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https://www.readbyqxmd.com/read/28332262/haploidentical-peripheral-blood-stem-cell-transplantation-without-irradiation-or-busulfan-after-reduced-intensity-conditioning-for-kmt2a-mll-rearranged-infant-b-cell-precursor-acute-lymphoblastic-leukemia-report-of-two-cases
#1
Ai Yoshimi, Keisuke Kato, Sho Hosaka, Ryoko Suzuki, Hiroko Fukushima, Tomohei Nakao, Chie Kobayashi, Takashi Fukushima, Kazutoshi Koike, Ryo Sumazaki, Masahiro Tsuchida
We present two infants with KMT2A(MLL)-gene-R-associated BCP-ALL, who received HLA haploidentical PBSCT after RIC. The patients developed ALL at age 6 months and 3 months, respectively. Case 1 underwent PBSCT at the second CR with detectable KMT2A-AFF1(MLL-AF4) fusion gene transcript at 11 months of age, and Case 2 at the first CR without KMT2A-MLLT1(MLL-ENL) fusion gene transcript at 8 months of age. Both patients received G-CSF-mobilized unmanipulated peripheral blood mononuclear cells from their HLA haploidentical mothers after administration of FLU, MEL, and ATG...
March 22, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28331127/the-impact-of-a-humanized-ccr4-antibody-mogamulizumab-on-patients-with-aggressive-type-adult-t-cell-leukemia-lymphoma-treated-with-allogeneic-hematopoietic-stem-cell-transplantation
#2
Noriaki Kawano, Takuro Kuriyama, Shuro Yoshida, Sayaka Kawano, Yoshihisa Yamano, Kousuke Marutsuka, Seiichirou Minato, Kiyoshi Yamashita, Hidenobu Ochiai, Kazuya Shimoda, Fumihiko Ishikawa, Ikuo Kikuchi
Although a humanized CCR4 antibody (mogamulizumab) was reported to be effective for refractory adult T-cell leukemia-lymphoma (ATL), several reports regarding the use of mogamulizumab before allo-hematopoietic stem cell transplantation (HSCT) strongly indicated a high incidence of severe acute graft-versus-host-disease (GVHD) and treatment-related mortality (TRM). We retrospectively analyzed nine aggressive-type ATL patients who underwent allo-HSCT at a single institution in Miyazaki from 2006.1.1 to 2015.7...
2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/28330901/azacitidine-mitigates-graft-versus-host-disease-via-differential-effects-on-the-proliferation-of-t-effectors-and-natural-regulatory-t-cells-in-vivo
#3
Matthew L Cooper, Jaebok Choi, Darja Karpova, Kiran Vij, Julie Ritchey, Mark A Schroeder, John F DiPersio
Azacitidine (AzaC) mitigates graft-versus-host disease (GvHD) in both murine preclinical transplant models and in human clinical trials while maintaining a robust graft-versus-leukemia effect. Previous studies have failed to investigate the role of natural regulatory T cells (nTregs) on the mitigation of GvHD by AzaC, instead focusing on the generation of suppressive Tregs (CD4(+)CD25(+)FOXP3(+)) through the in vivo conversion of alloreactive donor T effectors (Teffs; CD4(+)CD25(-)FOXP3(-)) and the direct antiproliferative effects of AzaC on allogeneic T cells...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28330607/association-between-anti-thymocyte-globulin-exposure-and-survival-outcomes-in-adult-unrelated-haemopoietic-cell-transplantation-a-multicentre-retrospective-pharmacodynamic-cohort-analysis
#4
Rick Admiraal, Stefan Nierkens, Moniek A de Witte, Eefke J Petersen, Ger-Jan Fleurke, Luka Verrest, Svetlana V Belitser, Robbert G M Bredius, Reinier A P Raymakers, Catherijne A J Knibbe, Monique C Minnema, Charlotte van Kesteren, Jurgen Kuball, Jaap J Boelens
BACKGROUND: Anti-thymocyte globulin (ATG) is used to prevent graft-versus-host disease (GvHD) after allogeneic haemopoietic cell transplantation (HCT). However, ATG can also cause delayed immune reconstitution of T cells, negatively affecting survival. We studied the relation between exposure to ATG and clinical outcomes in adult patients with acute leukaemia and myelodysplastic syndrome. METHODS: We did a retrospective, pharmacokinetic-pharmacodynamic analysis of data from patients with acute lymphoid leukaemia, acute myeloid leukaemia, or myelodysplastic syndrome receiving their first T-cell repleted allogeneic peripheral blood stem cell HCT with ATG (thymoglobulin) as part of non-myeloablative conditioning from March 1, 2004, to June 1, 2015...
