The Swiss Group for Clinical Cancer Research (SAKK) and the Nordic Lymphoma Group (NLG) conducted the SAKK 35/14 randomized phase-2 trial (NCT02451111) to evaluate the safety and efficacy of frontline treatment with ibrutinib plus rituximab compared to rituximab plus placebo in adult patients (pts) with advanced follicular lymphoma in need of therapy. Ibrutinib was administered orally (560 mg once a day) for 24 months (104 weeks), while rituximab was given intravenously (375 mg/m2) on day 1 of weeks 1, 2, 3, and 4, and subsequently every 2 months for 12 maintenance administrations, given either intravenous (375 mg/m2) or subcutaneous (1400 mg flat dose) based on local policy. The primary endpoint was the complete remission (CR) rate at 24 months after randomization determined on PET/CT scans by an independent review panel. In total, 192 pts were randomized (98 in arm A rituximab + placebo; 94 in arm B rituximab + ibrutinib) with stratification by rituximab maintenance route, lymphoma grade, follicular lymphoma international prognostic index, and bulky (≥6 cm) disease. The CR rate at 24 months was 36% (95% CI, 26%–46%) in arm A and 40% (95% CI, 30%–51%) in arm B with an odds ratio (OR) of 0.80 (95% CI, 0.44–1.46; p = 0.233). At a median follow-up of 42 months, the 3-year progression-free survival (PFS) rate was 36% in arm A (95% CI, 19%–54%) and 45% (95% CI, 25%–64%) in arm B, with a hazard ratio (HR) of 1.63 (95% CI, 0.99–2.7; p = 0.056). At 3 years after randomization, 45% (95% CI, 36%–56%) of pts in arm A and 39% (95% CI, 30%–50%) in arm B had already required a new treatment, with a HR of 1.47 (95% CI, 0.93–2.32; p = 0.099). The 3-year overall survival rate (OS) approximated 96% in both arms (95% CI, ∼89%–99%) with a HR of 1.02 (95% CI, 0.29–3.55; p = 0.979). The percentage of pts experiencing at least one adverse event (AE) was similar in the two arms (100% and 99%). However, 29% of pts experienced at least one AE of grade ≥3 in arm A while this was the case for 49% of pts in arm B. The percentage of pts experiencing AEs related to trial treatment was also lower in arm A (67%) than in arm B (84%). A total of 93 SAEs were reported, 42 in arm A, affecting 26% of pts, and 51 in arm B, involving 39% of pts. A total of 7 SUSARS occurred, 1 in arm A and 6 in arm B. The most frequent AEs of grade ≥3 during treatment were neutropenia (8% in arm A and 14% in arm B), lymphocytosis (5% in arm A and 10% in arm B), hypertension (5% in each arm), and maculo-papular skin rash (not observed in arm A, 11% in arm B). The SAKK35/14 study was partly funded by Janssen Cilag AG, Roche Pharma (Schweiz) AG, and the Hubacher Fonds. Keywords: immunotherapy, indolent non-Hodgkin lymphoma, molecular Targeted Therapies Conflicts of interests pertinent to the abstract A. Stathis Consultant or advisory role: Janssen, Roche Research funding: Abbvie, ADC Therapeutics, Amgen, AstraZeneca, Bayer, Cellestia, Incyte, LoxoOncology, Merck, Novartis, Pfizer, Philogen, Roche Educational grants: AstraZeneca Other remuneration: Expert testimonies: Bayer, Eli/Lilly F. Hitz Consultant or advisory role: Takeda, Abbvie, Roche E. Zucca Consultant or advisory role: BeiGene, BMS/Celgene, Celltion Healthcare, Curis, Eli/Lilly, Incyte, Ipsen, Janssen, Kyte (a Gilead Company), Merck, Roche Research funding: AstraZeneca, BMS/Celgene, Incyte, Janssen, Merck, Roche Educational grants: Abbvie, BeiGene, Janssen, Roche.

