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Myeloablative Chemotherapy

Elwira Szychot, Jarosław Peregud-Pogorzelski, Paweł Wawryków, Andrzej Brodkiewicz
Neuroblastoma is the most common extra-cranial malignancy of childhood, with the highest incidence in children younger than 4 years. The prognosis depends on many factors, such as age at diagnosis, stage of disease and molecular genetic subtype. More than 50% of children who present with the disease are deemed to have high-risk neuroblastoma. The standard therapy for children with high-risk neuroblastoma consists of intensive chemotherapy, surgery, radiotherapy, myeloablative consolidation with autologous haematopoietic stem cell rescue followed by the treatment of minimal residual disease with 13-cis-retinoic acid...
September 28, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
Michał Romański, Anna Kasprzyk, Agnieszka Karbownik, Franciszek K Główka
Treosulfan (TREO) has an established position in chemotherapy of advanced ovarian cancer but has been also applied in uveal melanoma patients. Moreover, it is used as an orphan drug for a myeloablative conditioning prior to stem cell transplantation. In this paper, biodistribution of prodrug TREO and its active monoepoxide (S,S-EBDM) and diepoxide (S,S-DEB) into aqueous humor of the eye was studied for the first time. For that purpose, alone TREO and the mixture of TREO, S,S-EBDM and S,S-DEB were administered intravenously to New Zealand White rabbits...
October 2016: Drug Metabolism and Pharmacokinetics
Stephan Kemmner, Mareike Verbeek, Uwe Heemann
Acute kidney injury and long-term renal dysfunction are common problems following bone morrow transplantation (BMT) and highly related to mortality. The frequency and risk of renal dysfunction are directly related to the method of BMT, with myeloablative allogeneic BMT being associated to the highest risk followed by non-myeloablative allogeneic and myeloablative autologous BMT. The type of BMT is, thus, more important than co-factors such as advanced age, comorbidities, or high baseline serum creatinine. The causes for renal failure are multiple and include chemotherapy and high-dose radiation with fluid loss by diarrhea or vomiting, sepsis or nephrotoxic drugs such as calcineurin inhibitors and antimicrobials...
September 2, 2016: Journal of Nephrology
Maria Ester Bernardo, Alessandro Aiuti
Gene therapy (GT) approaches based on autologous hematopoietic stem cell (HSC) corrected ex vivo have shown therapeutic benefit in a number of inherited disorders. GT bares the advantage of allowing each patient to be her/his own donor while reducing the risks of immune-mediated complications as compared with allogeneic hematopoietic stem cells transplantation (HSCT). In order to achieve stable engraftment of HSC, patients undergoing transplantation of allogeneic or autologous HSC receive a chemotherapy- and/or radiotherapy-based preparation...
August 16, 2016: Human Gene Therapy
Eleonora Aricò, Paola Sestili, Giulia Carpinelli, Rossella Canese, Serena Cecchetti, Giovanna Schiavoni, Maria Teresa D'Urso, Filippo Belardelli, Enrico Proietti
Tumor-specific immune tolerance represents an obstacle for the development of effective anti-tumor immune responses through cancer vaccines. We here evaluated the efficacy of chemo-immunotherapy in breaking tumor-specific immune tolerance in an almost incurable mouse model of spontaneous carcinogenesis.Transgenic HER-2/neu mice bearing large mammary tumors received the adoptive transfer of splenocytes and serum isolated from immune donors, with or without pre-conditioning with cyclophosphamide. Treatment efficacy was assessed by monitoring tumor growth by manual inspection and by magnetic resonance imaging...
July 28, 2016: Oncotarget
M Wilhelm, M Smetak, P Reimer, E Geissinger, T Ruediger, B Metzner, N Schmitz, A Engert, K Schaefer-Eckart, J Birkmann
Current guidelines recommend consolidation with autologous stem cell transplantation (autoSCT) after induction chemotherapy for most patients with peripheral T-cell lymphoma (PTCL). This assumption is based on five prospective phase II studies, three of which included <50 patients with limited follow-up. Here we present the final analysis of the prospective German study. The treatment regimen consisted of four to six cycles of CHOP chemotherapy followed by mobilizing therapy and stem cell collection. Patients in complete remission (CR) or partial remission (PR) underwent myeloablative chemo(radio)therapy and autoSCT...
