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Aims: Subclassification of large B cell lymphoma (LBCL) is challenging due to the overlap in histopathological, immunophenotypical and genetic data. In particular, the criteria to separate diffuse large B cell lymphoma (DLBCL) and high‐grade B cell lymphoma (HGBL) are difficult to apply in practice. The Lunenburg Lymphoma Biomarker Consortium previously reported a cohort of over 5000 LBCL that included fluorescence in‐situ hybridisation (FISH) data. This cohort contained 209 cases with MYC rearrangement that were available for a validation study by a panel of eight expert haematopathologists of how various histopathological features are used. Methods and results: Digital whole slide images of haematoxylin and eosin‐stained sections allowed the pathologists to visually score cases independently as well as participate in virtual joint review conferences. Standardised consensus guidelines were formulated for scoring histopathological features and included overall architecture/growth pattern, presence or absence of a starry‐sky pattern, cell size, nuclear pleomorphism, nucleolar prominence and a range of cytological characteristics. Despite the use of consensus guidelines, the results show a high degree of discordance among the eight expert pathologists. Approximately 50% of the cases lacked a majority score, and this discordance spanned all six histopathological features. Moreover, none of the histological variables aided in prediction of MYC single versus double/triple‐hit or immunoglobulin‐partner FISH‐based designations or clinical outcome measures. Conclusions: Our findings indicate that there are no specific conventional morphological parameters that help to subclassify MYC‐rearranged LBCL or select cases for FISH analysis, and that incorporation of FISH data is essential for accurate classification and prognostication. [ABSTRACT FROM AUTHOR]

Summary: Lymphoplasmacytic lymphoma (LPL) not fulfilling the WHO diagnostic criteria (2017) for Waldenstrom's macroglobulinemia (WM) (named non‐WM LPL) is a rare disease and only a few systematic studies have been published. Here, we present a population‐based study of non‐WM LPL focusing on diagnostic difficulties, patient characteristics, and outcome. From 1511 patients included in the Swedish Lymphoma Registry 1 Jan 2000 – 31 Dec 2014 with a diagnosis of WM/LPL, we could confirm the diagnosis of non‐WM LP in only 33 patients. The median age at diagnosis was 69 years. A paraprotein was found in most (IgG in 54%, IgA in 15%) and 12% of the cases were non‐secretory. Compared with the WM patients, the non‐WM LPL patients were younger, had more adverse prognostic factors such as elevated LDH, anaemia, and lymphocytosis at diagnosis. In addition, the non‐WM LPL patients more often were symptomatic and received treatment at diagnosis. The overall survival (OS) did not significantly differ between the non‐WM LPL and WM groups (P = 0.247), with a median survival time of 71 and 96 months, respectively. To conclude, we found differences in clinical features between WM and non‐WM LPL, but no difference in survival. [ABSTRACT FROM AUTHOR]

Summary: The relapse of follicular lymphoma (FL) within 24 months (POD24) of chemoimmunotherapy has been associated with poor survival. We analyzed a pooled dataset of three randomized trials including FL patients with advanced disease, conducted by the Swiss Group for Clinical Cancer Research (SAKK). Overall, POD24 was observed in 27% of 318 patients, but rate variance among studies suggested that the rituximab schedule might affect POD24 rate. POD24 was associated with lower 10‐year overall survival rates than in the reference group (69% vs. 77%; hazard ratio, 3·12; 95% confidence interval, 1·73–5·65). POD24 retains its prognostic validity in patients treated without chemotherapy and may represent a useful end‐point for future studies. [ABSTRACT FROM AUTHOR]

Summary: Follicular lymphoma (FL) is a heterogeneous disease; therefore, reliable prognostic tools are needed to plan treatment strategies. The FL International Prognostic Index (FLIPI) was developed before the rituximab era, while the PRIMA‐PI was built on rituximab chemotherapy. Our objective was to evaluate these two prognostic tools in a cohort of 291 patients with FL treated in two prospective randomised Nordic Lymphoma Group trials with rituximab ± interferon. All patients had symptomatic/progressive disease and were previously untreated. The PRIMA‐PI was prognostic for both time to treatment failure (TTF) and overall survival (OS) (log‐rank P = 0·003 and P < 0·001, respectively). The PRIMA‐PI high‐risk identified a small group of patients with a very short TTF and OS compared to the low‐risk group, with a hazard ratio (HR) of 1·90 (95% confidence interval [CI] 1·30–2·78, P = 0·001) and HR of 3·19 (95% CI 1·75–5·83, P < 0·001), respectively. The FLIPI risk groups were prognostic only for OS (log‐rank P = 0·018). The simplified PRIMA‐PI was valid in our FL cohort with first‐line rituximab‐containing chemo‐free therapy and shows an improved risk stratification compared to the FLIPI, especially in patients aged >60 years. Patients in the PRIMA‐PI high‐risk group should be considered for alternative therapies. [ABSTRACT FROM AUTHOR]

