scholarly journals Alternative Consolidation Strategy after High Dose Methotrexate, Rituximab and Temozolamide in Primary CNS Lymphoma - the Henry Ford Experience

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 5-5
Author(s):  
Joyce Philip ◽  
Shivani Sharma ◽  
Vijayalakshmi Donthireddy
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Primary Cns Lymphoma ◽  
Autologous Stem Cell Transplant ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

Background: Treatment for primary CNS lymphoma involves a methotrexate-based induction therapy followed by consolidation. The optimal consolidation treatment after induction with a high dose Methotrexate (HD-MTX), Rituximab and Temozolomide regimen has not been fully established. The CALGB 50202 regimen using Etoposide and Cytarabine consolidation was associated with significant toxicity. We sought to review the results of alternative consolidation regimens and evaluate the progression free survival and overall survival. Methods: A retrospective cohort study was conducted to evaluate the efficacy of alternative consolidation regimens such as autologous stem cell transplant and HDMTx alone. Patients diagnosed with primary CNS lymphoma between November 2012 and March 2019 were identified. All patients received the same induction chemotherapy based on the CALGB 50202 protocol. Data was collected for baseline characteristics, progression free survival and overall survival. Results: 38 patients had a diagnosis of primary CNS lymphoma. 15 patients received treatment as per the CALBG 50202 induction protocol with high dose Methotrexate, Rituximab and Temozolomide. Of the 15 patients, 11 patients (69%) achieved a complete remission (CR) after induction therapy. 7 patients received an autologous stem cell transplant for consolidation, 5 patients received HD-MTX alone for consolidation and one patient was placed on Lenalidomide maintenance. 2 patients did not receive any consolidation therapy due to progressive disease and/or death. At a median follow up of 2.7 years for the entire cohort, median PFS was 31.7+ months and median OS was 32.5+ months. At a median follow up of 2.7 years for patients who were consolidated with an autologous stem cell transplant, median PFS and median OS was 27.2+ and 32.5+ months respectively. At a median follow up of 5.5 years for patients who were consolidated with treatments other than transplant, median PFS and OS was 65.6+ months. There were no deaths attributed to treatment related toxicity. To date, 4 patients of the entire cohort have died, with a median survival time among surviving patients of 3.6 years (range, 0.68-7.05 years). There were no deaths attributed to treatment related toxicity. Conclusion: Patients with primary CNS lymphoma who received induction therapy as per CALGB 50202 regimen and received alternative consolidation therapies with either autologous stem cell transplant or HD-MTX based consolidation achieved prolonged PFS and OS comparable if not superior to the Etoposide and Cytarabine consolidation. Results of the ongoing CALGB 51101 trial will determine the utility of EA consolidation. Disclosures No relevant conflicts of interest to declare.

Improved Survival for Patients Undergoing Autologous Stem Cell Transplant for Primary CNS Lymphoma in First or Later Remission.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1222-1222 ◽  
Author(s):  
Patrick B Johnston ◽  
Ivana N Micallef ◽  
Stephen M Ansell ◽  
David J Inwards ◽  
Luis F. Porrata ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Primary Cns Lymphoma ◽  
Autologous Stem Cell Transplant ◽  
Cns Lymphoma ◽  
Cell Transplant ◽  
Additional Therapy

Abstract Abstract 1222 Poster Board I-244 Background Survival for patients with primary CNS lymphoma (PCNSL), in general, is poor with patients requiring frequent chemotherapy treatments or receiving whole-brain radiation therapy, which can potentially result in significant neurologic decline and dementia. Because of the improved survival of high risk patients with aggressive lymphoma undergoing autologous stem cell transplant (ASCT), we began ASCT for patients with PCNSL in first or later remission with chemotherapy sensitive disease. We now update on outcomes of patients who have had at least 100 day follow up post ASCT. Baseline characteristics Between June, 2000 and January, 2009, 22 patients underwent ASCT for PCNSL. Median age at transplant was 50 years old (range 26-67). Median number of prior treatments 1 (range 1-3). Median time from diagnosis to transplant was 7.2 months (range 2.9 to 75.8). Median International Extranodal Working Study Group Prognostic Score: 2 (range 0-3). Disease status at transplant: First CR 10 patients, later CR or PR 12 patients. Results Twenty-two patients underwent ASCT for PCNSL and have a minimum of 100 days follow-up. All patients received BEAM conditioning. Median follow up post-transplant was 30 months (range 3-107 months). Eight patients have relapsed at a median of 217 days (range 40-1349). Of the patients who relapsed, four have died of disease progression and the remaining four are alive after additional therapy. Median overall survival from diagnosis or transplant has not been reached. Median progression free survival from transplant was 70 months. Conclusions Although limited by patient selection and retrospective biases, this review suggests that ASCT for PCNSL demonstrates improved overall survival when compared to historical controls with similar PCNSL Prognostic Scores (2 year survival for patients from diagnosis with PS 2-3 was 48% in a prior published study). ASCT in first remission in patients with PCNSL appears promising and may limit the need for additional therapy which can be myelosuppressive or result in neurologic decline secondary to radiation therapy in patients who are appropriate candidates. Disclosures No relevant conflicts of interest to declare.

