Search

Background: Diffuse large B‐cell lymphoma (DLBCL) is the most common form of lymphoma. European guidelines recommend FDG‐PET/CT for staging and end of treatment (EOT) response assessment, mid‐treatment response assessment is optional. We compared the Lugano classification and PET Response Criteria In Solid Tumours (PERCIST) for FDG‐PET/CT response assessment in DLBCL head‐to‐head. Methods: We retrospectively included patients with DLBCL who underwent first‐line R‐CHOP(‐like) therapy (2013−2020). Interim and EOT FDG‐PET/CT response were reevaluated using the Lugano classification and PERCIST. Response was dichotomized into complete metabolic response (CMR) versus non‐CMR (interim and EOT) and responders versus nonresponders (interim only). The cutoff for nonresponse at interim was a Deauville score of 5 (DS5) with the Lugano classification and a partial metabolic response with ≤66% reduction in SULpeak using PERCIST (PERCIST66). Results: In multivariable Cox regression (N = 170), DS5 at interim, PERCIST66 at interim, non‐CMR at EOT with the Lugano classification and non‐CMR at EOT with PERCIST were predictive of progression‐free survival (PFS). The Lugano classification and PERCIST agreed perfectly at interim and EOT and with 98.4% for the identification of nonresponders at interim. The accuracy for predicting events within 2 years of diagnosis was 84.2% for DS‐5 at interim, 87.6% for PERCIST66 at interim, 86% for non‐CMR with the Lugano classification at EOT and 83.3% for non‐CMR with PERCIST at EOT. Conclusion: The Lugano classification and PERCIST were equally predictive of PFS. Nonresponse at interim and non‐CMR at EOT were predictive of poor PFS with comparable accuracy for predicting events within 2 years. [ABSTRACT FROM AUTHOR]

Summary: Previous studies concerning reproductive patterns among non‐Hodgkin lymphoma (NHL) survivors are scarce and those available have reported conflicting results. Treatment regimens vary considerably between aggressive and indolent NHL and studies of reproductive patterns by subtypes are warranted. In this matched cohort study, we identified all NHL patients aged 18–40 years and diagnosed between 2000 and 2018 from the Swedish and Danish lymphoma registers, and the clinical database at Oslo University Hospital (n = 2090). Population comparators were matched on sex, birth year and country (n = 19 427). Hazard ratios (HRs) were estimated using Cox regression. Males and females diagnosed with aggressive lymphoma subtypes had lower childbirth rates (HRfemale: 0.43, 95% CI: 0.31–0.59, HRmale: 0.61, 95% CI: 0.47–0.78) than comparators during the first 3 years after diagnosis. For indolent lymphomas, childbirth rates were not significantly different from comparators (HRfemale: 0.71, 95% CI: 0.48–1.04, HRmale: 0.94, 95% CI: 0.70–1.27) during the same period. Childbirth rates reached those of comparators for all subtypes after 3 years but the cumulative incidence of childbirths was decreased throughout the 10‐year follow‐up for aggressive NHL. Children of NHL patients were more likely to be born following assisted reproductive technology than those of comparators, except for male indolent lymphoma patients. In conclusion, fertility counselling is particularly important for patients with aggressive NHL. [ABSTRACT FROM AUTHOR]

Neutrophil extracellular traps (NETs) may play a pathogenic role in the thrombosis associated with myeloproliferative neoplasms (MPNs). We measured serum NET levels in 128 pretreatment samples from patients with MPNs and in 85 samples taken after 12 months of treatment with interferon alpha‐2 (PEG‐IFNα‐2) formulations or hydroxyurea (HU). No differences in NET levels were observed across subdiagnoses or phenotypic driver mutations. In PV, a JAK2V617F+ allele burden ≥50% associated with increased NET levels (p = 0.006). Baseline NET levels correlated with neutrophil count (r = 0.29, p = 0.001), neutrophil‐to‐lymphocyte ratio (r = 0.26, p = 0.004) and JAK2V617F allele burden (r = 0.22, p = 0.03), particularly in patients with PV and with allele burden ≥50% (r = 0.50, p = 0.01, r = 0.56, p = 0.002 and r = 0.45, p = 0.03 respectively). In PV, after 12 months of treatment, NET levels decreased on average by 60% in patients with allele burden ≥50%, compared to only 36% in patients with an allele burden <50%. Overall, treatment with PEG‐IFNα‐2a or PEG‐IFNα‐2b reduced NETs levels in 77% and 73% of patients, respectively, versus only 53% of HU‐treated patients (average decrease across treatments: 48%). Normalization of blood counts did not per se account for these reductions. In conclusion, baseline NET levels correlated with neutrophil count, NLR and JAK2V617F allele burden, and IFNα was more effective at reducing prothrombotic NET levels than HU. [ABSTRACT FROM AUTHOR]

