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Primary central nervous system lymphomas (PCNSLs) classically remain confined within the CNS throughout their evolution for unknown reasons. Our objective was to analyse the rare extracerebral relapses of PCNSL in a nationwide population-based study. We retrospectively selected PCNSL patients who experienced extracerebral relapse during their follow-up from the French LOC database. Of the 1968 PCNSL included in the database from 2011, 30 (1.5%, median age 71 years, median KPS 70) presented an extracerebral relapse, either pure (n = 20) or mixed (both extracerebral and in the CNS) (n = 10), with a histological confirmation in 20 cases. The median delay between initial diagnosis and systemic relapse was 15.5 months [2-121 months]. We found visceral (n = 23, 77%), including testis in 5 (28%) men and breast in 3 (27%) women, lymph node (n = 12, 40%), and peripheral nervous system (PNS) (n = 7, 23%) involvement. Twenty-seven patients were treated with chemotherapy, either with only systemic targets (n = 7) or mixed systemic and CNS targets (n = 20), 4 were consolidated by HCT-ASCT. After systemic relapse, the median progression-free survival and overall survival (OS) were 7 and 12 months, respectively. KPS > 70 and pure systemic relapses were significantly associated with higher OS. Extracerebral PCNSL relapses are rare, mainly extranodal, and frequently involve the testis, breast, and PNS. The prognosis was worse in mixed relapses. Early relapses raise the question of misdiagnosed occult extracerebral lymphoma at diagnostic workup that should systematically include a PET-CT. Paired tumour analysis at diagnosis/relapse would provide a better understanding of the underlying molecular mechanisms., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Most relapses of primary central nervous system lymphoma (PCNSL) occur in the brain and are associated with a poor prognosis. Isolated intraocular relapses (IIORs) are rare and poorly described. We retrospectively selected from the French Lymphome Oculo-Cérébral database PCNSL patients who initially presented with cerebral localization and who experienced IIOR during the course of the disease. Of the 1472 patients included in the database, 55 patients presented an IIOR. Their median age was 68 years, and median Karnofsky Performance Status 80. IL-10 levels in the aqueous humor and/or in the vitreous were increased in 42/46 patients. 45/55 patients received systemic chemotherapy, and 11/55 received high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) as consolidation treatment. After a median follow-up of 69 months, 42/55 patients had relapsed, including 90% of the patients who did not receive HCT-ASCT at IIOR and 40% of the patients who received HCT-ASCT at IIOR (p < 0.001). The first relapse after the initial IIOR was exclusively in the eye in 23/42 patients, and 29/42 patients had a subsequent brain relapse during the course of the disease. The median progression-free survival, brain-free survival and overall survival from IIOR were 12.2, 48.6 and 57.1 months, respectively. Isolated intraocular relapse is not exceptional in the course of PCNSL and deserves systematic ophthalmological follow-up. Its prognosis is much better than the prognosis of brain relapse, with an evolution close to that of primary vitreoretinal lymphoma. With the exception of patients who received HCT-ASCT at IIOR, almost all patients subsequently relapsed, often with other IIORs., (© 2022 John Wiley & Sons Ltd.)

