Systemic non-Hodgkin Lymphoma Research Articles

Addition of Rituximab to High-Dose Methotrexate Regimens Improves Complete Response Rates and Median Overall Survival in Non-Germinal Center Primary CNS Lymphoma

Background:Primary central nervous system lymphoma (PCNSL) is a rare type of extranodal non-Hodgkin lymphoma (NHL). Most cases occur in the immunocompetent population. Despite advances in therapy, the prognosis of PCNSL remains poor, with 5-year overall survival (OS) rates at 30-50% (Ferreri 2011). The standard of care treatment regimen includes high-dose methotrexate (HD-MTX), often in combination with other multiagent CNS penetrating chemotherapies. Although the addition of rituximab in systemic aggressive B-cell NHLs has shown improvement in OS, the benefit of this agent in PCNSL has not been confirmed in a prospective dataset (Bromberg 2017). The majority of PCNSLs are classified as diffuse large B-cell lymphomas (DLBCL), and the outcomes based on treatment and cell of origin (germinal center B-cell (GCB) vs. non-GCB subtype) have yet to be fully elucidated. In this review, we report our findings from a series of PCNSL patients based on treatment regimen and cell of origin.Methods:This is a retrospective study of patients with PCNSL diagnosed and treated at the University of Colorado Hospital from 1995 to 2017. Chart abstraction included demographics, DLBCL subtype by Hans algorithm (Hans 2004), treatment details, and outcomes. OS was examined using Kaplan Meier methods, while bootstrap resampling and a z-test was used to compare median survival times across strata. Fisher's exact test was used to determine whether treatment responses were different between those that received treatment withHD-MTX and rituximab versus HD-MTX without rituximab. A significance level of 0.05 was used for all tests. When assessing differences by subtype, treatment type, relapse, and treatment response the data was subset to include only patients without a prior HIV diagnosis.Results:71 patients with PCNSL were identified. 13 patients were HIV positive (the HIV status of 1 patient was unknown). Of the remaining 57 immunocompetent patients, 39 patients were treated with HD-MTX, of which 29 patients received rituximab in combination therapy. The most commonly received regimen was rituximab with methotrexate, procarbazine, and vincristine (R-MPV) (43.6%, 17 of 39). Median age in the HD-MTX subgroup was 65 years, with 83% of patients with KPS>70 at diagnosis. EBV positivity was noted in only 4 of 39 samples (10.2%), while 25 of 39 (64.1%) tested negative; the remaining patients' data was not available.Median OS was 29.9 months for all 71 patients (Figure 1). There was no significant difference in median OS between those with and without HIV (p=0.127).22 of 29 (75.9%) patients in the HD-MTX with rituximab group achieved a complete response (CR) while no patients (0%; 0 of 10) in the HD-MTX without rituximab group achieved a CR. The number of patients with a CR was significantly higher for those that received HD-MTX with rituximab compared to those that received HD-MTX without rituximab (p<0.001).Median OS for HIV negative patients treated with HD-MTX without rituximab (N = 10) was 32.6 months whereas median OS for HIV negative patients treated with HD-MTX with rituximab (N = 29) has not been reached at a median follow up of 33.4 months (range 1.5 - 116.9 months) (Figure 2)Subtyping was available for 23 patients without HIV treated with HD-MTX with or without additional agents. 6 patients had GCB subtype and 16 had non-GCB subtype. Median OS for GCB subtype has not yet been reached, while median OS for non-GCB subtype was 33.4 months (Figure 3). When analyzing data for patients who received HD-MTX and rituximab, median OS for GCB has not been reached, while median OS for non-GCB was 43.8 months (Figure 4).Conclusions:Our review of patients with PCNSL suggests that the addition of rituximab to a high dose MTX-based regimen improves survival although numbers are too small to determine any overarching statistical conclusion. CR rates were significantly higher in patients receiving rituximab in addition to HD-MTX compared to HD-MTX without rituximab. Patients with non-GCB subtype treated with HD-MTX and rituximab had increased median OS compared to median OS of non-GCB patients treated with HD-MTX without rituximab. However, in line with previous data we demonstrated worse outcomes associated with non-GCB subtype compared to GCB subtype. Future research is needed to focus on the characteristics of this subtype of PCNSL to improve outcomes with novel therapeutics. [Display omitted] DisclosuresKamdar:Genentech: Consultancy; Seattle Genetics: Speakers Bureau. Haverkos:Viracta Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Distinctive Infectious Complications in Patients with Central Nervous System Lymphoma Undergoing Thiotepa, Busulfan, and Cyclophosphamide-conditioned Autologous Stem Cell Transplantation

