scholarly journals Role of one, two and three doses of high-dose chemotherapy with autologous transplantation in the treatment of high-risk or relapsed testicular cancer: a systematic review

2018 ◽  
Vol 53 (10) ◽  
pp. 1242-1254 ◽  
Author(s):  
Irbaz bin Riaz ◽  
Muhammad Umar ◽  
Umar Zahid ◽  
Muhammad Husnain ◽  
Ahmad Iftikhar ◽  
...  
Keyword(s):  
Systematic Review ◽  
High Risk ◽  
Testicular Cancer ◽  
Autologous Transplantation ◽  
High Dose Chemotherapy ◽  
High Dose

The role of autologous stem-cell transplantation in high-risk neuroblastoma consolidated by anti-GD2 immunotherapy: Results of 2 consecutive studies in a single referral institution.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10539-10539
Author(s):  
Jaume Mora ◽  
Alicia Castañeda ◽  
Miguel Angel Flores ◽  
Vicente Santa-María ◽  
Moira Garraus ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cooperative Groups ◽  
Gm Csf ◽  
Stem Cell Rescue ◽  
Single Center Study ◽  
Study Population

10539 Background: Treatment of high-risk NB within the major international cooperative groups (COG and SIOP) comprise intensive induction, consolidation with high dose chemotherapy and autologous stem cell rescue (ASCR) followed by anti-GD2 immunotherapy and isotretinoin as maintenance therapy. In the COG studies dinutuximab and cytokines (GM-CSF and IL-2) were used to treat patients in complete remission (CR) after ASCR whereas SIOPEN studies used dinutuximab-beta plus/minus IL-2 and included patients with responsive (no progression 109 days after ASCR) but refractory (skeletal metaiodobenzylguanidine positivity with three or fewer areas of abnormal uptake). Methods: Since December 2014, HR-NB patients referred to HSJD were eligible for consolidation with anti-GD2/GM-CSF immunotherapy in 2 consecutive studies (dinutuximab for EudraCT 2013-004864-69 and naxitamab for 017-001829-40) and naxitamab/GM-CSF compassionate use (CU) with or without prior ASCR. Patients were enrolled in 1st CR or with primary refractory bone/bone marrow (B/BM) disease. We accrued a study population of two groups whose consolidative therapy, aside from ASCR, was similar: anti-GD2 (dinutuximab or naxitamab) antibodies + GM-CSF and local radiotherapy. This is a retrospective analysis of their event-free survival (EFS) and overall survival (OS) calculated from study entry. Results: From Dec 14 til Dec 19, 67 study patients were treated with the COG (dinutuximab + GM-CSF+ IL-2 + RA) regimen (n = 21) in the HSJD-HRNB-Ch14.18 study or with Naxitamab and GM-CSF in the Ymabs study 201 (n = 12) or CU (n = 34). 23 patients were treated with primary refractory disease in the B/BM, and 44 in 1st CR. The 67 study patients included 13 (19%) treated following single ASCR and 54 following induction chemotherapy and surgery. Median follow-up for all surviving patients is 16.2 months. Two-year rates for ASCR and non-ASCR patients were, respectively: EFS 64% vs. 54% (p = 0.28), and OS 66.7% vs. 84% (p = 0.8). For the 44 pts in 1st CR, 2-year rates for ASCR and non-ASCR patients were, respectively: EFS 65% vs. 58% (p = 0.48), and OS 71% vs. 85% (p = 0.63). Conclusions: In this retrospective, single center study, ASCR did not provide survival benefit when anti-GD2 + GM-CSF based immunotherapy was used for consolidation after dose-intensive conventional chemotherapy.

High-dose chemotherapy followed by allogeneic stem cell transplantation in high-risk relapsed and refractory aggressive non-Hodgkin lymphoma: Results of a prospective study of the German high-grade non-Hodgkin lymphoma study group.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8004-8004
Author(s):  
Bertram Glass ◽  
Justin Hasenkamp ◽  
Gerald Wulf ◽  
Peter Dreger ◽  
Michael Pfreundschuh ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Refractory Disease ◽  
Reduced Intensity Conditioning ◽  
Early Relapse ◽  
Non Hodgkin Lymphoma ◽  
Reduced Intensity