Summary: Follicular lymphoma (FL) constitutes a significant proportion of lymphomas and shows frequent relapses. Beyond conventional chemotherapy, new therapeutic approaches have emerged, focussing on the interplay between lymphoma cells and the microenvironment. Here we report the immunophenotypic investigation of the microenvironment of a clinically well‐characterized prospective cohort (study SAKK35/10, NCT01307605) of 154 treatment‐naïve FL patients in need of therapy, who have been treated with rituximab only or a combination of rituximab and the immunomodulatory drug lenalidomide/Revlimid® A high ratio of CD4‐ to CD8‐positive T cells (P = 0·009) and increased amounts of PD1+ tumour‐infiltrating T cells (P = 0·007) were associated with inferior progression‐free survival in the whole cohort. Interestingly, the prognostic impact of PD1+ T cells and the CD4/CD8 ratio lost its significance in the subgroup treated with R2. In the latter group, high amounts of GATA3+ T helper (Th2) equivalents were associated with better progression‐free survival (P < 0·001). We identified tumour microenvironmental features that allow prognostic stratification with respect to immuno‐ and combined immuno‐ and immunomodulatory therapy. Our analysis indicates that lenalidomide may compensate the adverse prognostic implication of higher amounts of CD4+ and, particularly, PD1+ T cells and that it has favourable effects mainly in cases with higher amounts of Th2 equivalents. [Correction added on 11 February 2020, after online publication: The NCT‐trial number was previously incorrect and has been updated in this version]. [ABSTRACT FROM AUTHOR]

Summary: The clinical course of follicular lymphoma (FL) is highly variable. Recently the m7‐FL international prognostic index (FLIPI) integrating performance status, FLIPI score and the mutational status of seven genes, was shown to stratify patients into "low‐risk" and "high‐risk" with respect to 5‐year failure‐free survival after first‐line immunochemotherapy. Our aim was to evaluate the model after rituximab without chemotherapy. The Nordic Lymphoma Group performed two randomized clinical trials on indolent lymphoma patients receiving single rituximab and rituximab with interferon‐α2a. In total, 95 FL patients had sufficient fresh‐frozen diagnostic material for sequencing. A targeted panel for the genes EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP and CARD11 was utilized for m7‐FLIPI score calculation. With a median follow‐up of 10·6 years, 76% of patients were alive. No difference in time to treatment failure (TTF), defined as the interval between start of trial therapy and initiation of new therapy or death, nor overall survival (OS) was found between the m7‐FLIPI risk groups (log‐rank P = 0·94 and 0·99, respectively). EZH2 mutations were associated with longer TTF (log‐rank P = 0·04) and in EP300 mutations were associated with shorter TTF (log‐rank P = 0·01). We conclude that the prognostic value of the m7‐FLIPI clinicogenetic model seems dependent on therapeutic regimen. [ABSTRACT FROM AUTHOR]

We present a nationwide prospective Swedish registry‐based study of Waldenström macroglobulinaemia (WM), that focuses on incidence and survival in relation to clinical prognostic factors and primary systemic therapies. A total of 1511 patients with WM and lymphoplasmocytic lymphoma (LPL) were registered in the Swedish Lymphoma Registry (SLR) between 1 January 2000 and 31 December 2014. The age‐adjusted incidence of WM/LPL was 11·5 per million persons per year, three times higher than the reported incidence worldwide. Medical records were retrieved for 1135 patients (75%). A retrospective review showed that 981 (86·1%) of these patients fulfilled the World Health Organization diagnostic criteria for WM and these patients were analysed further. The overall survival (OS) improved between two periods – 2000–2006 and 2007–2014 – with a five‐year OS of 61% and 70%, respectively. Significant prognostic factors for OS, evaluated at the time of diagnosis, were age, elevated lactate dehydrogenase level and haemoglobin ≤115 g/l for patients receiving therapy 0–3 months after diagnosis, and age, poor performance status, haemoglobin ≤115 g/l, and female sex in "watch and wait" patients (multivariable analysis). The level of the IgM monoclonal immunoglobulin had no significant prognostic value. Rituximab included in first‐line therapy was associated with improved survival. [ABSTRACT FROM AUTHOR]

