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Lucía Fernández, Alejandra Leivas, Jaime Valentín, Adela Escudero, Dolores Corral, Raquel de Paz, Maria Vela, David Bueno, Rebeca Rodríguez, Juan Manuel Torres, Mariana Díaz-Almirón, Eduardo López-Collazo, Joaquin Martinez-Lopez, Antonio Pérez-Martínez
BACKGROUND: Cancer immunotherapy involving natural killer (NK) cells has gained interest. Here we report two methods to obtain interleukin (IL)-15-activated NK cells for clinical use. STUDY DESIGN AND METHODS: IL-15-activated NK cell products were obtained after 1) enrichment from healthy haploidentical donors' peripheral blood mononuclear cells (PBMNCs) collected by nonmobilized apheresis by a two-step magnetic procedure, depletion of CD3+ cells followed by selection of CD56+ cells and ex vivo overnight stimulation with IL-15 (NKIL15); and 2) expansion using the K562-mb15-41BBL cell line (NKAE), from autologous PBMNCs from patients with multiple myeloma or expansion from healthy haploidentical PBMNCs obtained from whole blood using the same previous cell line...
March 14, 2018: Transfusion
Kevin Rakszawski, Kosuke Miki, David Claxton, Henry Wagner, Hiroko Shike, Shin Mineishi, Seema Naik
Approximately 30-40% of patients with acute myeloid leukemia (AML) experience induction failures. In these patients who do not achieve remission with two cycles of standard induction therapies, the probability of achieving remission with subsequent inductions is very limited. Hematopoietic stem cell transplantation (HSCT) is the only curative option for these patients, but high relapse rate and transplant-related mortality often preclude them to proceed to transplant. Thus, AML not in remission at time of HSCT remains a huge unmet need in current HSCT practice, particularly if the patient does not have an HLA-matched donor identified by the time of two induction failures...
March 14, 2018: International Journal of Hematology
Jakob R Passweg, Helen Baldomero, Peter Bader, Grzegorz W Basak, Chiara Bonini, Rafael Duarte, Carlo Dufour, Nicolaus Kröger, Jürgen Kuball, Arjan Lankester, Silvia Montoto, Arnon Nagler, John A Snowden, Jan Styczynski, Mohamad Mohty
Hematopoietic cell transplantation (HCT) is an established procedure for acquired and congenital disorders of the hematopoietic system. In 2016, there was a tendency for continued activity in this field with 43,636 HCT in 39,313 patients [16,507 allogeneic (42%), 22,806 autologous (58%)] reported by 679 centers in 49 countries in 2016. The main indications were myeloid malignancies 9547 (24%; 96% allogeneic), lymphoid malignancies 25,618 (65%; 20% allogeneic), solid tumors 1516 (4%; 2% allogeneic), and non-malignant disorders 2459 (6%; 85% allogeneic)...
March 14, 2018: Bone Marrow Transplantation
Zhuoyan Li, Myriam Labopin, Fabio Ciceri, Didier Blaise, Johanna Tischer, Gerhard Ehninger, M T Van Lint, Yener Koc, Stella Santarone, Edouard Forcade, Luca Castagna, Emmanuelle Polge, Audrey Mailhol, Annalisa Ruggeri, Mohamad Mohty, Bipin N Savani, Arnon Nagler
Secondary acute myeloid leukemia (sAML) traditionally has inferior outcomes compared to de novo AML. Allogeneic hematopoietic cell transplantation (HCT) is the sole potentially curative therapy. This study analyzes the outcomes for unmanipulated haploidentical HCT (haploHCT) for sAML using the EBMT aute leukemia working group (ALWP) registry. We identified 154 patients with sAML who underwent haploHCT from 2006-2016. Median age at HCT was 60 years with time from diagnosis to HCT 5 months. At transplantation, 69 patients were in first CR and 85 had active disease...
