Concomitant systemic and central nervous system non-Hodgkin lymphoma: the role of consolidation in terms of high dose therapy and autologous stem cell transplantation. A 60-case retrospective study from LYSA and the LOC network

Abstract

© F e r r a t a S t o r t i F o u n d a t i o nto report on the therapeutic characteristics of these patients as well as on the role of high-dose therapy and autologous stem cell transplantation in these settings. Methods Study designPatients with histologically confirmed diagnosis of nonHodgkin lymphoma (NHL) made between May 2002 and January 2012 with concomitant systemic and neurological involvement were retrieved from the database of the participating centers, from The Lymphoma Study Association (LYSA) database and the French network for oculocerebral lymphoma (LOC).In accordance with the Declaration of Helsinki, approval of the University Hospital of Amiens Nord-Ouest II Ethics Committee was obtained. Patient eligibilityPatients 18 years or older with an sNHL diagnosis with nervous system involvement were eligible for this study. Diagnosis of NHL was made according to international diagnostic criteria used at the time of diagnosis. Diagnosis of systemic lymphoma was done on lymph nodes or using tissue biopsies. Nervous system involvement was defined by brain parenchyma, intra-ocular, cranial nerve, or meningeal involvement, as well as paravertebral mass and CSF involvement with lymphoma cells. Diagnosis was based on positive cerebrospinal fluid (CSF) cytology or immunophenotyping or by biopsy-proven parenchymal brain localization. Patients with CNS localization based on a typical CT-scan and/or magnetic resonance imaging (MRI) and concurrent sNHL were included as well. Treatment and assessmentsAt base-line assessments of patients and disease included ECOG score, Ann Arbor stage, international prognostic index (IPI), lactate dehydrogenase (LDH) level, bone marrow histology, CSF cytological and/or flow cytometry analysis, CT-scan of the thorax, abdomen and pelvis. Cerebral and vertebral CT-scan and/or MRI were also recorded. G. Damaj et al. 1200haematologica | 2015; 100(9) marrow, bones, spleen, liver, breast, testis, adrenal glands, ovaries, gastro-intestinal tract, lungs and parotid gland; intraventricular, parenchymal, meningeal, cranial © F e r r a t a S t o r t i F o u n d a t i o nThe type of chemotherapy administered, total dose of drugs per cycle and the use of high-dose therapy as well as radiotherapy were retrieved from the original patient files.Response assessment was performed by the on-site referent physician according to the International Working Group Criteria (IWC) for sNHL and the International Primary CNS Lymphoma Collaborative Group for CNS disease. 7,8 Statistical analysisQuantitative variables were expressed as mean±standard deviation or as median [range] and qualitative variables as percentages. The Student or Wilcoxon test was used for comparison of quantitative variables between two groups. χ 2 or Fisher's test were used to compare categorical variables. Overall survival (OS) was defined as the time between diagnosis and the date of death or last follow up. Univariate standard and time-varying (for intensive therapy) Cox models were used to assess prognostic factors for...

Treatment of initial parenchymal central nervous system involvement in systemic aggressive B-cell lymphoma

“…Notably, patients who obtain a CR have an excellent outcome and probably will not benefit from additional high dose therapy, especially those patients with a low IPI at start. This challenges the role of consolidation as suggested by the French lymphoma group LYSA, that showed a positive impact of high-dose therapy followed by autologous stem cell transplantation on 3year OS and PFS [12]. However, in our series 7 of 21 patients (33%) received consolidative radiotherapy.…”

“…Given its rarity, data on treatment for sysCNS B-NHL are sparse and there is no established standard of care. Recent data from two studies suggest a beneficial effect of intensive chemotherapy followed by ASCT [12,13]. In both studies, ASCT was only offered to patients in complete remission (CR) (31%-50%).…”

Treatment of diffuse large B‐cell lymphoma with secondary central nervous system involvement: encouraging efficacy using CNS‐penetrating R‐IDARAM chemotherapy

“…Few reports have concentrated on these patients. A French group recently published the outcomes of 60 heterogeneously‐treated patients with SCNSL at time of diagnosis (90% DLBCL) and reported a 3‐year PFS of 42% and OS 44% (Damaj et al , ): in the present study the 5‐year PFS was 50% and 5‐year OS 75%. In the French study, >50% of patients were initially treated with R‐CHOP + HD MTX + Ara‐C.…”

“…An early study in 24 patients receiving ASCT after CNS relapse of lymphoma showed disappointing results, with only 4 long-term survivors amongst transplant recipients (van Besien et al, 1998). More recently, encouraging results have been demonstrated in patients transplanted in first CR (Cote et al, 2012) and in first or second CR (Ferreri et al, 2014;Chen et al, 2014;Oh et al, 2015;Ferreri et al, 2015b;Damaj et al, 2015;Korfel et al, 2013;Doorduyn et al, 2012). The Centre for Blood and Bone Marrow Transplant Research group recently published data suggesting that outcomes following ASCT were similar in NHL patients with prior CNS involvement and a risk-matched cohort of patients without prior CNS disease, and suggested that high-dose therapy could overcome the adverse impact of this presentation in patients reaching transplant.…”

High‐dose therapy and autologous stem cell transplantation may only be applicable to selected patients with secondary CNS diffuse large B‐cell lymphoma

“…Our findings were consistent with other investigators who have reported markedly improved OS among those with responsive disease who ultimately proceeded to ASCT in retrospective series. (Maziarz et al , ; Damaj et al , ) Three prospective studies have evaluated ASCT in SCNSL. Ferreri et al () treated 38 patients with aggressive B‐cell lymphoma and CNS involvement (16 at initial lymphoma presentation).…”