Jakob Madsen

Efficacy of routine surveillance with positron emission tomography/computed tomography in aggressive non-Hodgkin lymphoma in complete remission: status in a single center

Post-therapy surveillance imaging in patients with lymphoma remains controversial. We report our experience with positron emission tomography/computed tomography (PET/CT) surveillance in patients with aggressive non-Hodgkin lymphoma in first complete remission (CR). The 138 PET/CTs performed in 52 patients revealed four unsuspected relapses. In one patient, relapse was visualized by fluorodeoxyglucose (FDG) accumulation without any significant CT pathology. The specificity and sensitivity of surveillance PET/CT were 89% and 100%, respectively. The predictive values of positive and negative PET/CTs were 21% and 100%, respectively. The cost of half-yearly routine PET/CT surveillance during the first 2 years in CR was

Increasing incidence of ophthalmic lymphoma in Denmark from 1980 to 2005

US8552 per patient and accounted for 81% of the total follow-up costs. PET/CT was effective in detecting unexpected relapse and normal PET/CT supported continuous CR. However, the impact of PET/CT was limited by the high number of false-positive results and PET/CT surveillance was costly compared to CT surveillance.

Human B-cell cancer cell lines as a preclinical model for studies of drug effect in diffuse large B-cell lymphoma and multiple myeloma

PURPOSE To evaluate patient characteristics and incidence of ophthalmic lymphoma in Denmark during the period 1980 to 2005. METHODS All patients in Denmark with a diagnosis of ophthalmic lymphoma during the period 1980 to 2005 were retrieved from three different population-based registries. Specimens from all patients were collected and reclassified according to the World Health Organization (WHO) classification system. Incidence rates were calculated by using Poisson regression models. RESULTS A total of 228 patients with a histologically verified diagnosis of ophthalmic lymphoma were included. There was an equal distribution of males and females. The most frequent lymphoma subtype was extranodal marginal zone B-cell lymphoma (MALT [mucosa-associated lymphoid tissue] lymphoma, 55.5%) and most cases were located in the orbit (56.8%). High-grade lymphoma subtypes were found more frequently in males than in females. Incidence rates were highly dependent on the patients age. For all ages, a statistically significant annual average increase of 3.4% during the 26-year period was found. This increase was primarily due to a rise in the incidence of MALT lymphoma. CONCLUSIONS In the Danish population ophthalmic lymphoma consists primarily of orbital MALT lymphoma. Although it is a rare disease in mostly elderly patients, the incidence of ophthalmic lymphoma is increasing at a rapid pace.

Utility of interim and end-of-treatment PET/CT in peripheral T-cell lymphomas: A review of 124 patients

Drug resistance in cancer refers to recurrent or primary refractory disease following drug therapy. At the cellular level, it is a consequence of molecular functions that ultimately enable the cell to resist cell death-one of the classical hallmarks of cancer. Thus, drug resistance is a fundamental aspect of the cancer cell phenotype, in parallel with sustained proliferation, immortality, angiogenesis, invasion, and metastasis. Here we present a preclinical model of human B-cell cancer cell lines used to identify genes involved in specific drug resistance. This process includes a standardized technical setup for specific drug screening, analysis of global gene expression, and the statistical considerations required to develop resistance gene signatures. The state of the art is illustrated by the first-step classical drug screen (including the CD20 antibody rituximab, the DNA intercalating topoisomerase II inhibitor doxorubicin, the mitotic inhibitor vincristine, and the alkylating agents cyclophosphamide and melphalan) along with the generation of gene lists predicting the chemotherapeutic outcome as validated retrospectively in clinical trial datasets. This B-cell lineage-specific preclinical model will allow us to initiate a range of laboratory studies, with focus on specific gene functions involved in molecular resistance mechanisms.

