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Leylagul Kaynar, Koray Demir, Esra Ermiş Turak, Çiğdem Pala Öztürk, Gökmen Zararsız, Zeynep Burçin Gönen, Selma Gökahmetoğlu, Serdar Şıvgın, Bülent Eser, Yavuz Köker, Musa Solmaz, Ali Ünal, Mustafa Çetin
INTRODUCTION: The use of αβ+ T-cell-depleted grafts is a novel approach to prevent graft failure, graft-versus-host disease (GVHD), and non-relapse mortality (NRM) in patients undergoing haploidentical hematopoietic stem cell transplantation. PATIENT AND METHOD: Thirty-four patients with acute leukemia and lacking a match donor were treated with αβ T-cell-depleted allografts from haploidentical family donors. A total of 24 patients had acute myeloid leukemia (AML) and 10 had acute lymphoblastic leukemia...
October 10, 2016: Hematology (Amsterdam, Netherlands)
Vincenzo Serretta, Cristina Scalici Gesolfo, Vincenza Alonge, Fabrizio Di Maida, Giovanni Caruana
Mitomycin C (MMC) intravesical therapy for "superficial" papillary bladder tumors was firstly introduced in the early seventies with promising results. In the following years, several pharmacokinetic studies investigated its mechanism of action to optimize the intravesical administration. Numerous studies confirmed thereafter both the ablative and the prophylactic efficacy and the low toxicity of MMC when intravesically given. In 1984, a complete response rate of 42% in 60 patients not responsive to thiotepa was reported with intravesical MMC at the dose of 40 mg diluted in 40 ml for 8 weeks...
September 28, 2016: Urologia
Alberto Mussetti, Nancy A Kernan, Susan E Prockop, Andromachi Scaradavou, Rachel Lehrman, Julianne M Ruggiero, Kevin Curran, Rachel Kobos, Richard O'Reilly, Farid Boulad
Nonmalignant hematologic disorders (NMHD) of childhood comprise a variety of disorders, including acquired severe aplastic anemia and inherited marrow failure syndromes. Patients with high-risk NMHD without matched related donors fare poorly with allogeneic hematopoietic alternative donor stem cell transplantation (allo-HSCT) and are at high risk for developing graft-versus-host disease following unmodified grafts. The authors retrospectively analyzed data on 18 patients affected by NMHD, lacking a human leukocyte antigen (HLA)-identical sibling donor, who underwent an alternative donor allo-HSCT at their institution between April 2005 and May 2013...
October 7, 2016: Pediatric Hematology and Oncology
Michael Scordo, Valkal Bhatt, Meier Hsu, Antonio M Omuro, Matthew J Matasar, Lisa M DeAngelis, Parastoo B Dahi, Craig H Moskowitz, Sergio A Giralt, Craig S Sauter
High-dose therapy and autologous stem cell transplantation (HDT-ASCT) with thiotepa, busulfan, cyclophosphamide (TBC) conditioning has emerged as an effective post-induction treatment strategy for patients with primary (PCNSL) or secondary central nervous system lymphoma (SCNSL), but it is associated with considerable toxicity and transplant-related mortality (TRM) in the modern era. Forty-three adult patients with chemosensitive PCNSL or SCNSL received TBC conditioned ASCT between 2006 and 2015. Twenty-eight of these patients received pharmacokinetically (PK)-targeted busulfan dosing...
October 3, 2016: Biology of Blood and Marrow Transplantation
Sandra Eder, Eric Beohou, Myriam Labopin, Jaime Sanz, Jürgen Finke, William Arcese, Reuven Or, Francesca Bonifazi, Mahmoud Aljurf, Gerard Socié, Jakob Passweg, Sebastian Giebel, Mohamad Mohty, Arnon Nagler
In this study, we analyzed a thiotepa-based conditioning regimen for allogeneic stem cell transplantation in adults with acute lymphoblastic leukemia, using the EBMT database. A total of 323 patients were identified. The median age was 43 years. Disease status at transplant was first complete remission (CR1) in 48.9%, CR2 in 21.7%, CR3 in 6.2%, while 23.2% of the patients had an active disease at the time of transplant. This was performed from a HLA-matched sibling (49.8%) or a matched-unrelated donor (51.2%)...
