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Myeloablative Chemotherapy

E Palmerini, R L Jones, E Setola, P Picci, E Marchesi, R Luksch, G Grignani, M Cesari, A Longhi, M E Abate, A Paioli, Z Szucs, L D'ambrosio, K Scotlandi, F Fagioli, S Asaftei, S Ferrari
BACKGROUND: Data on temozolomide (TEM) and irinotecan (IRI) activity in recurrent Ewing sarcoma (EWS), especially in adult patients, are limited. METHODS: Patients receiving TEM 100 mg/m2 /day oral, and IRI 40 mg/m2 /day intravenous, days 1-5, every 21 days, were included in this multi-institutional retrospective study. Disease control rate (DCR) [overall response rate (ORR) [complete response (CR) + partial response (PR)] + stable disease (SD)], 6-months progression-free survival (6-mos PFS) and 1-year overall survival (OS) were assessed...
March 13, 2018: Acta Oncologica
Christopher C Dvorak, Prakash Satwani, Elliot Stieglitz, Mitchell S Cairo, Ha Dang, Qinglin Pei, Yun Gao, Donna Wall, Tali Mazor, Adam B Olshen, Joel S Parker, Samir Kahwash, Betsy Hirsch, Susana Raimondi, Neil Patel, Micah Skeens, Todd Cooper, Parinda A Mehta, Stephan A Grupp, Mignon L Loh
BACKGROUND: Most patients with juvenile myelomonocytic leukemia (JMML) are curable only with allogeneic hematopoietic cell transplantation (HCT). However, the current standard conditioning regimen, busulfan-cyclophosphamide-melphalan (Bu-Cy-Mel), may be associated with higher risks of morbidity and mortality. ASCT1221 was designed to test whether the potentially less-toxic myeloablative conditioning regimen containing busulfan-fludarabine (Bu-Flu) would be associated with equivalent outcomes...
March 12, 2018: Pediatric Blood & Cancer
Satoshi Ichikawa, Noriko Fukuhara, Shunsuke Hatta, Masahito Himuro, Hiroki Katsushima, Kentaro Nasu, Koya Ono, Kyoko Inokura, Masahiro Kobayashi, Yasushi Onishi, Hiroshi Fujii, Kenichi Ishizawa, Ryo Ichinohasama, Hideo Harigae
A 16-year-old boy, who had been initially examined for bilateral blepharedema and slight eruption, presented with rapidly deteriorating symptoms in associating with headache and consciousness disturbance. He was diagnosed to have primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (PCAE-CTL) by a biopsy of the skin and brain. After whole-brain radiation and some courses of chemotherapy, cord blood transplantation was performed with myeloablative conditioning. After transplantation, the cerebral dysfunction gradually improved...
March 9, 2018: Internal Medicine
Musa Alzahrani, Maryse Power, Yasser Abou Mourad, Michael Barnett, Raewyn Broady, Donna Forrest, Alina Gerrie, Donna Hogge, Stephen Nantel, David Sanford, Kevin Song, Heather Sutherland, Cynthia Toze, Thomas Nevill, Sujaatha Narayanan
BACKGROUND: The natural history of patients with myelodysplastic syndromes (MDS) is variable. The revised international prognostic score (IPSS-R) is commonly used in practice to predict outcome in patients with MDS both at diagnosis and pre-transplant. However the effect of change in IPSS-R pre-allogeneic stem cell transplant with chemotherapy or hypomethylating agents on post-transplant outcomes is currently unknown. AIM: We assessed if improvement in IPSS-R prognostic score pre HSCT would result in improvement in clinical outcomes post-transplant...
February 20, 2018: Biology of Blood and Marrow Transplantation
Amar Desai, Yongyou Zhang, Youngsoo Park, Dawn M Dawson, Gretchen A Larusch, Lakshmi Kasturi, David Wald, Joseph M Ready, Stanton L Gerson, Sanford D Markowitz
Hematopoietic stem cell transplantation following myeloablative chemotherapy is a curative treatment for many hematopoietic malignancies. However, profound granulocytopenia during the interval between transplant and marrow recovery exposes recipients to risks of fatal infection, a significant source of transplant associated morbidity and mortality. We have previously described the discovery of a small molecule, SW033291, that potently inhibits the prostaglandin degrading enzyme 15-PGDH, increases bone marrow PGE2, and accelerates hematopoietic recovery following murine transplant...