Patients with high-risk diffuse large B-cell lymphoma (DLBCL) have poor outcomes following first-line cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R-CHOP). Evidence shows chemotherapy and immune checkpoint blockade can increase antitumor efficacy. This study investigated durvalumab, a programmed death-ligand 1 inhibitor, combined with R-CHOP or lenalidomide + R-CHOP (R2-CHOP) in newly diagnosed high-risk DLBCL. Patients received durvalumab 1125 mg every 21 days for 2–8 cycles + R-CHOP (non-activated B-cell [ABC] subtype) or R2-CHOP (ABC), then durvalumab consolidation (1500 mg every 28 days). Of 46 patients, 43 received R-CHOP and three R2-CHOP. All patients had the high-risk disease; 14 (30.4%) and eight (17.4%) had double- or triple-hit DLBCL, respectively. Following induction, 20/37 (54.1%) patients receiving durvalumab + R-CHOP achieved complete response (CR), and seven (18.9%) partial response (PR); 25 (67.6% [95% CI 50.2–82.0]) continued to consolidation and were progression-free at 12 months. Among efficacy-evaluable patients with double- or triple-hit DLBCL (n = 12), five achieved CR and five PR. Adverse events were generally consistent with R-CHOP. Correlative analyses did not identify conclusive biomarkers of response. Durvalumab + R-CHOP is feasible in DLBCL with no new safety signals, but the combination provided no greater benefit than R-CHOP. [ABSTRACT FROM AUTHOR]

Treatment with PEGylated interferon‐alpha2 (IFN) of patients with essential thrombocythemia and polycythemia vera induces major molecular remissions with a reduction in the JAK2V617F allele burden to undetectable levels in a subset of patients. A favorable response to IFN has been argued to depend upon the tumor burden, implying that institution of treatment with IFN should be as early as possible after the diagnosis. However, evidence for this statement is not available. We present a thorough analysis of unique serial JAK2V617F measurements in 66 IFN‐treated patients and in 6 untreated patients. Without IFN treatment, the JAK2V617F allele burden increased exponentially with a period of doubling of 1.4 year. During monotherapy with IFN, the JAK2V617F allele burden decreased mono‐ or bi‐exponentially for 33 responders of which 28 patients satisfied both descriptions. Bi‐exponential description improved the fits in 19 cases being associated with late JAK2V617F responses. The decay of the JAK2V617F allele burden during IFN treatment was estimated to have half‐lives of 1.6 year for the monoexponential response and 1.0 year in the long term for the bi‐exponential response. In conclusion, through data‐driven analysis of the JAK2V617F allele burden, we provide novel information regarding the JAK2V617F kinetics during IFN‐treatment, arguing for early intervention. [ABSTRACT FROM AUTHOR]

Background: Hemoglobin (Hgb) concentration at diagnosis is associated with outcome in cancer. In a recently reported simplified 3-factor prognostic score in Hodgkin lymphoma, Hgb, along with age and clinical stage, outperformed the classical International Prognostic Score with seven parameters. Methods: In the present study, we investigated if pretherapeutic Hgb concentration added prognostic information to the NCCN-IPI in diffuse large B-cell lymphoma. We included patients from the Danish Lymphoma Registry (LYFO; N = 3499) and from the Molecular Epidemiology Resource (MER; N = 1225), Mayo Clinic and University of Iowa. Four sex-specific Hgb groups were defined: below transfusion threshold, from transfusion threshold to below lower limit of normal, from lower limit of normal to the population mean, and above the mean. We used multivariable Cox regression to estimate the hazard rate ratios (HR) and 95% CIs for overall survival (OS) and event-free survival (EFS), adjusting for sex, NCCN-IPI, comorbidity, and rituximab treatment. Results: Approximately half of the patients had Hgb levels below the lower limit of normal. Compared to patients with Hgb levels above the mean, an inferior OS was directly correlated with lower pretreatment Hgb within the predefined groups (HR=1.23, HR=1.51, and HR=2.05, respectively). These findings were validated in the MER. Conclusion: Based on multivariable analysis, lower pretreatment Hgb, even within the normal range but below the mean, added prognostic information to established indices such as the NCCN-IPI and the Charlson comorbidity index. [ABSTRACT FROM AUTHOR]

