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Aimee G Kim, Jesse D Vrecenak, Matthew M Boelig, Linda Eissenberg, Michael P Rettig, John S Riley, Matthew S Holt, Michael A Conner, Stavros P Loukogeorgakis, Haiying Li, John F DiPersio, Alan W Flake, William H Peranteau
In utero hematopoietic cell transplantation (IUHCT) is a novel nonmyeloablative approach that results in donor specific tolerance and mixed allogeneic chimerism. Clinical application is limited by low levels of donor cell engraftment. Competition from endogenous hematopoietic stem cells (HSCs) for limited "space" in fetal hematopoietic organs remains a significant barrier to successful IUHCT. AMD3100, a CXCR4 inhibitor, and firategrast, an α4β1 and α4β7 integrin inhibitor (α4β1/7) have been shown to disrupt HSC retention in the postnatal hematopoietic niche (HN)...
September 20, 2016: Blood
V Bhatt, L Shune, E Lauer, M Lubin, S M Devlin, A Scaradavou, R Parameswaran, M A Perales, D M Ponce, S Mantha, N A Kernan, J N Barker
Autoimmune hemolysis (AH) and immune thrombocytopenic purpura (ITP) are recognized complications after cord blood transplantation (CBT). We evaluated the incidence and characteristics of AH/ITP after double-unit CBT in a day 100 landmark analysis of 152 patients (median age 36 years, range 0.9-70 years) transplanted for hematologic malignancies with myeloablative or nonmyeloablative conditioning and calcineurin inhibitor (CNI)/mycophenolate mofetil. With a median 5.2-year (range 1.6-9.7 years) survivor follow-up, 10 patients developed autoimmune cytopenias (8 AH, 1 ITP, 1 both) at a median of 10...
September 19, 2016: Bone Marrow Transplantation
Kiyohiko Hotta, Akihiro Aoyama, Tetsu Oura, Yohei Yamada, Makoto Tonsho, Kyu Ha Huh, Kento Kawai, David Schoenfeld, James S Allan, Joren C Madsen, Gilles Benichou, Rex-Neal Smith, Robert B Colvin, David H Sachs, A Benedict Cosimi, Tatsuo Kawai
Successful induction of allograft tolerance has been achieved in nonhuman primates (NHPs) and humans via induction of transient hematopoietic chimerism. Since allograft tolerance was achieved in these recipients without durable chimerism, peripheral mechanisms are postulated to play a major role. Here, we report our studies of T cell immunity in NHP recipients that achieved long-term tolerance versus those that rejected the allograft (AR). All kidney, heart, and lung transplant recipients underwent simultaneous or delayed donor bone marrow transplantation (DBMT) following conditioning with a nonmyeloablative regimen...
July 7, 2016: JCI Insight
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
Stephanie L Goff, Mark E Dudley, Deborah E Citrin, Robert P Somerville, John R Wunderlich, David N Danforth, Daniel A Zlott, James C Yang, Richard M Sherry, Udai S Kammula, Christopher A Klebanoff, Marybeth S Hughes, Nicholas P Restifo, Michelle M Langhan, Thomas E Shelton, Lily Lu, Mei Li M Kwong, Sadia Ilyas, Nicholas D Klemen, Eden C Payabyab, Kathleen E Morton, Mary Ann Toomey, Seth M Steinberg, Donald E White, Steven A Rosenberg
PURPOSE: Adoptive cell transfer, the infusion of large numbers of activated autologous lymphocytes, can mediate objective tumor regression in a majority of patients with metastatic melanoma (52 of 93; 56%). Addition and intensification of total body irradiation (TBI) to the preparative lymphodepleting chemotherapy regimen in sequential trials improved objective partial and complete response (CR) rates. Here, we evaluated the importance of adding TBI to the adoptive transfer of tumor-infiltrating lymphocytes (TIL) in a randomized fashion...
July 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Moufida Ben Nasr, Roberto Bassi, Vera Usuelli, Alessandro Valderrama-Vasquez, Sara Tezza, Francesca D'Addio, Paolo Fiorina
Hematopoietic stem cells (HSCs) have been shown recently to hold much promise in curing autoimmune diseases. Newly diagnosed Type 1 diabetes individuals have been successfully reverted to normoglycemia by administration of autologous HSCs in association with a nonmyeloablative regimen (antithymocyte globulin + cyclophasmide). Furthermore, recent trials reported positive results by using HSCs in treatment of systemic sclerosis, multiple sclerosis and rheumatoid arthritis as well. Early data suggested that HSCs possess immunological properties that may be harnessed to alleviate the symptoms of individuals with autoimmune disorders and possibly induce remission of autoimmune diseases...
