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allogeneic hematopoietic cell transplantation

Emmanuelle Ginoux, Diane Kottler, Bruno Anglaret, Brigitte Balme, Claude-Eric Bulabois, François Skowron
No abstract text is available yet for this article.
September 2016: JAAD Case Reports
Mª Carmen Herrero-Sánchez, Concepción Rodríguez-Serrano, Julia Almeida, Laura San Segundo, Susana Inogés, Ángel Santos-Briz, Jesús García-Briñón, Luis Antonio Corchete, Jesús F San Miguel, Consuelo Del Cañizo, Belén Blanco
BACKGROUND: Graft-versus-host disease (GvHD) remains the major obstacle to successful allogeneic hematopoietic stem cell transplantation, despite of the immunosuppressive regimens administered to control T cell alloreactivity. PI3K/AKT/mTOR pathway is crucial in T cell activation and function and, therefore, represents an attractive therapeutic target to prevent GvHD development. Recently, numerous PI3K inhibitors have been developed for cancer therapy. However, few studies have explored their immunosuppressive effect...
October 20, 2016: Journal of Hematology & Oncology
Nirali N Shah, Theresa M Watson, Bonnie Yates, David J Liewehr, Seth M Steinberg, David Jacobsohn, Terry J Fry
BACKGROUND: Diagnosis of engraftment syndrome (ES) following allogeneic hematopoietic stem cell transplantation (HSCT) can be a challenge due to the systemic presentation and alternative etiologies. With a goal of establishing biomarkers to more accurately distinguish ES, we prospectively analyzed levels of cytokines during HSCT. PROCEDURES: We performed a prospective study of children ≤21 years who underwent allogeneic HSCT. Blood samples for interleukin (IL)-6, IL-8, IL-10, IL-1b, IL-12p70, interferon-γ, tumor necrosis factor alpha (TNF-α) and procalcitonin were obtained from each subject prior to conditioning, at day 0, and then biweekly through engraftment and at days 30, 60 and 100...
October 20, 2016: Pediatric Blood & Cancer
Katsuto Takenaka, Kazuya Shimoda, Naoyuki Uchida, Taizo Shimomura, Koji Nagafuji, Tadakazu Kondo, Hirohiko Shibayama, Takehiko Mori, Kensuke Usuki, Taichi Azuma, Yutaka Tsutsumi, Junji Tanaka, Hitomi Dairaku, Keitaro Matsuo, Keiya Ozawa, Mineo Kurokawa, Shunya Arai, Koichi Akashi
We conducted a 17-year nationwide survey (1999-2015) to elucidate the clinical outcomes of patients with primary myelofibrosis (PMF) in Japan. Questionnaires were sent annually to approximately 500 hematology departments. Newly diagnosed patients with PMF were enrolled in this study, and were followed up annually to collect prognostic information. Approximately 50 patients were enrolled per year, yielding a total of 780 patients with PMF included in this study. The median age at diagnosis was 66 years. At the time of analysis, the median survival duration was 47 months, and the 3-year overall survival rate was 59 %...
October 19, 2016: International Journal of Hematology
Corinna La Rosa, Jeff Longmate, Joy Martinez, Qiao Zhou, Teodora I Kaltcheva, Weimin Tsai, Jennifer Drake, Mary Carroll, Felix Wussow, Flavia Chiuppesi, Nicola Hardwick, Sanjeet Dadwal, Ibrahim Aldoss, Ryotaro Nakamura, John A Zaia, Don J Diamond
Attenuated poxvirus Modified vaccinia Ankara (MVA) is a useful viral-based vaccine for clinical investigation, because of its excellent safety profile and property of inducing potent immune responses against recombinant (r) antigens. We developed Triplex by constructing an rMVA encoding three immunodominant CMV antigens which stimulates a host anti-viral response: UL83 (pp65), UL123 (IE1-exon4), and UL122 (IE2-exon5). We completed the first clinical evaluation of the Triplex vaccine in 24 healthy adults, with or without immunity to CMV and vaccinia virus (previous DryVax smallpox vaccination)...
October 19, 2016: Blood
Hidekazu Nishikii, Byung-Su Kim, Yasuhisa Yokoyama, Yan Chen, Jeanette Baker, Antonio Pierini, Maite Alvarez, Melissa Mavers, Kristina Maas-Bauer, Yuqiong Pan, Shigeru Chiba, Robert S Negrin
CD4(+)Foxp3(+) regulatory T cells (Treg) are a subpopulation of T cells, which regulate the immune system and enhance immune tolerance after transplantation. Donor-derived Treg prevent the development of lethal acute graft versus host disease (GVHD) in murine models of allogeneic hematopoietic stem cell transplantation (HCT). We recently demonstrated that a single treatment of the agonistic antibody to DR3 (Death receptor 3, αDR3) to donor mice resulted in the expansion of donor derived Treg and prevented acute GVHD, although the precise role of DR3 signaling in GVHD has not been elucidated...
