High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system

Abstract Abstract 1219 Poster Board I-241 Background High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has been evaluated in several trials and has shown feasibility as first-line treatment of primary central nervous system lymphoma (PCNSL). However, the best conditioning regimen is still to be identified and high-dose chemotherapy of busulfan, cyclophosphamide, and etoposide (BuCyE) has not been tried although the regimen was shown to be effective for leukemia and systemic non-Hodgkin's lymphoma. Methods Between May 2005 and November 2008, 12 consecutive patients of PCNSL with pathologic diagnosis of diffuse large-B cell lymphoma were treated with the intent of upfront ASCT at Asan Medical Center, Seoul, Korea. We retrospectively analyzed the results of these patients. The treatment included induction chemotherapy of high-dose methotrexate/cytarabine (Abrey et al., JCO 21:4151, 2003), followed by BuCyE chemotherapy consisting of iv busulfan (3.2mg/kg from day -7 to day -5), iv cyclophosphamide (50mg/kg from day -3 to day -2), and etoposide (200mg/m2 every 12 hours from day -5 to day -4), and ASCT. Whole brain radiotherapy (WBRT) was reserved for patients who failed to achieve complete response (CR) after ASCT. Results Median age was 50 years (range, 33-65) and 9 were male. The test of cerebrospinal fluid (CSF) cytology came out to be positive for 3 patients. Eight patients achieved CR and 4 gained partial response (PR) after induction chemotherapy. All 12 patients managed to complete ASCT. Following ASCT, additional 2 patients gained CR, resulting in total number of 10 patients (83.3%). Patients who failed to reach CR were further treated with WBRT and 2 more patients achieved CR. Median duration of first CR was 12.8 months (95% confidence interval [CI], 4.6-20.9) at a median follow-up of 23.8 months (range, 8.8-50.7). Relapse of disease occurred in 7 patients (58.3%) and 5 of them were given salvage treatment (Table 1). Two patients could regain CR and sustained remission for more than 2 years. Two patients had died of disease at the time of analysis. Median event-free survival (EFS) from the first day of induction chemotherapy was 15.0 months (95% CI, 8.3-21.8) and median overall survival (OS) was not reached. The 2-year OS probability was 78.8% and 2-year EFS was 25.7%. No patient experienced veno-occlusive disease or treatment-related mortality (TRM). Three patients among those who were treated with WBRT or intrathecal chemotherapy developed leukoencephalopathy. Conclusion BuCyE chemotherapy might be an option of conditioning regimen for ASCT considering high CR rate of 83.3% and favorable toxicity profile in the treatment of PCNSL. However, high relapse rate of 58.3% suggests that more optimization of induction and conditioning chemotherapy is still required. Disclosures No relevant conflicts of interest to declare.

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High Efficiency of ICE (Ifosfamide-Carboplatin-Etoposide) in Relapse/Refractory Primary Central-Nervous System and Intra-Ocular Non Hodgkin Lymphoma, After First Line Treatment Containing High Doses of Methotrexate and Cytarabine. A Monocentric Retrospective Study From 2010 to 2012 On 17 Cases

Blood ◽

10.1182/blood.v120.21.3664.3664 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3664-3664 ◽

Cited By ~ 1

Author(s):

Sylvain Choquet ◽

Damien roos Weil ◽

Khe Hoang Xuan ◽

Nathalie Cassoux ◽

Helene Merle-Beral ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Hodgkin Lymphoma ◽