June 2016: Regenerative Medicine
Andrea Bacigalupo, Simona Sica
The use of high dose posttransplant cyclophosphamide (PT-CY) introduced by the Baltimore group approximately 10 years ago has been rapidly adopted worldwide and is becoming a standard for patients undergoing unmanipulated haploidentical (HAPLO) transplants. PT-CY has been used following nonmyeloablative as well as myeloablative conditioning regimens, for bone marrow or peripheral blood grafts, for patients with malignant and nonmalignant disorders. Retrospective comparisons of HAPLO grafts with conventional sibling and unrelated donor grafts have been published and suggest comparable outcome...
2016: Advances in Hematology
Rainer Storb, Brenda M Sandmaier
Most hematological malignancies occur in older patients. Until recently these patients and those with comorbidities were not candidates for treatment with allogeneic hematopoietic transplantation because they were unable to tolerate the heretofore used high-dose conditioning regimens. The finding that many of the cures achieved with allogeneic hematopoietic transplantation were due to graft-versus-tumor effects led to the development of less toxic and well-tolerated reduced intensity and nonmyeloablative regimens...
May 2016: Haematologica
Sabrina Peters, Christian Junghanss, Anne Knueppel, Hugo Murua Escobar, Catrin Roolf, Gudrun Knuebel, Anett Sekora, Iris Lindner, Ludwig Jonas, Mathias Freund, Sandra Lange
BACKGROUND: Langerhans cells (LC) are bone marrow-derived cells in the skin. The LC donor/recipient chimerism is assumed to influence the incidence and severity of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). In nonmyeloablative (NM) HSCT the appearance of acute GVHD is delayed when compared with myeloablative conditioning. Therefore, we examined the development of LC chimerism in a NM canine HSCT model. METHODS: 2 Gy conditioned dogs received bone marrow from dog leukocyte antigen identical littermates...
2016: BMC Hematology
Suk See De Ravin, Xiaolin Wu, Susan Moir, Sandra Anaya-O'Brien, Nana Kwatemaa, Patricia Littel, Narda Theobald, Uimook Choi, Ling Su, Martha Marquesen, Dianne Hilligoss, Janet Lee, Clarissa M Buckner, Kol A Zarember, Geraldine O'Connor, Daniel McVicar, Douglas Kuhns, Robert E Throm, Sheng Zhou, Luigi D Notarangelo, I Celine Hanson, Mort J Cowan, Elizabeth Kang, Coleen Hadigan, Michael Meagher, John T Gray, Brian P Sorrentino, Harry L Malech
X-linked severe combined immunodeficiency (SCID-X1) is a profound deficiency of T, B, and natural killer (NK) cell immunity caused by mutations inIL2RGencoding the common chain (γc) of several interleukin receptors. Gamma-retroviral (γRV) gene therapy of SCID-X1 infants without conditioning restores T cell immunity without B or NK cell correction, but similar treatment fails in older SCID-X1 children. We used a lentiviral gene therapy approach to treat five SCID-X1 patients with persistent immune dysfunction despite haploidentical hematopoietic stem cell (HSC) transplant in infancy...
April 20, 2016: Science Translational Medicine
Stephen M Ansell
DISEASE OVERVIEW: Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 9,050 new patients annually and representing approximately 11.2% of all lymphomas in the United States. DIAGNOSIS: HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups under the designation of classical HL...
June 2016: American Journal of Hematology
Scott R Solomon, Melhem Solh, Lawrence E Morris, H Kent Holland, Asad Bashey
Relapse is the main cause of treatment failure after nonmyeloablative haploidentical transplant (haplo-HSCT). In an attempt to reduce relapse, we have developed a myeloablative (MA) haplo-HSCT approach utilizing posttransplant cyclophosphamide (PT/Cy) and peripheral blood stem cells as the stem cell source. We summarize the results of two consecutive clinical trials, using a busulfan-based (n = 20) and a TBI-based MA preparative regimen (n = 30), and analyze a larger cohort of 64 patients receiving MA haplo-HSCT...
2016: Advances in Hematology
Dorothy R McKenna, Matthew R Sullivan, John M Hill, Christopher H Lowrey, Jeremiah R Brown, Joshua Hickman, Kenneth R Meehan
BACKGROUND: About 1 in 7 of all hospitalized patients is readmitted within 30 days of discharge. The cost of readmissions is significant, with Medicare readmissions alone costing the health care system an estimated $28 billion a year. OBJECTIVE: To identify the rates of and causes for readmission within 100 days of patients receiving a hematopoietic stem cell transplant. METHODS: We performed a retrospective review of 235 consecutive transplant recipients (autologous, n = 144; allogeneic, n = 91) to determine rates and causes for readmission within 100 days of patients receiving a transplant...