Summary: In chronic lymphocytic leukaemia (CLL) patients, treatment with the Bruton tyrosine kinase inhibitor ibrutinib induces a rapid shift of tumour cells from lymph nodes (LN) to peripheral blood (PB). Here, we characterized in depth the dynamics of ibrutinib‐induced inflammatory, transcriptional and cellular changes in different compartments immediately after treatment initiation in seven relapsed/refractory CLL patients. Serial PB and LN samples were taken before start and during the first 29 days of treatment. Changes in plasma inflammation‐related biomarkers, CLL cell RNA expression, B‐cell activation and migration markers expression, and PB mononuclear cell populations were assessed. A significant reduction of 10 plasma inflammation markers, the majority of which were chemokines and not CLL‐derived, was observed within hours, and was paralleled by very early increase of CD19+ circulating cells. At the RNA level, significant and continuous changes in transcription factors and signalling molecules linked to B‐cell receptor signalling and CLL biology was observed in both PB and LN CLL cells already after 2 days of treatment. In conclusion, ibrutinib seems to instantly shut off an ongoing inflammatory response and interfere with diverse sensitive pathways in the LN. [ABSTRACT FROM AUTHOR]

In recent decades, the prognosis of Mantle Cell Lymphoma ( MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen, developed by the Nordic Lymphoma Group. We here present the 15-year updated results of the Nordic MCL2 study after a median follow-up of 11·4 years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 12·7 and 8·5 years, respectively. The MCL International Prognostic Index ( MIPI), biological MIPI, including Ki67 expression ( MIPI-B) and the MIPI-B including mIR-18b expression ( MIPI-B-miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12 years, we still see an excess disease-related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma ( MCL) is a heterogenic non-Hodgkin lymphoma entity, with a median survival of about 5 years. In 2008 we reported the early - based on the median observation time of 4 years - results of the Nordic Lymphoma Group MCL2 study of frontline intensive induction immunochemotherapy and autologous stem cell transplantation ( ASCT), with more than 60% event-free survival at 5 years, and no subsequent relapses reported. Here we present an update after a median observation time of 6·5 years. The overall results are still excellent, with median overall survival and response duration longer than 10 years, and a median event-free survival of 7·4 years. However, six patients have now progressed later than 5 years after end of treatment. The international MCL Prognostic Index ( MIPI) and Ki-67-expression were the only independent prognostic factors. Subdivided by the MIPI-Biological Index ( MIPI + Ki-67, MIPI-B), more than 70% of patients with low-intermediate MIPI-B were alive at 10 years, but only 23% of the patients with high MIPI-B. These results, although highly encouraging regarding the majority of the patients, underline the need of a risk-adapted treatment strategy for MCL. The study was registered at as ISRCTN 87866680. [ABSTRACT FROM AUTHOR]

Summary The prognostic value of grading follicular lymphoma has been debated since the 1980s. There is consensus that World Health Organization (WHO) grades 1 and 2 are indolent, but not whether grades 3A or 3B are aggressive. We retrospectively reviewed the follicular lymphoma diagnoses according to the 2008 WHO classification in all diagnostic specimens from a population-based cohort of 505 patients with a median follow-up time of 10·0 years (range, 4·6-16·0). After excluding 43 patients with concomitant diffuse large B-cell lymphoma, 345 remained with grade 1-2, 94 with grade 3A, and 23 with grade 3B follicular lymphoma. Grades 1-2 and 3A seemed equally indolent, with indistinguishable clinical courses, even in patients receiving anthracyclines. Compared with grades 1-3A and independently of clinical factors, grade 3B correlated with higher mortality ( P = 0·008), but outcome was improved after upfront anthracycline-containing therapy ( P = 0·015). In contrast to grade 1-3A patients, grade 3B patients experienced no relapses or deaths beyond 5 years of follow-up. Furthermore, patients with grade 3B were predominantly male and seldom presented with bone-marrow involvement. We conclude that follicular lymphoma grade 1-3A is indolent and incurable with conventional therapy. Grade 3B appears to be an aggressive but curable disease. [ABSTRACT FROM AUTHOR]

