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Tocilizumab transplant

Ramya Uppuluri, Meena Sivasankaran, Shivani Patel, Venkateswaran Vellaichamy Swaminathan, Kesavan Melarcode Ramanan, Nikila Ravichandran, Balasubramaniam Ramakrishnan, Indira Jayakumar, Lakshman Vaidhyanathan, Revathi Raj
Haploidentical stem cell transplantation (haplo SCT) has emerged as an acceptable alternative to matched family donor transplantation for children diagnosed to have primary immune deficiency disorders (PIDs). We present data over 4 years on the challenges and efficacy of unmanipulated T cell replete haplo SCTs with post-transplant cyclophosphamide (PTCy) in children diagnosed to have PIDs. We performed a retrospective study in the pediatric blood and marrow transplantation unit where all children less than 18 years of age diagnosed to have PIDs and who underwent haplo SCT with PTCy from January 2014 to February 2018 were included in the study...
February 18, 2019: Journal of Clinical Immunology
Yanli Zhao, David K C Cooper, Huiyun Wang, Pengfei Chen, Chen He, Zhiming Cai, Lisha Mou, Shaodong Luan, Hanchao Gao
The major limitation of organ transplantation is the shortage of available organs from deceased human donors which leads to the deaths of thousands of patients each year. Xenotransplantation is considered to be an effective way to resolve the problem. Immune rejection and coagulation dysfunction are two major hurdles for the successful survival of pig xenografts in primate recipients. Pro-inflammatory cytokines, such as IL-6, TNF-α, and IL-17, play important roles in many diseases and in allotransplantation...
February 16, 2019: Xenotransplantation
Filiz Yucebay, Christina Matthews, Marcin Puto, Junan Li, Basem William, Samantha M Jaglowski, Sam L Penza, Sumithira Vasu, Don M Benson, Leslie A Andritsos, Steven M Devine, Yvonne A Efebera, Julianna V F Roddy
Acute graft-versus-host-disease (aGVHD) is a complication after allogeneic stem cell transplant. After the failure of treatment with high dose corticosteroids, steroid-refractory aGVHD (SR aGVHD) is associated with high rates of mortality. Tocilizumab has evidence of activity in SR aGVHD. For patients ineligible for trials, the OSU James Comprehensive Cancer Center has been utilizing tocilizumab as first-line therapy for SR aGVHD. We retrospectively report on 15 patients who received tocilizumab. aGVHD grading and responses were based on consensus criteria...
February 15, 2019: Leukemia & Lymphoma
Larisa Shelikhova, Maria Ilushina, Zhanna Shekhovtsova, Daria Shasheleva, Rimma Khismatullina, Elena Kurnikova, Dmitriy Pershin, Dmitriy Balashov, Svetlana Radygina, Pavel Trakhtman, Irina Kalinina, Yakov Muzalevskii, Alexei Kazachenok, Viktoria Zaharova, Varvara Kalinina, Yulia Olshanskaya, Agnesa Panferova, Elena Zerkalenkova, Dina Baidildina, Galina Novichkova, Alexander Rumyantsev, Alexei Maschan, Michael Maschan
We evaluated the outcome of αβ T cell cell-depleted haploidentical transplantation in a cohort of children with chemorefractory acute myeloid leukemia. Twenty-two patients with either primary refractory (n=10) or relapsed refractory (n=12) acute myeloid leukemia in active disease status received a transplantation from haploidentical donors. The preparative regimen included cytoreduction with fludarabine and cytarabine and subsequent myeloablative conditioning with treosulfan and thiotepa. Anti-thymocyte globulin was substituted with tocilizumab in all patients and additionally with abatacept in 10 patients...
January 21, 2019: Biology of Blood and Marrow Transplantation
Sophie De Seigneux, Belen Ponte, Karine Hadaya, Patrick Saudan
Major advances in the treatment of ANCA associated-renal vasculitides, IGA nephropathy and renal autosomal dominant polycystic disease were published within the past year. There is neither clear benefit of early initiation of renal replacement therapy in the intensive care unit nor with the use of chloride-poor solutions to prevent kidney failure. Maintenance parenteral iron supplementation in hemodialysis patients is neither associated with infectious nor cardiovascular risks. Cognitive decline may be more associated with hemodialysis than peritoneal dialysis...
January 9, 2019: Revue Médicale Suisse
Guoqiang Zhang, Hidetaka Hara, Takayuki Yamamoto, Qi Li, Abhijit Jagdale, Yong Li, David K C Cooper, Hayato Iwase
BACKGROUND: There is well-documented systemic inflammatory response in xenograft recipients to the presence of a pig graft. Serum amyloid A (SAA) is an inflammatory marker that is elevated in various pathological states. The assay used to measure it is (i) simple, (ii) relatively inexpensive, and (iii) provides an answer within minutes. METHOD: The levels of SAA (n = 11) and C-reactive protein (C-RP) (n = 8) were measured retrospectively in the serum of baboons with pig kidney transplants, who received therapy with an IL-6R inhibitor and a TNF-α antagonist...
