PURPOSE MYC rearrangement ( MYC-R) occurs in approximately 10% of diffuse large B-cell lymphomas (DLBCLs) and has been associated with poor prognosis in many studies. The impact of MYC-R on prognosis may be influenced by the MYC partner gene (immunoglobulin [IG] or a non-IG gene). We evaluated a large cohort of patients through the Lunenburg Lymphoma Biomarker Consortium to validate the prognostic significance of MYC-R (single-, double-, and triple-hit status) in DLBCL within the context of the MYC partner gene. METHODS The study cohort included patients with histologically confirmed DLBCL morphology derived from large prospective trials and patient registries in Europe and North America who were uniformly treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy or the like. Fluorescence in situ hybridization for the MYC, BCL2, BCL6, and IG heavy and light chain loci was used, and results were correlated with clinical outcomes. RESULTS A total of 5,117 patients were identified of whom 2,383 (47%) had biopsy material available to assess for MYC-R. MYC-R was present in 264 (11%) of 2,383 patients and was associated with a significantly shorter progression-free and overall survival, with a strong time-dependent effect within the first 24 months after diagnosis. The adverse prognostic impact of MYC-R was only evident in patients with a concurrent rearrangement of BCL2 and/or BCL6 and an IG partner (hazard ratio, 2.4; 95% CI, 1.6 to 3.6; P < .001). CONCLUSION The negative prognostic impact of MYC-R in DLBCL is largely observed in patients with MYC double hit/triple-hit disease in which MYC is translocated to an IG partner, and this effect is restricted to the first 2 years after diagnosis. Our results suggest that diagnostic strategies should be adopted to identify this high-risk cohort, and risk-adjusted therapeutic approaches should be refined further.

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These findings identify specific domains of life in which cancer has a significant and long-term impact for AYA lymphoma survivors. Future investigations are needed to identify and test administrations and timing of psychosocial support interventions having potential to reduce long-term late effects in specific HRQoL domains and promote function and adaptability after cancer treatment.

Intravascular large B-cell lymphoma (IVLBCL) is a rare variant of extranodal diffuse large B-cell lymphoma (DLBCL). It is characterized by proliferation of blastic, neoplastic B cells within the lumina of small-or intermediate-sized blood vessels and capillaries. 1 IVLBCL may potentially involve any organ and is often widely disseminated. Two major patterns have been recognized. In Western patients, predominantly the skin and the central nervous system (CNS) are involved, whereas in Asian countries, the disease often involves multiple other organs and is accompanied by hemophagocytosis. 2 Additionally, a cutaneous variant, with skin-limited disease at time of diagnosis, has been described in younger, Western women. 3 Standard treatment of IVLBCL consists of rituximab-containing chemotherapeutic regimens, demonstrating an estimated 3-year overall survival (OS) of 60% to 81%. 4,5

The mortality associated with post-transplant lymphoproliferative disorder (PTLD) induced by EBV infection can be reduced by monitoring EBV by polymerase-chain-reaction and rituximab given pre-emptively. We performed a retrospective analysis of the risk factors for the occurrence of EBV infection/disease and EBV-related mortality among 273 consecutive recipients of a T-cell-depleted allo-SCT during two periods: (a) before the implementation of a comprehensive protocol (2006)(2007)(2008) and (b) afterwards (2009)(2010)(2011). EBV infection was detected in 61 (22%) cases, and 28 cases were considered to have had EBV disease. Treatment with antithymocyte globulin was the most important risk factor (odds ratio (OR) 2.4; 95% confidence interval (CI) 1.3-4.2, P ¼ 0.001). After implementation of the protocol, in patients experiencing EBV infection, pre-emptive therapy was started more often and sooner (median 3 vs 6 days, P ¼ 0.002). Moreover, there were fewer cases of monomorphic PTLD (4/33 (12%) vs 11/28 (39%), P ¼ 0.01), and the EBV-related mortality was lower for patients experiencing EBV infection (2/33 (6%) vs 8/28 (29%), OR 0.2; 95% CI 0.05-0.9, P ¼ 0.03). The EBV protocol proved feasible and resulted in faster initiation of pre-emptive therapy, the diagnosis in an earlier stage of EBV disease, and decreased EBV-related mortality.

MCL recurrence within 1 year after autoSCT has an extremely dismal outcome, while the prognosis of patients with longer remission durations after autoSCT is significantly better. AlloSCT may offer the possibility of durable survival when performed for patients with a remission duration of more than 12 months after first autoSCT, but the favourable effect of a salvage alloSCT in this setting needs further validation.

In follicular lymphoma, studies addressing the prognostic value of microenvironment-related immunohistochemical markers and tumor cell-related genetic markers have yielded conflicting results, precluding implementation in practice. Therefore, the Lunenburg Lymphoma Biomarker Consortium performed a validation study evaluating published markers. To maximize sensitivity, an end of spectrum design was applied for 122 uniformly immunochemotherapy-treated follicular lymphoma patients retrieved from international trials and registries. The criteria were: early failure, progression or lymphoma-related death <2 years versus long remission, response duration of >5 years. Immunohistochemical staining for T cells and macrophages was performed on tissue microarrays from initial biopsies and scored with a validated computer-assisted protocol. Shallow whole-genome and deep targeted sequencing was performed on the same samples. The 96/122 cases with complete molecular and immunohistochemical data were included in the analysis. EZH2 wild-type ( P =0.006), gain of chromosome 18 ( P =0.002), low percentages of CD8+ cells ( P =0.011) and CD163+ areas ( P =0.038) were associated with early failure. No significant differences in other markers were observed, thereby refuting previous claims of their prognostic significance. Using an optimized study design, this Lunenburg Lymphoma Biomarker Consortium study substantiates wild-type EZH2 status, gain of chromosome 18, low percentages of CD8+ cells and CD163+ area as predictors of early failure to immunochemotherapy in follicular lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP [-like]), while refuting the prognostic impact of various other markers.

Burkitt lymphoma is an aggressive B cell malignancy accounting for 1–2% of all adult lymphomas. Treatment with dose-intensive, multi-agent chemotherapy is effective but associated with considerable toxicity. In this observational study, we compared real-world efficacy, toxicity, and costs of four frequently employed treatment strategies for Burkitt lymphoma: the Lymphome Malins B (LMB), the Berlin-Frankfurt-Münster (BFM), the HOVON, and the CODOX-M/IVAC regimens. We collected data from 147 adult patients treated in eight referral centers. Following central pathology assessment, 105 of these cases were accepted as Burkitt lymphoma, resulting in the following treatment groups: LMB 36 patients, BFM 19 patients, HOVON 29 patients, and CODOX-M/IVAC 21 patients (median age 39 years, range 14–74; mean duration of follow-up 47 months). There was no significant difference between age, sex ratio, disease stage, or percentage HIV-positive patients between the treatment groups. Five-year progression-free survival (69%, p = 0.966) and 5-year overall survival (69%, p = 0.981) were comparable for all treatment groups. Treatment-related toxicity was also comparable with only hepatotoxicity seen more frequently in the CODOX/M-IVAC group (p = 0.004). Costs were determined by the number of rituximab gifts and the number of inpatients days. Overall, CODOX-M/IVAC had the most beneficial profile with regards to costs, treatment duration, and percentage of patients completing planned treatment. We conclude that the four treatment protocols for Burkitt lymphoma yield nearly identical results with regards to efficacy and safety but differ in treatment duration and costs. These differences may help guide future choice of treatment.Electronic supplementary materialThe online version of this article (10.1007/s00277-017-3167-7) contains supplementary material, which is available to authorized users.