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https://www.readbyqxmd.com/read/29222306/therapy-of-primary-cns-lymphoma-role-of-intensity-radiation-and-novel-agents
#1
REVIEW
Andrés José María Ferreri
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...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29054815/whole-brain-radiotherapy-or-autologous-stem-cell-transplantation-as-consolidation-strategies-after-high-dose-methotrexate-based-chemoimmunotherapy-in-patients-with-primary-cns-lymphoma-results-of-the-second-randomisation-of-the-international-extranodal-lymphoma
#2
Andrés J M Ferreri, Kate Cwynarski, Elisa Pulczynski, Christopher P Fox, Elisabeth Schorb, Paul La Rosée, Mascha Binder, Alberto Fabbri, Valter Torri, Eleonora Minacapelli, Monica Falautano, Fiorella Ilariucci, Achille Ambrosetti, Alexander Roth, Claire Hemmaway, Peter Johnson, Kim M Linton, Tobias Pukrop, Jette Sønderskov Gørløv, Monica Balzarotti, Georg Hess, Ulrich Keller, Stephan Stilgenbauer, Jens Panse, Alessandra Tucci, Lorella Orsucci, Francesco Pisani, Alessandro Levis, Stefan W Krause, Hans J Schmoll, Bernd Hertenstein, Mathias Rummel, Jeffery Smith, Michael Pfreundschuh, Giuseppina Cabras, Francesco Angrilli, Maurilio Ponzoni, Martina Deckert, Letterio S Politi, Jürgen Finke, Michele Reni, Franco Cavalli, Emanuele Zucca, Gerald Illerhaus
BACKGROUND: The International Extranodal Lymphoma Study Group-32 (IELSG32) trial is an international randomised phase 2 study that addresses two key clinical questions in the treatment of patients with newly diagnosed primary CNS lymphoma. Results of the first randomisation have demonstrated that methotrexate, cytarabine, thiotepa, and rituximab (called the MATRix regimen) is the induction combination associated with significantly better outcome compared with the other induction combinations tested...
November 2017: Lancet Haematology
https://www.readbyqxmd.com/read/29035395/replacing-carmustine-by-thiotepa-and-cyclophosphamide-for-autologous-stem-cell-transplantation-in-hodgkin-s-and-non-hodgkin-s-b-cell-lymphoma
#3
E Joffe, D Rosenberg, U Rozovski, C Perry, I Kirgner, S Trestman, O Gur, F Aviv, N Sarid, A Kolomansky, L Gepstein, Y Herishanu, E Naparstek
This study aimed to compare the real-life results of TECAM, a thiotepa-based conditioning regimen consisting of thiotepa (40 mg/m(2) days -5 to -2), etoposide (200 mg/m(2) days -6 to -3), cytarabine (200 mg/m(2) days -4 to -1), cyclophosphamide (60 mg/kg day -3), and melphalan (60 mg/m(2) days -2 to -1) with that of the conventional carmustine-based regimen BEAM. We reviewed 125 consecutive patients who underwent a first autologous transplantation (ASCT) for B-cell lymphomas at a large tertiary transplantation center between 1999 and 2014...
October 16, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28905508/tandem-thiotepa-with-autologous-hematopoietic-cell-rescue-in-patients-with-recurrent-refractory-or-poor-prognosis-solid-tumor-malignancies
#4
Diana S Osorio, Ira J Dunkel, Kelly Ann Cervone, Rakesh K Goyal, K M Steve Lo, Jonathan L Finlay, Sharon L Gardner
BACKGROUND: The purpose of this study was to determine the feasibility and tolerability of tandem courses of high-dose thiotepa with autologous hematopoietic cell rescue (AHCR) in patients with recurrent, refractory solid tumors who were ineligible for a single course of high-dose therapy due to greater than minimal residual disease. Patients with decreased hearing or poor renal function were eligible. PROCEDURE: Thiotepa was administered intravenously at a dose of 200 mg/m(2) /day (6...