September 27, 2016: American Journal of Hematology
S Eder, M Labopin, J Finke, D Bunjes, A Olivieri, S Santarone, A Rambaldi, L Kanz, G Messina, M Mohty, A Nagler
This study evaluated the safety and efficacy of thiotepa-based regimens before allogeneic stem cell transplantation in 310 adult patients with AML. Disease status at the time of transplantation was CR1 in 50%, CR2+ in 23.5% and advanced disease in 26.5%. Transplantation was performed from haploidentical (35%), matched sibling (27%), unrelated (20%) or cord blood (18%) donors. As for safety: mucositis occurred in 46.8% of the patients and the cumulative incidence (CI) of sinusoidal obstruction syndrome was 4...
September 19, 2016: Bone Marrow Transplantation
Surapol Issaragrisil, Chutima Kunacheewa
PURPOSE OF REVIEW: Bone marrow transplantation is the only curative treatment for severe thalassemia. Since its successful first report in 1981, more than 4000 patients with this disease worldwide underwent bone marrow transplantation. The purpose of this review is to update the most recent reports of matched sibling donor hematopoietic stem cell transplantation in thalassemia. RECENT FINDINGS: Advanced and improved transplant techniques result in the improved outcomes in those transplants from a matched sibling donor with transplant-related mortality less than 5%...
November 2016: Current Opinion in Hematology
Tymofii Yu Nikolaienko, Leonid A Bulavin, Leonid F Sukhodub
Non-covalent complexes of methylated nitrogenous DNA base guanine (m(9) Gua) with 1 to 6 molecules of anticancer drug ThioTEPA (1,1',1''-phosphorothioyltriaziridine) have been investigated by molecular modeling techniques (molecular docking and DFT geometry optimization), ab initio wavefunction calculations and the quantum theory of atoms in molecules (QTAIM). The accuracy of complex structures predicted by standard molecular docking techniques have been assessed by comparing them with ab initio calculations, and the most important differences have been discussed...
February 2014: Molecular Informatics
Gerald Illerhaus, Benjamin Kasenda, Gabriele Ihorst, Gerlinde Egerer, Monika Lamprecht, Ulrich Keller, Hans-Heinrich Wolf, Carsten Hirt, Stephan Stilgenbauer, Mascha Binder, Peter Hau, Matthias Edinger, Norbert Frickhofen, Martin Bentz, Robert Möhle, Alexander Röth, Michael Pfreundschuh, Louisa von Baumgarten, Martina Deckert, Claudia Hader, Heidi Fricker, Elke Valk, Elisabeth Schorb, Kristina Fritsch, Jürgen Finke
BACKGROUND: High-dose methotrexate-based chemotherapy is standard for primary CNS lymphoma, but most patients relapse. High-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) is supposed to overcome the blood-brain barrier and eliminate residual disease in the CNS. We aimed to investigate the safety and efficacy of HCT-ASCT in patients with newly diagnosed primary CNS lymphoma. METHODS: In this prospective, single-arm, phase 2 trial, we recruited patients aged 18-65 years with newly diagnosed primary CNS lymphoma and immunocompetence, with no limitation on clinical performance status, from 15 hospitals in Germany...
August 2016: Lancet Haematology
J A Moormeier, S F Williams, L S Kaminer, E D Ellis, M Garner, R Farah, R R Weichselbaum, J D Bitran
Twenty-six patients with refractory or relapsed Hodgkin's disease were treated with high dose cyclophosphamide, BCNU, etoposide, and thiotepa followed by autologous hematopoietic stem cell rescue. Involved field radiotherapy was given following hematologic recovery in selected patients. The overall response rate to the high dose chemotherapy was 69% with 34% complete responses. Following radiotherapy, the complete response rate increased to 50%. The predicted disease-free survival at two years is 22%. Toxicity with this regimen was significant, with five patients dying as a result of transplant related complications...