Evaluation of clinical trial eligibility and prognostic indices in a population-based cohort of systemic peripheral T-cell lymphomas from the Danish Lymphoma Registry

According to the updated guidelines for imaging in lymphoma, 18F‐FDG positron emission tomography/computed tomography (PET/CT) is recommended for staging and evaluation of treatment response in FDG‐avid lymphomas. The purpose of the study was to evaluate the utility of PET/CT in nodal peripheral T‐cell lymphomas (PTCL). Patients with newly diagnosed nodal PTCL (peripheral T‐cell lymphoma NOS, anaplastic large‐cell lymphoma, or angioimmunoblastic T‐cell lymphoma) seen at five Danish hematology centers during the period 2006 to 2012 were included, if they had been pretherapeutically staged with PET/CT. Medical records were reviewed for baseline clinical and follow‐up information. Staging, interim (I‐PET), and end‐of‐treatment PET/CT (E‐PET) studies were centrally reviewed, and reported using the Deauville 5‐point score (DS). A total of 124 patients fulfilled the inclusion criteria. The median age was 58 years, and 88% received CHOP/CHOP‐like therapy. Five years PFS and OS of the study population was 36.8% (95% CI 27.3–46.4) and 49.7% (95% CI 38.9–59.6), respectively. The presence of PET/CT‐ascertained lung and/or liver involvement was associated with a worse outcome. The sensitivity of PET/CT for detecting biopsy‐defined bone marrow involvement was only 18% (95% CI 4–43). An interim DS >3 was not prognostic for worse OS and PFS among CHOP/CHOP‐like treated patients in uni‐ or multivariate analyses. A DS >3 after treatment predicted a worse prognosis. In conclusion, I‐PET was not predictive of outcome in CHOP/CHOP‐like treated PTCL patients when using the DS. Prospective studies are needed to determine the optimal use of PET/CT in PTCL including the role of quantitative PET/CT analysis. Am. J. Hematol. 90:975–980, 2015.

Performance Comparison of Affymetrix SNP6.0 and Cytogenetic 2.7M Whole-Genome Microarrays in Complex Cancer Samples

Clinical trials (CTs) are needed to improve the outcome for peripheral T‐cell lymphomas (PTCL), and accrual into CTs is one of the main recommendations in international treatment guidelines. The use of risk‐adapted strategies has been suggested as a way to optimize treatment outcome in PTCL. The aim of the present study was to evaluate CT eligibility and selected prognostic indices in a population‐based PTCL cohort of 481 PTCL patients identified from the Danish Lymphoma Registry in the period 2000–2010. According to five predefined parameters (age, performance status, P‐creatinine, P‐ALAT and measurable tumour lesion), patients were subdivided into four groups: ‘younger fit’, ‘elderly fit’, ‘frail’ and ‘not CT eligible’. International prognostic index (IPI), prognostic index for T‐cell lymphoma (PIT) and anaplastic lymphoma kinase (ALK) protein expression were tested at subtype‐specific level. Overall, 41% of the patients were considered eligible for interventional CTs implicating curatively intended multiagent chemotherapy, including, if considered appropriate, consolidating stem cell transplantation (SCT), as part of the upfront management strategy. Moreover, 28% was elderly fit and eligible for interventional CT, including those with SCT as part of the trial design. Approximately 7% were defined as ‘too frail’ for aggressive treatment schedules, whereas 24% were deemed not to be eligible for any CT. Both overall and progression‐free survivals were effectively predicted by IPI and PIT (p < 0.001). ALK‐positive anaplastic large cell lymphoma patients were significantly younger (median age 40 vs. 62, p < 0.001) and had a better outcome than their ALK‐negative counterparts (p < 0.001). However, ALK expression lost its prognostic significance when adjusting for age. In a population‐based cohort of adult Caucasian PTCL patients, approximately half were eligible for multiagent chemotherapy with or without consolidating SCT. Both IPI and PIT are useful prognostic indices in all ‘primary nodal’ PTCL entities. The prognostic value of ALK protein expression in anaplastic large cell lymphoma is significantly downsized when adjusting for age. Copyright

Incidence of venous thromboembolism in patients with diffuse large B-cell lymphoma