Autologous stem cell transplant for primary CNS lymphoma results in prolonged progression free and overall survival

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7623-7623
Author(s):  
P. B. Johnston ◽  
B. P. O’Neill ◽  
S. M. Ansell ◽  
D. J. Inwards ◽  
L. F. Porrata ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Primary Cns Lymphoma ◽  
Autologous Stem Cell Transplant ◽  
Cns Lymphoma ◽  
Cell Transplant ◽  
Free Survival ◽  
Additional Therapy

7623 Background: Survival for patient with primary CNS lymphoma (PCNSL), in general, is poor with patients requiring frequent chemotherapy treatments or receiving whole-brain radiation therapy, which can potentially result in significant neurologic decline and dementia. Because of the improved survival of high risk patients with aggressive lymphoma undergoing autologous stem cell transplant (ASCT), we began ASCT for patients with PCNSL in first or later remission with chemotherapy sensitive disease. We now report on outcomes of patients who have had at least 1 year follow up post ASCT. Methods: Between June, 2000 and September, 2004, 11 patients underwent ASCT for PCNSL. The medical records of consenting patients were abstracted for the following information. Median age at transplant was 47 years old (range 30–67). Median number of prior treatments 1 (range 1–3). Median time from diagnosis to transplant was 7.5 months (range 2.9 to 75.8). Median International Extranodal Working Study Group Prognostic Score: 2 (range 0–3). Disease status at transplant: First CR 5 patients, later CR or PR 6 patients. Results: Eleven patients underwent ASCT for PCNSL and have a minimum of 1 year follow-up. All patients received BEAM conditioning. Median follow up was 28.3 months. Four patients have relapsed at a median of 200 days (range 40–523). Of the patients who relapsed, one has died of disease progression and the remaining three are alive after additional therapy. Median overall survival and progression free survival from transplant have not been reached. Two year overall and event free survival are 89% and 61%, respectively. Conclusions: Although limited by patient selection and retrospective biases, this review suggests that ASCT for PCNSL demonstrates improved overall survival when compared to historical controls with similar PCNSL Prognostic Scores (2 year survival for patients from diagnosis with PS 2–3 was 48% in a prior published study). ASCT in first remission in patients with PCNSL appears promising and may limit the need for additional therapy which can be myelosuppressive or result in neurologic decline. No significant financial relationships to disclose.

scholarly journals Age-adjusted high-dose chemotherapy and autologous stem cell transplant in elderly and fit primary CNS lymphoma patients

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Elisabeth Schorb ◽  
Juergen Finke ◽  
Gabriele Ihorst ◽  
Benjamin Kasenda ◽  
Heidi Fricker ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Primary Cns Lymphoma ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cell Transplant

scholarly journals High-dose chemotherapy and autologous stem cell transplant in elderly patients with primary CNS lymphoma: a pilot study

2020 ◽  
Vol 4 (14) ◽  
pp. 3378-3381
Author(s):  
Elisabeth Schorb ◽  
Benjamin Kasenda ◽  
Gabriele Ihorst ◽  
Florian Scherer ◽  
Julia Wendler ◽  
...  
Keyword(s):  
Stem Cell ◽  
Elderly Patients ◽  
Stem Cell Transplant ◽  
Primary Cns Lymphoma ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Key Points

Key Points Age-adapted high-dose chemotherapy and autologous stem cell transplantation is safe and highly effective in elderly patients with PCNSL.

