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    National Trends and In-Hospital Outcomes of Patients With Solid Organ Transplant Undergoing Spinal Fusion.
    Spine (Phila Pa 1976) 2017 May 25. Epub 2017 May 25.
    *Department of Orthopaedic Surgery & Rehabilitation Medicine SUNY Downstate Medical Center †Department of Medicine, University of Tokyo Graduate School of Medicine ‡Minimum Invasive SpineCARE, Lumin Health §Niigata Spine Surgery Center.
    Study Design: A retrospective analysis of population-based national hospital discharge data collected for the Nationwide Inpatient Sample (NIS) OBJECTIVES.: To examine the demographics and in-hospital outcomes of patients with solid organ transplant (SOT) undergoing spinal fusion on a national level SUMMARY OF BACKGROUND DATA.: Solid organ transplantation has become more common in recent years and some of these patients undergo spinal fusion surgery. Read More

    Current Status of Bruton's Tyrosine Kinase Inhibitor Development and Use in B-Cell Malignancies.
    Drugs Aging 2017 May 23. Epub 2017 May 23.
    CLL Center and Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA.
    The B-cell receptor (BCR) pathway plays an important role in the survival, proliferation and trafficking of cancer cells in a variety of B-cell malignancies. Recently, a number of agents have been developed to target various components of the BCR pathway. One such target is Bruton's tyrosine kinase (BTK), a Tec family kinase member found near the cell membrane that is involved in upstream BCR signaling. Read More

    Advances in the Use of Regulatory T-Cells for the Prevention and Therapy of Graft-vs.-Host Disease.
    Biomedicines 2017 May 16;5(2). Epub 2017 May 16.
    Division of Hematology and Bone Marrow Transplantation, University of Kentucky, Markey Cancer Center 800 Rose Street, Lexington, KY 40536, USA.
    Regulatory T (Tregs) cells play a crucial role in immunoregulation and promotion of immunological tolerance. Adoptive transfer of these cells has therefore been of interest in the field of bone marrow and solid organ transplantation, autoimmune diseases and allergy medicine. In bone marrow transplantation, Tregs play a pivotal role in the prevention of graft-verus-host disease (GvHD). Read More

    HLA-C KIR-Ligands Determine the Impact of Anti-Thymocyte Globulin (ATG) on Graft versus Host and Graft versus Leukemia Effects Following Hematopoietic Stem Cell Transplantation.
    Biomedicines 2017 Mar 28;5(2). Epub 2017 Mar 28.
    Department of Hematology and Oncology, Medical University, 6020 Innsbruck, Austria.
    Rabbit anti-thymocyte globulins (ATGs) are widely used for the prevention of acute and chronic graft versus host disease (aGVHD, cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). However, most prospective and retrospective studies did not reveal an overall survival (OS) benefit associated with ATG. Homozygosity for human leukocyte antigen (HLA)-C group 1 killer-cell immunoglobulin-like receptor ligands (KIR-L), i. Read More

    [Disruption of gut immune system caused by damage of intestinal stem cells and their niche in graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.]
    Clin Calcium 2017 ;27(6):829-833
    Department of Hematology, Hokkaido University Faculty of Medicine, Japan.
    Allogeneic hematopoietic stem cell transplantation(allo-SCT)is curative therapy for various hematological diseases. Graft-versus-host disease(GVHD)and infection remain the main problems in allo-SCT. Gastrointestinal tract is targeted by GVHD. Read More

    CCR8(+)FOXp3(+) Treg cells as master drivers of immune regulation.
    Proc Natl Acad Sci U S A 2017 May 22. Epub 2017 May 22.
    Department of Immunology, Technion, Haifa 31096, Israel;
    The current study identifies CCR8(+) regulatory T cells (Treg cells) as drivers of immunosuppression. We show that in human peripheral blood cells, more than 30% of Treg up-regulate CCR8 following activation in the presence of CCL1. This interaction induces STAT3-dependent up-regulation of FOXp3, CD39, IL-10, and granzyme B, resulting in enhanced suppressive activity of these cells. Read More