2016: Blood Cancer Journal
Andreas Hausmann, Norbert Fischer, Stephan Breitkopf, Franziska Menne, Kerstin Jess, Stefan Schmidmayr, Clemens M Wendtner, Marcus Hentrich
BACKGROUND: Autologous peripheral blood stem cells (PBSCs) are usually cryopreserved before high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (PBSCT). The freezing process requires the addition of cryoprotectants such as dimethyl sulfoxide (DMSO), which is vital for cell viability in frozen aliquots. DMSO has a number of well-described side effects. However, severe neurologic side effects assigned to DMSO are exceedingly rare. CASE REPORT: A 64-year-old female underwent HDCT followed by PBSCT as consolidation therapy in relapsed high-grade (Grade 3B) Stage IIIA follicular lymphoma...
October 2016: Transfusion
J Versluis, F E M In 't Hout, R Devillier, W L J van Putten, M G Manz, M-C Vekemans, M-C Legdeur, J R Passweg, J Maertens, J Kuball, B J Biemond, P J M Valk, B A van der Reijden, G Meloni, H C Schouten, E Vellenga, T Pabst, R Willemze, B Löwenberg, G Ossenkoppele, F Baron, G Huls, J J Cornelissen
Post-remission treatment (PRT) in patients with cytogenetically normal (CN) acute myeloid leukemia (AML) in first complete remission (CR1) is debated. We studied 521 patients with CN-AML in CR1, for whom mutational status of NPM1 and FLT3-ITD was available, including the FLT3-ITD allelic ratio. PRT consisted of reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (alloHSCT) (n=68), myeloablative conditioning (MAC) alloHSCT (n=137), autologous hematopoietic stem cell transplantation (autoHSCT) (n=168) or chemotherapy (n=148)...
July 15, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Maiko Shimomura, Takaki Asano, Aya Furue, Mizuka Miki, Yasuhiko Sera, Hiroshi Kawaguchi, Kazuhiro Nakamura, Masao Kobayashi
Pediatric blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy that has an extremely poor prognosis despite the use of intensive chemotherapy. Recently, treatment of BPDCN with bone marrow transplantation (BMT) using myeloablative conditioning has been reported to increase survival in adults. We report a 9-year-old girl with cutaneous BPDCN who was successfully treated with combination chemotherapy followed by BMT using reduced intensity conditioning (RIC), without any adverse complications...
June 2016: Indian Journal of Hematology & Blood Transfusion
Yuhki Koga, Utako Oba, Wakako Kato, Hiroaki Ono, Kentaro Nakashima, Hidetoshi Takada
We report a patient with non-Down syndrome AML, also known as AMKL, with monosomy 7, who was also obese and had a hearing impairment and mental retardation. Non-myeloablative bone marrow transplantation was performed successfully after the patient received less aggressive azacitidine treatment, without the usual intensive induction chemotherapy regimen for AML.
September 2016: Pediatric Transplantation
Daniel A Morgenstern, Gulrukh Ahsan, Margaret Brocklesby, Stuart Ings, Carmen Balsa, Paul Veys, Penelope Brock, John Anderson, Persis Amrolia, Nicholas Goulden, Catherine M Cale, Michael J Watts
Standard quality assurance (QA) of cryopreserved peripheral blood stem cells (PBSC) uses post-thaw viable CD34(+) cell counts. In 2013, concerns arose at Great Ormond Street Hospital (GOSH) about 8 patients with delayed engraftment following myeloablative chemotherapy with cryopreserved cell rescue, despite adequate post-thaw viable cell counts in all cases. Root cause analysis was undertaken; investigations suggested the freeze process itself was a contributing factor to suboptimal engraftment. Experiments were undertaken in which a single PBSC product was divided into three and cryopreserved in parallel using a control-rate freezer (CRF) or passive freezing method (-80°C freezer) at GOSH, or the same passive freezing at another laboratory...
September 2016: British Journal of Haematology
R Phelan, E Mann, C Napurski, T E DeFor, A Petryk, W P Miller, J E Wagner, M R Verneris, A R Smith
Gonadal failure is a health and quality-of-life concern in hematopoietic cell transplant (HCT) survivors. While ovarian dysfunction is nearly universal following myeloablative (MA) conditioning, the risk is unclear after reduced-intensity conditioning (RIC). Gonadotropin-releasing hormone agonists decrease ovarian failure rates following conventional chemotherapy, but little is known about its effectiveness with HCT. We investigated the impact of leuprolide on ovarian function after MA conditioning and monitored ovarian function after RIC in this descriptive pilot study...