We investigated the incidence of viral, fungal, bacterial, and parasitic infections observed in 57 patients with central nervous system lymphoma after thiotepa, busulfan, and cyclophosphamide-conditioned autologous stem cell transplantation (TBC-ASCT) and 79 patients with systemic non-Hodgkin lymphoma after traditional carmustine, etoposide, cytarabine, and melphalan–conditioned ASCT (BEAM-ASCT). Twenty of 57 (35%) TBC-ASCT patients had detectable viremia with human herpesvirus 6, cytomegalovirus, adenovirus, or BK virus, versus 9 of 79 (11%) BEAM-ASCT patients. Eight TBC-ASCT patients had clinically relevant viral infections (4 human herpesvirus 6, 2 cytomegalovirus, 1 adenovirus, 2 BK virus), versus 0 in the BEAM-ASCT group. Four TBC-ASCT patients suffered infections from either a fungal or parasitic pathogen versus 1 BEAM-ASCT patient. TBC was associated with greater risk of viral reactivation compared with BEAM, independent of other factors (hazard ratio, 4.42; 95% confidence interval, 1.9 to 11.3; P < .001). Prolonged lymphopenia and steroid use in the peri- and post-ASCT period did not explain these observed differences. The pathogenesis of these unusual infections in TBC-ASCT patients remains incompletely understood, and may involve more potent immune suppression with TBC conditioning. Clinicians should be aware of these differences in infection risk in TBC-ASCT patients, which more closely parallel those seen in allogenic hematopoietic cell transplantation recipients. New prophylactic approaches to help minimize these infections should be considered in this population.

Evaluation of tenascin-C by tenatumomab in T-cell non-Hodgkin lymphomas identifies a new target for radioimmunotherapy

The clinical outcome of T-cell non-Hodgkin lymphoma (NHL) is poor and innovative treatments are needed. Tenascin-C is a large extracellular glycoprotein not expressed under physiological conditions, but overexpressed in cancer. Aim of the study was to evaluate tenascin-C expression within pathologic tissue of T-cell NHL and determine its clinical significance. We used an immunohistochemistry approach using the anti-tenascin-C monoclonal antibody Tenatumomab in 75 systemic T-cell NHL (including 72 mature and 3 precursor T-cell NHL), and 25 primary cutaneous T-cell NHL. Data were analyzed in terms of staining intensity, proportion of involved areas and histologic pattern, and results were correlated with clinical characteristics and outcome. Ninety-three percent of the cases were tenascin-C positive and 59% of systemic diseases were characterized by a predominant involvement (>50%). Stromal expression was detected in all the cases while vascular and vascular plus cytoplasmic expression was present in 49% and 23%. The constant overexpression of the tenascin-C gene was observed in two independent publicly available T-cell NHL gene expression datasets. In conclusions, tenascin-C represents an attractive target that sets the rationale to investigate the therapeutic activity of radiolabeled Tenatumomab in T-cell NHL.

Can metabolic tumour parameters on primary staging 18F-FDG-PET/CT contribute to risk stratification of primary central nervous system lymphomas for patient management as a prognostic model?