This phase II study ( n = 20) aimed to evaluate type, severity and duration of side-effects and efficacy following subcutaneous (SC) alemtuzumab, without dose-escalation, in advanced-stage relapsed chronic lymphocytic leukaemia (CLL) patients. Alemtuzumab 30 and 3 mg was administered SC simultaneously day 1, followed by 30 mg three times per week. Injection-site-reactions were recorded every 6–24 h until resolved using National Cancer Institute criteria and a new skin toxicity subscale. The first doses of 30 mg and 3 mg produced injection-site-reactions (all but one were grade 1/2) in 13/20 and 9/20 patients, respectively. The second dose (on day 3) resulted in skin-reactions in 10/20 patients and the third, fourth, fifth and sixth injections produced reactions in 6/20, 1/20, 2/20 and 0/20 patients, respectively. Mild “flu-like” symptoms occurred during week 1 in 10/20 patients. All side-effects had subsided by the sixth dose. 15/20 patients (75%) responded (12 partial responses, three complete responses) with a median time-to-treatment-failure of 20 months. Symptomatic cytomegalovirus-reactivation occurred in 6/20 patients. Two deaths occurred: one bacterial pneumonia and one adenovirus-infection. The present study showed how to assess cutaneous-toxicity in detail and that 30 mg alemtuzumab SC administered upfront was well tolerated. Optimized alemtuzumab therapy in properly selected patients may result in high efficacy even in advanced CLL. Our results need to be confirmed in extended studies. [ABSTRACT FROM AUTHOR]

Background: Elective laparoscopic splenectomy (LS) is performed with increasing frequency rather than open splenectomy (OS) because of reduced morbidity. LS is feasible also in patients with haematological diseases with splenomegaly, a group that is subject to more postoperative complications, such as bleeding, infections and portal vein thrombosis (PVT). Method: We retrospectively reviewed the medical records of 69 patients splenectomised for haematological diseases during a 5-yr period at a single centre with the aim of comparing the results and complications after LS and OS. Results: Thirty-nine patients underwent LS and 30 OS. The median durations of surgery were 138 and 115 min (ns) in the LS and OS groups respectively. Three conversions (7.7%) from laparoscopic surgery to open surgery were necessary because of bleeding and/or splenomegaly. Thromboembolic complications occurred in totally seven of 69 patients. PVT was diagnosed in five of 37 (13.5%) patients with haematological malignancies (three with indolent lymphoma and two with myeloproliferative disease), one after LS and four after OS. All patients with PVT had splenomegaly and had received thromboembolic prophylaxis with low-molecular-weight heparin of short duration. Two patients were diagnosed with deep vein thromboses in the lower leg. Both had idiopathic thrombocytopenic purpura (ITP) and LS. Conclusions: Patients with malignant haematological diseases and splenomegaly seem to have a high risk of developing PVT after splenectomy why careful observation and prolonged thromboprophylaxis is recommended for these patients. Ultrasonography or computerised tomography should be considered in all patients with abdominal symptoms after splenectomy. [ABSTRACT FROM AUTHOR]

Abstract: We have earlier reported overexpression of the central and peripheral cannabinoid receptors CB1 and CB2 in mantle cell lymphoma (MCL), a B cell non-Hodgkin lymphoma. In this study, treatment with cannabinoid receptor ligands caused a decrease in viability of MCL cells, while control cells lacking CB1 were not affected. Interestingly, equipotent doses of the CB1 antagonist SR141716A and the CB1/CB2 agonist anandamide inflicted additive negative effects on viability. Moreover, treatment with the CB1/CB2 agonist Win-55,212-2 caused a decrease in long-term growth of MCL cells in culture. Induction of apoptosis, as measured by FACS/Annexin V–FITC, contributed to the growth suppressive effect of Win-55,212-2. Our data suggest that cannabinoid receptors may be considered as potential therapeutic targets in MCL. [Copyright &y& Elsevier]