1991: Leukemia & Lymphoma
Heiko-Manuel Teltschik, Frank Heinzelmann, Bernd Gruhn, Tobias Feuchtinger, Patrick Schlegel, Michael Schumm, Bernhard Kremens, Ingo Müller, Martin Ebinger, Carl Philipp Schwarze, Hellmut Ottinger, Daniel Zips, Rupert Handgretinger, Peter Lang
Graft failure is a life-threatening complication after allogeneic haematopoietic stem cell transplantation (HSCT). We report a cohort of 19 consecutive patients (median age: 8·5 years) with acute leukaemias (n = 14) and non-malignant diseases (n = 5) who experienced graft failure after previous HSCT from matched (n = 3) or haploidentical donors (n = 16) between 2003 and 2012. After total nodal irradiation (TNI)-based reconditioning combined with fludarabine, thiotepa and anti-T cell serotherapy, all patients received T cell-depleted peripheral blood stem cell grafts from a second, haploidentical donor...
October 2016: British Journal of Haematology
Kellie J Nazemi, Violet Shen, Jonathan L Finlay, James Boyett, Mehmet Kocak, Deborah Lafond, Sharon L Gardner, Roger J Packer, H Stacy Nicholson
BACKGROUND: The outcomes with high-risk central nervous system (CNS) embryonal tumors remain relatively poor despite aggressive treatment. The purposes of this study using postirradiation myeloablative chemotherapy with autologous hematopoietic stem cell rescue (ASCR) were to document feasibility and describe toxicities of the regimen, establish the appropriate dose of thiotepa, and estimate the overall survival (OS) and event-free survival (EFS). PROCEDURE: The Children's Cancer Group conducted this pilot study in children and adolescents with CNS embryonal tumors...
September 2016: Pediatric Blood & Cancer
Barbara Spitzer, Miguel-Angel Perales, Nancy A Kernan, Susan E Prockop, Emily C Zabor, Nicholas Webb, Hugo Castro-Malaspina, Esperanza B Papadopoulos, James W Young, Andromachi Scaradavou, Rachel Kobos, Sergio A Giralt, Richard J O'Reilly, Farid Boulad
Relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) remains one of the leading causes of mortality in patients with leukemia. Treatment options in this population remain limited, with concern for both increased toxicity and further relapse. We treated 18 patients with acute leukemia for marrow ± extramedullary relapse after a previous alloHSCT with a myeloablative cytoreductive regimen including clofarabine, melphalan, and thiotepa followed by a second or third transplantation from the same or a different donor...
August 2016: Biology of Blood and Marrow Transplantation
Andrés J M Ferreri, Kate Cwynarski, Elisa Pulczynski, Maurilio Ponzoni, Martina Deckert, Letterio S Politi, Valter Torri, Christopher P Fox, Paul La Rosée, Elisabeth Schorb, Achille Ambrosetti, Alexander Roth, Claire Hemmaway, Angela Ferrari, Kim M Linton, Roberta Rudà, Mascha Binder, Tobias Pukrop, Monica Balzarotti, Alberto Fabbri, Peter Johnson, Jette Sønderskov Gørløv, Georg Hess, Jens Panse, Francesco Pisani, Alessandra Tucci, Stephan Stilgenbauer, Bernd Hertenstein, Ulrich Keller, Stefan W Krause, Alessandro Levis, Hans J Schmoll, Franco Cavalli, Jürgen Finke, Michele Reni, Emanuele Zucca, Gerald Illerhaus
BACKGROUND: Standard treatment for patients with primary CNS lymphoma remains to be defined. Active therapies are often associated with increased risk of haematological or neurological toxicity. In this trial, we addressed the tolerability and efficacy of adding rituximab with or without thiotepa to methotrexate-cytarabine combination therapy (the MATRix regimen), followed by a second randomisation comparing consolidation with whole-brain radiotherapy or autologous stem cell transplantation in patients with primary CNS lymphoma...
May 2016: Lancet Haematology
Elisabeth Schorb, Juergen Finke, Andrés J M Ferreri, Gabriele Ihorst, Kristina Mikesch, Benjamin Kasenda, Kristina Fritsch, Heidi Fricker, Elvira Burger, Olga Grishina, Elke Valk, Emanuele Zucca, Gerald Illerhaus
BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a highly aggressive Non-Hodgkin lymphoma (NHL) with rising incidence over the past 30 years in immunocompetent patients. Although outcomes have improved, PCNSL is still associated with inferior prognosis compared to systemic NHL. Many questions regarding the optimal therapeutic approach remain unanswered. METHODS/DESIGN: This is a randomized, open-label, international phase III trial with two parallel arms...