Combination Therapy with BCNU/Etoposide/Melphalan (BEM) as Conditioning Regimen for Autologous Stem Cell Transplant In Multiple Myeloma.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4587-4587
Author(s):  
Shanshan Liu ◽  
Ann Mohrbacher ◽  
Dan Douer ◽  
Vishesh R Kothary ◽  
Lisa Hanna ◽  
...  
Keyword(s):  
Body Weight ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Conditioning Regimen ◽  
Autologous Stem Cell Transplant ◽  
Bone Lesions ◽  
High Dose ◽  
Cell Transplant ◽  
Lytic Bone Lesions

Abstract Abstract 4587 Background: High-dose chemotherapy and autologous stem cell transplant (ASCT) remains an important therapeutic modality for MM patients. Traditionally high-dose single agent melphalan (200 mg/m2; Mel-200) has been used as the conditioning regimen prior to ASCT for MM. We investigated the combination regimen of BCNU, etoposide and melphalan (BEM) in this setting at our center. Methods: All patients who had undergone ASCT for MM utilizing BEM conditioning regimen at Norris Cancer Center, University of Southern California, Los Angeles were eligible. BEM consisted of BCNU 12 mg/kg (actual body weight or ideal body weight whichever was lower) iv on day -5, etoposide 60 mg/Kg iv on day -3, and melphalan 140 mg/m2 iv on day -1, prior to stem cell reinfusion on day 0. Overall survival (OS) was defined as time from MM diagnosis to death, or in patients still alive, the date of last follow-up. Progression-free survival (PFS) was defined as time from ASCT to date of relapse, or in patients without documented relapse, date of death or last follow up, whichever was sooner. Survival for patients with different clinical and disease-specific characteristics was explored using logrank test. Response was assessed according to International Uniform Response Criteria for MM. Results: A total of 44 MM patients underwent ASCT utilizing the BEM conditioning regimen. Of these, evaluable data was available for 42 patients (25 males; 60%, 17 females; 40%) with a median follow up of 27.6 mths. Median age at diagnosis was 54.5 yr (range 34–68) while median time from MM diagnosis to ASCT was 10.5 mths (range 2.8–47.8). MM subtypes included IgA (n=5, 12%), IgG (n=30, 71%) and light chain-only (n=7, 17%). Median bone marrow (BM) plasmacytosis at diagnosis was 42.5% (range 0%-100%). Durie-Salmon (DS) stages included stage I (12%), II (36%) and III (52%), while 4 patients (10%) had renal dysfunction at the time of initial MM diagnosis. Majority of the patients (71%) had lytic bone lesions at the time of diagnosis and 86% (n=36) hade secretory disease. Patients had received a median of 1 prior treatment (range 1–5), while 23 (55%) patients had received novel agents (proteasome inhibitors or IMiDs) prior to the BEM regimen. Response rates prior to and after the regimen are summarized in Table 1. After BEM-ASCT an additional 16 (38%) patients achieved a CR. Median duration of hospitalization and time to engraftment were 19 days (range 15–41) and 10.5 days (range 7–19), respectively. One patient died prior to discharge from the hospital post ASCT (Day 36 post ASCT) for a treatment related mortality of 2%. CR rate post BEM-ASCT was 64% with an ORR of 97%. Relapses have been noted in 25 patients to date. Median OS for all patients was 4.9 yrs (5.6 yrs for patients in CR and 6.6 yrs for patients in PR after BEM-ASCT). Median PFS was 23.9 mths for all patients (25 mths for patients in CR and 21.8 mths for those in PR after BEM-ASCT). No statistically significant differences were noted in OS based on patient gender (p=0.47), age at diagnosis (< or ≥60 yr), MM subtype (p=0.52), DS stage at diagnosis (0.09), patients without lytic bone lesions at diagnosis (p=0.054), secretor status (p=0.2), response status at the time of BEM-ASCT (p=0.9) or prior exposure to novel agents (p=0.62). Conclusions: BEM is a well-tolerated conditioning regimen prior to ASCT in MM and has efficacy comparable to Mel-200. BEM can be effectively employed in patients where Mel-200 is not feasible. We are particularly intrigued by its ability to deliver high CR rates (64%) compared to <30% (historical control). Very encouraging median OS (4.9 yr) and PFS (23.9 mth) rates were noted which were even better in patients who had a measurable response after this regimen. Further investigations will be needed to optimally define its potential as standard conditioning regimen in MM patients undergoing ASCT. Disclosures: No relevant conflicts of interest to declare.