    Graft-versus-Host Disease of the Gut: A Histologic Activity Grading System and Validation.
    Biol Blood Marrow Transplant 2017 May 19. Epub 2017 May 19.
    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Pathology, University of Washington, Seattle, Washington.
    The pathologic interpretation of gut biopsies in hematopoietic cell transplant recipients to assess graft-versus-disease (GVHD) is well accepted and supplements clinical and endoscopic findings. However, the histologic activity grading of GVHD is controversial, with attempts to predict prognosis or response to treatment largely unsuccessful. GVHD is being diagnosed earlier in its course, raising the possibility that the pathologic grading system can be profitably modified. Read More

    Pre-transplantation thymic function is associated with the risk of acute graft versus host disease and cytomegalovirus viremia after allogeneic hematopoietic stem cell transplantation.
    Hematology 2017 May 22:1-8. Epub 2017 May 22.
    a Hematopoietic Stem Cell Transplantation Center, Institute of Hematology and Blood Diseases Hospital , Peking Union Medical College and Chinese Academy of Medical Sciences , Tianjin , PR China.
    Objectives: To analyze the kinetics of T-cell subsets and thymic function reconstitution after allogeneic hematopoietic stem cell transplantation (AHSCT); to determine whether sjTREC (signal joint TCR rearrangement excision circle) and CD31-positive recent thymic emigrant (CD31 + RTE) are correlated with acute graft versus host disease (aGVHD) or CMV (cytomegalovirus) viremia after AHSCT.

    Methods: Forty-nine patients who underwent AHSCT in our institution were prospectively enrolled. Periphery blood samples were collected before conditioning and at 1, 2, 3 months after AHSCT. Read More

    Immunomodulatory function of whole human umbilical cord derived mesenchymal stem cells.
    Mol Immunol 2017 May 19;87:293-299. Epub 2017 May 19.
    Department of Hematology, Affiliated Hospital of Jining Medical University, No. 79, Guhuai Road, Jining, Shandong 272000, China; Department of Graduate School, Jining Medical University, Jining 272000, Shandong Province, China; Cell and Gene Therapy Center of Academy of Military Medical Sciences, No. 8, East Street, Fengtai District, Beijing 100071, China. Electronic address:
    Bone marrow derived mesenchymal stem cells (MSCs) play a critical role in immune modulation. However, immunomodulatory function of whole human umbilical cord derived mesenchymal stem cells (UC-MSCs) remains unclear. In this study, UC-MSCs were separated from whole umbilical cord using a single enzyme digestion. Read More

    Adoptive Cell Therapy with Tregs to Improve Transplant Outcomes: The Promise and the Stumbling Blocks.
    Curr Transplant Rep 2016 Dec 25;3(4):265-274. Epub 2016 Oct 25.
    Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
    The contribution of regulatory T cells (Treg) to the induction and maintenance of tolerance is well-recognized in rodents and may contribute to long-term human organ allograft survival. The therapeutic efficacy of adoptively-transferred Treg in promoting tolerance to organ allografts is well-recognized in mouse models. Early phase 1/2 clinical studies of Treg therapy have been conducted in patients with type-1 (autoimmune) diabetes and refractory Crohn's disease, and for inhibition of graft-versus-host disease following bone marrow transplantation with proven safety. Read More

    Role of major histocompatibility complex variation in graft-versus-host disease after hematopoietic cell transplantation.
    F1000Res 2017 3;6:617. Epub 2017 May 3.
    Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
    Graft-versus-host disease (GVHD) remains a significant potentially life-threatening complication of allogeneic hematopoietic cell transplantation (HCT). Since the discovery of the human leukocyte antigen (HLA) system over 50 years ago, significant advances have clarified the nature of HLA variation between transplant recipients and donors as a chief etiology of GVHD. New information on coding and non-coding gene variation and GVHD risk provides clinicians with options to consider selected mismatched donors when matched donors are not available. Read More

