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https://www.readbyqxmd.com/read/28780238/tcr%C3%AE-%C3%AE-and-cd19-cell-depleted-haploidentical-and-mismatched-hematopoietic-stem-cell-transplantation-in-primary-immune-deficiency
#1
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 using 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 TCRαβCD3+ cells from the graft...
August 2, 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
#2
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
#3
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
#4
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
#5
Sandra Eder, Jonathan Canaani, Eric Beohou, Myriam Labopin, Miguel A 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 hematopoieitic stem cell transplantation in acute lymphoblastic leukemia (ALL) is still undecided, and while 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)...
June 14, 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
#6
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...
June 12, 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
#7
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)...
June 5, 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
#8
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
#9
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
#10
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 CNS lymphoma (PCNSL). We conducted a single-arm multicentre study for immunocompetent patients (<66 years) with PCNSL failing high-dose methotrexate (HD-MTX) based chemotherapy. Induction consisted of 2 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. Conditioning for HCT-ASCT consisted of rituximab 375 mg/m(2), carmustine 400 mg/m(2) and thiotepa (4 × 5 mg/kg)...
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
#11
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
#12
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...
May 16, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28472509/multicenter-phase-ii-study-of-temozolomide-and-myeloablative-chemotherapy-with-autologous-stem-cell-transplant-for-newly-diagnosed-anaplastic-oligodendroglioma
#13
Alissa A Thomas, Lauren E Abrey, Robert Terziev, Jeffrey Raizer, Nina L Martinez, Peter Forsyth, Nina Paleologos, Matthew Matasar, Craig S Sauter, Craig Moskowitz, Stephen D Nimer, Lisa M DeAngelis, Thomas Kaley, Sean Grimm, David N Louis, J Gregory Cairncross, Katherine S Panageas, Samuel Briggs, Geraldine Faivre, Nimish A Mohile, Jayesh Mehta, Philip Jonsson, Debyani Chakravarty, Jianjiong Gao, Nikolaus Schultz, Cameron W Brennan, Jason T Huse, Antonio Omuro
Background: Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytomas (AOA) are chemotherapy-sensitive tumors with prolonged survival after radiochemotherapy. We report a prospective trial using induction temozolomide (TMZ) followed by myeloablative high-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT), as a potential strategy to defer radiotherapy. Methods: Patients with AO/AOA received 6 cycles of TMZ (200mg/m2 X5/28-day). Responding patients were eligible for HDC (thiotepa 250mg/m2/day X3 days then busulfan 3...
May 2, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28463397/treatment-and-outcomes-of-uk-and-german-patients-with-relapsed-intracranial-germ-cell-tumors-following-uniform-first-line-therapy
#14
Matthew J Murray, Shivani Bailey, Katja Heinemann, Jillian Mann, Ulrich K Göbel, Frank Saran, Juliet P Hale, Gabriele Calaminus, James C Nicholson
We aimed to retrospectively assess treatments/outcomes, including the value of high-dose-chemotherapy and autologous-stem-cell-rescue (HDC + AuSCR) and re-irradiation, in a large, European patient-cohort with relapsed intracranial germ-cell-tumors (GCTs) receiving uniform first-line therapy, including radiotherapy as standard-of-care. Fifty-eight UK/German patients (48 male/10 female) with relapsed intracranial-GCTs [13 germinoma/45 non-germinomatous GCT (NGGCT)] treated 1996-2010 as per the SIOP-CNS-GCT-96 protocol were evaluated...
August 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28436974/high-dose-thiotepa-based-chemotherapy-with-autologous-stem-cell-support-in-elderly-patients-with-primary-central-nervous-system-lymphoma-a-european-retrospective-study
#15
E Schorb, C P Fox, K Fritsch, L Isbell, A Neubauer, A Tzalavras, R Witherall, S Choquet, O Kuittinen, D De-Silva, K Cwynarski, C Houillier, K Hoang-Xuan, V Touitou, N Cassoux, J-P Marolleau, J Tamburini, R Houot, V Delwail, G Illerhaus, C Soussain, B Kasenda
In this retrospective multicentre study, we investigated the outcomes of elderly primary central nervous system lymphoma (PCNSL) patients (⩾65 years) who underwent high-dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT) at 11 centres between 2003 and 2016. End points included remission, progression-free survival (PFS), overall survival (OS) and treatment-related mortality. We identified 52 patients (median age 68.5 years, median Karnofsky Performance Status before HDT-ASCT 80%) who all underwent thiotepa-based HDT-ASCT...
