scholarly journals ML-18 High-dose chemotherapy supported by autologous stem cell transplant in relapsed and refractory primary CNS lymphoma

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi25-vi25
Author(s):  
Motoo Nagane ◽  
Nobuyoshi Sasaki ◽  
Kuniaki Saito ◽  
Keiichi Kobayashi ◽  
Ryo Onoda ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase I ◽  
Stem Cell Transplant ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Phase Ii Trials ◽  
Treatment Indications ◽  
Conditioning Regimens

Abstract While whole brain radiation therapy (WBRT) has been performed as consolidation therapy in primary central nervous system lymphoma (PCNSL), high-dose chemotherapy supported by autologous stem cell transplant (HDC/ASCT) is widely investigated today as an alternative treatment strategy, given the high risk for radiation-induced neurotoxicity in WBRT. Various conditioning regimens have been investigated in phase II trials, which report non-inferiority of HDC/ASCT in efficacy and preservation of neurocognitive function in comparison with WBRT. Besides its promising efficacy, treatment-related deaths are reported in 11% in patients treated by a conditioning regimen using thiotepa, busulfan and cyclophosphamide (TBC), which raises a concern for safety. Among several conditioning regimens, analysis using registry data of Japan Society for Hematopoietic Cell Transplantation has revealed that the use of conditioning regimens containing thiotepa was a positive factor for longer PFS. According to the result of a phase I trial in Japan which investigated HDC/ASCT using thiotepa and busulfan (BuTT), thiotepa was approved by the pharmaceuticals and medical devices agency (PMDA) on March 2020. In comparison with the TBC regimen, cyclophosphamide is omitted, and the dose of thiotepa is lower (250 mg/m2, 3 days in TBC; 5 mg/kg, 2 days in BuTT) in BuTT, therefore BuTT could be less toxic in comparison with TBC, and no treatment-related deaths were observed in the phase I study in Japan. Further investigation on the efficacy and safety of BuTT in actual clinical practice is warranted. We have constituted a multi-disciplinary team in our institution in order to perform HDC/ASCT using BuTT in relapsed/refractory PCNSL. Treatment indications are as follows; 65 years old or younger, previously treated by rituximab, methotrexate, procarbazine and vincristine (R-MPV), good organ function and neurological status. Future directions along with preliminary treatment results will be discussed at the meeting.

High dose chemotherapy with autologous stem cell transplant for patients with transformed B-cell non-Hodgkin lymphoma in the rituximab era

2014 ◽  
Vol 55 (10) ◽  
pp. 2319-2327 ◽  
Author(s):  
Yngvild N. Blaker ◽  
Marianne B. Eide ◽  
Knut Liestøl ◽  
Grete F. Lauritzsen ◽  
Arne Kolstad ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Stem Cell Transplant ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Non Hodgkin Lymphoma

The Addition of Rituximab to Standard High Dose BEAM Chemotherapy for Autologous Stem Cell Transplant in Patients with Lymphoma Does Have a Significant Effect on Engraftment.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5325-5325
Author(s):  
Francis K. Buadi ◽  
Brian McClune ◽  
Yoriann S. Hull ◽  
Furhan Yunus ◽  
Sohail Minhas ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Neutrophil Recovery ◽  
Cell Dose ◽  
Time Period ◽  
Neutrophil Engraftment