    Personalized Prognostic Risk Score for Long-Term Survival for Children with Acute Leukemia after Allogeneic Transplant.
    Biol Blood Marrow Transplant 2017 May 17. Epub 2017 May 17.
    Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI. Electronic address:
    We studied leukemia-free (LFS) and overall survival (OS) in children with acute myeloid (AML; n=790) and acute lymphoblastic leukemia (ALL; n=1096), transplanted between 2000 and 2010, who survived for at least 1 year in remission after related or unrelated donor transplantation. Analysis of patient-, disease- and transplantation characteristics and acute and chronic graft versus host disease (GVHD) were performed to identify factors with adverse effects on LFS and OS. These data were used to develop risk scores for survival. Read More

    Prognostic factors on graft-versus-host disease-free and relapse-free survival after allogeneic hematopoietic stem cell transplantation for adults with acute leukemia.
    Leuk Res 2017 May 12;59:1-7. Epub 2017 May 12.
    Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. Electronic address:
    The cure of acute leukemia by allogeneic hematopoietic stem cell transplantation (allo-HSCT) is closely linked to major complications leading to adverse outcomes, including graft-versus-host disease (GVHD), disease relapse and death. This study retrospectively investigated a consecutive series of 312 adult patients with acute leukemia receiving allo-HSCT by using a novel concept of GVHD-free/relapse-free survival (GRFS), and further evaluated the impact of clinical factors on GRFS. Results indicated that the 1- and 2-year GRFS were 54. Read More

    Mesenchymal stem cells (MSCs) attenuate cutaneous sclerodermatous graft-versus-host disease (Scl-GVHD) through inhibition of immune cell infiltration in a mouse model.
    J Invest Dermatol 2017 May 16. Epub 2017 May 16.
    Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea; Leukemia Research Institute, The Catholic University of Korea, Seoul, Korea. Electronic address:
    Human chronic graft-versus-host disease (CGVHD) shares clinical characteristics with a murine sclerodermatous GVHD (Scl-GVHD) model that is characterized by skin thickening and lung fibrosis. A B10.D2 → BALB/c transplant model of Scl-GVHD was used to address the therapeutic effect of mesenchymal stem cells (MSCs) on the development of CGVHD. Read More

    Ocular surface analysis in hematological patients before and after allogeneic hematopoietic stem cell transplantation: implication for daily clinical practice.
    Eye (Lond) 2017 May 19. Epub 2017 May 19.
    Ophthalmology Unit, DIMES, Alma Mater Studiorum, University of Bologna, S. Orsola-Malpighi Teaching Hospital, Bologna, Italy.
    PurposeTo evaluate ocular surface parameters before and after hematopoietic stem cell transplantation (HSCT) and to correlate them with clinical and transplant variables.MethodsThis is a retrospective analysis of data from 93 patients affected by hematological malignancies undergoing HSCT. Values from Ocular Surface Disease Index, Schirmer test, Break-up Time, ocular surface staining, and Meibomian Gland Dysfunction score obtained before HSCT and 3-6 months after were retrieved from charts. Read More

    Impact of Human Leukocyte Antigen Loci and Haplotypes on Intestinal Acute Graft-versus-host Disease after Human Leukocyte Antigen-matched Sibling Peripheral Blood Stem Cell Transplantation.
    Chin Med J (Engl) 2017 Jun;130(11):1290-1295
    Hematopoietic Stem Cell Transplantation Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
    Background: Acute graft-versus-host disease (aGVHD) is a common and severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Some studies have found that the presence of certain specific human leukocyte antigen (HLA) loci could affect the occurrence of aGVHD. Meanwhile, the impact of HLA haplotypes on aGVHD has been rarely studied. Read More

    Salivary biomarkers and proteomics: future diagnostic and clinical utilities.
    Acta Otorhinolaryngol Ital 2017 Apr;37(2):94-101
    Department of Head and Neck Surgery, "A. Gemelli" Hospital Foundation, Catholic University, Rome, Italy.
    Saliva testing is a non-invasive and inexpensive test that can serve as a source of information useful for diagnosis of disease. As we enter the era of genomic technologies and -omic research, collection of saliva has increased. Recent proteomic platforms have analysed the human salivary proteome and characterised about 3000 differentially expressed proteins and peptides: in saliva, more than 90% of proteins in weight are derived from the secretion of three couples of "major" glands; all the other components are derived from minor glands, gingival crevicular fluid, mucosal exudates and oral microflora. Read More

