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In the workup of follicular lymphoma (FL), bone marrow biopsy (BMB) assessment is a key component of FLIPI and FLIPI2, the most widely used outcome scores. During the previous decade, several studies explored the role of FDG-PET/CT for detecting nodal and extranodal disease, with only one large study comparing both techniques.The aim of our study was to evaluate the diagnostic accuracy and the prognostic impact of both procedures in a retrospective cohort of 299 FL patients with both tests performed at diagnosis. In order to avoid a collinearity bias, FLIPI2 was deconstructed in its founding parameters, and the bone marrow involvement (BMI) parameter separately included as: a positive BMB, a positive PET/CT, the combined "PET/CT and BMB positive" or "PET/CT or BMB positive". These variables were also confronted independently with the POD24 in 233 patients treated with intensive regimens.In the total cohort, bone marrow was involved in 124 and 60 patients by BMB and PET/CT, respectively. In terms of overall survival, age 60 y.o. and the combined "PET/CT or BMB positive" achieved statistical independence as a prognostic factor. In patients treated with an intensive regimen, only the combined "PET/CT or BMB positive" added prognostic value for a shorter overall survival, when confronted with the POD24.Our results show that in FL both BMB and PET/CT should be considered at diagnosis, as their combined assessment provides independent prognostic value in the context of the most widely use clinical scores.

© The Author(s) 2021., Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL, 20–30%) after diffuse large B-cell lymphoma (DLBCL). Despite the introduction of rituximab and the high response rate to first-line treatment, approximately 20% of the FL patients relapse or progress within 2 years of receiving first-line therapy. Therefore, the major challenge is finding biomarkers that identify high-risk patients at diagnosis., This work was partially supported by the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness PI15/01393, PI18/00410, CIBERONC-CB16/12/00233, and “Una manera de hacer Europa” (Innocampus; CEI-2010-1-0010)”, the Education Council or Health Council of the Junta de Castilla y León (CAS102P17, GRS 1180/A/15), Spanish Association Against Cancer (AECC; PROYE18020BEA), and Gilead Sciences (GLD17/00334). CJ, MES, and AMe are supported by the ISCII (CD19/00030, CPII18/00028, and FI19/00320). MGA, IPC, and CJ were supported by the Spanish Society of Hematology Foundation (FEHH). All Spanish funding is co-sponsored by the European Union FEDER program.

The Hodgkin lymphoma (HL) genomic landscape is hardly known due to the scarcity of tumour cells in the tissue. Liquid biopsy employing circulating tumour DNA (ctDNA) can emerge as an alternative tool for non-invasive genotyping. By using a custom next generation sequencing (NGS) panel in combination with unique molecule identifiers, we aimed to identify somatic variants in the ctDNA of 60 HL at diagnosis. A total of 277 variants were detected in 36 of the 49 samples (73·5%) with a good quality ctDNA sample. The median number of variants detected per patient was five (range 1–23) with a median variant allele frequency of 4·2% (0·84–28%). Genotyping revealed somatic variants in the following genes: SOCS1 (28%), IGLL5 (26%), TNFAIP3 (23%), GNA13 (23%), STAT6 (21%) and B2M (19%). Moreover, several poor prognosis features (high LDH, low serum albumin, B-symptoms, IPI ≥ 3 or at an advanced stage) were related to significantly higher amounts of ctDNA. Variant detection in ctDNA by NGS is a feasible approach to depict the genetic features of HL patients at diagnosis. Our data favour the implementation of liquid biopsy genotyping for the routine evaluation of HL patients., This work was partially supported by the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness CIBERONC-CB16/12/00233, and “Una manera de hacer Europa” (Innocampus; CEI-2010-1-0010)”, the Health Council of the Junta de Castilla y León (GRS2037/A/19) (GRS1845/A/18) and private Gilead (GLD/18/00063). MGA is supported with a grant from the Accelerator consortia (Cancer Research UK; C355/A26819). CJ and AM are supported by the ISCII (CD19/00030 and FI19/00320). MES is supported by Contrato Miguel Servet tipo II (CPII18/00028). MA is financed by CIBER-CB16/12/00233. All Spanish funding is co-sponsored by the European Union FEDER program.