March 16, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28328614/a-newborn-with-familial-hemophagocytic-lymphohistiocytosis-complicated-with-transfusion-associated-graft-versus-host-disease
#5
Ahmet Ozdemir, Tamer Gunes, Samuel C C Chiang, Ekrem Unal
Hemophagocytic lymphohistiocytosis (HLH) is characterized by activation of cytotoxic T and natural killer (NK) cells, and macrophages related to a spectrum of hyperinflammatory disorders. The clinical findings mainly include high fever, cytopenia, splenomegaly, phagocytosis, and proliferation of histiocytes in lymphoreticular tissue. To the best of our knowledge, transfusion-associated graft versus host disease (TA-GVHD) in a 13-day old male newborn with HLH is being reported first time in the literature. The aim of this report was to emphasize the importance of blood products irradiation in the prevention of the development of graft versus host disease especially among high-risk subjects such as newborns with HLH...
March 21, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28328331/st2-and-endothelial-injury-as-a-link-between-gvhd-and-microangiopathy
#6
LETTER
Seth J Rotz, Christopher E Dandoy, Stella M Davies
No abstract text is available yet for this article.
March 23, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28323004/fresh-or-cryopreserved-cd34-selected-mobilized-peripheral-blood-stem-and-progenitor-cells-for-the-treatment-of-poor-graft-function-following-allogeneic-hematopoietic-cell-transplantation
#7
Armin Ghobadi, Mark A Fiala, Giridharan Ramsingh, Feng Gao, Camille N Abboud, Keith Stockerl-Goldstein, Geoffrey L Uy, Brenda J Grossman, Peter Westervelt, John F DiPersio
CD34(+)-selected stem cell boost (SCB) without conditioning have recently been utilized for poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with promising results. Unfortunately, many patients have been unable to receive the boost infusion as their donors were unwilling or unable to undergo an additional stem cell collection. Therefore, we conducted this study utilizing either fresh or cryopreserved peripheral blood stem cell products to create CD34(+)-selected boost infusions for the treatment of PGF...
March 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28319565/bone-marrow-graft-versus-host-disease-in-major-histocompatibility-complex-matched-murine-reduced-intensity-allogeneic-hemopoietic-cell-transplantation
#8
Kifah Shahin, Zamil Mattar, Pablo Silveira, Wei-Hsun Hsu, Linda Bendall, Derek Hart, Kenneth F Bradstock
BACKGROUND: Most clinical allogeneic hemopoietic cell transplants (alloHCT) are now performed using reduced intensity conditioning (RIC) instead of myeloablative (MAC) conditioning, however, the biology underlying this treatment remains incompletely understood. METHODS: We investigated a murine model of major histocompatibility complex (MHC)-matched multiple minor histocompatibility antigen mismatched alloHCT, using bone marrow (BM) cells and splenocytes from B6 (H-2) donor mice transplanted into BALB...
March 18, 2017: Transplantation
https://www.readbyqxmd.com/read/28319080/adverse-impact-of-high-donor-cd3-cell-dose-on-outcome-following-tandem-auto-nma-allogeneic-transplantation-for-high-risk-myeloma
#9
A P Nair, P Walker, A Kalff, K Bergin, J Hocking, S Avery, D J Curtis, S Patil, T Das, D Klarica, S Morgan, J Muirhead, M Gorniak, J Reynolds, A Spencer
High-risk (HR) multiple myeloma (MM) has poor outcomes with conventional therapy. Tandem autologous-non-myeloablative (NMA) allogeneic stem cell transplantation (autologous stem cell transplantation (ASCT)-NMA allogeneic SCT) is potentially curative secondary to graft-versus-myeloma effect. We retrospectively analysed ASCT-NMA allogeneic SCT outcomes of 59 HR and relapsed MM patients. At a median follow-up of 35.8 months, the outcomes for HR-MM upfront tandem ASCT-NMA allogeneic SCT and standard-risk (SR) MM upfront ASCT alone were comparable (median PFS 1166 days versus 1465 days, P=0...
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28319079/permanent-diffuse-alopecia-after-haematopoietic-stem-cell-transplantation-in-childhood
#10
D Bresters, D C M Wanders, M Louwerens, L M Ball, M Fiocco, R van Doorn
Permanent alopecia after haematopoietic stem cell transplantation (HSCT) is distressing and few studies have investigated this late effect. The aim of the study was to assess the percentage of patients with alopecia and investigate risk factors for alopecia. Patients who underwent allogeneic HSCT before age 19 years, from January 1990 to January 2013, who were at least 2 years after transplant and in follow-up in our clinic were included. Alopecia was defined as clinically apparent decreased hair density. Possible risk factors considered for alopecia after HSCT included: gender, age, diagnosis, donor type, conditioning regimen: cranial irradiation (TBI/cranial radiotherapy) and/or chemotherapy, which chemotherapeutic agents were used and acute/chronic GvHD...