    Ceramide synthesis regulates T cell activity and GVHD development.
    JCI Insight 2017 May 18;2(10). Epub 2017 May 18.
    Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective immunotherapy for a variety of hematologic malignances, yet its efficacy is impeded by the development of graft-versus-host disease (GVHD). GVHD is characterized by activation, expansion, cytokine production, and migration of alloreactive donor T cells. Hence, strategies to limit GVHD are highly desirable. Read More

    Intrathymic injection of hematopoietic progenitor cells establishes functional T cell development in a mouse model of severe combined immunodeficiency.
    J Hematol Oncol 2017 May 16;10(1):109. Epub 2017 May 16.
    Department of Pediatrics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
    Background: Even though hematopoietic stem cell transplantation can be curative in patients with severe combined immunodeficiency, there is a need for additional strategies boosting T cell immunity in individuals suffering from genetic disorders of lymphoid development. Here we show that image-guided intrathymic injection of hematopoietic stem and progenitor cells in NOD-scid IL2rγ(null) mice is feasible and facilitates the generation of functional T cells conferring protective immunity.

    Methods: Hematopoietic stem and progenitor cells were isolated from the bone marrow of healthy C57BL/6 mice (wild-type, Luciferase(+), CD45. Read More

    No effect of HLA-C mismatch after allogeneic hematopoietic stem cell transplantation with unrelated donors and T-cell depletion in patients with hematological malignancies.
    Clin Transplant 2017 May 16. Epub 2017 May 16.
    Department of Oncology-Pathology, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
    HLA-C mismatch in unrelated donors hematopoeitic stem cell transplantation (HSCT) has been associated with poor patient outcome. However, the impact of HLA-C mismatch in the context of HSCT combined with in vivo T-cell depletion remains unclear. We therefore performed a single-center, retrospective analysis of the clinical outcome on patients with hematological malignancies treated with allo-HSCT, who underwent T-cell depletion. Read More

    The misleading effect of serum galactomannan testing in high-risk hematology patients receiving prophylaxis with micafungin.
    Clin Microbiol Infect 2017 May 12. Epub 2017 May 12.
    Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón; Instituto de Investigación Sanitaria Hospital Gregorio Marañón, Madrid, Spain; CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid Spain; Medicine Department, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain. Electronic address:
    Objectives: To investigate the performance of the routine serum galactomannan (sGM) assay in the diagnosis of invasive aspergillosis (IA) in high-risk hematology patients receiving prophylaxis with micafungin.

    Methods: Retrospective study including all hematological patients who received prophylaxis with micafungin during high-risk IA episodes (neutropenic patients after chemotherapy for acute myeloid leukaemia/myelodysplastic syndrome; allogeneic HSCT during early neutropenic phase or graft-versus-host disease requiring high prednisone doses). and for whom at least 1 sGM result was available. Read More

    A possible role of low regulatory T cells in anti-acetylcholine receptor antibody positive myasthenia gravis after bone marrow transplantation.
    BMC Neurol 2017 May 15;17(1):93. Epub 2017 May 15.
    Department of Neurology, Fukushima Medical University, 1 Hikariga-oka, Fukushima, Fukushima, 960-1295, Japan.
    Background: Chronic graft-versus-host disease (GVHD) appears several months following allogenic hematopoietic stem cell transplantation (HSCT) and is clinically analogous to autoimmune disorder. Polymyositis is a common neuromuscular disorder in chronic GVHD, but myasthenia gravis (MG) is extremely rare. Hence, its pathophysiology and treatment have not been elucidated. Read More

    Upper GI GVHD: similar outcomes to other grade II graft-versus-host disease.
    Bone Marrow Transplant 2017 May 15. Epub 2017 May 15.
    Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
    The significance of upper gastrointestinal tract (UGI) acute GVHD (aGVHD) compared with other grade II aGVHD is not clearly defined. We compared the outcomes of patients with grade II aGVHD with or without biopsy-proven UGI involvement in three groups: grade II aGVHD without UGI (n=178), grade II aGVHD with UGI and other sites (n=102) and isolated UGI aGVHD (n=32). The overall response (ORR) to steroids at day 28 differed among the three groups (76, 67 and 91%, respectively, P=0. Read More