ObjectivePrimary central nervous system (CNS) lymphoma is an aggressive and fatal extranodal non-Hodgkin lymphoma (NHL) jailed in CNS at initial diagnosis. Its prognosis is poor and the disease has a fatal outcome when compared with systemic NHL. A few baseline risk stratification scoring systems have been suggested to estimate the prognosis mainly based on serum lactate dehydrogenase (LDH) level, age, Karnofsky performance score (KPS), involvement of deep brain structures (DBS) and cerebrospinal fluid protein concentration. 18F-FDG-PET/CT has a high prognostic value with respect to overall survival (OS) and disease-free survival (DFS) in many cancers and lymphomas. We aimed to investigate metabolic tumour indexes on primary staging 18F-FDG-PET/CT as prognostic markers in primary CNS lymphoma. Material and methods14 patients with primary CNS diffuse large B-cell lymphoma (stage I) were enrolled in this retrospective cohort study. Primary staging 18F-FDG-PET/CT was performed and quantitative parameters like maximum standardized uptake value (SUVmax), average standardized uptake value (SUVmean), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated for all patients before the treatment. Cox regression models were performed to determine their relation with survival time. ResultsIn the evaluation of all potential risk factors impacting recurrence/metastases (age, sex, serum LDH, involvement of DBS, SUVmax, SUVmean, MTV, TLG) with univariate analysis, TLG remained statistically significant (p=0.02). ConclusionMetabolic tumour parameters are useful in prognosis estimation of primary CNS lymphomas, especially TLG, which is the most important one and may play a role in patient management.

Malignant lymphomas of the eye

The eye and the ocular adnexae are rare sites for malignant non-Hodgkin lymphoma (NHL). Based on their anatomical location, intraocular lymphomas must be discerned from NHL of adnexal structures including conjunctiva, lacrimal gland, and orbit. Whereas the latter group mostly consists of indolent extranodal marginal zone B‑cell lymphomas of mucosa-associated lymphoid tissue (MALT) type or secondary manifestations of systemic NHL, most primary intraocular lymphomas are classified as diffuse large B‑cell lymphomas (DLBCL) and are considered avariant of primary DLBCL of the central nervous system. The most common form is primary vitreoretinal lymphoma (PVRL), which presents with nonspecific symptoms and is difficult to discern from uveitis. Diagnosis of PVRL is usually made by cytological, immunocytochemical, and molecular analysis of vitreous aspirates. Degenerative changes, limited material, and the occurrence of pseudoclonality in the molecular analysis of B‑cell clonality can hamper diagnostic assessment. Novel techniques such as detection of MYD88 mutations common in PVRL can increase diagnostic sensitivity. Close cooperation with clinical colleagues and rapid specimen processing are fundamental for successful diagnosis.

Incidence and outcomes of primary central nervous system lymphoma in solid organ transplant recipients.

Primary central nervous system lymphoma (PCNSL) risk is greatly increased in immunosuppressed human immunodeficiency virus-infected people. Using data from the US transplant registry linked with 17 cancer registries (1987-2014), we studied PCNSL and systemic non-Hodgkin lymphoma (NHL) in 288 029 solid organ transplant recipients. Transplant recipients had elevated incidence for PCNSL compared with the general population (standardized incidence ratio=65.1; N=168), and this elevation was stronger than for systemic NHL (standardized incidence ratio=11.5; N=2043). Compared to kidney recipients, PCNSL incidence was lower in liver recipients (adjusted incidence rate ratio [aIRR]=0.52), similar in heart and/or lung recipients, and higher in other/multiple organ recipients (aIRR=2.45). PCNSL incidence was higher in Asians/Pacific Islanders than non-Hispanic whites (aIRR=2.09); after induction immunosuppression with alemtuzumab (aIRR=3.12), monoclonal antibodies (aIRR=1.83), or polyclonal antibodies (aIRR=2.03); in recipients who were Epstein-Barr virus-seronegative at the time of transplant and at risk of primary infection (aIRR=1.95); and within the first 1.5years after transplant. Compared to other recipients, those with PCNSL had increased risk of death (adjusted hazard ratio [aHR]=11.79) or graft failure/retransplantation (aHR=3.24). Recipients with PCNSL also had higher mortality than those with systemic NHL (aHR=1.48). In conclusion, PCNSL risk is highly elevated among transplant recipients, and it carries a poor prognosis.