August 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28427529/primary-central-nervous-system-lymphoma
#16
REVIEW
Giovanni Citterio, Michele Reni, Gemma Gatta, Andrés José Maria Ferreri
Primary CNS lymphomas (PCNSL) represent a subgroup of malignancies with specific characteristics, aggressive course, and unsatisfactory outcome in contrast with other lymphomas comparable for tumour burden and/or histological type. Despite a high chemo- and radiosensitivity, remissions are frequently shortlasting, mainly because the blood brain-barrier limits the access of many drugs to the CNS. Moreover, survivor patients are at high risk of developing severe treatment-related toxicity, mainly disabling neurotoxicity, raising the question of how to balance therapy intensification with side-effects control...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28396159/a-time-to-event-model-for-acute-kidney-injury-after-reduced-intensity-conditioning-stem-cell-transplantation-using-a-tacrolimus-and-sirolimus-based-graft-versus-host-disease-prophylaxis
#17
José Luis Piñana, Alejandro Perez-Pitarch, Irene Garcia-Cadenas, Pere Barba, Juan Carlos Hernandez-Boluda, Albert Esquirol, María Laura Fox, María José Terol, Josep M Queraltó, Jaume Vima, David Valcarcel, Rafael Ferriols-Lisart, Jorge Sierra, Carlos Solano, Rodrigo Martino
There is a paucity of data evaluating acute kidney injury (AKI) incidence and its relationship with the tacrolimus-sirolimus (Tac-Sir) concentrations in the setting of reduced-intensity conditioning (RIC) after allogeneic stem cell transplantation (allo-HSCT). This multicenter retrospective study evaluated risk factors of AKI defined by 2 classification systems, Kidney Disease Improving Global Outcome (KDIGO) score and "Grade 0-3 staging," in 186 consecutive RIC allo-HSCT recipients with Tac-Sir as graft-versus-host disease prophylaxis...
July 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28390983/allogeneic-stem-cell-transplantation-for-relapsed-refractory-b-cell-lymphomas-results-of-a-multicenter-phase-ii-prospective-trial-including-rituximab-in-the-reduced-intensity-conditioning-regimen
#18
Anna Dodero, Francesca Patriarca, Giuseppe Milone, Barbara Sarina, Rosalba Miceli, Anna Iori, Francesco Barretta, Elisabetta Terruzzi, Alberto Mussetti, Massimo Pini, Alberto Bosi, Alida Dominietto, Nicola Cascavilla, Francesco Onida, Franco Narni, Lucia Farina, Alessandro Rambaldi, Paolo Corradini
The treatment of patients with refractory/relapsed B cell non-Hodgkin lymphoma (NHL) is evolving because of the availability of novel drugs. Allogeneic stem cell transplantation (alloSCT) can be curative, but its morbidity and mortality remain a matter of concern. We conducted a multicenter prospective phase II trial to evaluate the benefit of including only 1 dose of rituximab in the conditioning regimen before alloSCT. The primary endpoint was progression-free survival. The study enrolled 121 patients with relapsed/refractory B cell lymphomas...
July 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28369839/high-dose-chemotherapy-with-thiotepa-busulfan-and-cyclophosphamide-and-autologous-stem-cell-transplantation-for-patients-with-primary-central-nervous-system-lymphoma-in-first-complete-remission
#19
Zachariah DeFilipp, Shuli Li, Areej El-Jawahri, Philippe Armand, Lakshmi Nayak, Nancy Wang, Tracy T Batchelor, Yi-Bin Chen
BACKGROUND: High-dose chemotherapy and autologous stem cell transplantation (HDC-ASCT) is a therapeutic option for patients with primary central nervous system lymphoma (PCNSL). To the authors' knowledge, data are limited regarding its use among patients in first complete remission (CR1) with the CNS-directed conditioning regimen of thiotepa, busulfan, and cyclophosphamide (TBC). METHODS: A retrospective analysis of patients with PCNSL in CR1 who underwent transplantation using a TBC-based conditioning regimen at 2 academic institutions was performed...
April 3, 2017: Cancer
https://www.readbyqxmd.com/read/28293402/treosulfan-based-conditioning-regimen-in-sibling-and-alternative-donor-hematopoietic-stem-cell-transplantation-for-children-with-sickle-cell-disease
#20
Antonio Marzollo, Elisabetta Calore, Manuela Tumino, Marta Pillon, Maria Vittoria Gazzola, Roberta Destro, Raffaella Colombatti, Piero Marson, Tiziana Tison, Anna Colpo, Chiara Mainardi, Maria Gabelli, Maria Paola Boaro, Sara Rossin, Aurora Strano, Nadia Quaglia, Federica Menzato, Giuseppe Basso, Laura Sainati, Chiara Messina
BACKGROUND AND OBJECTIVES: Lack of suitable donors and regimen related toxicity are major barriers for hematopoietic stem cell transplantation (HSCT) in patients with sickle cell disease (SCD). The aim of the study is the assessment of efficacy and toxicity of Treosulfan-based conditioning regimen for SCD also when alternative donors such as mismatched unrelated donor and haploidentical donor are employed. METHODS: We report our single-center experience: 11 patients with SCD received HSCT with a Treosulfan/Thiotepa/Fludarabine/Anti-thymoglobulin conditioning regimen between 2010 and 2015...
2017: Mediterranean Journal of Hematology and Infectious Diseases
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