This article belongs to the Special Issue Personalized Medicine: Recent Progress in Cancer Therapy., The biology and clinical impact of bone marrow (BM) infiltration in patients with diffuse large B-cell lymphoma (DLBCL) remains unclear in the rituximab era. We retrospectively analyzed 232 patients diagnosed with DLBCL at our center between 1999 and 2014. Concordant-presence of large cells similar to those of the lymph node biopsy- and discordant-infiltration by small cells forming lymphoid aggregates, lacking cytological atypia-BM infiltration was defined by histological criteria and further characterized by flow cytometry (FCM). Cell of origin (COO) was determined using Hans’ algorithm. For the clonal relationship between tumor and discordant BM, the VDJH rearrangement was analyzed. Survival analyses were restricted to 189 patients treated with rituximab and chemotherapy. Thirty-six (16%) had concordant, and 37 (16%) discordant BM infiltration. FCM described different indolent lymphomas among discordant cases, clonally related with DLBCL in 10/13 available samples. Median follow-up was 58 months. 5-year-progression-free survival (PFS) for non-infiltrated, discordant and concordant groups was 68%, 65% and 30%, respectively (p < 0.001). Combining COO and BM infiltration, patients with discordant BM and non-germinal center B-cell COO also had decreased 5-year-PFS (41.9%). In multivariate analysis, concordant BM had an independent effect on PFS (HR 2.5, p = 0.01). Five-year cumulative incidence of central nervous system (CNS) relapse was 21%, 4% and 1% in concordant, discordant and non-infiltrated groups, respectively (p < 0.001). In conclusion, concordant BM infiltration represents a subset with poor prognosis, whereas the prognostic impact of discordant BM infiltration could be limited to non-CGB cases., This work was partially supported by the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness PI13/02644, PI15/01393, RD12/0036/0069, CIBERONC-CB16/12/00233, and “Una manera de hacer Europa” (Innocampus; CEI-2010-1-0010)”, the Health Council of the Junta de Castilla y León (GRS 850/A/13, GRS 1180/A/15, GRS 1350/A/16, GRS 1846/A/18, GRS 2035/A/19, and BIO/SA78/15), and Gilead Sciences (GLD17/00334). All Spanish funding is co-sponsored by the European Union FEDER program.

Context: Outcomes of patients with transformed lymphoma have historically been poor, prompting many centres to include stem-cell transplant (SCT) as part of the treatment strategy. However, several studies in the rituximab era suggest that survival may be more favourable than previously recognized, questioning the need for such intensive therapies. Objective: We analyzed the efficacy of SCT in transformed lymphomas at a single reference Transplant Unit. Design: We collected data from 51 patients; the indication was a diagnosis of diffuse large B-cell lymphoma (DLBCL) transformed from an indolent lymphoma, from 1995 to 2018. Of them, 36 received an auto-SCT and 15 an allo-SCT. Results: Median age was 60 (range, 40-69) and 52 (range, 35-65) years for patients receiving auto-SCT and allo-SCT, respectively. Patients in the allo-SCT group had been more intensively pretreated, as 13 (87%) patients received >3 lines of treatment before SCT and 13 (87%) underwent a previous auto-SCT, whereas patients in the auto-SCT group were pretreated with a median of 2 (range, 1 to 4) lines of treatment. Regarding disease status at transplant, most patients (78% and 73% in the auto and allo-SCT groups, respectively) were transplanted in complete remission (CR). All auto-SCT patients received BEAM as conditioning regimen, whereas patients in the allo-SCT group received several fludarabine-based combinations. Transplant-related mortality (TRM) was 3.2% and 27% in the auto and allo-SCT groups, respectively. With a median follow-up of 61 and 50 months,4-year overall survival (OS) and progression-free-survival (PFS) were 87% and 76%, for the auto-SCT patients, and 52% and 56%, respectively, for the allo-SCT patients. In the auto-SCT group, 12 (33%) patients experienced disease progression and 7 (19.5%) died (5 [13.9%] from lymphoma), whereas in the allo-SCT group, only 2 (13%) patients had disease progression but 4 (27%) died due to transplant-related causes. Conclusions: SCT is a potentially curative option for patients with transformed lymphoma, since more than a half of patients are long-term survivors. Progression is the major cause of failure in auto-SCT whereas allo-SCT patients died because of toxicity. Efforts need to be made to identify patients who do not benefit from auto-SCT to avoid toxicity.