February 22, 2018: Haematologica
Laura Cudillo, Raffaella Cerretti, Alessandra Picardi, Benedetta Mariotti, Gottardo De Angelis, Maria Cantonetti, Massimiliano Postorino, Eleonora Ceresoli, Giovanna De Santis, Daniela Nasso, Francesco Pisani, Enrico Scala, Fabio Di Piazza, Alessandro Lanti
In our retrospective study, 16 patients affected by advanced cutaneous T cell lymphoma (CTCL) underwent allogeneic hematopoietic stem cell transplantation (HSCT). Two patients (12.5%) were in complete remission (CR), nine (56.3%) in partial remission (PR), and five (31.2%) with active disease. The patients were transplanted from an HLA-identical (n = 7) from a mismatched (n = 1) or haploidentical (n = 1) sibling, from matched unrelated donor (n = 5), or from a single cord blood unit (n = 2). Conditioning regimen was standard myeloablative in 6 patients and at reduced intensity in 10...
February 13, 2018: Annals of Hematology
Akira Nakagawara, Yuanyuan Li, Hideki Izumi, Katsumi Muramori, Hiroko Inada, Masanori Nishi
Neuroblastoma is one of the most common solid tumors in children and has a diverse clinical behavior that largely depends on the tumor biology. Neuroblastoma exhibits unique features, such as early age of onset, high frequency of metastatic disease at diagnosis in patients over 1 year of age and the tendency for spontaneous regression of tumors in infants. The high-risk tumors frequently have amplification of the MYCN oncogene as well as segmental chromosome alterations with poor survival. Recent advanced genomic sequencing technology has revealed that mutation of ALK, which is present in ~10% of primary tumors, often causes familial neuroblastoma with germline mutation...
January 25, 2018: Japanese Journal of Clinical Oncology
Nelli Bejanyan, Mei-Jie Zhang, Hai-Lin Wang, Aleksandr Lazaryan, Marcos de Lima, David I Marks, Brenda M Sandmaier, Veronika Bachanova, Jacob Rowe, Martin Tallman, Partow Kebriaei, Mohamed Kharfan-Dabaja, Robert Peter Gale, Hillard M Lazarus, Celalettin Ustun, Edward Copelan, Betty Ky Hamilton, Gary Schiller, William Hogan, Shahrukh Hashmi, Matthew Seftel, Christopher Kanakry, Richard F Olsson, Rodrigo Martino, Wael Saber, H Jean Khoury, Daniel J Weisdorf
Allogeneic hematopoietic cell transplantation (alloHCT) is curative for patients with acute lymphoblastic leukemia (ALL) who achieve complete remission (CR1) with chemotherapy. However, the benefit of consolidation chemotherapy remains uncertain in patients undergoing alloHCT. We compared clinical outcomes of 524 adult patients with ALL in CR1 who received ≥2 (n=109), 1 (n=93), or 0 cycles (n=322) of consolidation prior to myeloablative alloHCT from 2008-2012. As expected, time to alloHCT was longer with increasing cycles of consolidation...
December 21, 2017: Biology of Blood and Marrow Transplantation
Justine Decroocq, Raphaël Itzykson, Stéphane Vigouroux, Mauricette Michallet, Ibrahim Yakoub-Agha, Anne Huynh, Florence Beckerich, Felipe Suarez, Patrice Chevallier, Stéphanie Nguyen-Quoc, Marie-Pierre Ledoux, Laurence Clement, Yosr Hicheri, Gaëlle Guillerm, Jérôme Cornillon, Nathalie Contentin, Martin Carre, Natacha Maillard, Mélanie Mercier, Mohamad Mohty, Yves Beguin, Jean-Henri Bourhis, Amandine Charbonnier, Charles Dauriac, Jacques-Olivier Bay, Didier Blaise, Eric Deconinck, Charlotte Jubert, Nicole Raus, Regis Peffault de Latour, Nathalie Dhedin
Patients with acute myeloid leukemia (AML) in relapse or refractory to induction therapy have a dismal prognosis. Allogeneic hematopoietic stem cell transplantation is the only curative option. In these patients, we aimed to compare the results of a myeloablative transplant versus a sequential approach consisting in a cytoreductive chemotherapy followed by a reduced intensity conditioning regimen and prophylactic donor lymphocytes infusions. We retrospectively analyzed 99 patients aged 18-50 years, transplanted for a refractory (52%) or a relapsed AML not in remission (48%)...