Abstract The addition of Rituximab to standard combination chemotherapy has significantly improved outcomes in both young and elderly patients with Non-hodgkins lymphoma (NHL). High dose chemotherapy with autologous stem cell transplant is currently the standard of care for patients with relapsed hodgkins lymphoma (HL) and NHL. However the effect of the addition of Rituximab to standard high dose chemotherapy regimen for autologous stem cell transplant on neutrophil and platelet engraftment is unknown. There are however, reported cases of neutropenia developing in patients treated with Rituximab. We performed a retrospect review of all patients with HL and NHL treated in our institution with RBEAM (Rituximab, Carmustine, Etoposide, Cytarabine, Melphalan) chemotherapy between July 2000 and June 2005 and compared it to patients receiving BEAM in the same time period. Rituximab was given at a dose of 375mg/m2 one day prior to beginning standard BEAM high dose chemotherapy. Peripheral blood was the main source of stem cells. The purpose of this study was to determine the effect of the addition of Rituximab on neutrophil and platelet engraftment. A total of 46 patients were treated during this time period. Twelve patients received RBEAM and 34 received BEAM. There was a statistical significant difference in age between the two groups. There was however no difference between the two groups in terms of race, sex and primary diagnosis. Median stem cell dose was not significantly different between the two groups. Characteristic of both groups are shown in Table: 1 Characteristics of Both Groups Median Age (yrs) Race Diagnosis Median Stem Cell Dose(x10^6) AA White HL NHL RBEAM 50.5 3 9 3 9 3.9 BEAM 36 13 21 17 17 3.8 P-VALUE 0.01 0.49 0.2 0.54 Neutrophil engraftment was defined as the first day of ANC > 500 on 3 consecutive days. Platelet engraftment was defined as the first day of platelet count > 20,000 with no platelet transfusion in the next seven days. The median time to neutrophil engraftment was 12 day in RBEAM compared to 11 days in BEAM (p=0.09). Platelet engraftment was however significantly delayed in patients receiving RBEAM 18days versus 12 days for BEAM (p= 0.02). Looking at both cohorts together we found that patients with HL had a significant delay in platelet engraftment compared to those with NHL (p=0.04). However there was no difference in neutrophil recovery. Although, stem cell dose affected neutrophil recovery, it had no effect on platelet engraftment. There was no increased toxicity in the early post transplant period associated with the addition of Rituximab. No bleeding complications resulted form the delay in platelet engraftment in the patients who received RBEAM. In a linear regression model the only factor that significantly affected engraftment was conditioning regimen. We conclude that the addition of Rituximab to standard high dose BEAM chemotherapy for autologous stem cell transplant has no effect on neutrophil engraftment; however platelet engraftment may be delayed. The continue use of this regimen despite the small delay in platelet engraftment will depend on whether there is any benefit, in terms of response rate, progression free and overall survival.

Role of High-Dose Chemotherapy with Autologous Stem Cell Transplantation in Primary Systemic Amyloidosis: A Systematic Review and Meta-Analysis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2872-2872
Author(s):  
Madhusmita Behera ◽  
Ambuj Kumar ◽  
Mohamed A. Kharfan-Dabaja ◽  
Benjamin Djulbegovic
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Meta Analysis ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Conventional Chemotherapy

Abstract Background: Primary systemic amyloidosis (AL) is a rare plasma cell clonal disorder(8/million) characterized by extracellular deposits of material composed mainly of fragments of light chain immunoglobulin throughout a body. Standard chemotherapy (e.g. melphalan and prednisone) is associated with poor outcomes (typical median survival is between 12–18 months with less than 5% survive 10 years). Autologous stem cell transplant (ASCT) has been increasingly advocated for treatment of AL. However, it is uncertain whether ASCT is better than standard chemotherapy. To address this uncertainty, we undertook a systematic review/meta-analysis to evaluate the efficacy of high-dose chemotherapy and autologous stem-cell transplant (HSCT) versus conventional chemotherapy in patients with AL. Methods: Data search of published studies included Medline [all randomized controlled trials (RCTs)], Cochrane library and hand search of references. Studies were included if they were comparison trials of HSCT versus conventional chemotherapy, regardless if they were RCTs, prospective studies with historical control, or single arm studies. The studies were eligible if patients had biopsy proven AL with at least one major organ involved. Data were extracted on benefits as well as harms (overall survival, event-free survival, response, treatment related mortality, treatment-related morbidity). Results: Out of 34 identified studies only 13 met the inclusion criteria for the current systematic review (2 RCTs, 2 prospective non-randomized trials involving historical control, and 9 single arm trials). Altogether these trials enrolled 1056 patients. Pooled data from 4 trials with controls (RCT and non-RCT) found similar overall survival for ASCT and conventional therapy arms [hazard ratio (HR) of 1.10 (95% CI 0.88, 1.36, p=0.4); p= 0.6]. Analysis of data according to trial design also did not find any difference in survival [HR for RCTs was 1.10 (95% CI 0.88, 1.37) and for non RCTs HR was 0.98 (95% CI 0.29, 3.35)]. The complete hematological response was also similar in both arms in RCTs (Odds ratio [OR]=1.38, 95%CI 0.67, 2.85; p=0.4) and non RCTs (OR=1.78, 95%CI 0.22, 14.65; p=0.32). The pooled proportion of treatment-related deaths in the single arm studies for AHCT was 0.119 (95% CI = 0.09 to 0.14)]. Conclusion: The results from the meta-analysis indicate that there is no statistically significant difference between the treatment effects from high-dose chemotherapy with ASCT and conventional chemotherapy. Hence, the efficacy of ASCT in improving overall survival and complete hematological response remains to be proven.

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