In this study, we analyzed the evolution of the prognosis of primary central nervous system lymphoma (PCNSL) patients as they reach selected progression-free survival (PFS) milestones after high-dose methotrexate (HD-MTX)-based therapy. In total, 258 and 146 patients were included from Denmark and British Columbia, respectively. All patients were diagnosed during 2000–2017. The 5-year PFS was 27% (95% CI 23; 32); however, for patients reaching 5 years of PFS, this increased to 71% (95% CI 57; 86). Within the first 5 years after diagnosis, patients lost 2.0 years (95% CI 1.8; 2.2) when compared to a similar background population. This reduced to 0.5 years (95% CI 0.2; 0.9) for patients reaching 5 years of PFS. Treatment with rituximab was associated with improved outcomes. The prognosis of patients with PCNSL treated with HD-MTX-based regimens in this cohort is poor, although it improves as patients survive without progression/relapse. However, survival does not conclusively normalize to that of a similar background population. [ABSTRACT FROM AUTHOR]

The article examines impact of frontline rituximab maintenance for follicular lymphoma. Patients who had been consolidated with radioimmunotherapy or high-dose treatments were excluded from the study. The researchers evaluated the medical records and statistical tests were conducted by making use of R software.

Involvement of the internal female reproductive organs by diffuse large B-cell lymphoma ( DLBCL) is uncommon, and there are sparse data describing the outcomes of such cases. In total, 678 female patients with DLBCL staged with positron emission tomography/computed tomography and treated with rituximab-containing chemotherapy were identified from databases in Denmark, Great Britain, Australia, and Canada. Overall, 27/678 (4%) had internal reproductive organ involvement: uterus ( n = 14), ovaries ( n = 10) or both ( n = 3). In multivariate analysis, women with uterine DLBCL experienced inferior progression-free survival and overall survival compared to those without reproductive organ involvement, whereas ovarian DLBCL was not predictive of outcome. Secondary central nervous system ( CNS) involvement ( SCNS) occurred in 7/17 (41%) women with uterine DLBCL (two patients with concomitant ovarian DLBCL) and 0/10 women with ovarian DLBCL without concomitant uterine involvement. In multivariate analysis adjusted for other risk factors for SCNS, uterine involvement by DLBCL remained strongly associated with SCNS (Hazard ratio 14·13, 95% confidence interval 5·09-39·25, P < 0·001). Because involvement of the uterus by DLBCL appears to be associated with a high risk of SCNS, those patients should be considered for CNS staging and prophylaxis. However, more studies are needed to determine whether the increased risk of secondary CNS involvement also applies to women with localized reproductive organ DLBCL. [ABSTRACT FROM AUTHOR]

Discovery of somatic mutations in the calreticulin gene (CALR) has identified a subgroup of Philadelphia-negative chronic myeloproliferative neoplasms (MPN) with separate haematological characteristics and prognosis. CALR mutations serve as novel markers both of diagnostic value and as targets for monitoring molecular responses during therapy. Interferon-α (IFN) selectively targets the malignant clone in a subset of MPN patients and can induce both haematological and molecular remissions in CALR mutated essential thrombocythemia (ET) patients. We investigated the response to IFN in a cohort of 21 CALR mutated MPN patients including ET, prefibrotic primary myelofibrosis (pre-PMF), and primary myelofibrosis (PMF) with a median follow-up of 31 months. For evaluation of a molecular response, we developed highly sensitive quantitative PCR (qPCR) assays for monitoring the mutant allele burden of the two most prevalent CALR mutations (type 1 and type 2). Thirteen patients (62%) experienced a decrease in the mutant allele burden with a median decline of 29% from baseline. However, only four patients, including patients with ET, pre-PMF, and PMF diagnosis, achieved molecular responder (MR) status with >50% reduction in mutant allele burden according to European LeukemiaNet (ELN) guidelines. MR patients displayed significant differences in the dynamics of the CALR mutant load with regard to time to response and dynamics in mutant allele burden after discontinuation of IFN treatment. Furthermore, we highlight the prognostic value of the CALR mutant allele burden by showing a close association with leucocyte- and platelet counts, hemoglobin concentration, in addition to plasma lactate dehydrogenase (LDH) irrespective of molecular response and treatment status. [ABSTRACT FROM AUTHOR]