Introduction: The Nordic Lymphoma Group (NLG) performed a dose-finding/expansion trial evaluating pixantrone, etoposide, bendamustine and, in CD20+ lymphomas, rituximab (P[R]EBEN) in patients (pts) with relapsed diffuse large B-cell (DLBCL) or peripheral T-cell (PTCL) lymphomas. The regimen was out-patient based, and applicable in frail, heavily pre-treated pts. Here we present a long-term follow-up of the trial and a per-protocol correlative biological analysis of pre-therapeutic tumour biopsies looking for gene expression profiles associated with long-term response. Methods: We enrolled 60 pts (37 DLBCL and 23 PTCL; age range: 39–84 yrs, median: 71 yrs). Time to event parameters were analyzed by Kaplan-Meier estimates, log-rank test and Cox regression models. Pre-therapeutic biopsies from 42 pts (25 DLBCL, 17 PTCL) were analyzed for gene expression by NanoString PanCancer Pathways and Immune profiling panels (altogether 1348 genes). Results: Of the original 60 patients, 22 were alive at the time of the present analysis. The median follow-up of surviving pts was 41 mo (range 26–76 mo). The 38 deaths were due to: lymphoma (24; 63%), infections (3; 8%) and other causes (11; 29%: 1 lung carcinoma, 5 acute myeloid leukemia-AML, 1 myelodysplasia-MDS, 1 lung embolism, 1 allotransplant related and 2 unknown). Of the 6 pts with AML/MDS, 5 were PTCL and 1 DLBCL. Of 58 evaluable pts, 38 (65%) had a complete (CR) and 1 (3%) a partial response (B: 51%; T: 70%). The median duration of response (DoR) of the 38 CR pts was 17 mo (range 0.5–55 mo; B: 18 mo; T: 17 mo). Four pts were bridged to allogeneic transplant. The overall 5-yr OS and PFS were 33% and 19%, respectively. The median OS for DLBCL was 16.0 mo [IQR 7.0>] and for PTCL 18.0 mo [IQR 8.0>]. The median PFS for DLBCL was 10.0 mo [IQR 4.0–32.0] and for PTCL 10.0 mo [IQR 5.0–26.0]. To better understand molecular alterations underlying the delay of relapse in this heavily pre-treated elderly population, we determined differentially expressed genes between short (<12 mo) and long term (>12 mo) responders. In DLBCL, 31 genes showed significant differential expression between short- and long-term responders (P < 0.05). The latter had higher expression of genes related to transcription factor activity. The gene most significantly associated with long-term response was Neutrophil Cytosolic Factor 4 (NCF4). In PTCL, 23 genes were differentially expressed between short- and long-term responders, the latter showing enrichment in Ras signaling pathway genes (e.g., Rac Family Small GTPase 3, RAC3, and phospholipase A2 group IIA, PLA2G2A). The research was funded by: Servier Laboratoires Keywords: Aggressive B-cell non-Hodgkin lymphoma, Aggressive T-cell non-Hodgkin lymphoma, Combination Therapies No conflicts of interests pertinent to the abstract.