    Vulvar and Vaginal Graft versus Host Disease: A Healthcare Clinic Initiative.
    Asia Pac J Oncol Nurs 2017 Apr-Jun;4(2):116-119
    Department of Bone Marrow Transplantation, Hadassah Medical Center, Jerusalem, Israel.
    Objective: In patients receiving bone marrow transplantation (BMT), their mucosa becomes altered and sclerotic changes in the female external genital organs occur. Although a few studies have specifically addressed vulvar and vaginal graft versus host disease (VVGvHD) and its repercussions on the sexual health and quality of life of patients, VVGvHD can be overlooked by health practitioners. The objective of the study is to describe the initiation of a health care clinic specializing in VVGvHD in a general tertiary hospital. Read More

    Haploidentical Allogeneic Hematopoietic Cell Transplantation for Multiple Myeloma Using Post Transplant Cyclophosphamide GVHD Prophylaxis.
    Biol Blood Marrow Transplant 2017 May 9. Epub 2017 May 9.
    Division of Hematology and Bone Marrow Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address:
    Allogeneic Hematopoietic Cell Transplantation (allo-HCT) currently represents the only potentially curative therapy for patients affected by multiple myeloma (MM). Up to 30% of patients in western countries do not have a matched donor. Haploidentical HCT (haplo-HCT) may be an option, but currently, there is are available data regarding this treatment. Read More

    UCBT Without Antithymocyte Globulin Results in Similar Survival but Better Quality of Life Compared with UPBSCT for the Treatment of Acute Leukemia - a Retrospective Study in China.
    Biol Blood Marrow Transplant 2017 May 9. Epub 2017 May 9.
    Department of Hematology, Anhui Provincial Hospital. Electronic address:
    While previous studies have demonstrated improved outcomes in umbilical cord blood transplantation (UCBT) by omitting antithymocyte globulin (ATG) in the conditioning regimen, this approach has not been comparatively studied in unrelated peripheral blood stem cell transplantation (UPBSCT). To compare the risks and benefits between UCBT without ATG and UPBSCT in patients with acute leukemia (AL). This was a multicenter retrospective study of 79 patients who underwent UCBT (myeloablative conditioning without ATG) and 96 patients who underwent UPBSCT (myeloablative conditioning with ATG). Read More

    Development and Characterization of Novel Monoclonal Antibodies Against Human DNAM-1.
    Monoclon Antib Immunodiagn Immunother 2017 May 12. Epub 2017 May 12.
    1 Department of Immunology, Faculty of Medicine , Tsukuba, Japan .
    DNAM-1 (CD226) is an activating immunoreceptor expressed on lymphocytes and myeloid cells. CD155 and CD112 are the ligands for DNAM-1. DNAM-1 plays an important role in tumor immunity mediated by CD8(+) T cells and NK cells. Read More

    Toxic epidermal necrolysis in a child 6 months post-hematopoietic stem cell transplantation.
    Pediatr Transplant 2017 May 12. Epub 2017 May 12.
    Department of Pediatrics, Oita University Faculty of Medicine, Oita University, Oita, Japan.
    TEN is a rare and critical disease mostly caused by drugs. It is mediated by activated CD8+ T cells that cause keratinocyte apoptosis with the assistance of cytokines/chemokines. We herein report a pediatric case of TEN after allogeneic HSCT with precursor B-cell acute lymphoblastic leukemia (pre-B-ALL) in second complete remission. Read More

    An endpoint associated with clinical benefit after initial treatment for chronic graft-versus-host disease.
    Blood 2017 May 11. Epub 2017 May 11.
    Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
    No gold standard has been established as a primary endpoint in trials of initial treatment for chronic graft-versus-host disease (GVHD), and evidence showing the association of any proposed primary endpoint with clinical benefit has not been conclusively demonstrated. To address this gap, we analyzed outcomes in a cohort of 328 patients enrolled in a prospective, multicenter, observational study within 3 months after diagnosis of chronic GVHD. Complete and partial response, stable disease and progressive disease were defined according to the 2014 NIH Consensus Development Conference on Criteria for Clinical Trials in Chronic Graft-versus-host Disease. Read More