8004 Background: The role of allogeneic stem cell transplantation (alloSCT) in high-risk aggressive NHL is poorly defined; the role of graft-versus-lymphoma effect is unclear. Reduced intensity conditioning has shown limited efficacy in patients with refractory disease. Methods: Patients with primary refractory disease, early relapse (<12 months) or relapse after autologous SCT of aggressive B-cell (n=61) or T-cell (n=23) NHL were enrolled from June 2004 to March 2009. Myeloablative conditioning (fludarabine 125mg/m2, busulfan 12mg/kg, cyclophosphamide 120 mg/kg) was followed by alloSCT from related (n=24) or unrelated (n=60) donors. 57/84 patients received a 10 HLA-loci compatible graft. Results: Overall survival at 3 years was 42% (95% CI, 31% to 52%), progression-free survival (PFS) was 40% (95% CI 29% to 50%). Non-relapse mortality (NRM) was 12% at 100 days and 35% at one year. Graft-versus-host disease (GVHD) and infection were the predominant causes of NRM. Relapse rate was 30% with latest relapse at day +327. Patients with an HLA fully compatible donor (plus ATG with unrelated donors) (n=40) had the best outcome (NRM at 1y 10.4 vs 57.2%, PFS at 3y 64.7% vs 31.8%, p < 0.0001). GVHD > grade I correlated with improved PFS (HR 0.45, p=0.0088). Patients with refractory disease or early relapse (n=60) experienced PFS at 3y of 33%. Conclusions: Lymphoma-debulking (high-dose) chemotherapy followed by alloSCT shows excellent results in heavily pretreated patients with early relapse or primary refractory aggressive lymphoma. There was evidence of graft-versus-lymphoma activity in this setting. For patients with a fully matched (10/10) related or unrelated donor the results compare favorably to autoSCT or alloSCT following reduced-intensity conditioning.

Salvage treatment for testicular cancer with standard- or high-dose chemotherapy: a systematic review of 59 studies

2017 ◽  
Vol 34 (8) ◽  
Author(s):  
Fausto Petrelli ◽  
Andrea Coinu ◽  
Giovanni Rosti ◽  
Paolo Pedrazzoli ◽  
Sandro Barni
Keyword(s):  
Systematic Review ◽  
Testicular Cancer ◽  
High Dose Chemotherapy ◽  
Salvage Treatment ◽  
High Dose

A Novel Strategy for Combining Immunotherapy with High Dose Chemotherapy and Auto-Transplantation in High Risk Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2920-2920
Author(s):  
Susann Szmania ◽  
Michele Cottler-Fox ◽  
Nancy Rosen ◽  
Sanjaya Viswamitra ◽  
Amberly Moreno ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
High Risk ◽  
Complete Remission ◽  
Antibody Response ◽  
Autologous Transplantation ◽  
High Dose Chemotherapy ◽  
Delayed Type Hypersensitivity ◽  
High Dose ◽  
Novel Strategy

Abstract Although high dose chemotherapy and autologous transplantation (AT) can induce complete remission in approximately 50% of multiple myeloma (MM) patients, the majority eventually relapse. We hypothesize that a combination of AT and vaccination may sustain remissions by inducing specific cytotoxic T cells against chemotherapy resistant plasma cells. Vaccinations are typically given after AT when the immune system is very defective. We tested the novel strategy of priming anti-myeloma T-cells before AT and protecting the primed T-cells from high-dose chemotherapy by apheresis and cryopreservation of the primed cells. After high-dose chemotherapy induced cytoreduction, the primed T-cells were returned early after AT and preferentially expanded by a series of booster vaccinations (figure 1). The vaccines are monocyte derived-dendritic cells (DC) loaded with myeloma lysate (ML) and tracer antigen keyhole limpet hemocyanin (KLH), matured with trimeric CD40-ligand, administered intranodally, and followed by 5 days of low dose subcutaneous IL-2. Four patients with poor prognosis MM (characterized by abnormal metaphase cytogenetics) have been vaccinated and three are evaluable (the 4th patient is 60 days post AT2 and only 14 days post vaccine 8). ML specific immune responses were detected by delayed type hypersensitivity reactions and proliferation in 2/3 and by ELISPOT in 3/3 patients. Strong responses to KLH were observed in 3/3 patients. The pattern of response is a dramatic and rapid increase in ML specific T cell proliferation (figure 2) and IFN-g secretion after LP2 infusion plus booster vaccinations post AT, suggesting that the primed T-cells had been protected by collection and storage during AT. A high pre-existing ML specific antibody response was observed in 2/3 patients and a low antibody response pre-vaccination was clearly boosted in a third patient. The patient receiving the lowest DC dose (50 versus 115 and 139 x106) had a response to ML only detected by IFNg secretion assays, but is in near complete remission, 719 days post AT2, while disease progression was observed in the other two patients 496 and 626 days after AT. Our immune monitoring data suggest that the problem of applying vaccination in heavily treated patients may be overcome by early vaccination, collection and subsequent reinfusion of primed cells followed by repeated booster vaccination. Optimization of the vaccine regimen by increasing the frequency of vaccination or the use of highly immunogenic, well characterized tumor-associated antigens may further improve efficacy. We have an ongoing trial for high risk MM patients utilizing NY-ESO-1 and MAGE-A3 peptide vaccines based on a similar strategy to preserve immune competence.

scholarly journals Efficacy of High Dose Chemotherapy with Autologous Transplantation for Primary CNS Lymphoma Treatment