The Affymetrix cytogenetic 2.7M whole-genome microarray (Cyto2.7M) detects genomic aberrations. The Cyto2.7M array has increased coverage in regions with cancer-related genes, ∼4-fold reduced processing time, and 5-fold reduced input requirements (100 ng) compared to the commonly used Affymetrix SNP6.0 genome-wide microarray (SNP6.0). We set out to compare the performance of these microarrays on cancer samples containing complex genomic changes. We analyzed genomic DNA from 8 lymphoma samples and 1 blood sample using both SNP6.0 and Cyto2.7M microarrays. We compared the arrays with respect to 4 parameters, including detection of copy number variations (CNV), CNV boundaries, the actual copy number (CN) assigned to the aberrations, and loss of heterozygosity. The CN state of selected regions was validated by quantitative PCR. Very high consistency between arrays on all parameters tested was observed, hence only 30 of 224 aberrations disagreed on the CN state, corresponding to a total of ∼12 Mb or 0.06% of the analyzed base pairs. Thus, the SNP6.0 and Cyto2.7M arrays are equally well suited to detect genomic aberrations in complex samples such as cancer samples. With reduced processing time and lower input requirements, the Cyto2.7M array enables genomic analysis of samples where only limited DNA is available.

Occupational allergic airborne contact dermatitis caused by pethoxamid

Abstract Venous thromboembolism (VTE) in patients with diffuse large B-cell lymphoma (DLBCL) is an important complication. We aimed to asses the risk of VTE and the quality of VTE discharge diagnosis in a cohort of DLBCL patients. Objective confirmed VTE events during two years of follow-up were identified by the review of medical records of consecutive patients with DLBCL at Aalborg University Hospital from 2007 until 2013. Information on baseline disease stage, lifestyle factors, and anticoagulant therapy were registered. Cox regression was used to assess VTE risk factors. The data quality on VTE discharge diagnosis was evaluated by comparing data on VTE discharge diagnosis from the Danish National Registry of Patients with information from the medical records. Eleven percent of patients were diagnosed with VTE. Prior VTE, performance status, and Ann Arbor stage were associated with VTE. The positive predictive value of a VTE discharge diagnosis was 85% and the sensitivity 53%.

Utility of interim and end-of-treatment PET/CT in peripheral T-cell lymphomas: A review of 124 patients: PET/CT in Nodal Peripheral T-Cell Lymphomas

Keywords: 2-chloro-N-(2-ethoxyethyl)-N-(2-methyl-1-phenylprop-1-enyl)acetamide; CAS no. 106700-29-2; case report; contact allergy; contact dermatitis; herbicide; occupational; pethoxamid

Utility of interim and end-of-treatment PET/CT in peripheral T-cell lymphomas

According to the updated guidelines for imaging in lymphoma, 18F‐FDG positron emission tomography/computed tomography (PET/CT) is recommended for staging and evaluation of treatment response in FDG‐avid lymphomas. The purpose of the study was to evaluate the utility of PET/CT in nodal peripheral T‐cell lymphomas (PTCL). Patients with newly diagnosed nodal PTCL (peripheral T‐cell lymphoma NOS, anaplastic large‐cell lymphoma, or angioimmunoblastic T‐cell lymphoma) seen at five Danish hematology centers during the period 2006 to 2012 were included, if they had been pretherapeutically staged with PET/CT. Medical records were reviewed for baseline clinical and follow‐up information. Staging, interim (I‐PET), and end‐of‐treatment PET/CT (E‐PET) studies were centrally reviewed, and reported using the Deauville 5‐point score (DS). A total of 124 patients fulfilled the inclusion criteria. The median age was 58 years, and 88% received CHOP/CHOP‐like therapy. Five years PFS and OS of the study population was 36.8% (95% CI 27.3–46.4) and 49.7% (95% CI 38.9–59.6), respectively. The presence of PET/CT‐ascertained lung and/or liver involvement was associated with a worse outcome. The sensitivity of PET/CT for detecting biopsy‐defined bone marrow involvement was only 18% (95% CI 4–43). An interim DS >3 was not prognostic for worse OS and PFS among CHOP/CHOP‐like treated patients in uni‐ or multivariate analyses. A DS >3 after treatment predicted a worse prognosis. In conclusion, I‐PET was not predictive of outcome in CHOP/CHOP‐like treated PTCL patients when using the DS. Prospective studies are needed to determine the optimal use of PET/CT in PTCL including the role of quantitative PET/CT analysis. Am. J. Hematol. 90:975–980, 2015.