    Humoral Immune Reconstitution Kinetics Following Allogeneic Hematopoietic Stem Cell Transplantation in Children: a Maturation Block of IgM Memory B Cells May Lead to Impaired Antibody Immune Reconstitution.
    Biol Blood Marrow Transplant 2017 May 8. Epub 2017 May 8.
    Division of Hematology, Oncology, and Blood and Marrow Transplantation, Children's Hospital Los Angeles; University of Southern California Keck School of Medicine, Los Angeles, California.
    Although T cell immune reconstitution following allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been well studied, long-term B cell immune reconstitution remains less characterized. We evaluated humoral immune reconstitution among 71-pediatric allo-HSCT recipients. While tetanus toxoid (TT) antibody levels were normal at 1-year post allo-HSCT, anti-polysaccharide carbohydrate (PRP) antibodies remained persistently low for up to 5-years. Read More

    Feasibility of Lenalidomide Therapy for Persistent Chronic Lymphocytic Leukemia after Allogeneic Transplantation.
    Biol Blood Marrow Transplant 2017 May 8. Epub 2017 May 8.
    Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX.
    In patients with chronic lymphocytic leukemia (CLL), persistence of disease after allogeneic stem cell transplantation (alloSCT) can result in poor outcomes. In an effort to improve these outcomes, patients with persistent CLL who were 90-100 days post alloSCT with no evidence of graft-versus-host-disease (GVHD) were randomized to receive lenalidomide or standard care (withdrawal of immunosuppression followed by donor lymphocyte infusion). Lenalidomide was initiated at 5 mg every other day and increased to 10 mg daily if tolerated in each patient. Read More

    Safety and Efficacy of Infliximab Therapy in the Setting of Steroid-Refractory Acute Graft Versus Host Disease.
    Biol Blood Marrow Transplant 2017 May 8. Epub 2017 May 8.
    Division of Hematology, Mayo Clinic, Rochester, MN, USA. Electronic address:
    Acute graft versus host disease (aGVHD) is the leading cause of morbidity and mortality following allogenic hematopoietic cell transplantation (HCT). Corticosteroids are the first line treatment; however, less than half of the patients achieve durable remissions. Studies suggest that tumor necrosis factor alpha (TNF-α), a cytokine released from the bone marrow during conditioning, is involved in the pathogenesis of aGVHD. Read More

    Sources of Hematopoietic Stem and Progenitor Cells and Methods to Optimize Yields for Clinical Cell Therapy.
    Biol Blood Marrow Transplant 2017 May 8. Epub 2017 May 8.
    Department of Transfusion Medicine, Cell Processing Section, Clinical Center, National Institutes of Health, Building 10, 2N-326, Center Drive, Bethesda, MD 20892.. Electronic address:
    Bone marrow (BM) aspirates, mobilized peripheral blood (PB) and umbilical cord blood (UCB) have developed as graft sources of hematopoietic stem and progenitor cells (HSPC) for stem cell transplantation and other cellular therapeutics. Individualized techniques are necessary to enhance graft HSPC yields and cell quality from each graft source. BM aspirates yield adequate CD34+cells but can result in relative delays in engraftment. Read More

    AAV Vectors and Stem Cells - Friends or Foes?
    Hum Gene Ther 2017 May 10. Epub 2017 May 10.
    University of North Carolina at Chapel Hill, 2331 , 7009 THurston , 104 manning drive , Chapel Hill, North Carolina, United States , 27515 ;
    The infusion of healthy stem cells into a patient, termed stem cell therapy, has shown great promise for the treatment of genetic and non-genetic diseases including mucopolysaccharidosis type 1, Parkinson's disease, multiple sclerosis, numerous immunodeficiency disorders, and aplastic anemia. Stem cells for cell therapy can be collected from the patient (autologous) or collected from another "healthy" individual (allogeneic). The use of allogenic stem cells is accompanied with the potentially fatal risk that the transplanted donor T cells will reject the patient's cells, a process termed graft-versus-host disease. Read More