The role of transcript variants of cyclin D1 in cancer biology is unclear. Most tumors with high levels of cyclin D1 express 2 transcripts due to alternative splicing: one full-length transcript of 4.4 kb and one short transcript of approximately 1.7 kb. The short transcript lacks part of the 3′UTR region regulating mRNA stability and has a longer half-life. In our study, the contribution of each of these mRNAs to gene expression and cell proliferation has been investigated in mantle cell lymphoma (MCL), a B cell lymphoma characterized by a specific gene translocation resulting in enhanced expression of cyclin D1. A subset of MCL tumors with low levels of the long cyclin D1 transcript (cyclin D1 3′UTR) was identified by quantitative PCR and by oligonucleotide array hybridization. This tumor-subset had 3.4-fold higher levels of the short form of cyclin D1 mRNA ( p < 0.0001) and had higher expression of cyclin D1 protein. Gene expression analysis identified a number of cell-cycle regulatory genes as upregulated. There was a significant difference in frequencies of cyclin B1 ( p = 0.0006) and cyclin A2 ( p = 0.0006) positive cells that discriminated MCL with low cyclin D1 3′UTR from other highly proliferative MCL. Among differentially expressed genes, there was a highly upregulated gene with homology to the group of cell-cycle promoting E2F transcription partners, E2F_TDP5. Several of the upregulated genes, such as TOP2A, AURORA A and RRM2 may influence a response to therapy. Identification of MCL with low cyclin D1 3′UTR is important because it seems to be associated with shorter overall survival. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Afsharian P, Möllgård L, Hassan Z, Xie H, Kimby E, Hassan M. The effect of ciprofloxacin on cyclophosphamide pharmacokinetics in patients with non-Hodgkin lymphoma. Eur J Haematol 2005: 75: 206–211. © Blackwell Munksgaard 2005. Cyclophosphamide (CPA) is widely used in chemotherapy. The CPA is a prodrug that requires metabolic transformation to generate the active metabolite, 4-hydroxy-CPA (4-OH-CPA). Ciprofloxacin (CF) is a fluoroquinolone antibiotic with a broad spectrum that is commonly used in treatment of a variety of infections. It has been reported that prophylactic administration of CF during CPA conditioning was a high-risk factor for relapse in patients undergoing allogeneic bone marrow transplantation. In the present study we investigated the pharmacokinetics of CPA and 4-OH-CPA in eight non-Hodgkin lymphoma (NHL) patients treated with CPA together with or without CF. Clearance and distribution volumes of CPA were significantly ( P < 0.01) lower (4.7 L/h and 42.3 L, respectively) when patients were treated with CF prior to CPA compared to that observed when the patients did not receive CF (5.9 L/h and 48.1 L, respectively). No change in the elimination half-life was observed. The CF administration prior to CPA has resulted in significantly ( P < 0.01) lower exposure to 4-OH-CPA as expressed as area under the plasma concentration curve (AUC). The metabolic ratio AUC4-OH-CPA/AUCCPA was lower in all patients treated with CF prior to CPA compared to that observed when patients received CPA only ( P = 0.008). Our study showed that CF administration alters CPA kinetics in patients with NHL. Other antibiotics than these contain fluoroquinolones should be used during CPA therapy. [ABSTRACT FROM AUTHOR]

Summary. In this national study, we have evaluated a new intensive chemotherapy protocol for adult patients with untreated acute lymphoblastic leukaemia (ALL). One hundred and fifty-three patients with median age 42 years received induction therapy with high-dose cytarabine (Ara-C), cyclophosphamide, daunorubicin, vincristine and betamethasone. A high complete remission (CR) rate (90%) was achieved in patients < 60 years compared with 70% in patients > 60 years (P = 0·004). The estimated 3 year overall survival for all patients was 29% (CI 21–36%) and the estimated continuous complete remission (CCR) at 3 years for the patients achieving CR according to the protocol was 36% (CI 27–45%). A favourable pretreatment characteristic was pre-B phenotype, especially for patients < 40 years without any high-risk factor, with an estimated CCR at 3 years of 62% (CI 41–82%). Stem cell transplantation (SCT) as post-remission therapy, mainly for high-risk patients, gave an estimated 3 year disease free survival (DFS) after SCT of 39% (CI 24–54%). No significant differences in DFS could be found between autologous, related or unrelated donor transplantation. We conclude that this intensive protocol resulted in a high CR rate combined with acceptable side-effects and a favourable CCR for patients with pre-B ALL. [ABSTRACT FROM AUTHOR]