March 14, 2018: American Journal of Hematology
Chunyan Yue, Yingying Ding, Yang Gao, Li Li, Yan Pang, Zenghui Liu, Hang Zhang, Yang Xiao, Zujun Jiang, Haowen Xiao
OBJECTIVES: In patients with very severe aplastic anemia (VSAA), neutropenia is prolonged and persistent, resulting in refractory overwhelming infections. Hematopoiesis recovery is urgently needed. METHODS: Six patients with de novo VSAA lacking HLA-identical sibling donors and those who experienced refractory infections, underwent haploidentical related donor (HRD) hematopoietic stem cell transplantation (HSCT) as a first-line therapy. The conditioning regimen consisted of busulfan, cyclophosphamide and rabbit antithymocyte globulin...
March 12, 2018: European Journal of Haematology
Zain A Bashey, Xu Zhang, Stacey Brown, Katelin Jackson, Lawrence E Morris, H Kent Holland, Asad Bashey, Scott R Solomon, Melhem Solh
Allografting from HLA-haploidentical donors (HID) is being increasingly utilized worldwide for patients lacking a conventional matched donor. However, its efficacy in older patients with AML and MDS is unclear. We analyzed 127 consecutive allografts for AML/MDS patients aged ≥ 60 years at our center to compare outcomes using HID to those of contemporaneous transplants using matched sibling (MRD) or matched unrelated (MUD) donors. Patient characteristics were similar except HID transplants were more likely in non-white patients and were more commonly performed with reduced intensity conditioning and a marrow graft...
March 9, 2018: Bone Marrow Transplantation
Mathias Debals-Gonthier, Carole Siani, Catherine Faucher, Rajae Touzani, Claude Lemarié-Basset, Christian Chabannon, Sabine Furst, Raynier Devillier, Samia Harbi, Luca Castagna, Laurence Caymaris, Didier Blaise, Anne-Gaëlle Le Corroller Soriano
Due to limited donor availability, high comorbidities, and cost issues, allogeneic hematopoietic stem cell transplant is not universally accessible. The aim of this study was to conduct a cost-effectiveness analysis of haploidentical vs matched unrelated transplant. This retrospective study included patients with hematological malignancies older than 55 years who underwent haploidentical or matched unrelated transplant between 2011 and 2013 in Marseille. The incremental cost-effectiveness ratio has been calculated using the mean overall survival and the mean transplant costs...
March 9, 2018: Bone Marrow Transplantation
Hideki Sano, Kazuhiro Mochizuki, Shogo Kobayashi, Yoshihiro Ohara, Masaki Ito, Tomoko Waragai, Nobuhisa Takahashi, Kazuhiko Ikeda, Hitoshi Ohto, Atsushi Kikuta
We evaluated the efficacy and toxicity of T-cell-replete haploidentical stem cell transplantation (TCR-haploSCT) using low-dose antithymocyte globulin (ATG) in children with refractory/relapsed (R/R) acute leukemia. From October 2009 to April 2016, 39 consecutive patients with R/R acute leukemia who underwent TCR-haploSCT were included. At the time of TCR-haploSCT, 17 patients were in complete remission (CR), but 22 had active disease. Thirty-three patients received a myeloablative regimen and six received a reduced-intensity conditioning regimen...
March 5, 2018: International Journal of Hematology
Karoline van de Loo, Stefan Balzer, Colin R MacKenzie, Thomas M Boemers, Monika Ortmann, Jörg Schaper, Arndt Borkhardt, Hans-Jürgen Laws, Michaela Kuhlen
BACKGROUND: Mycobacterium tuberculosis (M. tuberculosis) disease is a generally well-known problem among immunocompromised adults and children. In pediatric oncology, only few cases of M. tuberculosis disease are reported so far. CASE PRESENTATION: We report a case of concomitant lymphnode tuberculosis in a 4-year-old German boy with relapsed ganglioneuroblastoma. 18 months after the initial diagnosis, relapse with new paravertebral lesions and new lesions in the left lower lobe of the lung and in the perihilar lymphnodes suspicious of metastases of the ganglioneuroblastoma were detected...