October 19, 2016: Blood
Omar S Aljitawi, Soumen Paul, Avishek Ganguly, Tara L Lin, Sid Ganguly, George Vielhauer, Maegan L Capitano, Amy Cantelina, Brea Lipe, Jonathan D Mahnken, Amanda Wise, Abigale Berry, Anurag K Singh, Leyla Shune, Christopher Lominska, Sunil Abhyankar, Dennis Allin, Mary Laughlin, Joseph P McGuirk, Hal E Broxmeyer
Umbilical cord blood (UCB) engraftment is in part limited by graft cell dose, generally one log less than that of bone marrow (BM)/peripheral blood (PB) cell grafts. Strategies toward increasing hematopoietic stem/progenitor cell (HSPC) homing to BM have been assessed in order to improve UCB engraftment. Despite recent progress, a complete understanding of how HSPC homing and engraftment are regulated is still elusive. We provide evidence that blocking erythropoietin (EPO)-EPO receptor (R) signaling promotes homing to BM and early engraftment of UCB CD34(+) cells...
October 19, 2016: Blood
Paul J Martin, Wenhong Fan, Barry E Storer, David M Levine, Lue Ping Zhao, Edus H Warren, Mary E D Flowers, Stephanie J Lee, Paul A Carpenter, Michael Boeckh, Sangeeta Hingorani, Li Yan, Qiang Hu, Leah Preus, Song Liu, Stephen Spellman, Xiaochun Zhu, Marcelo Pasquini, Philip McCarthy, Daniel Stram, Xin Sheng, Loreall Pooler, Christopher A Haiman, Lara Sucheston-Campbell, Theresa Hahn, John A Hansen
Previous studies have identified single-nucleotide polymorphisms (SNPs) associated with the risk of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). The current study determined whether these associations could be replicated in large cohorts of donors and recipients. Each SNP was tested with cohorts of patients having the same donor type (HLA-matched related, unrelated or both) reported in the original publication, and testing was limited to the same genome (recipient or donor) and genetic model (dominant, recessive or allelic) reported in the original study...
October 6, 2016: Blood
Samuel Kim, Richard L Edelson, Brandon Sumpio, Stephanie Kwei, Deepak Narayan
We present a case of a 65-year-old man with cutaneous T-cell lymphoma treated with radiation therapy and an allogeneic hematopoietic stem cell transplant from his human leukocyte antigen-matched brother. Engraftment was successful, but the patient went on to develop painful, radiation-induced ulcers. The ulcers were fat-allografted using liposuctioned fat from his brother because of the patient's unique chimeric state. Postprocedure follow-up revealed epithelialization of the ulcer sites and significant improvement in neuropathic pain...
September 2016: Plastic and Reconstructive Surgery. Global Open
Yini Wang, Zhao Wang
PURPOSE OF REVIEW: Hemophagocytic lymphohistiocytosis (HLH) is a condition of uncontrolled immune activation with a high mortality rate. The recommended therapeutic guideline for HLH was published by the Histiocyte Society in 1994 and revised in 2004, which greatly improved the survival in patients with HLH. However, HLH is still a refractory disease for which the search for novel treatments continues. This article overviewed recent advances in treatment of HLH. RECENT FINDINGS: Current practices in treatment extend from chemo-immunotherapy to some new cytokine-targeting biologicals, which are more effective to eliminate pathologically activated T cells and resist exaggerated cytokine storm...
October 15, 2016: Current Opinion in Hematology
Michael Medinger, Claudia Lengerke, Jakob Passweg
Acute myeloid leukemia (AML) is a biologically complex and molecularly and clinically heterogeneous disease, and its incidence is increasing as the population ages. Cytogenetic anomalies and mutation testing remain important prognostic tools for tailoring treatment after induction therapy. Despite major advances in understanding the genetic landscape of AML and its impact on the pathophysiology and biology of the disease, as well as the rapid development of new drugs, standard treatment options have not experienced major changes during the past three decades...
2016: Leukemia Research Reports
Steven Wang, Jie Yan, Guangde Zhou, Rebecca Heintzelman, J Steve Hou
Myeloproliferative neoplasms (MPNs) are hematopoietic malignancies characterized by unchecked proliferation of differentiated myeloid cells. The most common BCR-ABL1-negative MPNs are polycythemia vera, essential thrombocythemia, and primary myelofibrosis. The discovery of JAK2 V617F mutation has improved our understanding of the molecular basis of MPN. The high frequency of JAK2 mutation in MPN makes JAK2 mutation testing an essential diagnostic tool and potential therapeutic target for MPN. Here, we present a rare case of a 34-year-old patient who was initially diagnosed with acute myeloid leukemia (AML) with mutated NPM1...
2016: Case Reports in Hematology
Yu Mi Seo, Seok Hwang-Bo, Seong Koo Kim, Seung Beom Han, Nack-Gyun Chung, Jin Han Kang
BACKGROUND: Although adenovirus (ADV) infection usually causes self-limiting respiratory disorders in immune competent children; severe and systemic ADV infection in children undergoing chemotherapy for leukemia has been continuously reported. Nevertheless, there has been no consensus on risk factors and treatment strategies for severe ADV infection in children undergoing chemotherapy. CASE SUMMARY: We report a case of a 15-year-old boy with a fatal systemic ADV infection...