High-dose Thiotepa, Busulfan, Cyclophosphamide, and Autologous Stem Cell Transplantation as Upfront Consolidation for Systemic Non-Hodgkin Lymphoma With Synchronous Central Nervous System Involvement.

Synchronous involvement of the central nervous system (CNS) at the diagnosis of systemic non-Hodgkin lymphoma (NHL) is associated with an increased risk for relapse despite complete remission to initial therapy. High-dose chemotherapy with a CNS-directed conditioning regimen followed by autologous stem cell transplantation (ASCT) holds promise as a consolidative approach. We conducted a retrospective analysis of all patients with systemic B-cell NHL and synchronous CNS involvement who received upfront consolidation with high-dose chemotherapy with thiotepa, busulfan, cyclophosphamide, and ASCT while in first complete remission between July 2008 and June 2016 at 2 partner academic institutions. Twenty patients were identified through the transplant database. The median age at diagnosis was 53 years (range, 37-65 years). The majority had diffuse large B-cell lymphoma histology (n= 17; 85%). The sites of CNS involvement were parenchymal (n= 12; 60%) and leptomeningeal disease (n= 9; 45%). All patients received systemic and CNS-directed therapy prior to transplant, with the most common approaches being R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone) (n= 13; 65%) and high-dose intravenous methotrexate (n= 16; 80%), respectively. With a median follow up of 4.4 years after ASCT (range, 2 months-8.5 years), the Kaplan-Meier estimates of 4-year progression-free and overall survival were 77% (95% confidence interval, 48%-91%) and 82% (95% confidence interval, 54%-94%), respectively. CNS-directed high-dose chemotherapy and ASCT provides durable remission for patients with synchronous aggressive lymphoma and should be strongly considered as consolidative therapy for eligible patients with systemic NHL with CNS involvement in first complete remission.

Systemic large B-cell non-Hodgkin lymphoma presenting as a massive hemorrhagic intracerebral mass

Systemic large B-cell non-Hodgkin lymphoma presenting as a massive hemorrhagic intracerebral mass

Difference in cardiovascular disease incidence by sociodemographic factors in adolescent and young adult (AYA) cancer survivors.

6565 Background: AYA cancer survivors are at increased risk of developing cardiovascular disease (CVD) compared to AYAs without a history of cancer. In AYA cancer survivors, few population-based studies have focused on CVD risk and none have considered whether the occurrence of CVD differs by sociodemographic factors. Methods: Analyses focused on 64,918 patients aged 15-39 y at diagnosis for one of 14 first primary cancers during 1996-2010 and surviving &gt; 2 years after diagnosis, with follow-up through 2013. Data were obtained from the California Cancer Registry and State hospital discharge data. CVD included coronary artery disease, heart failure, and stroke. We estimated the cumulative incidence of developing CVD, accounting for death as a competing risk, stratified by race/ethnicity, neighborhood socioeconomic status (SES) at diagnosis, health insurance status at diagnosis/initial treatment and cancer type. We examined the impact of CVD on mortality using multivariable Cox proportional hazards regression with CVD as a time-dependent covariate. Results: Overall, 2374 (3.7%) patients developed CVD, and 7690 (11.9%) died over the follow-up period. Survivors of acute myeloid leukemia (12.6%), acute lymphoid leukemia (11.1%), central nervous system cancer (9.0%) and non-Hodgkin lymphoma (6.0%) had the highest incidence of CVD at 10-years. Incidence was significantly higher among Blacks (6.7%) at 10-years than non-Hispanic Whites (3.0%), Hispanics (3.7%) and Asian/Pacific Islanders (3.7%) (p &lt; 0.001). AYA survivors with public or no insurance (vs private) had a higher 10-year incidence of CVD (5.8% vs 2.9%; p &lt; 0.001), as did survivors residing in low (vs high) SES neighborhoods (4.1% vs 2.7%; p &lt; 0.001). These sociodemographic differences in CVD incidence were apparent across most cancer sites. The risk of death was increased by five-fold or higher among AYAs who developed CVD. Conclusions: AYA cancer survivors who were uninsured or publicly insured, of Black race/ethnicity, or who resided in lower SES neighborhoods are at increased risk for developing CVD and experiencing higher mortality. The proactive management of CVD risk factors in these subgroups may improve patient outcomes.