September 2015: Journal of Community and Supportive Oncology
Gary J Schiller, Pamela Tuttle, Pinkal Desai
In recent years, allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become increasingly common in patients with acute myelogenous leukemia (AML) due to improved donor availability and the use of nonmyeloablative regimens. However, despite the potential clinical gains with allo-HSCT, the post-transplantation outcomes for many patients, especially those with high-risk disease, remain dismal. Patients with AML who have internal tandem duplication mutations in the tyrosine kinase receptor FLT3 (FLT3-ITD) face particularly poor outcomes, even after allo-HSCT, which appears to only partially mitigate the poor prognosis associated with this mutation...
June 2016: Biology of Blood and Marrow Transplantation
Justin A Wasko, James S Westholder, Pamala A Jacobson
PURPOSE: Patients undergoing hematopoietic cell transplantation are treated with multiple medications, potentially complicated by drug-drug interactions. Drug interactions with sirolimus, voriconazole, and rifampin are particularly difficult because of the complex and simultaneous enzyme inhibition and induction mechanisms. We report a hematopoietic cell transplantation patient receiving sirolimus and voriconazole who was given rifampin while being treated for presumed methicillin-resistant Staphylococcus aureus meningitis...
January 12, 2016: Journal of Oncology Pharmacy Practice
Matthew M Hsieh
No abstract text is available yet for this article.
March 2016: Biology of Blood and Marrow Transplantation
Tamara I Pestina, Phillip W Hargrove, Huifen Zhao, Paul E Mead, Matthew P Smeltzer, Mitchell J Weiss, Andrew Wilber, Derek A Persons
Patients with severe sickle cell disease (SCD) are candidates for gene therapy using autologous hematopoietic stem cells (HSCs), but concomitant multi-organ disease may contraindicate pretransplant conditioning with full myeloablation. We tested whether nonmyeloablative conditioning, a regimen used successfully for allogeneic bone marrow transplantation of adult SCD patients, allows engraftment of γ-globin gene-corrected cells to a therapeutic level in the Berkeley mouse model of SCD. Animals transplanted according to this regimen averaged 35% engraftment of transduced hematopoietic stem cells with an average vector copy < 2...
2015: Molecular Therapy. Methods & Clinical Development
Stephen M Ansell
Hodgkin lymphoma is a rare B-cell malignant neoplasm affecting approximately 9000 new patients annually. This disease represents approximately 11% of all lymphomas seen in the United States and comprises 2 discrete disease entities--classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. Within the subcategorization of classical Hodgkin lymphoma are defined subgroups: nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich Hodgkin lymphoma. Staging of this disease is essential for the choice of optimal therapy...
November 2015: Mayo Clinic Proceedings
Curtis L Cetrulo, Tessa Drijkoningen, David H Sachs
PURPOSE OF REVIEW: The present review summarizes current data on the induction of immunologic tolerance through mixed hematopoietic chimerism relevant to applying this approach to vascularized composite allotransplantation. RECENT FINDINGS: Clinical allograft tolerance has been achieved recently for kidney transplants, using nonmyeloablative conditioning regimens and bone marrow transplantation from living donors. The mixed chimerism attained in these studies was either transient or durable, and both permitted tolerance of the renal allografts to be achieved across MHC-matched and MHC-mismatched barriers...
December 2015: Current Opinion in Organ Transplantation
Tetsu Oura, Dicken S C Ko, Svjetlan Boskovic, John J O'Neil, Vaja Chipashvili, Maria Koulmanda, Kiyohiko Hotta, Kento Kawai, Ognjenka Nadazdin, R Neal Smith, A B Cosimi, Tatsuo Kawai
We have previously reported successful induction of transient mixed chimerism and long-term acceptance of renal allografts in MHC mismatched nonhuman primates. In this study, we attempted to extend this tolerance induction approach to islet allografts. A total of eight recipients underwent MHC mismatched combined islet and bone marrow (BM) transplantation after induction of diabetes by streptozotocin. Three recipients were treated after a nonmyeloablative conditioning regimen that included low-dose total body and thymic irradiation, horse Atgam (ATG), six doses of anti-CD154 monoclonal antibody (mAb), and a 1-month course of cyclosporine (CyA) (Islet A)...
2016: Cell Transplantation
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