We analysed the therapeutic outcomes of all consecutive patients with primary central nervous system lymphoma (PCNSL) registered in the prospective French database for PCNSL and treated with intensive chemotherapy (IC) followed by autologous stem cell transplantation (IC-ASCT) between 2011 and November 2019 (271 patients recruited, 266 analysed). In addition, treatment-related complications of thiotepa-based IC-ASCT were analysed from the source files of 85 patients from 3 centers. Patients had received IC-ASCT either in first-line treatment (n = 147) or at relapse (n = 119). The median age at IC-ASCT was 57 years (range: 22-74). IC consisted of thiotepa-BCNU (n = 64), thiotepa-busulfan (n = 24), BCNU-etoposide-cytarabine-melphalan (BEAM, n = 36) and thiotepa-busulfan-cyclophosphamide (n = 142). In multivariate analysis, BEAM and ASCT beyond the first relapse were adverse prognostic factors for relapse risk. The risk of treatment-related mortality was higher for ASCT performed beyond the first relapse and seemed higher for thiotepa-busulfan-cyclophosphamide. Thiotepa-BCNU tends to result in a higher relapse rate than thiotepa-busulfan-cyclophosphamide and thiotepa-busulfan. This study confirms the role of IC-ASCT in first-line treatment and at first-relapse PCNSL (5-year overall survival rates of 80 and 50%, respectively). The benefit/risk ratio of thiotepa-busulfan/thiotepa-busulfan-cyclophosphamide-ASCT could be improved by considering ASCT earlier in the course of the disease and dose adjustment of the IC., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Real-life studies on patients with primary CNS lymphoma (PCNSL) are scarce. Our objective was to analyze, in a nationwide population-based study, the current medical practice in the management of PCNSL., Methods: The French oculo-cerebral lymphoma network (LOC) database prospectively records all newly diagnosed PCNSL cases from 32 French centers. Data of patients diagnosed between 2011 and 2016 were retrospectively analyzed., Results: We identified 1,002 immunocompetent patients (43% aged >70 years, median Karnofsky Performance Status [KPS] 60). First-line treatment was high-dose methotrexate-based chemotherapy in 92% of cases, with an increasing use of rituximab over time (66%). Patients <60 years of age received consolidation treatment in 77% of cases, consisting of whole-brain radiotherapy (WBRT) (54%) or high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) (23%). Among patients >60 years of age, WBRT and HCT-ASCT consolidation were administered in only 9% and 2%, respectively. The complete response rate to initial chemotherapy was 50%. Median progression-free survival was 10.5 months. For relapse, second-line chemotherapy, HCT-ASCT, WBRT, and palliative care were offered to 55%, 17%, 10%, and 18% of patients, respectively. The median, 2-year, and 5-year overall survival was 25.3 months, 51%, and 38%, respectively (<60 years: not reached [NR], 70%, and 61%; >60 years: 15.4 months, 44%, and 28%). Age, KPS, sex, and response to induction CT were independent prognostic factors in multivariate analysis., Conclusions: Our study confirms the increasing proportion of elderly within the PCNSL population and shows comparable outcome in this population-based study with those reported by clinical trials, reflecting a notable application of recent PCNSL advances in treatment., (© 2020 American Academy of Neurology.)

Background: Bone mineral density (BMD) loss is poorly defined in lymphoma patients. The aim of this study was to measure the extent of BMD loss in newly diagnosed lymphoma patients receiving chemotherapy., Patients and Methods: This was a prospective, single-center study conducted in patients aged≥18 years with previously confirmed lymphoma treated by chemotherapy. Patients with low baseline BMD defined as Z/T-score less than or equal to -2.5 and/or history of osteoporotic fractures were excluded. BMD was measured at baseline before initiating chemotherapy and 1 year later. Predictive factors of BMD loss were investigated., Results: Forty-one lymphoma patients (31 males and 10 females) receiving chemotherapy were enrolled. The median age at diagnosis was 59 (range: 19-86) years. Histological subtypes were predominantly diffuse large B-cell lymphoma (58%), mostly stage III-IV (54%). All patients received chemotherapy and 22% of patients received second-line treatment due to relapse or progressive disease. Thirty-two patients were evaluable at 1 year. The mean BMD changes were: -2.7%±3.9% for lumbar spine (P<0.001), -2.2%±7.6% for femoral neck (P<0.01) and -2.6%±4.5% for total hip (P<0.0001). In multivariate analysis, predictive factors of BMD loss at baseline were (i) at lumbar spine: female gender (P=0.01), higher lactate dehydrogenase level (P=0.04) and lower creatinine clearance (P=0.01); (ii) at total hip: lower albumin (P=0.01), higher corrected serum calcium (P<0.01), lower alkaline phosphatase (AP) (P<0.01) and autologous stem cell transplant (P=0.03); and (iii) at femoral neck: higher corrected serum calcium (P=0.02) and lower bone AP (P=0.01)., Conclusion: Adult patients with known lymphoma receiving chemotherapy experienced significant BMD loss at 1 year.

In 2010, a multidisciplinary team within the clinical haematology and cellular therapy department of Amiens general hospital set up a project to optimise the care of patients suffering from lymphoma. The setting up of nurse diagnosis announcement consultations, telephone consultations, new clinical nursing practices, in collaboration with the medical teams, integrates new nursing roles in advanced practices in oncology.

It is commonly admitted that the diagnosis of lymphomas can be assessed by the image-guided needle biopsy (IGNB) of deep lymph nodes. However, when peripheral lymph nodes are present, surgical dissection remains the standard strategy. The aim of this study was to evaluate the diagnostic yield of IGNB of peripheral lymph nodes in patients with suspected lymphomas. The records of 180 multisampling IGNBs of peripheral lymph nodes in 180 patients were reviewed. One hundred and twenty-three IGNBs were observed at first diagnosis and 57 at progression using large-cutting core-biopsy needles ranging between 18 G and 14 G in size. Immunohistochemistry studies were performed in all cases and at least one biopsy was systematically frozen. A diagnosis of lymphoma with sufficient information such that a therapeutic decision could be made was obtained in 146 of the 152 patients with lymphoproliferative disorders (96%). IGNB was equally effective in making the correct diagnosis of lymphoma at the time of original diagnosis than at relapse. The results did not depend on the biopsy site, lymph nodes size, or needle type. We recommend that IGNB may be performed as an initial procedure for the diagnosis of lymphomas either in the presence of peripheral or deep lymph nodes, as it avoids surgery.

