P14.88 Management of primary CNS lymphomas. Experience of 32 cases

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii55-ii55
Author(s):  
A S Simonyan ◽  
L T Lepsveridze ◽  
Z K Simavonyan ◽  
A A Davtyan ◽  
A D Mikhaylova ◽  
...  
Keyword(s):  
Diagnostic Algorithm ◽  
Complete Removal ◽  
High Dose Chemotherapy ◽  
Effective Dosage ◽  
Cns Lymphoma ◽  
High Dose ◽  
Treatment Regimens ◽  
Immunohistochemical Studies ◽  
Cns Lymphomas ◽  
Histological Verification

Abstract BACKGROUND Lymphomas (primary and secondary) are rare tumors of the central nervous system. They can involve both the supratentorial areas and the posterior cranial fossa. Modern management of patients with suspected CNS lymphoma should include a stereotactic or navigation-guided biopsy and subsequently carrying out chemotherapy and, in rare cases, radiosurgery. MATERIAL AND METHODS We analyzed our experience of the diagnosis and treatment of PCNSL. Our work included 32 patients with PCNSL. The study did not include patients with suspected CNS lymphoma, according to MRI data, in whom the diagnosis was not confirmed after biopsy. RESULTS Thirty patients underwent biopsy (20 - navigation guided, 1 - open, 9 - “burr hole”) with preliminary intraoperative histological verification. Gross total resection was performed in 2 cases since, according to preoperative MRI data, it was assumed that the patient had glial tumors. Postoperative histological examination confirmed the diagnosis of CNS lymphoma in all cases. Subsequently, after detailed histological and immunohistochemical studies, 30 patients underwent intra-arterial chemotherapy or high-dose chemotherapy according to NCCN protocols. Palliative treatment was recommended in 2 cases due to acute deterioration of patients. In our work, we would like to present a diagnostic algorithm and treatment regimens used in the management of our patients. CONCLUSION In the treatment of CNS lymphomas, careful histological verification is required, which is possible if several key points are performed - discontinuation of dexamethasone at least 24 hours before the biopsy, MRI for intraoperative neuronavigation after discontinuation of dexamethasone, intraoperative preliminary histological verification. In our opinion, complete removal of the tumor is possible if there are no risks of developing a persistent neurological deficit. Various methods of opening the blood-brain barrier are currently used, which can significantly reduce the effective dosage of drugs and, accordingly, the side effects. Further research is needed to determine the dependence of the prognosis of the disease on the type of surgery (biopsy or resection).

scholarly journals Therapy of primary CNS lymphoma: role of intensity, radiation, and novel agents

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 565-577 ◽  
Author(s):  
Andrés José María Ferreri
Keyword(s):  
Primary Cns Lymphoma ◽  
High Sensitivity ◽  
High Dose Chemotherapy ◽  
Tumor Burden ◽  
Cns Lymphoma ◽  
High Dose ◽  
Whole Brain Irradiation ◽  
Curative Intent ◽  
Brain Irradiation ◽  
Cns Lymphomas

Abstract Primary central nervous system (CNS) lymphomas represent a subgroup of malignancies with specific characteristics, an aggressive course, and unsatisfactory outcome in contrast with other lymphomas comparable for tumor burden and histological type. Despite the high sensitivity to conventional chemotherapy and radiotherapy, remissions are frequently short lasting. Treatment efficacy is limited by several factors, including the biology and microenvironment of this malignancy and the “protective” effect of the blood-brain barrier, which limits the access of most drugs to the CNS. Patients who survive are at high risk of developing treatment-related toxicity, mainly disabling neurotoxicity, raising the question of how to balance therapy intensification with the control of side effects. Recent therapeutic progress and effective international cooperation have resulted in a significantly improved outcome over the past 2 decades, with a higher proportion of patients receiving treatment with curative intent. Actual front-line therapy consists of high-dose methotrexate-based polychemotherapy. Evidence supporting the addition of an alkylating agent and rituximab is growing, and a recent randomized trial demonstrated that the combination of methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) is associated with a significantly better overall survival. Whole-brain irradiation and high-dose chemotherapy supported by autologous stem cell transplantation are 2 effective consolidation strategies in patients with a disease responsive to induction chemotherapy. Different strategies such as alkylating maintenance, conservative radiotherapy, and nonmyeloablative consolidation are being addressed in large randomized trials and a more accurate knowledge of the molecular and biological characteristics of this malignancy are leading to the development of target therapies in refractory/relapsing patients, with the overall aim to incorporate new active agents as part of first-line treatment. The pros and cons of these approaches together with the best candidates for each therapy are outlined in this article.

scholarly journals SS-4 High dose chemotherapy with autologous hematopoietic stem cell transplantation for CNS lymphoma