BackgroundThe number of hematological malignancies is expected to increase as the Danish population ages within the next few decades. Despite this, data on the course of hematological cancers among the oldest patients are sparse with many intervention studies focusing on younger age groups. The aim of this study is to present Danish incidence and mortality rates among older patients with non-Hodgkin lymphomas (NHL), multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and acute myeloid leukemia (AML). Material and methodsNationwide population-based study presenting the incidence, prevalence and mortality rates of NHL, MM, and AML with a focus on the elderly population in Denmark during the last few decades. Data were drawn from the NORDCAN database. ResultsIncidence rates of NHL, MM, CLL and AML were 10–50 times higher among the population aged 70 years or more than among the younger population. An increasing incidence with stable or decreased mortality rates was seen mainly among elderly patients with NHL during the last few decades, leading to increased survival and a greater prevalence of patients with NHL. Increased relative survival and prevalence could also be seen among elderly patients with MM and CLL, while the trends of the incidence rates were inconclusive for these diseases. Survival among patients with AML improved most notably in those aged below 70 years leading to an increased prevalence of AML patients predominantly in this age group. ConclusionImprovements in diagnostics and treatment have led to increased survival and therefore prevalence of elderly patients with NHL, MM, CLL and AML during the past decades. [ABSTRACT FROM PUBLISHER]

BackgroundThe number of hematological malignancies is expected to increase as the Danish population ages within the next few decades. Despite this, data on the course of hematological cancers among the oldest patients are sparse with many intervention studies focusing on younger age groups. The aim of this study is to present Danish incidence and mortality rates among older patients with non-Hodgkin lymphomas (NHL), multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and acute myeloid leukemia (AML). Material and methodsNationwide population-based study presenting the incidence, prevalence and mortality rates of NHL, MM, and AML with a focus on the elderly population in Denmark during the last few decades. Data were drawn from the NORDCAN database. ResultsIncidence rates of NHL, MM, CLL and AML were 10–50 times higher among the population aged 70 years or more than among the younger population. An increasing incidence with stable or decreased mortality rates was seen mainly among elderly patients with NHL during the last few decades, leading to increased survival and a greater prevalence of patients with NHL. Increased relative survival and prevalence could also be seen among elderly patients with MM and CLL, while the trends of the incidence rates were inconclusive for these diseases. Survival among patients with AML improved most notably in those aged below 70 years leading to an increased prevalence of AML patients predominantly in this age group. ConclusionImprovements in diagnostics and treatment have led to increased survival and therefore prevalence of elderly patients with NHL, MM, CLL and AML during the past decades. [ABSTRACT FROM PUBLISHER]

The properties of the human motor cortex can be studied non-invasively using transcranial magnetic stimulation (TMS). Stimulation at high intensity excites corticospinal cells with fast conducting axons that make direct connections to motoneurones of human upper limb muscles, while low-intensity stimulation can suppress ongoing EMG. To assess whether these cells are used in normal voluntary contractions, we used TMS at very low intensities to suppress the firing of single motor units in biceps brachii ( n= 14) and first dorsal interosseous (FDI, n= 6). Their discharge was recorded with intramuscular electrodes and cortical stimulation was delivered at multiple intensities at appropriate times during sustained voluntary firing at ∼10 Hz. For biceps, high-intensity stimulation produced facilitation at 17.1 ± 2.1 ms (lasting 2.4 ± 0.9 ms), while low-intensity stimulation (below motor threshold) produced suppression (without facilitation) at 20.2 ± 2.1 ms (lasting 7.6 ± 2.2 ms). For FDI, high-intensity stimulation produced facilitation at 23.3 ± 1.2 ms (lasting 1.8 ± 0.4 ms), with suppression produced by low-intensity stimulation at 25.2 ± 2.6 ms (lasting 7.5 ± 2.6 ms). The difference between the onsets of facilitation and suppression was short: 3.1 ± 1.2 ms for biceps and 2.0 ± 1.5 ms for FDI. This latency difference is much less than that previously reported using surface EMG recordings (∼10 ms). These data suggest that low-intensity cortical stimulation inhibits ongoing activity in fast-conducting corticospinal axons through an oligosynaptic (possibly disynaptic) path, and that this activity is normally contributing to drive the motoneurones during voluntary contractions. [ABSTRACT FROM AUTHOR]