March 2018: American Journal of Hematology
Christian Flotho, Sebastian Sommer, Michael Lübbert
Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder, typically of older adults, which is characterized by ineffective hematopoiesis, peripheral blood cytopenias and risk of progression to acute myeloid leukemia. Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm occurring in young children. The common denominator of these malignant myeloid disorders is the limited benefit of conventional chemotherapy and a particular responsiveness to epigenetic therapy with the DNA-hypomethylating agents 5-azacytidine (azacitidine) or decitabine...
November 9, 2017: Seminars in Cancer Biology
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
Diarmuid Coughlan, Matthew Gianferante, Charles F Lynch, Jennifer L Stevens, Linda C Harlan
BACKGROUND: Childhood neuroblastoma describes a heterogeneous group of extracranial solid tumors, that are treated per risk profile. We sought to describe treatment patterns and survival using population-based data from throughout the United States. MATERIALS AND METHODS: Using the National Cancer Institute (NCI)'s Patterns of Care data, we analyzed treatment provided to newly diagnosed, histologically confirmed neuroblastoma patients in 2010 and 2011, registered to one of 14 Surveillance, Epidemiology, and End Results (SEER) cancer registries...
August 2017: Pediatric Hematology and Oncology
Loredana Amoroso, Riccardo Haupt, Alberto Garaventa, Mirco Ponzoni
Neuroblastoma (NB) is an embryonal tumor originating from undifferentiated neural crest cell, highly heterogeneous ranging from spontaneous regression to progression despite multimodal treatments. Approximately, 20% of patients are refractory to frontline therapy and 50% will relapse/progress after an initial response. The overall five year survival for high-risk neuroblastoma ranges from 35-45%. Despite enhanced understanding of NB biology and the addition of myeloablative chemotherapy, isotretinoin and immunotherapy, survival for high risk NB remains less than 50%...
November 2017: Expert Opinion on Investigational Drugs
A G J van Rossum, P C Schouten, K E Weber, V Nekljudova, C Denkert, C Solbach, C H Köhne, C Thomssen, H Forstbauer, G Hoffmann, A Kohls, S Schmatloch, C Schem, G von Minckwitz, T Karn, V J Möbus, S C Linn, S Loibl, F Marmé
PURPOSE: The BRCA1-like profile identifies tumors with a defect in homologous recombination due to inactivation of BRCA1. This profile has been shown to predict which stage III breast cancer patients benefit from myeloablative, DNA double-strand-break-inducing chemotherapy. We tested the predictive potential of the BRCA1-like profile for adjuvant non-myeloablative, intensified dose-dense chemotherapy in the GAIN trial. METHODS: Lymph node positive breast cancer patients were randomized to 3 × 3 dose-dense cycles of intensified epirubicin, paclitaxel, and cyclophosphamide (ETC) or 4 cycles concurrent epirubicin and cyclophosphamide followed by 10 cycles of weekly paclitaxel combined with 4 cycles capecitabine (EC-TX)...
August 18, 2017: Breast Cancer Research and Treatment
Vishal Dhere, Scott Edelman, Edmund K Waller, Amelia Langston, Michael Graiser, Erin C Connolly, Jeffrey M Switchenko, Natia Esiashvili, Mohammad K Khan
Fludarabine and melphalan (Flu/Mel) has emerged as a more tolerable chemotherapy-based conditioning regimen compared with busulfan and cyclophosphamide (Bu/Cy) for allogeneic stem cell transplant (allo-hematopoietic stem cell transplantation (HSCT)) patients with acute myelogenous leukemia (AML). We conducted a retrospective review of a single-institution database including patients with AML who received allo-HSCT following conditioning with Mel/Flu or Bu/Cy-based regimens. We performed descriptive statistical analysis to examine patient demographics and clinical outcomes...