March 5, 2018: BMC Infectious Diseases
Jonathan Canaani, Myriam Labopin, Xiao-Jun Huang, William Arcese, Fabio Ciceri, Didier Blaise, Giuseppe Irrera, Lucia Lopez Corral, Benedetto Bruno, Stella Santarone, Maria Teresa Van Lint, Antonin Vitek, Jordi Esteve, Mohamad Mohty, Arnon Nagler
Acute myeloid leukemia (AML) patients harboring the FLT3-ITD mutation are considered a high risk patient subset preferentially allocated for allogeneic stem cell transplantation in first remission. Whether FLT3-ITD retains a prognostic role in haploidentical stem cell transplantation (haplo-SCT) is unknown. To analyze the prognostic impact of FLT3-ITD in haplo-SCT, we performed a retrospective analysis of the multicenter registry of the acute leukemia working party of the European Society for Blood and Marrow Transplantation...
March 2, 2018: American Journal of Hematology
Lanping Xu, Hu Chen, Jing Chen, Mingzhe Han, He Huang, Yongrong Lai, Daihong Liu, Qifa Liu, Ting Liu, Ming Jiang, Hanyun Ren, Yongping Song, Zimin Sun, Jianmin Wang, Depei Wu, Daobin Zhou, Ping Zou, Kaiyan Liu, Xiaojun Huang
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely used to treat malignant hematological neoplasms and non-malignant hematological disorders. Approximately, 5000 allo-HSCT procedures are performed in China annually. Substantial progress has been made in haploidentical HSCT (HID-HSCT), pre-transplantation risk stratification, and donor selection in allo-HSCT, especially after the establishment of the "Beijing Protocol" HID-HSCT system. Transplant indications for selected subgroups in low-risk leukemia or severe aplastic anemia (SAA) differ from those in the Western world...
March 2, 2018: Journal of Hematology & Oncology
Yu-Qian Sun, Ying-Jun Chang, Xiao-Jun Huang
Haploidentical stem cell transplantation (Haplo-SCT) is currently a suitable alternative worldwide for patients with hematological diseases, who lack human leukocyte antigen (HLA)-matched siblings or unrelated donors. Areas covered: This review summarizes the advancements in Haplo-SCT in recent years, primarily focusing on the global trends of haploidentical allograft, the comparison of outcomes between Haplo-SCT and other transplantation modalities, strategies for improving clinical outcomes, including donor selection, hematopoietic reconstitution promotion, and graft-versus-host disease, and relapse prevention/management, as well as the expanded indications of Haplo-SCT, such as severe aplastic anemia, myeloma and lymphoma...
March 6, 2018: Expert Review of Hematology
Xiaofei Yang, Shuo Yang, Aining Sun, Huiying Qiu, Xiaowen Tang, Yue Han, Depei Wu
This paper aims to study whether cyclosporine-A (CSA) levels have an impact on the clinical outcome of patients with T-cell replete haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT). We analyzed 140 consecutive patients who had been given T-cell replete haploidentical allo-HSCT in our institute to assess the effect of CSA concentration in the early stages of allo-HSCT on clinical outcomes, such as hematopoietic recovery, acute graft vs host disease (aGVHD), infection, disease-free survival (DFS), and overall survival (OS)...
February 28, 2018: Clinical Transplantation
Lixin Xu, Zhouyang Liu, Yamei Wu, Xueliang Yang, Yongbin Cao, Xiaohong Li, Bei Yan, Songwei Li, Wanming Da, Xiaoxiong Wu
BACKGROUND: This study not only evaluated the clinical effects of treatment using haploidentical hematopoietic stem cells (haplo-HSCs) combined with human umbilical cord mesenchymal stem cells (UC-MSCs) in patients with severe aplastic anemia (SAA), but also investigated the factors related to graft versus host disease (GVHD). METHODS: Cotransplantation of haplo-HSCs and UC-MSCs was performed in 24 SAA patients. The conditioning regimens consisted of rabbit anti-human T-lymphocyte immunoglobulin (ATG), cyclophosphamide, and fludarabine with or without busulfan...
March 1, 2018: European Journal of Medical Research
M Vela, D Corral, P Carrasco, L Fernández, J Valentín, B González, A Escudero, A Balas, R de Paz, J Torres, A Leivas, J Martínez-López, A Pérez-Martínez
Primary refractory or relapsed pediatric leukemia yield significant morbidity and mortality, with long-term survival rates <40%. Here we present a post-hoc analysis assessing safety and efficacy of infusing activated and expanded Natural Killer cells (NKAE) from haploidentical donors in patients from 2 clinical trials. In total, 18 children, adolescents and young adults with relapse or refractory acute leukemia were treated with two cycles of rescue chemotherapy followed by fresh NKAE cells infusions and low doses of IL-2...