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-4
Author(s):  
Muhammad Khawar Sana ◽  
Syed Maaz Abdullah ◽  
Muhammad Tayyeb ◽  
Mohammad Ammad Ud Din ◽  
Amrat Ehsan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Effects ◽  
Autologous Transplantation ◽  
Primary Cns Lymphoma ◽  
High Dose Chemotherapy ◽  
Cns Lymphoma ◽  
High Dose ◽  
Phase 2 ◽  
Phase 2 Trial ◽  
Related Mortality

Introduction: Primary CNS lymphoma (PCNSL) is a highly aggressive non-Hodgkin lymphoma (NHL) variant limited to the CNS with rare evidence of systemic spread. It constitutes 4% of all CNS malignancies. Owing to the impenetrable blood-brain barrier to routine chemo-immunotherapy, the efficacy of such treatment is less than optimal. The combination of chemoradiotherapy has substantial associated risk of late neurotoxicity and increased disease recurrence. High dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) as rescue has been shown to be effective. We performed a systematic review of literature to explore the efficacy of HDT and ASCT in patients with PCNSL. Methods: We performed a comprehensive literature search (following PRISMA guidelines) on May 28, 2020 on Pubmed, Cochrane Library and Clinicaltrials.Gov by using the MeSH terms related to high-dose chemotherapy, autologous transplantation and primary CNS lymphoma which yielded 561 relevant articles. Following subsequent screening by 2 reviewers, we selected 16 published trials (n=745) and included data from these studies in our systematic review. We manually extracted data summarized the results. Results: 405/745 patients eventually underwent sequential HDT+ASCT the results of which are illustrated in table 1 and 2 stratified on the basis of newly diagnosed (ND) (n=641) and relapsed, refractory (RR) PCNSL patients (n=104) respectively. ND PCNSL: Among ND PCNSL patients, carmustine and thiotepa based regimens were the most widely studied HDT regimens (n= 351). Illerhaus et al. (2016, n= 81) in a phase 2 trial used HDT of intravenous (IV) combinations of rituximab, thiotepa and carmustine followed by ASCT on 73 patients which yielded partial response (PR) 13.9 %, complete response (CR) 77.2% and overall survival (OS) 81% at 36 months. 4 patients suffered transplant related mortality (TRM), mucositis (8%) and arrhythmias (2%) were the most common nonhematologic &gt;grade 4 adverse effects. Ferreri et al. (2017) [n=122] in a phase 2 trial (n=59) used ASCT following Carmustine + Thiotepa HDT and reported 2-year OS of 71% and CR of 93% with a modest toxicity profile (infections (8%), mucositis (5%) and 2 (3%) treatment related deaths). IV thiotepa, busulfan and cyclophosphamide (TBC) combination was used as HDT / ASCT in ND PCNSL patients (n=208). Omuro et al. (2015) (n=32) used HDT with TBC followed by ASCT in 26 patients. Whole brain radiation therapy (WBRT) was not given to any patient regardless of recurrence or relapse. At 5 years, the study reported PR=11%, CR=81%, and OS=81%. In a phase 2 trial, Houillier et al. (2019, n=140) used TBC combination as HDT followed by either WBRT or ASCT (2 separate arms), 44 patients of the latter arm exhibited a CR of 38% and OS of 66% at 5 years with 5 treatment related deaths. An IV combinations of carmustine, etoposide, cytarabine and melphalan (BEAM) have also been used as HDT with ASCT in 3 phase 2 trials (n=59). Abrey et al. (2003, n=28) in a phase 2 trial used high-dose BEAM therapy followed by ASCT which yielded PR of 14%, CR of 57% and OS of 55% at 28 months. Only 1 treatment related mortality occurred. RR PCNSL: TBC combination has been the most extensively used HDT regimen for RR PCNSL patients undergoing ASCT (n=65). Soussain et al. (2008, n=43) conducted a phase 2 trial in which high-dose TBC sequentially followed by ASCT was studied in 27 RR PCNSL patients. The results showed median PFS of 41.1 months with OS of 45% at 2 years however, 3 toxicity related deaths were observed. Kasenda et al. (2017, n=39) in a phase 2 trial used high-dose combination of rituximab, carmustine and thiotepa coupled with ASCT on RR PCNSL patients which yielded PR of 15.4%, CR of 56% and median PFS of 12.4 months with an OS of 56.4% at 2 years. However, there were 4 treatment related deaths and an extensive toxicity spectrum with widespread pancytopenia (thrombocytopenia =96.9%, leukopenia =100%, anemia =65.6%) and nonhematologic infections (65.6%) observed. Conclusion: HDT followed by ASCT rescue has exhibited favorable outcomes and can be used an alternative to WBRT especially in ND PCNSL patients. Evidence is limited by mainly phase II non randomized data. Although, hematologic adverse effects due to HDT were observed on a widespread basis, transplant related mortality was however minimal. There is need to carry out prospective randomized phase III trials to access the safety and efficacy profile of HDT / ASCT for ND and RR PCNSL. Table Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

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