December 3, 2018: International Journal of Surgery
Jariya Upadia, Alicia Gomes, Peter Weiser, Maria Descartes
Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare skeletal disorder caused by heterozygous mutations in the MAFB gene (v-maf musculoaponeurotic fibrosarcoma oncogene ortholog B). This is an autosomal dominant condition with a high frequency of sporadic cases. MCTO is characterized by osteolysis of the carpal, metacarpal, and tarsal bones beginning in early childhood with musculoskeletal rheumatologic symptoms such as pain and disability. Renal involvement can be seen in more than half of the patients; from ages 16 months to 42 years and manifests from proteinuria to end-stage renal failure requiring renal transplantation...
December 2018: Journal of Pediatric Genetics
Masatoshi Matsunami, Yoshifumi Ubara, Keiichi Sumida, Yoichi Oshima, Masahiko Oguro, Kazuya Kinoshita, Kiho Tanaka, Yuki Nakamura, Keiichi Kinowaki, Kenichi Ohashi, Takeshi Fujii, Takuro Igawa, Yasuharu Sato, Yasuo Ishii
BACKGROUND: Multicentric Castleman disease (MCD) is an uncommon lymphoproliferative disease characterized by systemic inflammatory reactions associated with the dysregulated production of interleukin-6 (IL-6). In patients with MCD, renal involvement is uncommon, with only one report published regarding kidney transplantation (KTx) to treat end-stage renal disease (ESRD) secondary to MCD. Recent clinical observations have shown that IL-6 production is implicated in allograft rejection, while IL-6 receptor blockade (with tocilizumab [TCZ]) reduces alloantibody generation and thereby improves graft survival; however, the efficacy and safety of TCZ in MCD patients undergoing KTx is still unknown...
October 11, 2018: BMC Nephrology
Christina G Katsiari, Theodora Simopoulou, Ioannis Alexiou, Lazaros I Sakkas
Systemic sclerosis (SSc) is a chronic systemic disease characterized by microvasculopathy, immune activation, and extensive collagen deposition. Microvasculopathy and immune activation occur very early in the disease process. Evidence from animal models and in vitro studies indicate that T-cells and B-cells activate fibroblasts to produce collagen. Traditional immunosuppressants, cyclophosphamide(CyP), methotrexate(MTX), and more recently mycophenolate mofetil(MMF), may prove more effective if used very early in the disease course...
July 9, 2018: Human Vaccines & Immunotherapeutics
Alex Ganetsky, Noelle V Frey, Elizabeth O Hexner, Alison W Loren, Saar I Gill, Selina M Luger, James K Mangan, Mary Ellen Martin, Daria V Babushok, William R Drobyski, Jacqueline Smith, Colleen Timlin, Craig W Freyer, Edward A Stadtmauer, David L Porter
Steroid-refractory (SR) acute gastrointestinal (GI) graft-versus-host disease (GVHD) is associated with significant mortality in allogeneic hematopoietic cell transplantation recipients. We retrospectively evaluated the efficacy of tocilizumab for the treatment of SR biopsy-proven acute lower GI GVHD in 16 consecutive adult transplant recipients between October 2015 and July 2016. Tocilizumab 8 mg/kg was administered every 2 weeks until achievement of complete response, defined as resolution of all manifestations of GI GVHD, or until patients had progression or initiation of other therapy...
May 24, 2018: Bone Marrow Transplantation
Andreu Fernández-Codina, Kyle M Walker, Janet E Pope
OBJECTIVE: There is a lack of agreement regarding treatment for many aspects of systemic sclerosis (SSc). We undertook this study to generate SSc treatment algorithms endorsed by a high percentage of SSc experts. METHODS: Experts from the Scleroderma Clinical Trials Consortium and the Canadian Scleroderma Research group (n = 170) were asked whether they agreed with SSc algorithms from 2012. Two consensus rounds refined agreement; 62, 54, and 48 experts (36%, 32%, and 28%, respectively) completed the first, second, and third surveys, respectively...
November 2018: Arthritis & Rheumatology
Amanda L Hulbert, Elizabeth N Pavlisko, Scott M Palmer
PURPOSE OF REVIEW: There is increasing recognition of the importance of antibody-mediated rejection (AMR) after lung transplantation. The development of donor-specific antibodies, a key feature of AMR, occurs in approximately 30% of lung transplant recipients and is associated with poor posttransplant outcomes. This review highlights recently developed AMR diagnostic criteria in lung transplantation, potential mechanisms that mediate the development of AMR, and discusses current and emerging treatment strategies for this significant, graft-limiting complication...