September 14, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28901730/reduced-toxicity-alternate-donor-stem-cell-transplantation-with-posttransplant-cyclophosphamide-for-primary-immunodeficiency-disorders
#5
Neha Rastogi, Satyendra Katewa, Dhwanee Thakkar, Shruti Kohli, Sagar Nivargi, Satya Prakash Yadav
We describe here the outcomes of reduced-toxicity alternate-donor stem cell transplant (SCT) with posttransplant cyclophosphamide (PTCy) for primary immunodeficiency disorders (PIDs) in eight children (haploidentical-seven and matched unrelated donor-one). The conditioning was with serotherapy (alemtuzumab-3/rabbit-anti-thymoglobulin-5); fludarabine, cyclophosphamide, and total body irradiation-5 (additional thiotepa-3); fludarabine and treosulfan-2; and fludarabine and busulfan-1. All received PTCy 50 mg/kg on days 3 and 4 as graft versus host disease prophylaxis along with tacrolimus and mycophenolate...
September 13, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28870642/high-dose-thiotepa-busulfan-cyclophosphamide-and-autologous-stem-cell-transplantation-as-upfront-consolidation-for-systemic-non-hodgkin-lymphoma-with-synchronous-central-nervous-system-involvement
#6
David Qualls, Andrew Sullivan, Shuli Li, Andrew M Brunner, Kerry Collier, Ephraim Hochberg, Philippe Armand, Tracy T Batchelor, Yi-Bin Chen, Zachariah DeFilipp
INTRODUCTION: Synchronous involvement of the central nervous system (CNS) at the diagnosis of systemic non-Hodgkin lymphoma (NHL) is associated with an increased risk for relapse despite complete remission to initial therapy. High-dose chemotherapy with a CNS-directed conditioning regimen followed by autologous stem cell transplantation (ASCT) holds promise as a consolidative approach. PATIENTS AND METHODS: We conducted a retrospective analysis of all patients with systemic B-cell NHL and synchronous CNS involvement who received upfront consolidation with high-dose chemotherapy with thiotepa, busulfan, cyclophosphamide, and ASCT while in first complete remission between July 2008 and June 2016 at 2 partner academic institutions...
August 15, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28859032/successful-reduced-intensity-conditioning-alternate-donor-stem-cell-transplant-for-wiskott-aldrich-syndrome
#7
Dhwanee Thakkar, Satyendra Katewa, Neha Rastogi, Shruti Kohli, Sagar Nivargi, Satya P Yadav
There are very few reports of reduced intensity conditioning (RIC) hematopoietic stem cell transplant (HSCT) with alternate donor for Wiskott-Aldrich syndrome (WAS) and there is no report of RIC with posttransplant cyclophosphamide (PTCy) in WAS. There is only 1 report of T cell receptor αβ and CD19-depleted haploidentical HSCT for WAS. Here we report successful outcome in 3 children with WAS who underwent successful RIC alternate donor HSCT of whom 2 (matched unrelated donor and T-cell replete haploidentical) received PTCy and 1 underwent T cell receptor αβ and CD19-depleted haploidentical HSCT...
November 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28843054/high-dose-treatment-for-malignant-rhabdoid-tumor-of-the-kidney-no-evidence-for-improved-survival-the-gesellschaft-f%C3%A3-r-p%C3%A3-diatrische-onkologie-und-h%C3%A3-matologie-gpoh-experience
#8
Rhoikos Furtwängler, Leo Kager, Patrick Melchior, Christian Rübe, Martin Ebinger, Nasenien Nourkami-Tutdibi, Felix Niggli, Steven Warmann, Jochen Hubertus, Gabriele Amman, Ivo Leuschner, Christian Vokuhl, Norbert Graf, Michael C Frühwald
BACKGROUND: Malignant rhabdoid tumor of the kidney (MRTK) is the most aggressive childhood renal tumor with overall survival (OS) rates ranging from 22% to 42%. Whether high-dose chemotherapy with autologous stem-cell transplantation (HDSCT) in an intensive first-line treatment offers additional benefit is an ongoing discussion. METHODS: A retrospective analysis of all 58 patients with MRTK from Austria, Switzerland, and Germany treated in the framework of consecutive, prospective renal/rhabdoid tumor studies SIOP9/GPO, SIOP93-01/GPOH (where SIOP is International Society of Pediatric Oncology and GPOH is German Society of Pediatric Oncology and Hematology), SIOP2001/GPOH, and European Rhabdoid Tumor Registry from 1991 to 2014...