The International prognostic Index (IPI) is the most widely used clinical prediction model for diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), but may be suboptimal in older patients. We aimed to develop and externally validate a clinical prediction model for older, RCHOP- treated DLBCL patients by examining geriatric assessment and lymphoma-related parameters in real-world cohorts. A population-based training set of 365 R-CHOP-treated DLBCL patients ≥70 years was identified through the Cancer Registry of Norway. The external test set consisted of a population-based cohort of 193 patients. Data on candidate predictors were retrieved from the Cancer Registry and through review of clinical records. Cox regression models for 2-year overall survival were used for model selection. Activities of daily living, the Charlson Comorbidity Index, age, sex, albumin, stage, Eastern Cooperative Oncology Group performance status and lactate dehydrogenase level were identified as independent predictors and combined into a Geriatric Prognostic Index (GPI). The GPI demonstrated good discrimination (optimismcorrected C-index 0.752), and identified low-, intermediate- and high-risk groups with significantly different survivals (2- year overall survival, 94%, 65%, and 25%, respectively). At external validation, the continuous and grouped GPI demonstrated good discrimination (C-index 0.727 and 0.710, respectively) and the GPI groups had significantly different survivals (2-year overall survival 95%, 65%, and 44%, respectively). Both the continuous and grouped GPI showed better discrimination than the IPI, revised-IPI and National Comprehensive Cancer Network (NCCN)-IPI (C-index 0.621, 0.583, and 0.670, respectively). In conclusion, we have developed and externally validated a GPI for older DLBCL patients treated with R-CHOP that outperformed the IPI, revised-IPI and NCCN-IPI. A web-based calculator is available at https://wide.shinyapps. io/GPIcalculator/.

SummaryB‐cell depletion induced by anti‐cluster of differentiation 20 (CD20) monoclonal antibody (mAb) therapy of patients with lymphoma is expected to impair humoral responses to severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) vaccination, but effects on CD8 T‐cell responses are unknown. Here, we investigated humoral and CD8 T‐cell responses following two vaccinations in patients with lymphoma undergoing anti‐CD20‐mAb therapy as single agent or in combination with chemotherapy or other anti‐neoplastic agents during the last 9 months prior to inclusion, and in healthy age‐matched blood donors. Antibody measurements showed that seven of 110 patients had antibodies to the receptor‐binding domain of the SARS‐CoV‐2 Spike protein 3–6 weeks after the second dose of vaccination. Peripheral blood CD8 T‐cell responses against prevalent human leucocyte antigen (HLA) class I SARS‐CoV‐2 epitopes were determined by peptide‐HLA multimer analysis. Strong CD8 T‐cell responses were observed in samples from 20/29 patients (69%) and 12/16 (75%) controls, with similar median response magnitudes in the groups and some of the strongest responses observed in patients. We conclude that despite the absence of humoral immune responses in fully SARS‐CoV‐2‐vaccinated, anti‐CD20‐treated patients with lymphoma, their CD8 T‐cell responses reach similar frequencies and magnitudes as for controls. Patients with lymphoma on B‐cell depleting therapies are thus likely to benefit from current coronavirus disease 2019 (COVID‐19) vaccines, and development of vaccines aimed at eliciting T‐cell responses to non‐Spike epitopes might provide improved protection.

Platelets can modulate cancer through budding of platelet microparticles (PMPs) that can transfer a plethora of bioactive molecules to cancer cells upon internalization. In acute myelogenous leukemia (AML) this can induce chemoresistance, partially through a decrease in cell activity. Here we investigated if the internalization of PMPs protected the monocytic AML cell line, THP-1, from apoptosis by decreasing the initial cellular damage inflicted by treatment with daunorubicin, or via direct modulation of the apoptotic response. We examined whether PMPs could protect against apoptosis after treatment with a selection of inducers, primarily associated with either the intrinsic or the extrinsic apoptotic pathway, and protection was restricted to the agents targeting intrinsic apoptosis. Furthermore, levels of daunorubicin-induced DNA damage, assessed by measuring gH2AX, were reduced in both 2N and 4N cells after PMP co-incubation. Measuring different BCL2-family proteins before and after treatment with daunorubicin revealed that PMPs downregulated the pro-apoptotic PUMA protein. Thus, our findings indicated that PMPs may protect AML cells against apoptosis by reducing DNA damage both dependent and independent of cell cycle phase, and via direct modulation of the intrinsic apoptotic pathway by downregulating PUMA. These findings further support the clinical relevance of platelets and PMPs in AML.