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28319078/late-recurrence-of-autologous-gvhd-in-a-myeloma-patient-a-myth-or-diagnostic-challenge
#11
N El-Jurdi, M Ueda, L Jia, H Lazarus
No abstract text is available yet for this article.
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28319073/ex-vivo-t-cell-depletion-in-allogeneic-hematopoietic-stem-cell-transplant-past-present-and-future
#12
REVIEW
A Saad, L S Lamb
The most common cause of post-transplant mortality in patients with hematological malignancy is relapse, followed by GvHD, infections, organ toxicity and second malignancy. Immune-mediated complications such as GvHD continue to be challenging, yet amenable to control through manipulation of the T-cell compartment of the donor graft with subsequent immunomodulation after transplant. However, risk of both relapse and infection increase concomitantly with T-cell depletion (TCD) strategies that impair immune recovery...
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28319046/t-cells-take-directions-from-supporting-cast-in-graft-versus-host-disease
#13
Derk Amsen
Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only treatment option for several severe hematological malignancies. The development of graft-versus-host disease (GVHD) is a common complication of the procedure and results when donor T cells become activated against recipient-specific antigens. The factors that drive the alloreactive T cell response are not completely understood. In this issue of the JCI, Chung and colleagues present evidence that stromal cells within lymphoid tissue express the Notch ligands Delta-like 1/4 (DLL1 and DLL4), which in turn directly activate T cells...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28319044/fibroblastic-niches-prime-t-cell-alloimmunity-through-delta-like-notch-ligands
#14
Jooho Chung, Christen L Ebens, Eric Perkey, Vedran Radojcic, Ute Koch, Leonardo Scarpellino, Alexander Tong, Frederick Allen, Sherri Wood, Jiane Feng, Ann Friedman, David Granadier, Ivy T Tran, Qian Chai, Lucas Onder, Minhong Yan, Pavan Reddy, Bruce R Blazar, Alex Y Huang, Todd V Brennan, D Keith Bishop, Burkhard Ludewig, Christian W Siebel, Freddy Radtke, Sanjiv A Luther, Ivan Maillard
Alloimmune T cell responses induce graft-versus-host disease (GVHD), a serious complication of allogeneic bone marrow transplantation (allo-BMT). Although Notch signaling mediated by Delta-like 1/4 (DLL1/4) Notch ligands has emerged as a major regulator of GVHD pathogenesis, little is known about the timing of essential Notch signals and the cellular source of Notch ligands after allo-BMT. Here, we have shown that critical DLL1/4-mediated Notch signals are delivered to donor T cells during a short 48-hour window after transplantation in a mouse allo-BMT model...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28304115/extracorporeal-photopheresis-in-pediatric-patients-practical-and-technical-considerations
#15
Robert A DeSimone, Joseph Schwartz, Jennifer Schneiderman
In adults, extracorporeal photopheresis (ECP) is widely utilized for a variety of indications, most commonly cutaneous T-cell lymphoma, acute or chronic graft-versus-host disease (GVHD), solid organ transplant rejection, and other autoimmune and T-cell-mediated disorders. In pediatric patients, the majority of case series and reports have focused on its use in the management of acute and chronic GVHD. Currently utilized ECP technologies were designed for adult patients and there are several challenges in adapting these technologies for use in children...
March 17, 2017: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/28302712/improved-survival-after-acute-graft-vs-host-disease-diagnosis-in-the-modern-era
#16
Hanna J Khoury, Tao Wang, Michael T Hemmer, Daniel Couriel, Amin Alousi, Corey Cutler, Mahmoud Aljurf, Joseph H Antin, Mouhab Ayas, Minoo Battiwalla, Jean-Yves Cahn, Mitchell Cairo, Yi-Bin Chen, Robert Peter Gale, Shahrukh Hashmi, Robert J Hayashi, Madan Jagasia, Mark Juckett, Rammurti T Kamble, Mohamed Kharfan-Dabaja, Mark Litzow, Navneet Majhail, Alan Miller, Taiga Nishihori, Muna Qayed, Helene Schoemans, Harry C Schouten, Gérard Socié, Jan Storek, Leo Verdonck, Ravi Vij, William A Wood, Lolie Yu, Rodrigo Martino, Matthew Carabasi, Christopher Dandoy, Usama Gergis, Peiman Hematti, Melham Solh, Kareem Jamani, Leslie Lehmann, Bipin Savani, Kirk R Schultz, Baldeep M Wirk, Stephen Spellman, Mukta Arora, Joseph Pidala
Acute graft vs. host disease remains a major threat to successful outcome after allogeneic hematopoietic cell transplantation. While improvements in treatment and supportive care have occurred, it is unknown whether these advances have resulted in improved outcome specifically among those diagnosed with acute graft vs. host disease. We examined outcome following diagnosis of grade II-IV acute graft vs. host disease according to time period, and examine effects according to original graft vs. host disease prophylaxis regimen and maximum overall grade of acute GVHD...