June 6, 2016: Bone Marrow Transplantation
Heather Allewelt, Jill El-Khorazaty, Adam Mendizabal, Mahsa Taskindoust, Paul L Martin, Vinod Prasad, Kristin Page, Jean Sanders, Joanne Kurtzberg
Infants and young children who undergo allogeneic cord blood transplantation (CBT) are at increased risk for late effects because of exposure of developing organs to chemotherapy and radiation therapy typically used in transplant conditioning regimens. Busulfan (Bu)-based myeloablative regimens were developed to eliminate radiation exposure in these young children with the hope that late effects would be minimized. We now describe the late effects in 102 consecutive patients surviving a minimum of 5 years (median follow-up, 12...
September 2016: Biology of Blood and Marrow Transplantation
Franco Cavalli, Luca Ceriani, Emanuele Zucca
Primary mediastinal large B-cell lymphoma (PMLBCL) is recognized as a distinct disease entity. Treatment outcomes appear better than in other diffuse large B-cell lymphoma (DLBCL) types, partly because of their earlier stage at presentation and the younger age of most patients. If initial treatment fails, however, the results of salvage chemotherapy and myeloablative treatment are poor. The need to avoid relapses after initial therapy has led to controversy over the extent of front-line therapy, particularly whether consolidation radiotherapy to the mediastinum is always required and whether the 18-fluorodeoxyglucose ((18)F-FDG) uptake detected by PET-CT scan can be used to determine its requirements...
2016: American Society of Clinical Oncology Educational Book
Gaurav Goyal, Krishna Gundabolu, Saraschandra Vallabhajosyula, Peter T Silberstein, Vijaya Raj Bhatt
Elderly patients (>60 years) with acute myeloid leukemia have a poor prognosis with a chemotherapy-alone approach. Allogeneic hematopoietic-cell transplantation (HCT) can improve overall survival (OS). However, myeloablative regimens can have unacceptably high transplant-related mortality (TRM) in an unselected group of older patients. Reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning regimens preserve the graft-versus-leukemia effects but reduce TRM. NMA regimens result in minimal cytopenia and may not require stem cell support for restoring hematopoiesis...
June 2016: Therapeutic Advances in Hematology
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
Carol Portwine, Charlene Rae, Jeff Davis, Pierre Teira, Tal Schechter, Victor Lewis, David Mitchell, Donna A Wall, Eleanor Pullenayegum, Ronald D Barr
PURPOSE: This study aimed to estimate the burden of morbidity, in terms of health-related quality of life (HRQL), in survivors of high-risk neuroblastoma (NBL) after myeloablative chemotherapy followed by autologous hematopoietic stem cell transplant (HSCT). PATIENTS AND METHODS: A national population-based survey was undertaken of survivors of high-risk NBL (N = 99), diagnosed between 1991 and 2010 and treated with HSCT. Parents completed a proxy questionnaire incorporating two HRQL measures, Health Utilities Index (HUI) 2 and 3...
September 2016: Pediatric Blood & Cancer
Erika Evangelina Coronado-Cerda, Moisés Armides Franco-Molina, Edgar Mendoza-Gamboa, Heriberto Prado-García, Lydia Guadalupe Rivera-Morales, Pablo Zapata-Benavides, María Del Carmen Rodríguez-Salazar, Diana Caballero-Hernandez, Reyes Silvestre Tamez-Guerra, Cristina Rodríguez-Padilla
Chemotherapy treatments induce a number of side effects, such as leukopenia neutropenia, peripheral erythropenia, and thrombocytopenia, affecting the quality of life for cancer patients. 5-Fluorouracil (5-FU) is wieldy used as myeloablative model in mice. The bovine dialyzable leukocyte extract (bDLE) or IMMUNEPOTENT CRP® (ICRP) is an immunomodulatory compound that has antioxidants and anti-inflammatory effects. In order to investigate the chemoprotection effect of ICRP on bone marrow cells in 5-FU treated mice, total bone marrow (BM) cell count, bone marrow colony forming units-granulocyte/macrophage (CFU-GM), cell cycle, immunophenotypification, ROS/superoxide and Nrf2 by flow cytometry, and histological and hematological analyses were performed...
2016: Journal of Immunology Research
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
Guoliang Ding, Hu Chen
Treatment outcomes of acute leukemia (AL) have not improved over the past several decades and relapse rates remain high despite the availability of aggressive therapies. Conventional relapsed leukemia treatment includes second allogeneic hematopoietic stem cell transplantation (allo-HSCT) and donor lymphocyte infusion (DLI), which in most cases mediate, at best, a modest graft-versus-leukemia effect, although their clinical efficacy is still limited. Although allo-HSCT following myeloablative conditioning is a curative treatment option for younger patients with acute myeloid leukemia (AML) in a first complete remission (CR), allo-HSCT as a clinical treatment is usually limited because of treatment-related toxicity...
July 2016: Science China. Life Sciences
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