The role of platelets in cancer development and progression is increasingly evident, and several platelet–cancer interactions have been discovered, including the uptake of platelet microparticles (PMPs) by cancer cells. PMPs inherit a myriad of proteins and small RNAs from the parental platelets, which in turn can be transferred to cancer cells following internalization. However, the exact effect this may have in acute myelogenous leukemia (AML) is unknown. In this study, we sought to investigate whether PMPs could transfer their contents to the THP-1 cell line and if this could change the biological behavior of the recipient cells. Using acridine orange stained PMPs, we demonstrated that PMPs were internalized by THP-1 cells, which resulted in increased levels of miR-125a, miR-125b, and miR-199. In addition, co-incubation with PMPs protected THP-1 and primary AML cells against daunorubicin-induced cell death. We also showed that PMPs impaired cell growth, partially inhibited cell cycle progression, decreased mitochondrial membrane potential, and induced differentiation toward macrophages in THP-1 cells. Our results suggest that this altering of cell phenotype, in combination with decrease in cell activity may offer resistance to daunorubicin-induced apoptosis, as serum starvation also yielded a lower frequency of dead and apoptotic cells when treated with daunorubicin.

F. d'Amore, S. Leppä, T. Relander, T. S. Larsen, P. Brown, J. Jørgensen, S. Mannisto, P. Lugtenburg, S.‐K. Leivonen, H. Holte, U. M. Fagerli, G. F. Lauritzsen, P. Meyer, G. Minotti, P. Menna, K. Liestøl, H. Toldbod Aarhus University Hospital, Hematology, Aarhus N, Denmark, Helsinki University Hospital, Oncology, Helsinki, Finland, Skane University Hospital, Oncology, Lund, Sweden, Odense University Hospital, Hematology, Odense, Denmark, Copenhagen University Hospital, Hematology, Copenhagen, Denmark, University Medical Center, Erasmus MC Cancer Institute, Rotterdam, Netherlands, Oslo University Hospital, Oncology, Oslo, Norway, St Olavs Hospital, Oncology, Trondheim, Norway, Stavanger University Hospital, Oncology, Stavanger, Norway, University Hospital Campus Bio‐Medico, Clinical Pharmaclogy Laboratory, Rome, Italy, University of Oslo, Informatics, Oslo, Norway

Survival of patients with high-risk diffuse large B-cell lymphoma (DLBCL) is suboptimal, and the risk of central nervous system (CNS) progression is relatively high. We conducted a phase 2 trial in 139 patients aged 18 to 64 years who had primary DLBCL with an age-adjusted International Prognostic Index (aaIPI) score of 2 to 3 or site-specific risk factors for CNS recurrence. The goal was to assess whether a dose-dense immunochemotherapy with early systemic CNS prophylaxis improves the outcome and reduces the incidence of CNS events. Treatment consisted of 2 courses of high-dose methotrexate in combination with biweekly rituximab (R), cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP-14), followed by 4 courses of R-CHOP-14 with etoposide (R-CHOEP) and 1 course of high-dose cytarabine with R. In addition, liposomal cytarabine was administered intrathecally at courses 1, 3, and 5. Coprimary endpoints were failure-free survival and CNS progression rates. Thirty-six (26%) patients experienced treatment failure. Progression occurred in 23 (16%) patients, including three (2.2%) CNS events. At 5 years of median follow-up, failure-free survival, overall survival, and CNS progression rates were 74%, 83%, and 2.3%, respectively. Treatment reduced the risk of progression compared with our previous trial, in which systemic CNS prophylaxis was given after 6 courses of biweekly R-CHOEP (hazard ratio, 0.49; 95% CI, 0.31-0.77; P = .002) and overcame the adverse impact of an aaIPI score of 3 on survival. In addition, outcome of the patients with BCL2/MYC double-hit lymphomas was comparable to the patients without the rearrangements. The results are encouraging, with a low toxic death rate, low number of CNS events, and favorable survival rates. This trial was registered at www.clinicaltrials.gov as #NCT01325194.