© The Author(s) 2019., Follicular lymphoma (FL) is a heterogeneous disease whose pathogenesis remains partially unknown. Around 20% of FL patients experience early progression or treatment-refractory disease and 2–3% of patients per year experience histological transformation (HT) into a more aggressive lymphoma (tFL). Here, we evaluate the immunoglobulin heavy chain variable (IGHV) gene usage and mutational status in 187 FL cases to assess its impact on clinical outcome and histological transformation. The IGHV gene repertoire was remarkably biased in FL. The IGHV4-34 (14%), IGHV3-23 (14%), IGHV3-48 (10%), IGHV3-30 (9%) and IGHV3-21 (7%) genes accounted for more than half of the whole cohort. IGHV3-48 was overrepresented in cases of tFL (19%) compared with non-transformed FL at 5 years (5%, P = 0.05). Patients with the IGHV3-48 gene were significantly more likely to have had HT after 10 years than those who used other genes (71% vs. 25%, P, This work was partially supported by the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness PI15/01393, PI18-00410, RD12/0036/0069, CIBERONC-CB16/12/00233, and “Una manera de hacer Europa” (Innocampus; CEI-2010-1-0010)”, the Education Council or Health Council of the Junta de Castilla y León (CAS102P17, GRS 1180/A/15), and Gilead Sciences (GLD17/00334). M.G.A., I.P.C. and C.J. are supported by the Fundación Española de Hematología y Hemoterapia (FEHH, co-funded by Fundación Cris in the latter case), and M.E.S. by the ISCIII (CPII18/00028). All Spanish funding is co-sponsored by the European Union FEDER program.

This study was conducted to investigate the prognostic effect and implications of gallium 67 scintigraphy (gallium scan) at mid-treatment and at the end of first-line treatment in patients with early- and advanced-stage Hodgkin's lymphoma (HL). A total of 216 HL patients were included in the study. Gallium scan was performed at mid-treatment and at the end of first-line treatment. The overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan-Meier method. The log-rank test was used to identify univariate predictors of EFS and OS. For early-stage disease, bulky mediastinal involvement (yes vs. no, 98 vs. 79%, respectively; P=0.01), erythrocyte sedimentation rate (good vs. adverse, 98 vs. 88%, respectively; P=0.03), presence of B symptoms (no vs. yes, 94 vs. 78%, respectively; P=0.006), post-chemotherapy disease status [complete response (CR) vs. unconfirmed CR (uCR) vs. partial response (PR) vs. progressive disease (PGR), 95 vs. 90 vs. 87 vs. 0%, respectively; P

Several studies have reported uneven results when evaluating the prognostic value of bone marrow biopsy (BMB) and PET/CT as part of the staging of diffuse large B‐cell lymphoma (DLBCL). The heterogeneity of the inclusion criteria and not taking into account selection and collinearity biases in the analysis models might explain part of these discrepancies. To address this issue we have carried a retrospective multicenter study including 268 DLBCL patients with a BMB and a PET/CT available at diagnosis where we estimated both the prognosis impact and the diagnostic accuracy of each technique. Only patients treated with R‐CHOP/21 as first line (n = 203) were included in the survival analysis. With a median follow‐up of 25 months the estimated 3‐year progression‐free survival (PFS) and overall survival (OS) were 76.3% and 82.7% respectively. In a multivariate analysis designed to avoid a collinearity bias with IPI categories, BMB‐BMI [bone marrow involvement](+) (HR: 3.6) and ECOG PS > 1 (HR: 2.9) were independently associated with a shorter PFS and three factors, age >60 years old (HR: 2.4), ECOG PS >1 (HR: 2.4), and abnormally elevated B2‐microglobulin levels (HR: 2.2) were independently associated with a shorter OS. In our DLBCL cohort, treated with a uniform first‐line chemotherapy regimen, BMI by BMB complemented performance status in predicting those patients with a higher risk for relapse or progression. In this cohort BMI by PET/CT could not independently predict a shorter PFS and/or OS.