2016: BMC Cancer
Shu-Ting Pan, Zhi-Ling Li, Zhi-Xu He, Jia-Xuan Qiu, Shu-Feng Zhou
Chemotherapy is one of the prevailing methods used to treat malignant tumours, but the outcome and prognosis of tumour patients are not optimistic. Cancer cells gradually generate resistance to almost all chemotherapeutic drugs via a variety of distinct mechanisms and pathways. Chemotherapeutic resistance, either intrinsic or acquired, is caused and sustained by reduced drug accumulation and increased drug export, alterations in drug targets and signalling transduction molecules, increased repair of drug-induced DNA damage, and evasion of apoptosis...
August 2016: Clinical and Experimental Pharmacology & Physiology
Jonathan Jarow, V Ellen Maher, Shenghui Tang, Amna Ibrahim, Geoffrey Kim, Rajeshwari Sridhara, Richard Pazdur
There are few approved drugs available for the treatment of patients with non-muscle invasive bladder cancer (NMIBC) and none have been approved in the twenty-first century. Four drugs; thiotepa in 1959, BCG Tice in 1989, BCG Connaught in 1990, and valrubicin in 1998, have been approved for the treatment of NMIBC. In addition to these four agents, mitomycin is commonly used off-label as an intravesical treatment for NMIBC. New drugs are needed for the management of NMIBC. This article outlines important aspects of the design and conduct of clinical trials to develop new therapies for these patients and to obtain marketing approval...
2015: Bladder Cancer
B Shao, H P Li, L J DI, G H Song, H F Jiang, X Liang, C Y Wang, Y Yan, X L Lin, L N Wang, F L Wan, Y H Yuan, M N You
OBJECTIVE: To detect the proportion of lymphocyte subsets in peripheral blood of the advanced breast cancer patients before and after chemotherapy with docetaxel and thiotepa, as well as the association between the proportion of peripheral blood lymphocyte subsets with the response rate and prognosis. METHODS: The proportions of lymphocyte subsets (CD3+ T cell, CD3+/CD4+ T cell, CD3+/CD8+ T cell, CD3-/CD16+56+ NK cell, CD3+/CD16+56+ T cell, CD19+ B cell, CD4+/CD25+ T cell, CD8+/CD28- T cell, CD8+/CD28+ T cell) in the peripheral blood of 86 patients were analyzed with flowcytometry before and after chemotherapy...
April 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
María Forte Pérez-Minayo, Eva Castillo Bazán, Marta Hernández Segurado, María Ángeles Arias Moya, Paloma Pelegrín Torres, Francisco Javier Bécares Martínez
OBJECTIVE: In the setting of the increasing use of closed systems for reconstitution and preparation of these drugs, we intend to analyze the correct use of these systems in the Hospital Pharmacy, with the objective to minimize the risks of exposure not only for those professionals directly involved, but also for all the staff in the unit, taking also into account efficiency criteria. METHOD: Since some systems protect against aerosol formation but not from vapours, we decided to review which cytostatics should be prepared using an awl with an air inlet valve, in order to implement a new working procedure...
March 2016: Farmacia Hospitalaria
Philip C Schouten, Oleg Gluz, Nadia Harbeck, Svjetlana Mohrmann, Raihana Diallo-Danebrock, Enrico Pelz, Janneke Kruizinga, Arno Velds, Marja Nieuwland, Ron M Kerkhoven, Cornelia Liedtke, Markus Frick, Ronald Kates, Sabine C Linn, Ulrike Nitz, Frederik Marme
BRCA1 is an important protein in the repair of DNA double strand breaks (DSBs), which are induced by alkylating chemotherapy. A BRCA1-like DNA copy number signature derived from tumors with a BRCA1 mutation is indicative for impaired BRCA1 function and associated with good outcome after high dose (HD) and tandem HD DSB inducing chemotherapy. We investigated whether BRCA1-like status was a predictive biomarker in the WSG AM 01 trial. WSG AM 01 randomized high-risk breast cancer patients to induction (2× epirubicin-cyclophosphamide) followed by tandem HD chemotherapy with epirubicin, cyclophosphamide and thiotepa versus dose dense chemotherapy (4× epirubicin-cyclophospamide followed by 3× cyclophosphamide-methotrexate-5-fluorouracil)...
August 15, 2016: International Journal of Cancer. Journal International du Cancer
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