    Natural Killer Cells in Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation.
    Front Immunol 2017 25;8:465. Epub 2017 Apr 25.
    Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
    Allogeneic hematopoietic cell transplantation (HCT) is a well-established therapeutic modality effective for a variety of hematological malignancies but, unfortunately, is associated with significant morbidity and mortality related to cancer relapse as well as to transplant-related complications including graft-versus-host-disease (GvHD). Natural killer (NK) cells are the first donor-derived lymphocyte subset to recover after HCT, and their crucial role in protection against cancer relapse and infections is well established. Conversely, the role played by NK cells in GvHD is still controversial. Read More

    The recipient CCR5 variation predicts survival outcomes after bone marrow transplantation.
    Transpl Immunol 2017 May 6. Epub 2017 May 6.
    Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan. Electronic address:
    The chemokine receptor CCR5 plays roles in the trafficking of effector cells towards the site of inflammation. We retrospectively examined the impact of the CCR5 variation (rs1800023, -2086A>G) on transplant outcomes in a cohort of 329 patients who underwent unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies through the Japan Marrow Donor Program. A multivariate analysis showed that the recipient CCR5 -2086A/A genotype was significantly associated with a lower relapse rate but not with the development of graft-versus-host disease (GVHD) or transplant-related mortality, thereby resulting in better disease-free and overall survival rates than other variations. Read More

    Mesenchymal Stem Cell Derived Extracellular Vesicles: A Role in Hematopoietic Transplantation?
    Int J Mol Sci 2017 May 9;18(5). Epub 2017 May 9.
    Scientific Direction, IRCCS-Referral Cancer Center of Basilicata (CROB), 85028 Rionero in Vulture, Italy.
    Mesenchymal stem cells (MSCs) are a heterogeneous cellular population containing different progenitors able to repair tissues, support hematopoiesis, and modulate immune and inflammatory responses. Several clinical trials have used MSCs in allogeneic hematopoietic stem cell transplantation (allo-HSCT) to prevent hematopoietic stem cell (HSC) engraftment failure, reduce aplasia post chemotherapy, and to control graft versus host disease (GvHD). The efficacy of MSCs is linked to their immune suppressive and anti-inflammatory properties primarily due to the release of soluble factors. Read More

    Hematopoietic stem cell transplantation and acute kidney injury in children: A comprehensive review.
    Pediatr Transplant 2017 Jun;21(4)
    Department of Pediatric Hematology & Oncology Pediatrics, Nationwide Children's Hospital/Ohio State University, Columbus, OH, USA.
    AKI in the setting of HSCT is commonly investigated among adult patients. In the same way, malignancies requiring treatment with HSCT are not limited to the adult patient population, AKI following HSCT is frequently encountered within pediatric patient populations. However, inadequate information regarding epidemiology and pathophysiology specific to pediatric patients prevents development of appropriate and successful therapeutic strategies for those afflicted. Read More

    The ST2/IL-33 Axis in Immune Cells during Inflammatory Diseases.
    Front Immunol 2017 24;8:475. Epub 2017 Apr 24.
    Department of Pediatrics, Indiana University, Indianapolis, IN, USA.
    Il1rl1 (also known as ST2) is a member of the IL-1 superfamily, and its only known ligand is IL-33. ST2 exists in two forms as splice variants: a soluble form (sST2), which acts as a decoy receptor, sequesters free IL-33, and does not signal, and a membrane-bound form (ST2), which activates the MyD88/NF-κB signaling pathway to enhance mast cell, Th2, regulatory T cell (Treg), and innate lymphoid cell type 2 functions. sST2 levels are increased in patients with active inflammatory bowel disease, acute cardiac and small bowel transplant allograft rejection, colon and gastric cancers, gut mucosal damage during viral infection, pulmonary disease, heart disease, and graft-versus-host disease. Read More