Autologous stem-cell transplantation is widely used as part of the treatment of poor prognosis lymphoma patients. Since 1986, peripheral blood progenitor cells (PBPC) mobilized by chemotherapy and/or hematopoietic growth factors have progressively been used instead of autologous bone marrow (BM) cells. Toxicity, engraftment and long-term outcome were compared in a population of relapsing or refractory lymphoma patients given high-dose therapy. During 1986 to 1993, 150 patients with refractory or relapsed non-Hodgkin's lymphomas (n = 93) or Hodgkin's disease (n = 57) received intensive therapy followed by the reinjection of BM (n = 72) or PBPC (n = 78). PBPC were collected by aphereses during the phase of hematologic recovery after mobilization by chemotherapy alone (n = 36) or associated with GCSF (n = 43). Conditioning regimens included chemotherapy alone in 77%, associated with total body irradiation (TBI) in 23%. After stem-cell reinfusion, 55% of the PBPC group received GCSF versus 24% in the BM group. Results show that the median time to neutrophil counts > 500/microliters and platelets > 50,000/microliters was significantly shorter in the PBPC than the BM group, respectively 13 versus 23 days and 18 versus 26 days (P < 0.05). This difference remained significant (P < 0.05) when patients were stratified according to the administration or not of GCSF after transplantation. PBPC grafting after high-dose therapy was associated with a median reduction of the hospital stay of 10 days. The majority of patients (90%) maintained normal blood counts at 3 months, and no secondary graft failure was observed in either group. The use of TBI in the conditioning regimen was the only significant factor affecting long-term hematologic recovery. For relapsing patients with histologically aggressive lymphomas, overall survival and failure-free survival were similar in both groups. In conclusion, PBPC transplantation is a safe procedure associated with improvement of hematopoietic recovery and a shortened hospital stay.

Following treatment for mediastinal lymphoma, residual masses are defined as a mass greater than 2 cm observed on the CT scan in the absence of other evolutive signs of lymphoma. In this study, we examined 55 patients with residual mediastinal mass after optimal therapy, using gallium scan (37 cases) or magnetic resonance imaging (MRI, 44 cases). The group comprised 41 subjects with Hodgkin's disease and 14 with non Hodgkin's lymphoma, stages I and II (32 cases) and stages III and IV (23 cases); 35 subjects (64%) having bulky mediastinal involvement at diagnosis. A negative gallium scan or fibrotic signal on MRI was correlated with complete remission in 48 cases (87%). In seven of these 48 patients, MRI was not conclusive with a high signal of indeterminate tissue following radiotherapy, but four of the seven had fibrotic tissue on biopsy and none relapsed. Positive gallium scan was observed in six cases. In conclusion, we suggest performing a gallium scan at the end of induction chemotherapy and when it is negative, treatment may be continued without surgical biopsy or salvage therapy. MRI is of value when it shows fibrotic tissue but can be inconclusive.

Peripheral T-cell lymphomas consist of a clinically heterogeneous group of malignant disorders whose immunophenotype usually corresponds to that of normal mature T cells. We describe and correlate the clinical, histopathologic, phenotypic, and genotypic findings in two patients with malignant lymphoma presenting with hepatosplenic disease. The morphologic pattern of lymphoma was that of a sinusal/sinusoidal infiltration in spleen, marrow, and liver. This morphologic characteristic was associated with the presence of a productive clonal rearrangement of the T-cell receptor (TCR) delta gene. Lymphoma cells expressed a CD3-TCR-gamma delta- phenotype. They were also double negative (ie, CD4-CD8-) and lacked the CD5 and CD7 antigens. In one patient, tumor progression was associated with phenotypic changes that resulted in a CD3-TCR-gamma delta- phenotype with the same delta-gene rearrangement as initially. These observations suggest the existence of a new type of peripheral T-cell lymphoma characterized by its hepatosplenic presentation, and by the sinusal/sinusoidal tropism and the TCR-gamma delta phenotype of the malignant cells.