First‐line autologous stem cell transplantation in primary CNS lymphoma

Brevet, Marie; Garidi, Réda; Gruson, Bérengère; Royer, Bruno; Vaida, Ioana; Damaj, Gandhi

doi:10.1111/j.1600-0609.2005.00508.x

Cited by 54 publications

(37 citation statements)

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“…In other studies, brain irradiation was systematically used after BEAM + ASCT, thus making the role of ASCT difficult to assess. 23,24 In sCNSL, BEAM and similar regimen has been used in 70 patients (46%) and TBI-based conditioning regimen in 35 patients (23%) by Marziaz et al 9 A prospective study was conducted by the HOVON group for patients in CNS relapse of an sNHL and treated with R-DHAP MTX followed by IC consisting of busulfan and cyclophosphamide. Results were disappointing with a median PFS of only six months.…”

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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

et al. 2015

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© 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...

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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

et al. 2015

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“…The other 4 patients were alive without relapse or neurotoxicity, but the study had a small number of patients and relatively short follow-up. 31 Cheng and colleagues 32 evaluated 7 patients with PCNSL with at least one poor prognostic factor (poor performance status, age > 60 years or relapsed disease). These patients were treated with high-dose MTX-based chemotherapy followed by consolidation with thiotepa-busulfancyclophosphamide and ASCT, without WBRT.…”

Section: Autologous Stem-cell Transplantmentioning

confidence: 99%

“…In two sequential studies, Bessell and colleagues 13 studied the effect of a reduced dose of RT in patients with PCNSL after achieving a complete response (CR) with chemotherapy. After chemotherapy, 31 patients from the first study received 45 Gy WBRT. In the second study, the RT dose was reduced to 30.6 Gy in 26 patients who had a CR after chemotherapy.…”

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An Update on Therapy of Primary Central Nervous System Lymphoma

DeAngelis¹,

Iwamoto²

2006

Hematology

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The most important advance in primary central nervous system (CNS) lymphoma treatment has been the convincing data that high-dose methotrexatebased chemotherapy regimens improve survival compared to historical controls treated with radiotherapy alone. However, the optimal treatment approach is still unclear and therapy can be associated with long-term neurotoxicity. Current research focuses on maximizing survival while minimizing neurologic sequelae.Primary central nervous system lymphoma (PCNSL) is an extranodal non-Hodgkin lymphoma (NHL) that arises from the brain parenchyma, eyes, meninges or spinal cord in the absence of systemic disease. Recent clinical trials have focused increased interest on this cancer, particularly because of its chemosensitivity compared to other primary brain tumors. Prognostic FactorsBaseline prognostic factors have a strong influence on the outcome of patients with PCNSL.1 The most consistent prognostic factors among several studies are age and performance status.1,2 Ferreri and colleagues 3 analyzed 378 patients retrospectively from a multicenter series and identified five prognostic factors that were associated with worse survival: 1) age more than 60 years; 2) ECOG performance status more than 1; 3) elevated serum lactate dehydrogenase level; 4) high CSF protein; and 5) involvement of deep regions of the brain. 3 An analysis of 338 patients from Memorial Sloan-Kettering Cancer Center could identify age and Karnofsky performance status (KPS) as the only significant prognostic factors; the other three failed to reach significance. 4 Molecular markers have been identified as a prognostic factor for lymphomas. Rosenwald and colleagues 5 identified three molecularly distinct forms of systemic diffuse large B-cell lymphoma (DLCL) based on gene expression patterns: germinal center-like, the activated B-cell-like (ABC) and the so-called type III. Patients with germinal center B-cell-like DLCL have a significantly better overall survival that is independent from clinical prognostic factors compared to patients with the activated B-cell-like DLCL. Initial studies showed that PCNSL had a germinal center B-cell origin. 6 However, a recent study of 83 biopsy specimens from patients with PCNSL showed that 96.3% were classified as activated B-cell-like DLCL by immunohistochemical markers. 7 Further studies are needed to clarify the importance of DCLC subtypes as prognostic factors in PCNSL. TreatmentHistorically, PCNSL was treated with radiotherapy (RT) alone, which produces an initial response in most patients. However, disease recurrence was very high and long-term survival was dismal. The addition of standard therapy for systemic NHL, such as cyclophosphamide-doxorubicinvincristine-prednisone (CHOP), was associated with only transient response and added no survival benefit over RT alone.8 This likely reflects the poor penetration of cyclophosphamide, doxorubicin and vincristine through the blood-brain barrier.The most important advance in PCNSL treatment has been the convincing data that hi...