Induction Therapy with Bortezomib and Dexamethasone Followed By Autologous Stem Cell Transplantation for Systemic Light Chain Amyloidosis: Our Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5907-5907
Author(s):  
Sandeep Jain ◽  
Luciano J Costa ◽  
Robert K Stuart ◽  
Saurabh Chhabra ◽  
Alice Mims ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cardiac Involvement ◽  
Stem Cell Transplant ◽  
Patient Characteristics ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
High Dose Melphalan

Abstract Introduction: The optimal treatment approach for systemic AL amyloidosis remains unclear. Autologous stem cell transplant (ASCT) is the only modality associated with long term survival, but failure to show survival benefit in randomized clinical trial raises doubts about its efficacy 1, 2. Outcomes after ASCT are better in patients who achieve complete hematologic response after the ASCT3. One report has shown improved outcomes with combining one dose of the proteasome inhibitor bortezomib with high dose melphalan as part of conditioning regimen 4. Preliminary data from a recent study suggest that the outcome of treating AL amyloidosis with two cycles of bortezomib and dexamethasone followed by ASCT was superior to the outcome of the ASCT alone5. We describe our experience with giving 4-6 cycles of bortezomib and dexamethasone induction prior to high dose melphalan and ASCT in patients with systemic AL amyloidosis. Patients and methods: We included all patients who underwent autologous transplant for symptomatic systemic AL amyloidosis at our institution from October 2010 till June 2014. Five patients were included in the analysis and patient characteristics are described in table 1. All patient received 4 -6 cycles of induction with bortezomib and dexamethasone followed by autologous stem cell transplant using high dose melphalan (200 mg/m2). One patient also received six cycles of lenalidomide and dexamethasone prior to bortezomib based induction for lack of response. Hematologic and organ response were assessed using the definitions from the 10th International symposium on Amyloid and Amyloidosis. Overall survival was calculated by Kaplan Meyer’s method using Graphpad Prism 6.0 software. Results: There was no transplant related mortality. After median follow up of 13 months (12-25 months) all patient are alive. Toxicities from the ASCT were mostly cytopenias in the immediate post-transplant period which were managed as per the standard of care. Two patients achieved hematological complete response while one more had very good partial response and other two achieved partial response. Of the four patients with nephrotic range proteinuria, two patients had > 95% reduction in proteinuria, one had > 75% reduction in proteinuria and another patient had > 50% reduction in proteinuria. One patient had Liver involvement with elevated alkaline phosphatase which normalized post-transplant (table 2). The responses were maintained on last follow up and none of the patient had hematological or organ relapses. Discussion: Bortezomib alone and in combination with steroids has shown efficacy in AL amyloidosis, but its role in induction prior to high dose melphalan/ASCT to help achieve deeper hematological response is unknown. Our experience shows that this combination may be highly efficacious without significant toxicity. Limitations of our study include the small number of patients and absence of any patients with cardiac involvement, which is a worse prognostic marker. We conclude that the bortezomib and dexamethasone induction followed by high dose melphalan/ASCT for AL amyloidosis should be studied in prospective trials. Table 1.Patient Characteristics n=5Age, years 51.2 (44-62)Race (Caucasian)4 (80%)Gender ( female)3 (60%)Cardiac involvement 0 (0)Renal involvement 4 (80%)Serum creatinine ≥ 2.5 0 (0)Organ involvement ≥21 (20%)BM plasma cells > 10%1 (20%)Hgb ≤ 10 g/dl0 (0)LVEF <50%0 (0)Induction therapy Bortezomib/dexamethasone only4 (80%)Lenalidomide/dexamethasone + Bortezomib/dexamethasone1 (20%) Table 2. Outcomes n=5 Baseline After ASCT Hematologic response n=5 M protein 0.772 gm/dl 0.096 gm/dl 2 CR, 1 VGPR, 2 PR Renal response n=4 24 hours proteinuria 3.13 gm 0.432 gm 2 > 95% reduction, 1 >75% reduction, 1 >50 % reduction. Liver response n=1 Alkaline phosphatase 700 IU/L 62 IU/L Disclosures No relevant conflicts of interest to declare.