March 16, 2017: Haematologica
https://www.readbyqxmd.com/read/28302045/complications-following-stem-cell-therapy-in-inflammatory-bowel-disease
#17
Hongyun Wei, Xiaowei Liu, Chunhui Ouyang, Jie Zhang, Shuijiao Chen, Fanggen Lu, Linlin Chen
Pharmacotherapy and surgery constitute the mainstay of treatment for inflammatory bowel disease (IBD). However, post-treatment relapsing and recurrence persist as concerns in patients with IBD. Together with a considerable economic burden, stem cell therapy (SCT) has emerged as a promising treatment strategy in IBD, including hematopoietic stem cells (HST), mensenchymal stem cells (MSCs). HSCT could restore the immune tolerance following chemotherapy-induced immune ablation, and MSCs could affect immune cells or secret trophic factors to treat IBD...
March 15, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28301690/optimal-dose-of-rabbit-thymoglobulin-in-conditioning-regimens-for-unmanipulated-haploidentical-hematopoietic-stem-cell-transplantation-long-term-outcomes-of-a-prospective-randomized-trial
#18
Ying-Jun Chang, Yu Wang, Xiao-Dong Mo, Xiao-Hui Zhang, Lan-Ping Xu, Chen-Hua Yan, Huan Chen, Yu-Hong Chen, Yao Chen, Wei Han, Feng-Rong Wang, Jing-Zhi Wang, Kai-Yan Liu, Xiao-Jun Huang
BACKGROUND: Antithymocyte globulin (ATG) is an important component of conditioning regimens to prevent severe graft-versus-host disease (GVHD) in patients undergoing unmanipulated, haploidentical stem cell transplantation (haplo-SCT). However, to the authors' knowledge, the optimal dose of ATG is unknown. METHODS: In this prospective, randomized trial, the authors compared the long-term outcomes of 2 ATG doses (rabbit thymoglobulin) used in myeloablative conditioning before unmanipulated haplo-HSCT...
March 16, 2017: Cancer
https://www.readbyqxmd.com/read/28298913/cathepsin-e-deficiency-ameliorates-graft-versus-host-disease-and-modifies-dendritic-cell-motility
#19
Jörg Mengwasser, Liane Babes, Steffen Cordes, Sarah Mertlitz, Katarina Riesner, Yu Shi, Aleixandria McGearey, Martina Kalupa, Thomas Reinheckel, Olaf Penack
Microbial products influence immunity after allogeneic hematopoietic stem cell transplantation (allo-SCT). In this context, the role of cathepsin E (Ctse), an aspartate protease known to cleave bacterial peptides for antigen presentation in dendritic cells (DCs), has not been studied. During experimental acute graft-versus-host disease (GVHD), we found infiltration by Ctse-positive immune cells leading to higher Ctse RNA- and protein levels in target organs. In Ctse-deficient allo-SCT recipients, we found ameliorated GVHD, improved survival, and lower numbers of tissue-infiltrating DCs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28296584/intestinal-microbiota-and-relapse-after-hematopoietic-cell-transplantation
#20
Jonathan U Peled, Sean M Devlin, Anna Staffas, Melissa Lumish, Raya Khanin, Eric R Littmann, Lilan Ling, Satyajit Kosuri, Molly Maloy, John B Slingerland, Katya F Ahr, Kori A Porosnicu Rodriguez, Yusuke Shono, Ann E Slingerland, Melissa D Docampo, Anthony D Sung, Daniela Weber, Amin M Alousi, Boglarka Gyurkocza, Doris M Ponce, Juliet N Barker, Miguel-Angel Perales, Sergio A Giralt, Ying Taur, Eric G Pamer, Robert R Jenq, Marcel R M van den Brink
Purpose The major causes of mortality after allogeneic hematopoietic-cell transplantation (allo-HCT) are relapse, graft-versus-host disease (GVHD), and infection. We have reported previously that alterations in the intestinal flora are associated with GVHD, bacteremia, and reduced overall survival after allo-HCT. Because intestinal bacteria are potent modulators of systemic immune responses, including antitumor effects, we hypothesized that components of the intestinal flora could be associated with relapse after allo-HCT...
March 15, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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