Salvage Chemotherapy ◽

High Dose ◽

Line Treatment ◽

First Line ◽

Non Hodgkin Lymphoma ◽

High Doses ◽

First Line Treatment

Abstract Abstract 3664 Background: Primary central nervous system lymphoma (PCNSL) and primary intra-ocular lymphoma (PIOL) are at very high risk of relapse after a first line treatment, and then carry a very poor prognosis. Autologous stem cell transplantation (ASCT) can offer prolonged responses but its results clearly depend on efficiency of salvage chemotherapy (Soussain, haemtologica, 2012). Since recent publications on first line treatment of PCNSL and PIOL recommend high dose methotrexate (Mtx) and cytarabine (AraC) (Ferreri, Lancet 2009), salvage chemotherapy must use other drugs with high level of penetration in the central nervous system (CNS). In this setting, ICE regimen, validated in systemic non Hodgkin lymphoma, seems to be appropriated but no data is published in PCNSL and PIOL. Methods: From june 2010 to may 2012, all relapse/refractory PCNSL and PIOL treated in first line by high doses of Mtx and AraC in the Pitie-Salpetriere Hospital, Paris, France, where treated by ICE regimen : ifosfamide (5g/m2 at day 2), carboplatine (AUC 5 at day 2) and etoposide (100mg/m2/d days 1 to 3). Doses where adapted on patient general status and ASCT proposed when possible. Results: Seventeen patients have been treated, 7 females and 10 males, median age 62 [28–84]. Four where refractory and 13 in relapse, with a mean progression free survival (PFS) of 368 days [85–1763], 4 had a second line, one a third before ICE. At moment of ICE treatment, localizations where 10 CNS, 2 CNS + PIOL, 3 PIOL and 2 meningitis. The mean number of cycles was 4 [1–6] and 4 patients needed a dose reduction. During treatment, grade 3/4 WHO toxicities where: 6 neutropenic fever (one death), 5 anemia, 9 neutropenia, 10 thrombopenia and one CNS complication (coma and hypersalivation). ASCT have been made in 6 patients (5 in CR, 1 in PR) and are pending in 3. Complete response (CR) have been obtained in 13 patients (76%), partial in 2. With a mean follow-up of 405 days, 6/15 patients in response relapsed (only one after ASCT), in a median of 81 days, 9 patients died (7 by progression, one during treatment and one in CR). Median Overall survival (OS) was 220 days for all patients but was not reached in case of ASCT. Conclusion: ICE regimen is very effective in relapse/refractory PCNSL and PIOL heavily treated by high dose Mtx and AraC. This efficacy can allow to perform ASCT in eligible patients, chemosensitivity being the most important factor influencing the OS and PFS after ASCT. ICE can represent a new standard in this setting. Disclosures: Leblond: Roche: Advisory Board Other, Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; Janssen-Cilag: Honoraria.

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The results of multicenter treatment of atypical teratoid/rhabdoid tumors of the central nervous system in children under 3 years

Pediatric Hematology/Oncology and Immunopathology ◽

10.24287/1726-1708-2021-20-2-121-132 ◽

2021 ◽

Vol 20 (2) ◽

pp. 121-132

Author(s):

L. V. Olkhova ◽

O. G. Zheludkova ◽

L. S. Zubarovskaya ◽

A. Yu. Smirnova ◽

Yu. V. Dinikina ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Radiation Therapy ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

High Dose Chemotherapy ◽

High Dose ◽

Hematopoietic Stem ◽

Atypical Teratoid ◽

The Central Nervous System

Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system (CNS) is an aggressive malignant tumor that is mainly found in younger children and is associated with poor prognosis. Our objectives: to present the results of treatment of children with CNS AT/RT under 3 years of age and assess the impact of various prognostic factors on patient survival. The study was approved by the Independent Ethics Committee and the Scientific Council of the N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation. The study included 106 patients with CNS AT/RT aged 0–3 years who had been treated and monitored from 2008 to 2020. The median age was 16 (9; 23) months. All the patients underwent primary tumor resection with subsequent chemotherapy according to various protocols. At the time of the analysis, 47 patients (44.4%) were alive, 1 patient (0.9%) was lost to follow-up and 58 patients (54.7%) were dead, of whom 52 patients (90%) had died of disease progression and 6 (10%) – of polychemotherapy complications. One patient developed shunt-related intraabdominal metastasis within 10 months of the diagnosis. The 1-year progression-free survival (PFS) was 0.50; the 2-year PFS was 0.29; the 5-year PFS – 0.27. The median PFS was 12 months. The 1-year overall survival (OS) was 0.72; the 2-year OS was 0.53; the 5-year OS – 0.40. The median OS was 27 months. An analysis of patients with CNS AT/RT under 3 years of age showed that PFS was statistically significantly higher in: children aged > 12 months; children with totally resected tumours; children who had received polychemotherapy in accordance with the ATRT-2006 protocol that included radiotherapy and regional administration of a triplet of chemotherapeutic agents. The OS in patients with CNS AT/RT aged < 3 years was statistically significantly higher in: children aged > 12 months; children who had been treated with radiation therapy; patients who had received cytosar/etoposide intrathecally/intraventricularly; patients who had undergone high-dose chemotherapy with subsequent autologous hematopoietic stem cell transplantation. A multivariate analysis revealed that PFS was influenced by age, tumor location, extent of resection and exposure to radiation therapy, regional chemotherapy or high-dose chemotherapy with autologous hematopoietic stem cell transplantation, while OS was affected by age and exposure to radiation therapy.

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