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“…2,6 Clearly, TEAM is a variation of BEAM, with the primary differences being replacement of carmustine with thiotepa and modification to etoposide and/or cytarabine doses, depending on the comparator BEAM regimen. 7,8 Indeed, at the doses employed, carmustine penetrates the blood --brain barrier into the central nervous system most avidly in the four-drug BEAM regimen. 6 However, the replacement of carmustine with thiotepa resulted from concerns over pulmonary toxicity and not out of any benefit in blood brain barrier penetration with thiotepa.…”

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“…In the two largest trials, only 50 --77% of patients enrolled progressed through induction to receive autologous HSCT, with many patients dropping out due to toxicity. 7,8 PCNSL is a disease that necessitates swift and effective therapy. Collaboratively, we must re-double the efforts to elucidate new and effective therapies, including optimizing HSCT in this patient population.…”

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Putting caution in TEAM: high-dose chemotherapy with autologous HSCT for primary central nervous system lymphoma

Tombleson

Green

Fancher

2012

Bone Marrow Transplant

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We read with great interest the recent manuscript on treatment of primary central nervous system lymphoma (PCNSL) with highdose chemotherapy followed by autologous hematopoietic SCT. 1 The authors highlight several important issues regarding the difficulties with treating this disease. Indeed, a recent review of clinical experience with PCNSL concluded that high-dose chemotherapy ± whole-brain radiotherapy followed by autologous HSCT holds promise to improve patient outcomes. 2 Although this latest review of PCNSL is thought-provoking, we find discrepancies that may confound the authors' conclusions.As acknowledged by the authors, there is a great heterogeneity of both induction and conditioning regimens employed in studies for newly-diagnosed PCNSL. 2 Bearing in mind not only the variations in chemotherapy regimens, but also the variations of survival seen in these studies, we are surprised to find the authors' conclusion of superiority with 'thiotepa/busulfan based conditioning' and recommendation of this strategy as a 'suggested treatment approach in patients with PCNSL'. 1 Although these two agents may have a role in conditioning for autologous HSCT to treat newly-diagnosed PCNSL, the scarcity of data makes their role ill-defined. 2 The majority of conditioning regimens employed in studies on newly-diagnosed PCNSL do not contain thiotepa and fewer still contain BU. 2 The total number of patients with newlydiagnosed PCNSL who had received a BU and thiotepa-based conditioning regimen before autologous HSCT was 53, a number far too small to use as the basis for an algorithm for the treatment of newly-diagnosed PCNSL patients. 3,4,5 Additionally, we express our trepidation regarding the authors' preferred multi-agent conditioning regimen of thiotepa, etoposide, cytarabine, and melphalan (TEAM). The only agent in this regimen that has appreciable blood --brain barrier penetration at the doses referenced is thiotepa, even in patients with impaired blood --brain barrier due to PCNSL. 6 Minimal improvements in survival were seen when using BEAM as a conditioning regimen for newly-diagnosed PCNSL following a high-dose MTX-based induction regimen, a finding attributed to lack of dose intensity in the central nervous system from etoposide, cytarabine and melphalan. 2,6 Clearly, TEAM is a variation of BEAM, with the primary differences being replacement of carmustine with thiotepa and modification to etoposide and/or cytarabine doses, depending on the comparator BEAM regimen. 7,8 Indeed, at the doses employed, carmustine penetrates the blood --brain barrier into the central nervous system most avidly in the four-drug BEAM regimen. 6 However, the replacement of carmustine with thiotepa resulted from concerns over pulmonary toxicity and not out of any benefit in blood brain barrier penetration with thiotepa. 9 It stands to reason that similar outcomes would be expected with the use of TEAM compared with those, which have historically been seen with BEAM. Inexplicably, the authors' preference given to the TEAM conditioning...

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First‐line autologous stem cell transplantation in primary CNS lymphoma

Cited by 54 publications

References 18 publications

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

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

An Update on Therapy of Primary Central Nervous System Lymphoma

Putting caution in TEAM: high-dose chemotherapy with autologous HSCT for primary central nervous system lymphoma

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