The SAKK 35/10 phase 2 trial, developed by the Swiss Group for Clinical Cancer Research and the Nordic Lymphoma Group, compared the activity of rituximab vs rituximab plus lenalidomide in untreated follicular lymphoma patients in need of systemic therapy. Patients were randomized to rituximab (375 mg/m2 IV on day 1 of weeks 1-4 and repeated during weeks 12-15 in responding patients) or rituximab (same schedule) in combination with lenalidomide (15 mg orally daily for 18 weeks). Primary end point was complete response (CR)/unconfirmed CR (CRu) rate at 6 months. In total, 77 patients were allocated to rituximab monotherapy and 77 to the combination (47% poor-risk Follicular Lymphoma International Prognostic Index score in each arm). A significantly higher CR/CRu rate at 6 months was documented in the combination arm by the investigators (36%; 95% confidence interval [CI], 26%-48% vs 25%; 95% CI, 16%-36%) and confirmed by an independent response review of computed tomography scans only (61%; 95% CI, 49%-72% vs 36%; 95% CI, 26%-48%). After a median follow-up of 4 years, significantly higher 30-month CR/CRu rates and longer progression-free survival (PFS) and time to next treatment (TTNT) were observed for the combination. Overall survival (OS) rates were similar in both arms (≥90%). Toxicity grade ≥3 was more common in the combination arm (56% vs 22% of patients), mainly represented by neutropenia (23% vs 7%). Addition of lenalidomide to rituximab significantly improved CR/CRu rates, PFS, and TTNT, with expected higher, but manageable toxicity. The excellent OS in both arms suggests that chemotherapy-free strategies should be further explored. This trial was registered at www.clinicaltrials.gov as #NCT01307605.

Introduction: Survival of patients with high-risk diffuse large B-cell lymphoma (DLBCL) is suboptimal, and the risk of central nervous system (CNS) progression is relatively high. We aimed to assess, whether a dose-dense immunochemotherapy approachwith early systemic CNS prophylaxis improves outcome and reduces the incidence of CNS events. Methods: We conducted a Nordic Lymphoma Group phase II (NLG-LBC-05) trial during 2011-2014 in patients aged 18–64 years with untreated DLBCL including BCL-2/MYC double hit lymphomas, and an age-adjusted international prognostic index (aaIPI) 2-3 or site specific risk factors for CNS recurrence. Treatment consisted of two courses of high-dose methotrexate (HD-Mtx) in combination with biweekly rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP-14), followed by four courses of R-CHOP-14 with etoposide (R-CHOEP-14) and one course of high dose cytarabine with R (R-HD-AraC). In addition, liposomal AraC was administered intrathecally at courses 1, 3 and 5. Our co-primary endpoints were failure free survival and CNS progression rates. Results: Of 143 enrolled patients, 139 patients were eligible with a median age of 56 (range 20-64). The majority of the patients had advanced stage (92%), elevated LDH (91%), more than one extranodal site, (67%) and B-symptoms (63%). Four (2.9%) patients developed AML/MDS. Treatment related death occurred in five (3.6%) patients. Of the 119 patients who underwent PET-CT, 91 (77%) achieved a metabolic CR, and 19 of 35 patients (21%) with CT-based CRu/PR were in metabolic CR according to PET-CT. Only one out of 15 biopsies (9%) from the PET+ lesions contained vital lymphoma. At five years of median follow-up, failure free survival (FFS), overall survival (OS) and CNS progression rates were 74%, 84% and 2.3%, respectively. Deauville score 5, but not 4 at the end of treatment was associated with increased risk of progression and death. Treatment reduced the risk of progression compared to our previous NLG-LBC-04 trial, where systemic CNS prophylaxis was given after six courses of biweekly R-CHOEP (HR=0.493; 95% CI 0.312-0.780, p=0.003), and overcame the adverse impact of aaIPI3 and BCL-2/MYC double hit lymphomas on survival. Conclusion: The results are encouraging with favorable survival rates, low toxic death rate and low number of CNS events. Keywords: “double-hit” lymphomas; CNS prophylaxis; diffuse large B-cell lymphoma (DLBCL). Disclosures: Leppä, S: Research Funding: Mundipharma, Amgen.

