treatment options have improved, updated and accurate epidemiologic and BOI data are needed to better characterize the impact that novel treatments in development may have on the overall clinical, BOI and patient-reported outcomes in DBLCL and FL. Disclosures:Dulac: Celgene Corporation: Employment. Joy: IMS Health: Employment. Ndindjock: IMS Health: Employment. Coyle: IMS Health: Employment. Wade: IMS Health: Employment, Research Funding.

Malignant lymphoma with diffuse cardiac involvement detected by multiple imaging examinations: a case report

IntroductionIn malignant lymphoma, cardiac involvement, which usually forms pathologically focal and firm nodules in the cardiac walls, is considered to be a late manifestation of the disease.Case presentationWe describe the case of a 71-year-old Asian Japanese woman whose first presentation of lymphoma was congestive heart failure. Multiple imaging examinations and laboratory findings led to a presumed diagnosis of a malignant lymphoma. A tissue diagnosis of the mediastinal mass could not be performed due to our patient’s generally poor condition. Our patient received corticosteroid therapy, but died 42 days after her admission. An autopsy revealed lymphoid cells encircling her ventricular wall and infiltrating her endocardium. A histological examination confirmed the diagnosis of diffuse large B-cell lymphoma.ConclusionImaging examinations such as echocardiography, computed tomography with three-dimensional reconstruction, and gallium-67-citrate scintigraphy could clearly detect the diffuse cardiac involvement antemortem. A combination of these imaging techniques could provide a working diagnosis and allow empirical initiation of treatment in patients with poor general condition.

Sunitinib in Relapsed or Refractory Diffuse Large B Cell Lymphoma: Results of a Phase II Multi-Center Study of the NCIC Clinical Trials Group.

Abstract 2729Poster Board II-705 Background:There are limited effective treatment options for patients with diffuse large B cell lymphoma who relapse post autologous stem cell transplant or are transplant-ineligible. The detection of vascular endothelial growth factor (VEGF )A, B and C isoforms and their receptors on many large cell lymphoma samples suggests that the VEGF pathway is critically important and may contribute to disease progression. Sunitinib maleate, is an orally bioavailable inhibitor of VEGF receptor-1 (VEGFR-1), -2, and -3, PDGFR-α and β as well as KIT, FLT3, RET and CSF-1 (Chow, LQ JCO 2007). We tested the efficacy, safety and biomarker activity of sunitinib in patients with relapsed diffuse large B cell lymphoma in a multi-center prospective phase II study. Methods:Eligibility included age 18 or older, histologically confirmed relapsed or refractory diffuse large B-cell (DLBCL), primary mediastinal (PMBCL), or transformed indolent lymphoma, at least one and no more than 2 prior chemotherapy regimens (one anthracycline-containing). The primary endpoint was objective response defined by 1999 Cheson criteria. The secondary endpoints were progression-free and overall survival, toxicity and the effect of sunitinib on peripheral blood circulating endothelial cells (CECs) and their precursors (CEPs). Patients self administered sunitinib 37.5 mg po daily with no breaks in 4 week cycles for up to 1 year. CT imaging was performed every 2 cycles and CEC/CEP assays were done at baseline, day 1 of cycles 2, 3 then q 3 months thereafter. A Simon 2-stage design was used with at least 1 response needed after 15 evaluable patients to complete a planned accrual of 25 patients total. Results:Between Feb 2007 and September 2008 we enrolled 19 patients at 7 Canadian sites - 17 were eligible and are evaluable for toxicity and 15 are evaluable for response. The median age was 65 and patients were a median of 20.3 months(m) from diagnosis (range 5.8–132 m). Fourteen (82%) had a diagnosis of DLBCL, 10 (58%) had responded to their preceding line of chemotherapy - 5 (29%) had relapsed post high dose chemotherapy. The median number of cycles of sunitinib received was 2 (1–5) with only 5 patients remaining on drug for 3 or more cycles. Only 35% of patients received > 90% planned dose intensity with 14 patients missing doses and 5 undergoing dose reductions necessitated by toxicities. Hematological toxicity (grade 3 neutropenia in 5 pts, grades 3–4 thrombocytopenia in 6 pts) and was the most common reason for dose omission. Of the 15 evaluable pts, no objective responses were seen, and 9 achieved stable disease (median duration 3.4 m); and 6 had primary progressive disease. As a result, the study was closed at the end of the first stage. With limited serial sampling, there was no discernable relationship between the change in absolute or apoptotic CEC over time with clinical response as measured by best response or change in bi-dimensional measurements. Conclusions:Sunitinib 37.5 mg po daily showed no evidence of anti-tumour activity in relapsed/refractory large B cell lymphoma and is associated with greater than expected hematological toxicity. Disclosures:Buckstein:Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Off Label Use: It is being tested in NHL.

Tratamiento de rescate y movilización de progenitores hematopoyéticos de sangre periférica con altas dosis de ifosfamida y etopósido en pacientes con linfoma

Several groups have used salvage chemotherapy in relapsed or refractory lymphomas to mobilize peripheral blood stem cells. The objective of this study was to evaluate the antilymphomatous efficacy, the ability of mobilization and the toxicity of a regimen containing high-dose ifosfamide, etoposide, methylprednisolone (IFOVM) and granulocyte colony-stimulating factor (G-CSF). Twenty-four patients with relapsed or refractory lymphoma received IFOVM and G-CSF. The median age was 45 years and 13 were males. The histologyc subtypes of lymphoma were: diffuse large B cell (DLBCL) (n = 15), Hodgkin (n = 2), Burkitt (n = 2), mantle cell (n = 2), anaplastic (n = 1), peripheral T-cell (n = 1) and follicular (n = 1). Two patients died of sepsis within the pancytopenia period. In 17 (77%) of the remaining patients more than 1.5 x 10(6) CD34+ cells/kg (median: 7.7 x 10(6) CD34+ cells/kg) were collected. The median time to peripheral blood stem cells harvest was 17 (range: 13-24) days and 4 patients required 2 procedures of apheresis. Sixteen patients (67%) developed neutropenic fever. The median time to achieve granulocyte cell count > 1 x 10(9)/l and platelet count > 20 x 10(9)/l was 15 and 16 days, respectively. The only factor predicting successful mobilization was the diagnosis of DLBCL (p = 0.04). Ten patients underwent peripheral blood stem cells transplantation. The regimen IFOVM and G-CSF allows an effective peripheral blood stem cells mobilization in patients with lymphoma, particularly in those with DLBCL, but it is associated with significant toxicity.