An unusual cause of haemorrhage in the subthalamic nucleus of luys: A post-mortem study with 7.0 tesla magnetic resonance imaging correlates

The present case report is the first one of an isolated haemorrhage in the subthalamic nucleus of a patient with an isolated central nervous system relapse of systemic non-Hodgkin lymphoma. The neuropathological findings and 7.0-tesla magnetic resonance imaging correlates are presented.

Treatment of Severe Autoimmune Diseases with Autologous Hematopoietic Stem Cell Transplantation

Abstract Introduction. Autoimmune diseases are a family of more than 100 heterogeneous conditions that affect 5 to 8% of the world’s population. The etiology is still un-known but the disregulation of the regulatory T-lymphocytes play a central role inthe autoimmunity and the success of the long-term remission. Although conventional immunosuppression and new biological agents can provide disease control in severely affected patients, such treatments are rarely curative and alternative strategies are needed. Indeed, severe forms of systemic autoimmune diseases, such as multiple sclerosis (MS), systemic sclerosis (SSc), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA), hematologic immune cytopenia (HIC) and Crohn’s disease are difficult to be treated. High-dose immunosuppressive therapy followed by autologous stem cells transplantation is reliable option for a successive treatment of this group of patients. Aim. To determine the safety of the procedure of autologous stem cell transplantation in patients with autoimmune diseases and concomitant malignant hematological disorders. Methods. During a period of 15 years (from September 2000 to September 2015) at the University Clinic of Hematology in Skopje we have treated 6 patients with autoimmune disease and concomitant hematological neoplasm. None of the patients was treated for primary autoimmune diseases. Two men and 4 women, with median age of 47 years were treated. Sjogren syndrome and multiple myeloma were found in 2 patients, polyartheritis nodosa and multiple myeloma in 1 patient, rheumatoid arthritis and acute myeloblastic leukemia in 1, systemic lupus erythematosus and non-Hodgkin lymphoma in 1; severe psoriasis and acute myeloblastic leukemia in 1 patient. Results. All treated patients are alive after trans-planted procedure, with transplant related mortality day +100: 0. Conclusion. Autologous stem cell transplantation is safe and recommended option for treatment ofpatients with autoimmune disease and hematologic neoplasm.

Prognostic factors in HIV-positive patients with non-Hodgkin lymphoma: A Peruvian experience.

e19045Background: Non-Hodgkin lymphoma (NHL) is the most common cancer in people with HIV. The aim of this study was to determine the prognostic factors in HIV positive patients with systemic NHL. ...

Efficacy of Thiotepa-Busulfan-Cyclophosphamide (TBC) Conditioning and Autologous Transplantation As Consolidation for Systemic Non-Hodgkin Lymphoma with Synchronous CNS Involvement

Efficacy of Thiotepa-Busulfan-Cyclophosphamide (TBC) Conditioning and Autologous Transplantation As Consolidation for Systemic Non-Hodgkin Lymphoma with Synchronous CNS Involvement

ESHAP chemotherapy is efficient in refractory/relapsed primary central nervous system lymphoma: report of four cases.