Purpose For indolent lymphoma, the optimal timing, sequence, and choice of therapeutic regimens remain a matter of debate. In two Nordic Lymphoma Group randomized trials, symptomatic or clearly progressing patients were treated first line with a rituximab-containing regimen without chemotherapy. The purpose of this study was to assess long-term survival, risk of transformation, and need of new therapies. Methods Data were collected at cross-sectional follow-up for 321 patients with indolent lymphoma (84% with follicular lymphomas [FL]) included in one of two Nordic Lymphoma Group trials (accrual 1998 to 1999 and 2002 to 2008). All patients received first-line therapy with one or two cycles of four weekly infusions of rituximab 375 mg/m2, and 148 were randomly allocated to the addition of interferon alfa-2a. Follow-up data were retrieved from initial trial databases and medical records on repeated clinical evaluations. Results At the end of follow-up, 73% of patients were alive, with a median follow-up after random assignment of 10.6 years. Among all, 36% (38% with FL) had never needed chemotherapy. For patients with FL who required new therapy within 24 months because of early disease progression, the 10-year survival rate was 59% versus 81% for those with longer remission. Interferon was not shown to improve long-term outcome. Transformation was diagnosed in 20% of all patients (2.4% per person-year) and in 18% with FL. An additional malignancy was found in 12%. Conclusion Approximately one third of patients with symptomatic indolent lymphoma (30% with FL, 23% without FL) did not need new therapy in the long term after first-line rituximab without chemotherapy. In the entire cohort, 10-year survival was excellent with no major safety issues, which suggests that chemotherapy can be delayed safely in the majority of patients.

Background: Survival of patients with high-risk diffuse large B-cell lymphoma (DLBCL) is suboptimal, and the risk of central nervous system (CNS) progression is relatively high. We investigated the efficacy of dose-dense chemoimmunotherapy and systemic CNS prophylaxis in two completed Nordic trials including patients less than 65 years with high-risk DLBCL. We combined individual patient data from these studies to compare clinical outcome and prognostic factors in patients treated with CNS prophylaxis given in the beginning (CHIC) vs at the end (CRY-04) of therapy. Patients and Methods: Inclusion criteria were age 18-65 years, primary DLBCL or grade 3 follicular lymphoma without signs of CNS involvement, WHO performance score 0-3, age-adjusted International Prognostic Index (aaIPI 2-3) and/or involvement of anatomical sites associated with an increased risk for CNS recurrence (e.g. testis, facial sinuses, orbita). In CRY-04, six courses of R-CHOEP14 were followed by HD-Mtx and HD-Ara-C. In CHIC, treatment consisted of two courses of HD-Mtx in combination with R-CHOP14, followed by four courses of R-CHOEP14 and one course of R-HD-AraC. In addition, liposomal AraC was administered intrathecally at courses 1, 3 and 5. Primary end points were failure free survival (FFS; disease progression, discontinuation of protocolled therapy due to toxicity, death from any cause) at 3 years and CNS progression rate at 1.5 years. Secondary end points included progression-free survival (PFS; disease progression or death from any cause) and overall survival (OS) at 3 years. Results: Among 303 patients enrolled in the trials (CRY-04, n = 160 and CHIC, n = 143), 295 (CRY-04, n = 154 and CHIC, n = 139) met inclusion criteria and were evaluable for baseline characteristics and primary end points. Median age (54 and 56 years, p = 0.222), male/female ratio, stage and aaIPI scores were comparable in the two cohorts. Three-year FFS was 63% in CRY-04 and 77% in CHIC (p = 0.018) after a median follow-up of 5 and 3 years, respectively. Cumulative incidence rates of CNS progression were 5.0% and 2.4% (p = 0.22), and 3-year OS 80% and 86% (p = 0.508), respectively. Treatment in the CHIC reduced the risk of systemic progression (aaIPI adjusted RR = 0.484, 95%CI 0.300-0.782, p = 0.003). PFS benefit with CHIC vs CRY-04 was observed across pre-specified subgroups, and particularly in patients <60 years old (p = 0.007), with low proliferation index (Ki67 expression <75%, p = 0.029), and BCL2 positivity (p = 0.006). In the subsets of patients with available PET data, Deauville score 5 at the end of treatment was associated with increased rate of progression and death in both trials (p = 0.012). Only one out of 17 biopsies from PET positive lesions (DS 3-5) contained vital lymphoma tissue. Conclusions: Our results derived from trial data with homogenous treatment support the use of HD-Mtx in the beginning rather than at the end of therapy. Superior outcome seems to be primarily due to better systemic control of the disease. In addition, number of CNS recurrences is reduced. Keywords: CNS prophylaxis; diffuse large B-cell lymphoma (DLBCL); immunochemotherapy