August 26, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28780238/t-cell-receptor-%C3%AE-%C3%AE-and-cd19-cell-depleted-haploidentical-and-mismatched-hematopoietic-stem-cell-transplantation-in-primary-immune-deficiency
#9
Ravi M Shah, Reem Elfeky, Zohreh Nademi, Waseem Qasim, Persis Amrolia, Robert Chiesa, Kanchan Rao, Giovanna Lucchini, Juliana M F Silva, Austen Worth, Dawn Barge, David Ryan, Jane Conn, Andrew J Cant, Roderick Skinner, Intan Juliana Abd Hamid, Terence Flood, Mario Abinun, Sophie Hambleton, Andrew R Gennery, Paul Veys, Mary Slatter
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is used as a therapeutic approach for primary immunodeficiencies (PIDs). The best outcomes have been achieved with HLA-matched donors, but when a matched donor is not available, a haploidentical or mismatched unrelated donor (mMUD) can be useful. Various strategies are used to mitigate the risk of graft-versus-host disease (GvHD) and rejection associated with such transplants. OBJECTIVE: We sought to evaluate the outcomes of haploidentical or mMUD HSCT after depleting GvHD-causing T-cell receptor (TCR) αβ CD3(+) cells from the graft...
August 3, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28729147/adult-umbilical-cord-blood-transplantation-using-myeloablative-thiotepa-total-body-irradiation-and-fludarabine-conditioning
#10
Sarah Anand, Samantha Thomas, Kelly Corbet, Cristina Gasparetto, Gwynn D Long, Richard Lopez, Ashley K Morris, David A Rizzieri, Keith M Sullivan, Anthony D Sung, Stefanie Sarantopoulos, Nelson J Chao, Mitchell E Horwitz
Treatment-related mortality (TRM) remains elevated in adult patients undergoing umbilical cord blood transplantation (UCBT), including an early rise in TRM suggestive of excessive toxicity associated with the standard myeloablative total body irradiation (TBI), fludarabine, and cyclophosphamide regimen. In an attempt to reduce regimen-related toxicity, we previously studied a modified myeloablative regimen with TBI (1350 cGy) and fludarabine (160 mg/m(2)); TRM was decreased, but neutrophil engraftment was suboptimal...
July 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28713390/hematopoietic-stem-cell-transplantation-in-an-infant-with-immunodeficiency-centromeric-instability-and-facial-anomaly-syndrome
#11
Katharina L Gössling, Cyrill Schipp, Ute Fischer, Florian Babor, Gerhard Koch, Friedhelm R Schuster, Jutta Dietzel-Dahmen, Dagmar Wieczorek, Arndt Borkhardt, Roland Meisel, Michaela Kuhlen
Immunodeficiency, centromeric instability, and facial anomaly (ICF) syndrome is a rare autosomal recessive genetic condition with severe immunodeficiency, which leads to lethal infections if not recognized and treated in early childhood. Up-to-date treatment regimens consist of prophylactic and supportive treatment of the recurrent infections. Here, we report the case of a 1-year-old boy of Moroccan consanguineous parents, who was diagnosed at 4 months of age with ICF syndrome with a homozygous missense mutation in the DNMT3B gene...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28647558/durable-chimerism-and-long-term-survival-after-unrelated-umbilical-cord-blood-transplantation-for-pediatric-hemophagocytic-lymphohistiocytosis-a-single-center-experience
#12
Sachit A Patel, Heather A Allewelt, Jesse D Troy, Paul L Martin, Timothy A Driscoll, Vinod K Prasad, Joanne Kurtzberg, Kristin M Page, Suhag H Parikh
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune dysregulation characterized by fever, hepatosplenomegaly, cytopenias, central nervous system disease, increased inflammatory markers, and hemophagocytosis. Currently, allogeneic hematopoietic stem cell transplantation is the only curative approach for patients with HLH, with reported survival ranging from 50% to 70% with myeloablative conditioning (MAC) regimens. However, donor availability and transplantation-related mortality associated with conventional MAC are major barriers to success...