Primary central nervous system non-Hodgkin’s lymphoma is a rare presentation, almost always of diffuse large B-cell type. Although there is no consensus regarding therapy for this condition, induction regimens are based on high-dose methotrexate and consolidation whole-brain radiotherapy, or, more preferred recently, blood–brain barrier penetrating drugs such as etoposide, cytarabine, and alkylating agents like temozolomide, ifosfamide, and lomustine. We present here four cases of relapsed/refractory primary central nervous system lymphoma treated with ESHAP (etoposide, solumedrol, high-dose cytarabine, and platinum) chemotherapy to complete remission, with the eligible patients proceeding to autologous transplantation. We want to draw attention to this interesting, relatively well tolerated, underused therapeutic option, in a setting where treatment options are scarce and evidence-based recommendations are lacking.

Primary Central Nervous System Lymphoma in Immunocompetent Patient

We report a case of primary central nervous system non-Hodgkin lymphoma (PCNSL) located in the right temporoparietal lobe with destruction of ethmoid and sphenoid bones in healthy immunocompetent adult. PCNSL accounts for <5% of all cases of primary intracranial neoplasms. The tumor is limited to the central neuroaxis with the absence of systemic lymphoma. For intraoperative neurosurgical consultation, the tissue is usually analyzed by touch imprint cytology and frozen section analysis. The imprint cytology is a rapid and less expensive method with better cellular morphology and fewer artifacts. The clinicopathologic findings of PCNSL in an immunocompetent woman are described herein.

Herpes simplex lymphadenitis in association with chronic lymphocytic leukaemia

Herpes simplex lymphadenitis is a rare condition that is most commonly seen in immunocompromised patients. To date, less than 30 cases have been reported in the literature. It is most commonly seen in patients with haematological malignancy, especially with chronic lymphocytic leukaemia. However, it can be associated with other neoplasms such as Hodgkin lymphoma, mantle and marginal zone B-cell lymphoma, acute and chronic myeloid leukaemia. Presentation can be varied from localised lymphadenopathy, generalised lymphadenopathy with or without a rash, and disseminated HSV infection with multiple organ involvement. Histologically, it shows areas of coalescing necrosis and inflammatory cell infiltrates including histiocytes and neutrophils. Multinucleate cells with ground glass nuclei and Cowdry type A intranuclear inclusions are diagnostic; the diagnosis can be confirmed with herpes simplex virus in-situ hybridisation or immunohistochemistry. Differential diagnoses to consider include cat scratch lymphadenitis, mycobacterial tuberculosis lymphadenitis, Kikuchi-Fujimoto lymphadenitis, systemic lupus erythematosus, Hodgkin lymphoma and large cell non-Hodgkin lymphoma. Herpes simplex lymphadenitis is an important diagnosis which can mimic transformation of an underlying haematological malignancy. We present a case of a 68-year-old male with localised lymphadenopathy and history of chronic lymphocytic leukaemia.

Defining Criteria for Diagnosis of Occult Lymphomatous Involvement in Cerebrospinal Fluid