BACKGROUND:The role of consolidative radiotherapy (RT) in advanced diffuse large B-cell lymphoma (DLBCL) is not established. PATIENTS AND METHODS:In a population-based retrospective analysis of patients with DLBCL in Western Norway during 2003 to 2008, 170 consecutive patients admitted to Haukeland University Hospital (HUS) and 94 to Stavanger University Hospital (SUS) were included. The mean age was 64 years (range, 17-95 years), 147 patients (56%) were male, 80 patients (30%) had stage I/II, 126 patients (48%) stage III/IV, and 57 patients (22%) had primary extranodal disease. RESULTS:There were no differences between hospitals in patient characteristics, use of rituximab, number of chemotherapy courses or cumulative doses, or in distribution of response categories after chemotherapy. The use of RT was significantly different: 17 patients (23%) received RT at SUS and 92 patients (65%) at HUS (P < .001). For 219 patients with International Prognostic Index (IPI) score of 0 to 3, 5-year cancer-specific survival (CSS) was 67% at SUS and 81% at HUS (P = .012). For 73 patients with complete response after chemotherapy there were no differences in survival between patients with and without RT. For 138 patients with any residual mass after chemotherapy, there were highly significant differences in favor of receiving RT (n = 81) versus no RT (n = 57): 5-year CSS 89% versus 69% (P < .001), and 5-year overall survival 82% versus 59% (P = .005). The effect of RT on residual mass was evident in most subgroups, mainly in low to intermediate risk, but not in high-risk (IPI 4-5) patients. CONCLUSION:With the limitations of a retrospective study, these data suggest that consolidative RT might improve survival in DLBCL patients with a residual mass after chemotherapy, also in advanced disease.