Treatment of Primary CNS Lymphoma in the Elderly with High-Dose Methotrexate Containing Chemotherapy Followed Radiotherapy or Chemotherapy Alone Plus Deferred Radiotherapy: Evaluation of Modification of Treatment Modalities in Leon Berard Cancer Center.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2702-2702
Author(s):  
Hervé Ghesquières ◽  
Agathe Bajard ◽  
Gilles Albrand ◽  
Khaoula Alaoui-Slimani ◽  
Philippe Rey ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Visual Inspection ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Time Periods ◽  
Over Time

Abstract Abstract 2702 Poster Board II-678 Background: Treatment of Primary CNS lymphoma (PCNSL) is based on high-dose methotrexate (HD-MTX) and cytarabine containing chemotherapy (CT) followed by brain radiotherapy (RT). However, the risk of leukoencephalopathy (LE) is important after chemoradiotherapy, especially for patients older than 60 years old. To reduce neurotoxicity in clinical practice, RT is restricted at relapse or for not responding patients after CT, but no formal randomized trial had evaluated this two modalities of treatment. The objective of this study is to evaluate this modification of clinical practice in our institution over time. Methods: 74 patients older than 60, median age 68 years old (range, 60–81) were treated in our institution between 1986 and 2008. Before 2003, 51 patients were treated with HD-MTX CT followed by RT. Most patients (59%) were treated with HD-MTX + CHOP-like with intermediate dose of MTX (1.5g/m2) and only 25% received 3g/m2 of MTX per course. Evaluation of this schedule in the prospective phase II GELA trial LNHCP93 showed excessive rate of toxic death during CT. Since 2004, 23 patients were treated with expected less toxic protocol and increased dose of MTX (3g/m2, 83% of patients), and RT was omitted for patients in complete response (CR) in order to limit risk of LE. Acute toxicity, initial response, risk of relapse, overall survival (OS) and risk of neurotoxicity were compared between these two periods. As acute treatment toxicity had a powerful impact for these categories of patients especially for patients treated in first period, we access if hazard ratio (HR) was constant over time by determining Schoenfeld residuals. A piecewise Cox proportional model was used in defining time periods after visual inspection of Schoenfeld residuals. Strategy (CT+RT vs.CT only) was tested during each time period in order to detect a difference on survival. Results: Comparison of clinical characteristics showed that patients in second period were slightly older (71 vs. 67, p=0.008) but Performance Status, LDH level, rate of involvement of deep structures of brain, CSF protein level, leptomeningeal involvement were not different between the 2 cohorts. Toxic death rate during treatment was significantly more important in first period (31% vs. 9% p=0.04). CR after CT was significantly better for patients treated after 2003 (33% vs. 48% p=0.01), but was similar at the end of treatment, CT + RT (49%) vs. CT strategy (48%). The follow-up of cohort 1 and 2 was 95 and 27 months, respectively. Median OS was 16.1 and 18.1 months (p=0.8) and progression free survival (PFS) was 9.7 and 5.1 months (p=0.24) between the 2 cohorts, respectively. With CT + RT strategy, 10 patients did not relapse after first line therapy and eleven were alive at last follow-up. With CT strategy four patients were in persistent CR at 13.5, 14.9, 20.3, 21.5 months, respectively. Among patients in partial response (1 pt), progressive disease (9 pts) or in relapse after CR (7 pts) after CT strategy, 4 died after supportive care, 3 patients were treated with CT alone but died rapidly, and 10 had RT alone (4 pts) or after CT (6 pts). Among patients who received deferred RT, 4 were alive at last follow-up. Regarding neurotoxicity, in first cohort, 7 patients (14%) presented treatment-related neurologic toxicity with 4 deaths of LE. Among patients treated with CT strategy, 2 patients died of LE but received deferred RT at relapse and 2 patients presented severe LE after CT alone and deferred RT, respectively (17% of treatment-related neurologic toxicity). The piecewise Cox proportional model could define two time periods after visual inspection of Schoenfeld residuals, before and after 3 months. We observed that CT + RT strategy presented after the first 3 months a better PFS than CT alone strategy (HR 2.71 [1.29–5.73] p=0.009) but OS was not significant with this method. The cumulative risk of LE in the 2 cohorts was not significantly different (p=0.95) Conclusion: This institutional study of modification of treatment practice for elderly patients with PCNSL showed that i) MTX + CHOP like CT had an excessive acute toxicity without any benefit in term of CR rates over others schedules with 3g/m2 of MTX per course ii) OS of patients was in accordance to recent series with the similar median age iii) 59% of patients treated with CT strategy received finally deferred RT iv) a time varying effect was observed for PFS with after treatment period a benefit for CT + RT. An effort to conduct a randomized trial testing CT alone + deferred RT versus CT + RT for patients with PCNSL remained necessary. Disclosures: No relevant conflicts of interest to declare.

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