Introduction: Currently, there is no consensus regarding diagnosis and treatment of occult lymphomatous menigeal involvement of cerebrospinal fluid (CSF) in patients with systemic non-Hodgkin lymphomas (NHL), especially in patients with minimal number of clonal cells detected by flow cytometry (FCM) or by cytology.Aim of the study: To describe a cohort of patients with occult lymphomatous involvement in cerebrospinal fluid including the diagnostic methods as well as management.Patients and methods: CSF at diagnosis of B-NHL was examined by FCM, cytology, biochemistry and microRNA analysis in a cohort of 62 patients (systemic DLBCL N=45, MCL N=15, Burkitt lymphoma N=2) between 2010 and 2013. Occult meningeal involvement was defined by: a/ FCM: absolute positive number of clonal cells <20 and concomitant negative finding by cytology; b/ FCM negative for clonal cells and concomitant positive finding by cytology; c/ by abundance of increased levels (≥ 200% of the threshold levels) of oncogenic microRNAs (members of miR-17-92 cluster and miR-21, evaulated by Taq-Man RT PCR) in cerebrospinal fluid in patients either passing a/ or b/. The threshold of individual microRNA abundance was defined by statistical analysis of patients with or without CNS involvement. The patients qualified for occult meningeal involvement were considered to be at high risk of CNS relaps. As a control group, the patients with elevated oncogenic microRNAs and negative FCM or cytology of CSF (N=10), were used. All patients received some form of CNS prophylaxis as a part of standard first line treatment.Results and conclusions: According to described criteria we identified 8 patients with occult meningeal involvement at diagnosis (systemic DLBCL N=4, MCL N=3, Burkitt lymphoma N=1) out of 62 patients: 3 with negative FCM and positive cytology (2-14 cells/ul); and 5 with positive FCM <20 clonal cells and negative cytology, 3 out of them with positive microRNAs. None of these patients with occult meningeal involvement relapsed/progressed into CNS within 12 months. In contrast three out of ten control patients (characterized by elevated oncogenic microRNAs in CSF, but negative for FCM and cytology) relapsed to CNS within 6 months after diagnosis. None of ”triple” negative (FCM, cytology, microRNA) patients (N=44) developed clinically manifest CNS involvement.These results suggest that examination of oncogenic microRNA in CSF at diagnosis is more sensitive method than FCM and cytology of CSF to detect the patients with occult CNS involvement and higher risk of CNS involvement and this should be reflected in treatment strategy in further clinical trials.Grants: GACR305 13-12449P, UNCE204021, PRVOUK: P24/LF1/3, P27/LF1/1, P 27/2012 LF3 DisclosuresSpacek:Roche: Consultancy, Travel grants Other.

Concomitant Systemic and Neuro-Meningeal Non-Hodgkin’s Lymphoma: The Role of Consolidation with Intensive Chemotherapy and Autologous Stem Cell Transplantation. a Retrospective Study of 65 Cases

PurposeTo determine the characteristics of Non-Hodgkin’s lymphoma (NHL) patients with concomitant systemic and central nervous system localization at diagnosis, as well as the impact of consolidation with high dose chemotherapy followed by hematopoietic stem cell rescue on outcomePatients and MethodsNewly diagnosed NHL patients with concomitant systemic and cerebral or meningeal involvement at diagnosis have been included in this study. Patients were retrieved from the database of the participating centers of the LYSA and LOC study groupsResultsSixty-five patients (37 males; 28 females) were included. Median age was 60 years (23-85). Histological subtype was mainly diffuse large B-cell lymphoma (n=54; 83%). The IPI was >2 in 43 (66%) patients. LDH level was elevated in 27 (55%) patients. Median number of extranodal positive sites was 2 (1-5) and bone marrow involvement was documented in 30 (46%) patients. CNS involvement was documented in 51 patients. Paravertebral and epidural compressive mass with (n=5) or without (n=2) CSF involvement were present. Five patients had both CNS and peripheral nervous system involvement. Anthracycline-based chemotherapy with high dose metothrexate with or without cytarabine was the most chemotherapy used. Autologous stem cell transplantation was performed in 21 patients in response. BEAM (n=9) or thiotepa-based (n=9) conditioning regimen was the most intensive chemotherapy used before autologous SCTPost-chemotherapy ORR was 77%(CR69%;PR8%). 3-year overall survival (OS) and progression free survival (PFS) were 48±7% and 46±7% respectively. The consolidation strategy using high dose chemotherapy and autologous stem cell transplant positively impacted patient’s outcome. For the whole group as well as for patients ≤65 years, the 3-year OS and PFS were (77%vs29%;p=0.002) and (77%vs25%;p=0.001) and (75% vs 37%;p=0.002) and (75%vs32%;p=0.007) respectively.In multivariate analysis and for the whole group of patients, the absence high dose therapy had a negative impact on 3-year OS and PFS [p=0.003;HR=5.05[1.76-14.49]) and PFS by [p=0.002;HR=5.46(1.91-15.26)] respectively. This is remained true for younger patients 65 years or less who had poorer 3-year OS [p=0.036;HR=3.41 (1.08-10.75)].ConclusionFirst line consolidative high dose therapy followed by autologous SCT in patients with systemic and neuro-meningeal NHL improve patient’s outcome DisclosuresNo relevant conflicts of interest to declare.