Objectives: In Norway, initial treatment of febrile neutropenia (FN) has traditionally been benzylpenicillin plus an aminoglycoside. Internationally, FN is often treated with a broad-spectrum beta-lactam antibiotic. We aimed to compare these two regimens in a prospective, randomized, trial in patients with lymphoma or leukaemia with an expected period of neutropenia >= 7 days, and a suspected bacterial infection.Methods: Adult neutropenic patients with lymphoma or leukaemia, and a suspected bacterial infection, were randomized for treatment with benzylpenicillin plus an aminoglycoside or meropenem. The primary endpoint was clinical success, defined as no modification of antibiotics and clinical stability 72 h after randomization.Results: Among 322 randomized patients, 297 proved evaluable for analyses. Fifty-nine per cent (95% CI 51% e66%), (87/148) of the patients given benzylpenicillin plus an aminoglycoside were clinically stable, and had no antibiotic modifications 72 h after randomization, compared with 82% (95% CI 75% e87%), (122/149) of the patients given meropenem (p < 0.001). When the antibiotic therapy was stopped, 24% (95% CI 18% e32%), (36/148) of the patients given benzylpenicillin plus an aminoglycoside, compared with 52% (95% CI 44% e60%), (78/149) of the patients given meropenem, had no modifications of their regimens (p < 0.001). In the benzylpenicillin plus an aminoglycoside arm, the all-cause fatality within 30 days of randomization was 3.4% (95% CI 1.2% e7.9%), (5/148) of the patients, compared with 0% (95% CI 0.0% e3.0%), (0/149) of the patients in the meropenem arm (p 0.03).Conclusion: Clinical success was more common in FN patients randomized to meropenem compared with the patients randomized to benzylpenicillin plus an aminoglycoside. The all-cause fatality was higher among the patients given benzylpenicillin plus an aminoglycoside. (C) (C) 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Introduction: In the Nordic Lymphoma Group trial NLG T-01, patients with newly diagnosed peripheral T-cell Lymphoma (PTCL) were treated with six courses of CHOEP (up to 60 yrs) or CHOP (61-67 yrs) followed by high-dose chemotherapy (BEAM) and autologous stem cell transplantation (ASCT). At 5 years median follow-up, the progression-free survival of the trial cohort was 44%. On this background, the NLG-T01 treatment strategy has become the recommended first-line treatment for younger fit patients in the Nordic countries and in the latest ESMO guidelines for PTCL. Despite this intensive approach with up-front ASCT a fraction of patients still relapses. In an attempt to find factors predictive for survival after up-front ASCT we aimed to analyze the impact of radiologic response at the first interim evaluation on long-term survival.

Extranodal NK/T-cell lymphoma, nasal type (ENKTL) is a rare disease in the Western countries. Cases involving extranasal sites often have poorer prognosis than nasal cases.We report a patient with an extranodal NK/T[HYPHEN]cell lymphoma of nasal[HYPHEN]type, in the right ovary. She had surgical removement of the involved ovary and was treated with CEOP[HYPHEN]B based therapy followed by high[HYPHEN]dose therapy with autologous stem cell support. She remains in complete remission six years after diagnosis. Stage I ENKTL in the ovary is an unusual manifestation, and to our knowledge not described earlier.

Introduction: Survival of patients with high-risk diffuse large B-cell lymphoma (DLBCL) is suboptimal, and the risk of early central nervous system (CNS) progression is high. Here we present the final results from a Nordic phase II study, where dose-dense chemoimmunotherapy including early systemic CNS prophylaxis with high dose methotrexate (HD-Mtx), further intensified by intrathecally (IT) administered liposomal cytosine arabinoside (AraC), was given.

Objective Primary Sjogren's syndrome (SS) is associated with an increased risk of non-Hodgkin's lymphoma (NHL), but the reported prevalence and risk vary considerably. The objective of this study was to determine the risk of NHL in a well-defined population-based primary SS cohort in Norway. Methods The authors examined all patients fulfilling the AmericanEuropean Consensus Group criteria for primary SS from 2 Norwegian counties and compared the data to the Cancer Registry of Norway to identify the primary SS patients who had lymphoma. In addition, lymphoma patient files from the same period were reviewed for undiagnosed primary SS to ensure the quality of registry data. Results As of July 1, 2009, 443 living subjects with primary SS were identified in an area with 896,840 inhabitants, which is 18.6% of the total population of Norway. Seven cases of NHL (1.6%) were found during a total followup of 3,813 person-years, resulting in a standardized incidence ratio of 9.0 (95% confidence interval 7.126.3) for NHL in primary SS patients. Conclusion The risk of NHL in patients with primary SS in Norway is increased 9 times compared with the general population. This is in accordance with recent studies, and the quality and completeness of the registries and strict use of diagnostic criteria support the validity of the results.