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii2-ii2
Author(s):  
Eisei Kondo
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Primary Cns Lymphoma ◽  
High Dose Chemotherapy ◽  
Cns Lymphoma ◽  
High Dose ◽  
Hematopoietic Stem

Abstract High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDT-ASCT) is listed as a consolidation therapy option for primary central nervous system (CNS) lymphoma in the guidelines of western countries. The advantages of HDT-ASCT for primary CNS lymphoma as consolidation are believed to be high rates of long-term remission and lower neurotoxicity, even though its eligibility is limited to younger fit patients. In the Japanese guideline, HDT-ASCT for primary CNS lymphoma is however not recommended in daily practice, mainly because thiotepa was unavailable since 2011. The Japanese registry data for hematopoietic transplantation have shown that primary CNS lymphoma patients were treated with various HDT regimens and thiotepa-containing HDT was associated with better progression free survival (P=.019), lower relapse (P=.042) and a trend toward a survival benefit (Kondo E et al, Biol Blood Marrow Transplant 2019). A pharmacokinetic study of thiotepa(DSP-1958) in HDT-ASCT for lymphoma was conducted in 2017, and thiotepa was approved for HDT-ASCT in lymphoma this March, meaning that optimal HDT regimen for CNS lymphoma is now available in Japan. The treatment strategy of CNS lymphoma needs further development to improve survival and reduce toxicity.

scholarly journals Primary Central Nervous System Lymphoma in Elderly Patients: Management and Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3479
Author(s):  
Andrea Morales-Martinez ◽  
Fernando Lozano-Sanchez ◽  
Alberto Duran-Peña ◽  
Khe Hoang-Xuan ◽  
Caroline Houillier
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Elderly Patients ◽  
Treatment Strategies ◽  
Central Nervous System Lymphoma ◽  
High Dose Chemotherapy ◽  
Current Treatment ◽  
Cns Lymphoma ◽  
High Dose ◽  
Consolidation Phase

The management of elderly patients suffering from primary central nervous system (CNS) lymphoma, who represent a rapidly growing population, is challenging. Despite the advances made in PCNSL treatment, the prognosis in older patients remains unsatisfactory. The high risk of systemic and CNS toxicity induced by a high-dose chemotherapy regimen and radiation therapy, respectively, limits the use of consolidation phase treatments in elderly patients and contributes to the poor outcome of these patients. Here, we review the current treatment strategies and ongoing trials proposed for elderly PCNSL patients.

High-Dose Chemotherapy and Autologous Stem-Cell Transplantation for Primary CNS Lymphoma: Updated Results from a Pilot and Phase II Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3594-3594
Author(s):  
Gerald Illerhaus ◽  
Fabian Müller ◽  
Friedrich Feuerhake ◽  
J.ürgen Finke
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Pilot Trial ◽  
Primary Cns Lymphoma ◽  
High Dose Chemotherapy ◽  
Cns Lymphoma ◽  
High Dose

Abstract Introduction: High-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) demonstrated high efficacy in the treatment of newly-diagnosed primary CNS lymphoma (PCNSL) in younger patients (pts.). A 5-year overall survival probability (OS) of 69% could be demonstrated in 30 pts within a phase-II trial on HDT and ASCT with consolidating whole-brain-irradiation (WBRT) (Illerhaus et al. JCO 2006). A subsequent pilot trial on HDT and ASCT without WBRT showed a 5-year OS of 77% (Illerhaus et al. Haematologica 2008). Here we give an update of our two different treatment regimens and future perspectives. Patients and Methods: Thirty pts. ≤65 years were treated within the phase II trial, chemotherapy (CHT) consisted of 3 cycles of high-dose methotrexate (MTX, 8 g/m2), 1 cycle of AraC (2× 3 g/m2) plus thiotepa (TT, 40 mg/m2) followed by rG-CSF and stem-cell-mobilization. Conditioning regimen included BCNU (400 mg/m2) and TT (2×5 mg/kgBW) followed by ASCT. Hyperfractionated WBRT (45 Gy, 2×1Gy/d) was administered as consolidation. In our subsequent pilot trial 13 pts. (age 38–67 years) were treated without consolidating WBRT; CHT was intensified with 4 cycles MTX 8g/m2, 2 cycles AraC (2× 3 g/m2) and TT (40 mg/m2). Dose escalated HDT included BCNU (400 mg/m2) and TT (4×5 mg/kgBW) followed by ASCT. WBRT was reserved for pts. not responding to CHT. Results: Median follow-up of the 30 pts. treated within our phase II trial was extended to 95 months (mo), the updated 5-year OS of all pts. is 66.6% and 82,3% of the subgroup of pts. who underwent HDT and ASCT (n=23), respectively. Three additional deaths occurred due to relapse (n=2) after 45 and 71 mo and due to comorbidity (n=1) after 103 mo. Five of 30 pts. developed severe leukoencephalopathy during follow-up. With a median follow-up of 35 mo in the 13 pts. treated within the pilot-phase without consolidating WBRT 3-year OS of all pts. is 77%. No further relapse or non-relapse mortality occurred in this pilot-group during. Most recent follow-up data will be presented in detail. Conclusion: Sequential systemic application of high-dose cytostatic agents followed by HDT+ASCT is highly effective as initial therapy for pts. with PCNSL. The restriction of WBRT to refractory disease shows similar OS rates and a decrease in neurotoxicity. In an ongoing multicenter phase-II trial immunotherapy with rituximab is combined with HDT and ASCT to further increase remission rates. A future randomized trial should be focused on the efficacy of consolidation with HDT supported by ASCT.