Actualités des lymphomes cérébraux primitifs (LCP)

Primary central nervous system lymphomas (PCNSL) in immunocompetent patients have long suffered from their rarity. Biological studies as well as initiation of comparative prospective therapeutic studies have been delayed in this population. A significant improvement in survival was observed when radiotherapy was preceded by chemotherapy with high dose methotrexate (MTX). Median survival improved from 16 months, with radiotherapy alone, to 35-45 months with combined treatments, at the cost of a risk of neurological toxicity especially common among people over the age of 60. From then, many studies have attempted to improve outcomes while reducing the toxicity on the central nervous system. If the optimal treatment is not yet established, these studies, mostly retrospective, provide a better understanding of the therapeutic issues to be addressed. Controversies regarding the impact of monoclonal anti-CD 20 antibodies as well as the role and the best modalities of radiotherapy remain and intensive chemotherapy. The latest imaging techniques provide useful elements to rule out differential diagnosis, but histological diagnosis remains mandatory. The evaluation of therapeutic response needs to be improved. Recent biological studies initiated the biological characterization of PCNSL and potential therapeutic targets are identified. Target therapies used in systemic non-Hodgkin's lymphomas have to be tested in PCNSL. PCNSL occurring in the context of immunosuppression are increasingly rare, especially in human immunodeficiency virus (HIV) infected population. They are well characterized in terms of clinical and biological aspects. Epstein-Barr virus (EBV) plays a major role in their lymphomagenesis. Treatment depends mainly on the underlying cause and degree of immunodepression. Whenever possible, similar treatments to those used in immunocompetent PCNSL patients will be offered to immunocompromised patients.

The Clinical, Histopathological and Imaging Methods Characteristics of Non- Hodgkin Lymphomas in Patients with Brain Involvement

The Non- Hodgkin-lymphoma (NHL) brain infiltration carries a poor prognosis. Because of relatively rare incidence, we decided to share our experience. Retrospective analysis of patients with NHL brain infiltration dia-gnosed in 2001- 2011 at our university hospital. Twenty -seven patients with median age of 61 (range 42- 82) years were analyzed. The primary diffuse large cell B cell lymphoma of CNS was defined in 22/ 27 (81%) patients, in the others systemic NHL was present. Median positivity of the proliferative marker Ki 67 was 80%, the number of NHL lesions 1 (1- 8), diameter 28 × 30 × 29 (11 × 16 × 20 to 85 × 76 × 65) mm. The fundamental finding in brain lymphoma MRI imaging was lesion with predominantly homogenous contrast enhancement, diffusion restriction and collateral edema. Thirteen out of 27 (48%) patients underwent lumbar puncture, and lymphoma presence in fluid was detected in only two of them. The most frequent symptoms were limb paresis or hemiparesis (55%), bradypsichysm (22%), expressive aphasia (22%), cephalea (18%). Corticosteroid therapy, as a primary treatment option, was indicated in 15% of patients with a median overall survival of one month, CNS radiotherapy in 37% with a median survival of three months, and chemotherapy in 48% patients with a median overall survival 10 (2- 45) months. The brain lymphomas are rare and prognostically very unfavorable affection. When specifying brain focal lesions on MRI, it is necessary to consider this etiology and to elect imaging protocols with contrast agents and diffusion weighted sequence. Biopsy should be performed prior to start of corticosteroid therapy. Intensive chemotherapy or radiotherapy indication must be individually considered, and proposed treatment should be initiated immediately with a potential for somewhat prolonged survival.