October 2016: Medicine (Baltimore)
Tasuku Suzuki, Yoji Sasahara, Atsuo Kikuchi, Humihiko Kakuta, Toshihiko Kashiwabara, Takashi Ishige, Yoshiko Nakayama, Masanori Tanaka, Akihiro Hoshino, Hirokazu Kanegane, Daiki Abukawa, Shigeo Kure
PURPOSE: Pediatric inflammatory bowel disease (IBD) is a heterogeneous disorder caused by multiple factors. Although genetic and immunological analyses are required for a definitive diagnosis, no reports of a comprehensive genetic study of a Japanese population are available. METHODS: In total, 35 Japanese patients <16 years of age suffering from IBD, including 27 patients aged <6 years with very early-onset IBD, were enrolled in this multicenter study. Exome and targeted gene panel sequencing was performed for all patients...
October 17, 2016: Journal of Clinical Immunology
Marissa B Larochelle, Ryan Phan, John Craddock, Mark J Abzug, Donna Curtis, Christine C Robinson, Roger H Giller, Shaun Cosgrove, Frank Siringo, Emily McCourt, Alan G Palestine
PURPOSE: The incidence of cytomegalovirus (CMV) retinitis in the pediatric allogeneic hematopoietic stem cell transplant (HSCT) population is unknown. We report a cluster of 5 pediatric patients with CMV retinitis diagnosed in a 12-month period, and compare this to the rate of CMV viremia and retinitis in the four years prior. Presented is the ophthalmic screening protocol developed in response to this experience. DESIGN: Retrospective cross-sectional study. METHODS: A retrospective chart review was performed on patients at Children's Hospital of Colorado (CHCO) who received allogeneic HSCT between January 2010 and December 2014...
October 13, 2016: American Journal of Ophthalmology
Gretchen A Hoff, Johannes C Fischer, Katharine Hsu, Sarah Cooley, Jeffrey S Miller, Tao Wang, Michael Haagenson, Stephen Spellman, Stephanie J Lee, Markus Uhrberg, Jeffrey M Venstrom, Michael R Verneris
Natural Killer (NK) cells are important in graft versus leukemia responses following hematopoietic cell transplantation (HCT). A variety of surface receptors dictate NK cell function, including killer immunoglobulin receptor (KIR) recognition of HLA-C. Previous single center studies show that HLA-C epitopes, designated C1 and C2, were associated with allogeneic-HCT outcomes; specifically recipients homozygous for the C1 epitope (C1/C1) experienced a survival benefit. Additionally, mismatching at HLA-C was beneficial in recipients possessing at least one C2 allele, while the opposite was true for homozygous C1 (C1/C1) recipients where HLA-C mismatching resulted in worse outcomes...
October 13, 2016: Biology of Blood and Marrow Transplantation
Shanmuganathan Chandrakasan, Rebecca A Marsh, Gulbu Uzel, Steven M Holland, Kara N Shah, Jack Bleesing
Patients with NEMO deficiency tolerate myeloablative hematopoietic stem cell conditioning and transplant, and most patients achieve adequate immune reconstitution to correct the underlying immune deficiency.
October 12, 2016: Journal of Allergy and Clinical Immunology
Sung-Soo Park, Jae-Ho Yoon, Hee-Je Kim, Young-Woo Jeon, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min
BACKGROUND: Acute myeloid leukemia (AML) with t(8;21)(q22;q22) is classified into a favorable-risk group. Extramedullary (EM) involvement has frequently been reported in this subgroup as resulting in a poor prognosis. However, characteristics or standard treatments of t(8;21) AML with EM involvement (EM-positive t(8;21)) have not yet been elucidated. PATIENTS AND METHODS: We retrospectively analyzed 154 adult AML patients with t(8;21). Among them, 17 were EM positive and 137 were EM negative at the time of diagnosis...
September 17, 2016: Clinical Lymphoma, Myeloma & Leukemia
Gera D Te Raa, Arnon P Kater
Despite the availability of novel targeted agents, TP53 defects remain the most important adverse prognostic factor in chronic lymphocytic leukemia (CLL). Detection of deletion of TP53 locus (17p deletion) by fluorescent in situ hybridization (FISH) has become standard and performed prior to every line of treatment as the incidence dramatically increases as relapses occur. As monoallelic mutations of TP53 equally affect outcome, novel methods are being developed to improve detection of TP53 defects and include next-generation sequencing (NGS) and functional assays...
March 2016: Best Practice & Research. Clinical Haematology
Mohamed A Kharfan-Dabaja, Jessica El-Asmar, Farrukh T Awan, Mehdi Hamadani, Ernesto Ayala
Novel therapies targeting various kinases downstream of the B-cell receptor have emerged along with monoclonal antibodies and BCL-2 antagonists, and are changing the therapeutic landscape of chronic lymphocytic leukemia. However, cure remains unattainable unless eligible patients are offered an allogeneic hematopoietic cell transplant. Access to allogeneic hematopoietic cell transplantation has expanded considerably with availability of reduced intensity conditioning regimens which is capable offering durable remissions even in poor-risk disease...
March 2016: Best Practice & Research. Clinical Haematology
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