February 22, 2018: Cancer Letters
Alice Bertaina, Marco Andreani
Allogeneic hematopoietic stem cell transplantation (HSCT) represents a curative treatment for many patients with hematological malignant or non-malignant disorders. Evaluation of potential donors for HSCT includes a rigorous assessment of the human leukocyte antigens (HLA) match status of family members, and the identification of suitable unrelated donors. Genes encoding transplantation antigens are placed both within and outside the major histocompatibility complex (MHC). The human MHC is located on the short arm of chromosome 6 and contains a series of genes encoding two distinct types of highly polymorphic cell surface glycoproteins...
February 22, 2018: International Journal of Molecular Sciences
Simona Sestili, Myriam Labopin, Annalisa Ruggeri, Andrea Velardi, Fabio Ciceri, Johan Maertens, Lothar Kanz, Franco Aversa, Philippe Lewalle, Donald Bunjes, Mohamad Mohty, Arnon Nagler
BACKGROUND: T-cell-depleted, haploidentical transplantations (haplos) are commonly offered to patients who have high-risk, acute leukemia in the absence of a human leukocyte antigen (HLA) full-matched donor. METHODS: To determine the effect of transplantation period, the authors divided 308 adults with de novo, acute leukemia who underwent T-cell-depleted haplo from 2005 to 2015 into 2 groups, according the year in which they underwent transplantation (2005-2011 [n = 191] and 2012-2015 [n = 117])...
February 22, 2018: Cancer
Kiyosumi Ochi, Shigeo Fuji, Kuniko Takano, Kinuko Tajima, Ayumu Ito, Takashi Tanaka, Yoshihiro Inamoto, Saiko Kurosawa, Sung-Won Kim, Arinobu Tojo, Takahiro Fukuda
Polyclonal anti-thymocyte globulins (ATGs) are widely used in allogeneic stem cell transplantation (allo-SCT) for GvHD prophylaxis. ATGs exerted anti-tumor effects in in vitro experiments, but in vivo studies are lacking. We experienced a case of relapsed AML with cells positive for CD7 who underwent haploidentical SCT and unexpectedly achieved a significant reduction of AML cells in the peripheral blood after receiving ATGs before the administration of other drugs in the conditioning regimen. This patient achieved long-term survival after haploidentical SCT...
February 19, 2018: Bone Marrow Transplantation
Luisa Strocchio, Franco Locatelli
Although recent advances in gene therapy are expected to increase the chance of disease cure in thalassemia major, at present hematopoietic stem cell transplantation (HSCT) remains the only consolidated curative approach for this disorder. The widest experience has been obtained in the HLA-matched family donor (MFD) setting, with probabilities of overall and thalassemia-free survival exceeding 90% and 85%, respectively. As for most patients a suitable MFD is not available, alternative donors (HLA-matched unrelated donor, unrelated cord blood, HLA-haploidentical relative) have been increasingly explored, translating into the expansion of the number of patients treatable with HSCT...
April 2018: Hematology/oncology Clinics of North America
Maddalena Migliavacca, Andrea Assanelli, Maurilio Ponzoni, Roberta Pajno, Federica Barzaghi, Fabio Giglio, Francesca Ferrua, Marta Frittoli, Immacolata Brigida, Francesca Dionisio, Roberto Nicoletti, Miriam Casiraghi, Maria Grazia Roncarolo, Claudio Doglioni, Jacopo Peccatori, Fabio Ciceri, Maria Pia Cicalese, Alessandro Aiuti
Adenosine deaminase-deficient severe combined immunodeficiency disease (ADA-SCID) is a primary immune deficiency characterized by mutations in the ADA gene resulting in accumulation of toxic compounds affecting multiple districts. Hematopoietic stem cell transplantation (HSCT) from a matched donor and hematopoietic stem cell gene therapy are the preferred options for definitive treatment. Enzyme replacement therapy (ERT) is used to manage the disease in the short term, while a decreased efficacy is reported in the medium-long term...
2018: Frontiers in Immunology
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