    MicroRNA-146a reduces MHC-II expression via targeting JAK/STAT signaling in dendritic cells after stem cell transplantation.
    Leukemia 2017 May 9. Epub 2017 May 9.
    Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
    Acute Graft-versus-host disease (GVHD) is a major immunological complication after allogeneic hematopoietic cell transplantation and a better understanding of the molecular regulation of the disease could help to develop novel targeted therapies. Here we found that a G/C polymorphism within the human microRNA-146a (miR-146a) gene of transplant recipients, which causes reduced miR-146a levels, was strongly associated with the risk of developing severe acute GVHD (n=289). In mice, deficiency of miR-146a in the hematopoietic system or transfer of recipient-type miR-146a(-/-) dendritic cells (DCs) enhanced GVHD, while miR-146a mimic-transfected DCs ameliorated disease. Read More

    Targeting the interleukin-1 pathway in patients with hematological disorders.
    Blood 2017 May 8. Epub 2017 May 8.
    Department of Hematology, Radboud University Medical Center, Nijmegen, Netherlands.
    Interleukin-1α (IL-1α) and IL-1β are potent inflammatory cytokines that activate local and systemic inflammatory processes and are involved in protective immune responses against infections. However, their dysregulated production and signaling can aggravate tissue damage during infection, inflammatory diseases and chemotherapy-induced intestinal mucositis. Additionally, cytokines of the IL-1 family play an important role in homeostatic as well as 'emergency' hematopoiesis and are involved in the pathogenesis of several myeloid and lymphoid hematological malignancies. Read More

    Prophylactic Donor Lymphocyte Infusion (DLI) Followed by Minimal Residual Disease and Graft-Versus Host Disease Guided Multiple DLIs Could Improve Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Refractory/Relapsed Acute Leukemia.
    Biol Blood Marrow Transplant 2017 May 5. Epub 2017 May 5.
    Peking University Peoples Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation; Collaborative Innovation Center of Hematology; Nanfang Hospital, Southern Medical University; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies. Electronic address:
    Patients with refractory/relapsed acute leukemia who have received allogeneic hematopoietic stem cell transplantation (allo-HSCT) are still at a high risk for relapse post-transplant. To investigate the impact of prophylactic donor lymphocyte infusion (DLI) followed by minimal residual disease (MRD)-test and graft-versus-host disease (GvHD) guided multiple DLIs to prevent relapse and improve survival in patients with refractory/relapsed acute leukemia who received allo-HSCT. A multicenter prospective study was designed. Read More

    Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial.
    J Hematol Oncol 2017 May 8;10(1):102. Epub 2017 May 8.
    Unité de Thérapie cellulaire et Tissus and FR 3209, CHRU de Nancy, Vandoeuvre-Lès-Nancy, F54511, France.
    Background: Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB). Read More

    Predictive Value of Clinical Findings and Plasma Biomarkers after 14 Days of Prednisone Treatment for Acute Graft-Versus-Host Disease.
    Biol Blood Marrow Transplant 2017 May 3. Epub 2017 May 3.
    Division of Clinical Research, Fred Hutchinson Cancer Research Center; Departments of Medicine, University of Washington School of Medicine, Seattle, Washington.
    We examined the hypothesis that plasma biomarkers and concomitant clinical findings after initial glucocorticoid therapy can accurately predict failure of graft-versus-host-disease treatment and mortality. We analyzed plasma samples and clinical data in 165 patients after 14 days of glucocorticoid therapy and used logistic regression and areas under receiver-operating characteristic curves (AUC) to evaluate associations with treatment failure and non-relapse mortality (NRM). Initial treatment of GVHD was unsuccessful in 49 patients (30%). Read More

    Bacterial Pneumonia in Patients with Cancer: Novel Risk Factors and Management.
    Clin Chest Med 2017 Jun 1;38(2):263-277. Epub 2017 Mar 1.
    Division of Internal Medicine, Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1100, Houston, TX 77030, USA. Electronic address:
    Bacterial pneumonias exact unacceptable morbidity on patients with cancer. Although the risk is often most pronounced among patients with treatment-induced cytopenias, the numerous contributors to life-threatening pneumonias in cancer populations range from derangements of lung architecture and swallow function to complex immune defects associated with cytotoxic therapies and graft-versus-host disease. These structural and immunologic abnormalities often make the diagnosis of pneumonia challenging in patients with cancer and impact the composition and duration of therapy. Read More

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