April 2018: Leukemia & Lymphoma
Jin Kyung Suh, Seong Wook Lee, Kyung-Nam Koh, Ho Joon Im, Eun Seok Choi, Seongsoo Jang, Chan-Jeoung Park, Jong Jin Seo
Intensified chemotherapy, HSCT, and supportive care improve the survival of pediatric patients with AML. However, no consensus has been reached regarding the role of HSCT in patients without favorable cytogenetics. We evaluated OS and EFS according to prognostic factors that affect clinical outcomes, including cytogenetics risk group, conditioning regimen, donor type, disease status at the time of HSCT, and number of chemotherapy cycles prior to HSCT in 65 pediatric patients with AML without favorable cytogenetics who underwent HSCT...
November 2017: Pediatric Transplantation
Sarah J Stephens, Samantha Thomas, David A Rizzieri, Mitchell E Horwitz, Nelson J Chao, Ashley M Engemann, Martha Lassiter, Chris R Kelsey
PURPOSE: The purpose of this study was to compare leukemia-free survival (LFS) and other clinical outcomes in patients with acute myelogenous leukemia who underwent a myeloablative allogeneic stem cell transplant with and without total body irradiation (TBI). METHODS AND MATERIALS: Adult patients with acute myelogenous leukemia undergoing myeloablative allogeneic stem cell transplant at Duke University Medical Center between 1995 and 2012 were included. The primary endpoint was LFS...
October 2016: Advances in Radiation Oncology
Barbara Spitzer, Ann A Jakubowski, Esperanza B Papadopoulos, Kirsten Fuller, Patrick D Hilden, James W Young, Juliet N Barker, Guenther Koehne, Miguel-Angel Perales, Katharine C Hsu, Marcel R van den Brink, Nancy A Kernan, Susan E Prockop, Andromachi Scaradavou, Hugo Castro-Malaspina, Richard J O'Reilly, Farid Boulad
We sought to develop a myeloablative chemotherapeutic regimen to secure consistent engraftment of T-cell depleted (TCD) hematopoietic stem cell transplantations (HSCT) without the need for total body irradiation, thereby reducing toxicity while maintaining low rates of graft-versus-host disease (GVHD) and without increasing relapse. We investigated the myeloablative combination of busulfan (Bu) and melphalan (Mel), with the immunosuppressive agents fludarabine (Flu) and rabbit antithymocyte globulin (r-ATG) as cytoreduction before a TCD HSCT...
December 2017: Biology of Blood and Marrow Transplantation
Isabelle Westerlund, Yao Shi, Konstantinos Toskas, Stuart M Fell, Shuijie Li, Olga Surova, Erik Södersten, Per Kogner, Ulrika Nyman, Susanne Schlisio, Johan Holmberg
Neuroblastoma is a pediatric cancer characterized by variable outcomes ranging from spontaneous regression to life-threatening progression. High-risk neuroblastoma patients receive myeloablative chemotherapy with hematopoietic stem-cell transplant followed by adjuvant retinoid differentiation treatment. However, the overall survival remains low; hence, there is an urgent need for alternative therapeutic approaches. One feature of high-risk neuroblastoma is the high level of DNA methylation of putative tumor suppressors...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
Lucía López-Granados, Montserrat Torrent, Ana Sastre, Marta Gonzalez-Vicent, Cristina Díaz de Heredia, Bienvenida Argilés, Antonia Pascual, José M Pérez-Hurtado, Luisa Sisinni, Miguel Ángel Diaz, Izaskun Elorza, M Angeles Dasí, Isabel Badell
INTRODUCTION: Haematopoietic stem cell transplantation (HSCT) involves implanting cellular elements capable of generating a new and healthy haematopoietic system. Reduced intensity conditioning (RIC) consists of an immunosuppressive treatment to facilitate a progressive implant with lower morbidity. This type of conditioning can also lead to myelosuppression, which is potentially reversible over time. Reduced intensity conditioning enables HSCT to be performed on patients with genetic diseases for whom added comorbidity is undesirable due to the high doses of chemotherapy that accompanies conventional myeloablative regimens...
July 7, 2017: Anales de Pediatría: Publicación Oficial de la Asociación Española de Pediatría (A.E.P.)
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