June 21, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28614903/thiotepa-based-conditioning-versus-total-body-irradiation-as-myeloablative-conditioning-prior-to-allogeneic-stem-cell-transplantation-for-acute-lymphoblastic-leukemia-a-matched-pair-analysis-from-the-acute-leukemia-working-party-of-the-european-society-for
#13
COMPARATIVE STUDY
Sandra Eder, Jonathan Canaani, Eric Beohou, Myriam Labopin, Jaime Sanz, William Arcese, Reuven Or, Juergen Finke, Agostino Cortelezzi, Dietrich Beelen, Jakob Passweg, Gerard Socié, Gunhan Gurman, Mahmoud Aljurf, Matthias Stelljes, Sebastian Giebel, Mohamad Mohty, Arnon Nagler
The optimal conditioning regimen to employ before hematopoietic stem cell transplantation in acute lymphoblastic leukemia (ALL) is still undecided, and while cyclophosphamide/total body irradiation (Cy/TBI) is the most commonly used myeloablative regimen, there are concerns regarding long-term toxicity for patients conditioned with this regimen. Thiotepa-based conditioning is an emerging radiation-free regimen with recent publications indicative of comparable clinical outcomes to TBI-based conditioning. In this analysis of the acute leukemia working party of the EBMT, we performed a retrospective matched-pair analysis, evaluating the outcome of adult patients with ALL who received thiotepa-based conditioning (n = 180) with those receiving Cy/TBI conditioning (n = 540)...
October 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28604667/single-agent-gvhd-prophylaxis-with-tacrolimus-after-post-transplant-high-dose-cyclophosphamide-is-a-valid-option-for-haploidentical-transplantation-in-adults-with-hematological-malignancies
#14
A Esquirol, M J Pascual, M Ortiz, J L Piñana, C Ferra, I Garcia Cadenas, I Vilades, S Brunet, R Martino, J Sierra
Eighty-one patients with high-risk hematological malignancies received unmanipulated haploidentical stem cell transplants (haploSCT) using the same protocol at four Spanish institutions. The conditioning regimen was thiotepa, busulfan and fludarabine; following bone marrow or peripheral blood infusion. GvHD prophylaxis with high-dose cyclophosphamide on days +3 and +4, and IV tacrolimus from day +5 was administered. 62% were in complete remission, 17% had received previous allogeneic SCT and 44% had a high-very high refined disease risk index...
September 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28581466/high-dose-chemotherapy-and-autologous-stem-cell-transplantation-for-primary-central-nervous-system-lymphoma-a-multi-centre-retrospective-analysis-from-the-united-kingdom
#15
S Kassam, E Chernucha, A O'Neill, C Hemmaway, T Cummins, S Montoto, A Lennard, G Adams, K Linton, P McKay, D Davies, C Rowntree, S Easdale, T A Eyre, R Marcus, K Cwynarski, C P Fox
The prognosis of patients with primary central nervous system lymphoma (PCNSL) has improved in recent years. This has partly been achieved by remission induction protocols incorporating high-dose methotrexate (HD-MTX) and rituximab. Given the high rates of relapse, consolidation therapy is usually considered in first response. Whole brain radiotherapy may prolong PFS but appears to confer no long-term survival advantage and is associated with significant neurocognitive dysfunction. Attempts to improve efficacy and reduce neurotoxicity of consolidation therapy have included thiotepa-based high-dose chemotherapy and autologous stem cell transplant (HDC-ASCT)...
September 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28578010/unrelated-umbilical-cord-blood-transplantation-for-sickle-cell-disease-following-reduced-intensity-conditioning-results-of-a-phase-i-trial
#16
Allistair Abraham, Andrew Cluster, David Jacobsohn, David Delgado, Monica L Hulbert, Divyesh Kukadiya, Lisa Murray, Shalini Shenoy
Hematopoietic stem cell transplantation from HLA-matched sibling donors results in disease-free survival of >90% in patients with sickle cell disease (SCD); however, only approximately 18% of these patients have suitable donors available. Unrelated cord blood transplantation (UCBT) is one way to expand donor options for patients with severe SCD, but historically has been associated with high graft rejection rates (50% to 62%). We hypothesized that the addition of thiotepa to a previously tested reduced-intensity conditioning (RIC) regimen would support engraftment after UCBT in patients with SCD...
