Intensive chemotherapy with thiotepa, busulfan and cyclophosphamide and hematopoietic stem cell rescue in relapsed or refractory primary central nervous system lymphoma and intraocular lymphoma: a retrospective study of 79 cases

Soussain, Carole; Choquet, Sylvain; Fourme, Emmanuelle; Delgadillo, Daniel; Bouabdallah, Krimo; Ghesquières, Hervé; Damaj, Gandhi; Dupriez, Brigitte; Vargaftig, Jacques; González, Alicia; Houillier, Caroline; Taillandier, Luc; Hoang-Xuân, Khê; Leblond, Véronique

doi:10.3324/haematol.2011.060434

Cited by 94 publications

(81 citation statements)

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“…16,[22][23][24][25] In a multicenter phase-2 study (N 5 43), 16 TBC was used following a cytarabine/etoposide (CYVE) salvage chemotherapy, achieving PFS of 12 months and OS of 18 months. Among transplanted patients (N 5 27), PFS was 41 months.…”

Section: Discussionmentioning

confidence: 99%

R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma

Omuro¹,

Correa²,

DeAngelis³

et al. 2015

Blood

287

270

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• We conducted a phase-2 study in newly diagnosed PCNSL utilizing R-MPV and HDC with ASCT.• Excellent disease control and OS (2-year PFS: 79%) were observed, with an acceptable toxicity profile and minimal neurotoxicity.High-dose methotrexate-based chemotherapy is the mainstay of treatment of primary central nervous system lymphoma (PCNSL), but relapses remain frequent. High-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT) may provide an alternative to address chemoresistance and overcome the blood-brain barrier. In this single-center phase-2 study, newly diagnosed PCNSL patients received 5 to 7 cycles of chemotherapy with rituximab, methotrexate (3.5 g/m 2 ), procarbazine, and vincristine (R-MPV). Those with a complete or partial response proceeded with consolidation HDC with thiotepa, cyclophosphamide, and busulfan, followed by ASCT and no radiotherapy. Primary end point was 1-year progression-free survival (PFS), N 5 32. Median age was 57, and median Karnofsky performance status 80. Following R-MPV, objective response rate was 97%, and 26 (81%) patients proceeded with HDC-ASCT. Among all patients, median PFS and overall survival (OS) were not reached (median follow-up: 45 months). Two-year PFS was 79% (95% confidence interval [CI], 58-90), with no events observed beyond 2 years. Two-year OS was 81% (95% CI, 63-91). In transplanted patients, 2-year PFS and OS were 81%. There were 3 treatment-related deaths. Prospective neuropsychological evaluations suggested relatively stable cognitive functions posttransplant. In conclusion, this treatment was associated with excellent disease control and survival, an acceptable toxicity profile, and no evidence of neurotoxicity thus far. This trial was registered at www.clinicaltrials.gov as NCT00596154. (Blood. 2015;125(9):1403-1410 IntroductionMore than 90% of patients with primary central nervous system lymphoma (PCNSL) display a diffuse large B-cell lymphoma (DLBCL) phenotypic subtype, but standard DLBCL regimens such as cyclophosphamide, doxorubicin, vincristine and prednisone and variations are ineffective in this disease.1,2 This has been explained by poor penetration of these agents across the blood-brain barrier (BBB), a problem that has been partially addressed with the development of high-dose methotrexate-based regimens (HD-MTX) that result in therapeutic central nervous system (CNS) and cerebrospinal fluid (CSF) levels after rapid infusions of 1.5 to 8 g/m 2 . 3-5 Such high methotrexate doses are made possible with the concomitant use of leucovorin, which prevents bone marrow and systemic organ damage, while limiting rescue of lymphoma cells in the CNS because it has poor BBB penetration. This clever strategy, used with or without wholebrain radiotherapy (WBRT), has resulted in remarkable survival improvements, with recent studies reporting median overall survival (OS) of 31 to 79 months, 6-13 as compared with 12 months observed with WBRT alone.14 In spite of these improvements, early and late relapses remain frequent, and the majority of pa...

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Section: Discussionmentioning

confidence: 99%

R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma

Omuro¹,

Correa²,

DeAngelis³

et al. 2015

Blood

287

270

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“…BEAM regimen, mostly used in sNHL, and thiotepa-based regimens, mostly used in primary CNS lymphoma (PCNSL), have been reported along with TBI or busulfan-based regimens. Thiotepa, busulfan, cyclophosphamide (TBC) regimen has demonstrated excellent activity in relapse PCNSL 18 as well as in first-line PCNSL or in sCNSL.…”

Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 99%

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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“…The TBuCy regimen is a widely approved regimen for CNS lymphoma, allowing long-term disease control even in diseases refractory to chemotherapy [7]. Moreover, this regimen is associated with acute toxicities (particularly neutropenic fever and infection) responsible of a 5-7% toxicity-related mortality, but is not associated with acute or late neurological toxicities [8,9]. In our case, we observed a rapid neurological response after autologous transplant, as attested by mechanical ventilation withdrawn and gradual improvement of motor functions, suggesting that her neurological symptoms were mostly lymphoma-related.…”

Section: Discussionmentioning

confidence: 99%

Spinal cord involvement in a Burkitt lymphoma patient

Quentin-Gondard¹,

Legoff²,

Edjlali³

et al. 2017

Cancer Rep Rev

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Intensive chemotherapy with thiotepa, busulfan and cyclophosphamide and hematopoietic stem cell rescue in relapsed or refractory primary central nervous system lymphoma and intraocular lymphoma: a retrospective study of 79 cases

Cited by 94 publications

References 9 publications

R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma

R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma

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

Spinal cord involvement in a Burkitt lymphoma patient

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