Summary. A phase II study was undertaken to evaluate the efficacy and toxicity of a new schedule of cladribine administration (10 mg/m2 orally daily for 3 d every 3 weeks) in 107 patients with B-cell chronic lymphocytic leukaemia (CLL). To minimize toxicity, treatment withdrawal criteria were defined. The results of the 63 previously untreated patients were retrospectively compared with 63 from an earlier study using a 5-d monthly schedule. The compiled data were analysed for prognostic factors for survival. No significant difference regarding response were seen in the two cohorts of the 126 previously untreated patients. The complete response (CR), nodular partial response (nPR) and partial response (PR) rates were 15%, 21% and 41%. Quality of response had no impact on survival. The 3- and 5-year overall survival for previously untreated patients was 73% and 58%, respectively, with a median follow-up of 54 months. Pretreatment haemoglobin < 11·0 g/dl and elevated beta-2-microglobulin had a negative influence on survival. Major infections occurred in 21% of patients in the 3-d study compared with 35% in the 5-d study. The overall response (OR) and CR rates in the 40 previously treated patients were 34% and 5% respectively. Median overall survival was 24 months and median progression-free survival for responding patients was 14 months. Cladribine used as a single agent is an effective treatment with an acceptable safety profile for pretreated and untreated B-CLL. The achievement of complete remission was not a prerequisite for long-term survival. [ABSTRACT FROM AUTHOR]

Abstract: Background: Surface antigen expression can be used to define subgroups of patients with different clinical courses in chronic lymphocytic leukaemia of the B-cell type (CLL). Purpose–Methods: To study the clinical significance of functional markers linked to proliferation (CD25), adhesion (CD54), and apoptosis (CD95) on B- and T-cells in 68 patients with CLL using dual colour flow cytometry (FCM). Results: The mean proportion of CD19+ B-cells expressing CD25 was significantly higher in CLL patients compared to controls (P =0.02), while CD54+ and CD95+ B-cells did not differ significantly. In CLL with atypical morphology and in patients with trisomy 12, the mean percentage of CD25+ B-cells was lower than in typical CLL (P <0.02) and in patients with disomic tumor cells (P <0.03). Patients with >=30% of CD25+ B-cells had a shorter median time to treatment than CD25-negative cases (P =0.01). A low CD54 expression was associated with a prolonged median time to treatment (P =0.004), low WBC counts (P <0.05), and low S-LDH (P =0.03). A high CD95 expression was correlated with elevated S-LDH (P =0.02) and a finding of lymphadenopathy (P =0.02). In individual patients there was a strong correlation between B- and T-cell expression of CD25 (P <0.0001), CD54 (P =0.0002), and CD95 (P =0.0002), respectively. Conclusions: CD25 and CD54 expression on CD19+ cells seems to give prognostic information. The strong correlation between the expression of CD25, CD54 and CD95 on B-and T-cells suggests that the expression of these antigens is not an inherent characteristic of the malignant B-cell clone. [ABSTRACT FROM AUTHOR]

The article focuses on a study which found that conjugate vaccine produced better response in lymphoma patients than polysaccharide vaccine after 12 months of rituximab treatment. It informs that rituximab depletes malignant CD20 expressing B cells but also normal CD20+ cells. The study supported indication of immunogenic conjugate vaccines and vaccinations before rituximab or immunochemotherapy in B-cell lymphoma patients.

A correction to the article "Nordic MCL2 Trial Update: 6-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC + autologous stem-cell support: Still very long survival but late relapses do occur" published in previous issue is presented.

Follicular lymphoma is the most common indolent lymphoma accounting for approximately 20%-25% of all new non-Hodgkin lymphoma diagnoses in western countries. Whilst outcomes are mostly favorable, the spectrum of clinical phenotypes includes high-risk groups with significantly inferior outcomes. This review discusses recent updates in risk stratification and treatment approaches from upfront treatment for limited and advanced stage follicular lymphoma to the growing options for relapsed, refractory disease with perspectives on how to approach this from a personalized lens. Notable gaps remain on how one can precisely and prospectively select optimal treatment for patients based on varying risks, with an anticipation that an increased understanding of the biology of these different phenotypes and increasing refinement of imaging- and biomarker-based tools will, in time, allow these gaps to be closed., (© 2023 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

This report represents a further update of the consensus panel criteria for the assessment of clinical response in patients with Waldenström macroglobulinaemia (WM). These criteria have been updated in light of further data demonstrating an improvement in categorical responses with new drug regimens as well as acknowledgement of the fact that such responses are predictive of overall outcome. A number of key changes are proposed but challenges do however remain and these include the variability in kinetics of immunoglobulin M (IgM) reduction with different treatment modalities and the apparent discrepancy between IgM and bone marrow/tissue response noted with some regimens. Planned sequential bone marrow assessments are encouraged in clinical trials., (© 2012 Blackwell Publishing Ltd.)