September 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28573314/reduced-toxicity-myeloablative-hla-haploidentical-hematopoietic-stem-cell-transplantation-with-post-transplantation-cyclophosphamide-for-sickle-cell-disease
#17
Volker Wiebking, Sebastian Hütker, Irene Schmid, Stefanie Immler, Tobias Feuchtinger, Michael H Albert
Allogeneic hematopoietic stem cell transplantation (HSCT) offers the possibility of cure for sickle cell disease (SCD) patients. Unfortunately, the probability of finding an HLA-matched donor for SCD patients is low. HSCT from HLA-haploidentical donors using reduced intensity conditioning, unmanipulated bone marrow and post-transplantation cyclophosphamide (ptCy) has resulted in negligible toxicity but high rates of graft rejection. We hypothesized that combining ptCy with a myeloablative reduced toxicity conditioning including serotherapy to increase immune ablation would allow for better engraftment...
August 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28559537/high-dose-chemotherapy-with-autologous-haematopoietic-stem-cell-support-for-relapsed-or-refractory-primary-cns-lymphoma-a-prospective-multicentre-trial-by-the-german-cooperative-pcnsl-study-group
#18
B Kasenda, G Ihorst, R Schroers, A Korfel, I Schmidt-Wolf, G Egerer, L von Baumgarten, A Röth, J Bloehdorn, R Möhle, M Binder, U Keller, M Lamprecht, M Pfreundschuh, E Valk, H Fricker, E Schorb, K Fritsch, J Finke, G Illerhaus
To investigate safety and efficacy of high-dose chemotherapy followed by autologous stem cell transplantation (HCT-ASCT) in relapsed/refractory (r/r) primary central nervous system lymphoma (PCNSL), we conducted a single-arm multicentre study for immunocompetent patients (<66 years) with PCNSL failing high-dose methotrexate)-based chemotherapy. Induction consisted of two courses of rituximab (375 mg/m(2)), high-dose cytarabine (2 × 3 g/m(2)) and thiotepa (40 mg/m(2)) with collection of stem cells in between...
May 31, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28511709/incorporation-of-high-dose-131-i-metaiodobenzylguanidine-treatment-into-tandem-high-dose-chemotherapy-and-autologous-stem-cell-transplantation-for-high-risk-neuroblastoma-results-of-the-smc-nb-2009-study
#19
Ji Won Lee, Sanghoon Lee, Hee Won Cho, Youngeun Ma, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo, Eun Joo Cho, Suk-Koo Lee, Do Hoon Lim
BACKGROUND: In our previous SMC NB-2004 study of patients with high-risk neuroblastomas, which incorporated total-body irradiation (TBI) with second high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT), the survival rate was encouraging; however, short- and long-term toxicities were significant. In the present SMC NB-2009 study, only TBI was replaced with (131)I-meta-iodobenzylguanidine (MIBG) treatment in order to reduce toxicities. METHODS: From January 2009 to December 2013, 54 consecutive patients were assigned to receive tandem HDCT/auto-SCT after nine cycles of induction chemotherapy...
May 16, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28509337/impact-of-induction-chemotherapy-hyperfractionated-accelerated-radiotherapy-and-high-dose-thiotepa-on-brain-volume-loss-and-functional-status-of-children-with-primitive-neuroectodermal-tumour
#20
Elwira Szychot, Kiran Seunarine, Kshitij Mankad, Steffi Thust, Chris Clark, Mark N Gaze, Antony Michalski
BACKGROUND: The introduction of aggressive chemo-radiotherapy regimens has improved overall survival in children with primitive neuroectodermal tumours (PNET). However, these combinations may result in neurotoxicity. Previously reported magnetic resonance imaging abnormalities in children receiving intensive sequential chemotherapy, hyperfractionated accelerated radiotherapy (HART) and high-dose thiotepa prompted us to investigate the degree of brain volume loss and patients' functional status after therapy...
November 2017: Pediatric Blood & Cancer
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