High-Dose Chemotherapy With Autologous Stem-Cell Transplantation and Hyperfractionated Radiotherapy As First-Line Treatment of Primary CNS Lymphoma

2006 ◽  
Vol 24 (24) ◽  
pp. 3865-3870 ◽  
Author(s):  
Gerald Illerhaus ◽  
Reinhard Marks ◽  
Gabriele Ihorst ◽  
Roland Guttenberger ◽  
Christoph Ostertag ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Clinical Improvement ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Phase Ii ◽  
Primary Cns Lymphoma ◽  
High Dose Chemotherapy ◽  
Cns Lymphoma ◽  
High Dose

Purpose To improve survival and reduce toxicity in primary CNS lymphoma (PCNSL) treatment, we conducted a multicenter phase II study with early high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) followed by hyperfractionated whole-brain radiotherapy (WBRT) for newly diagnosed PCNSL patients younger than 65 years of age. Patients and Methods Chemotherapy included three steps: three cycles of methotrexate (8 g/m2); cytarabine (AraC; two doses of 3 g/m2) and thiotepa (40 mg/m2) followed by stem-cell harvest; HDT with carmustine (400 mg/m2) and thiotepa (two doses of 5 mg/kg body weight) followed by ASCT. WBRT (45 Gy, two doses of 1 Gy/d) was administered for consolidation. Results Thirty patients with PCNSL younger than 65 years of age (median, 54 years; range, 27 years to 64 years) were enrolled (nine pilot-phase; 21 phase II). Twenty-eight patients responded to methotrexate: six patients with complete remission (CR), 15 patients with partial remission (PR), and seven patients with stable disease (SD) with clinical improvement. Of 26 patients proceeding to AraC and thiotepa, 10 patients achieved CR, 14 patients achieved PR, one patient experienced SD with clinical improvement, and one patient suffered disease progression. Twenty-three patients received HDT plus ASCT, resulting in 15 patients with CRs and eight patients with PRs. After WBRT, 21 of 21 patients had CRs. One patient died from liver failure after methotrexate. HDT was well tolerated apart from WHO grade 3/4 cytopenia. With a median follow-up of 63 months (range, 4 months to 84 months), 5-year overall survival probability is 69% for all patients and 87% for the 23 patients receiving HDT plus ASCT. The 5-year probability of relapse-related death is 21% for all patients (n = 30) and 8.7% for patients treated with HDT plus ASCT (n = 23). Conclusion Sequential systemic methotrexate and AraC and thiotepa followed by HDT plus ASCT and hyperfractionated WBRT is very effective with little toxicity as initial therapy for PCNSL.

scholarly journals The treatment of small cell carcinoma of the ovary hypercalcemic type

2011 ◽  
pp. 61-66 ◽  
Author(s):  
Joseph Gerald Pressey
Keyword(s):  
Cell Carcinoma ◽  
Small Cell Carcinoma ◽  
High Dose Chemotherapy ◽  
Small Cell ◽  
High Dose ◽  
Cell Of Origin ◽  
Treatment Regimens ◽  
Stem Cell Rescue ◽  
Multiagent Chemotherapy ◽  
Carcinoma Of The Ovary

Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is an exceedingly rare and poorly characterized tumor with an unknown cell of origin. SCCOHT typically occurs in adolescents and young women with a peak incidence in the third decade of life. The initial description of SCCOHT noted a dismal outcome among patients, particularly those with advanced disease. However, recently published studies indicate that SCCOHT is often amenable to therapy and even in advanced stages potentially curable. Surgery paired with multiagent chemotherapy including platinum-based agents and etoposide are often cited in patients who achieve a complete remission. While reports of successfully treated patients have emerged, the scarcity of prospective clinical trials has slowed the validation of effective treatment regimens. The value of extensive surgery, radiation therapy, and high-dose chemotherapy with autologous stem cell rescue remain uncertain. Insight into the biology underlying SCCOHT is desperately needed to guide the implementation of novel therapeutics in SCCOHT.

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