June 2018: Current Opinion in Organ Transplantation
S Ishikawa, M Tasaki, T Kuroda, D Kobayashi, K Saito, Y Nakagawa, M Ikeda, K Takahashi, Y Tomita
Biologic agents are a beneficial therapy for juvenile idiopathic arthritis (JIA). However, there is a lack of evidence with regard to management of these agents for JIA patients who undergo kidney transplantation (KTx). A 36-year-old woman with JIA who was treated with tocilizumab targeting interleukin-6 (IL-6) receptor underwent ABO-incompatible kidney transplantation (ABOi KTx). To prevent over-immunosuppression, tocilizumab was discontinued before ABOi KTx. Rituximab, tacrolimus, mycophenolate mofetil, everolimus, and methylprednisolone were used for immunosuppression...
April 2018: Transplantation Proceedings
William R Drobyski, Aniko Szabo, Fenlu Zhu, Carolyn Keever-Taylor, Kyle M Hebert, Renee Dunn, Sharon Yim, Bryon Johnson, Anita D'Souza, Mary Eapen, Timothy S Fenske, Parameswaran Hari, Mehdi Hamadani, Mary M Horowitz, J Douglas Rizzo, Wael Saber, Nirav Shah, Bronwen Shaw, Marcelo Pasquini
We conducted a phase 2 study in which patients undergoing allogeneic hematopoietic stem cell transplantation received tocilizumab in addition to standard immune suppression with tacrolimus and methotrexate for graft- versus -host disease prophylaxis. Thirty-five patients were enrolled between January 2015 and June 2016. The median age of the cohort was 66 (range: 22-76). All patients received busulfan-based conditioning, and were transplanted with human leukocyte antigen-matched related or matched unrelated bone marrow or peripheral stem cell grafts...
April 2018: Haematologica
Byoung-Hoon Min, Jun-Seop Shin, Jong-Min Kim, Seong-Jun Kang, Hyun-Je Kim, Il-Hee Yoon, Su-Kyoung Park, Ji-Won Choi, Min-Suk Lee, Chung-Gyu Park
BACKGROUND: Pancreatic islet transplantation is currently proven as a promising treatment for type 1 diabetes patients with labile glycemic control and severe hypoglycemia unawareness. Upon islet transplantation, revascularization is essential for proper functioning of the transplanted islets. As IL-6 is important for endothelial cell survival and systemic inflammation related to xenograft, the effect of IL-6 receptor antagonist, tocilizumab, on revascularization of the transplanted islets was examined in pig to non-human primate islet xenotransplantation model...
January 2018: Xenotransplantation
Yuhong Chen, Yifei Cheng, Pan Suo, Chenhua Yan, Yu Wang, Yao Chen, Wei Han, Lanping Xu, Xiaohui Zhang, Kaiyan Liu, Lungji Chang, Lei Xiao, Xiaojun Huang
Relapse is a common cause of failure in patients with B-cell acute lymphoblastic leukaemia (B-ALL) after haploidentical haematopoietic stem cell transplantation (haplo-HSCT), and non-responders to donor lymphoblastic infusion after HSCT have a very poor prognosis. Although donor-derived CD19-directed chimeric antigen receptor-modified (CAR) T cells can potentially cure leukaemia, their effectiveness and safety have not been confirmed in relapsed B-ALL cases after haplo-HSCT. Between January 2015 and January 2017, two and four patients each received one and two infusions of CAR T cells from haplo-HSCT donors...
November 2017: British Journal of Haematology
Hiroshi Ureshino, Toshihiko Ando, Haruna Kizuka, Kana Kusaba, Haruhiko Sano, Atsujiro Nishioka, Hidekazu Itamura, Takero Shindo, Yasushi Kubota, Kensuke Kojima, Shinya Kimura
It has been well documented that patients may develop cytokine-release syndrome (CRS) following the administration of monoclonal antibodies, such as chimeric antigen receptor-modified T cell. Cytokine-release syndrome is a common complication in patients who have received haploidentical donor allogeneic haematopoietic cell transplantation (haplo-HCT). Although severe CRS after haplo-HCT is a potentially life-threatening toxicity, a standard treatment has not been established. Cytokine blockade with tocilizumab, an anti-IL-6 receptor antibody, has been effective for the treatment of patients with CRS after chimeric antigen receptor-modified T-cell treatment and has also improved CRS after haplo-HCT...
February 2018: Hematological Oncology
J Choi, O Aubert, A Vo, A Loupy, M Haas, D Puliyanda, I Kim, S Louie, A Kang, A Peng, J Kahwaji, N Reinsmoen, M Toyoda, S C Jordan
Extending the functional integrity of renal allografts is the primary goal of transplant medicine. The development of donor-specific antibodies (DSAs) posttransplantation leads to chronic active antibody-mediated rejection (cAMR) and transplant glomerulopathy (TG), resulting in the majority of graft losses that occur in the United States. This reduces the quality and length of life for patients and increases cost. There are no approved treatments for cAMR. Evidence suggests the proinflammatory cytokine interleukin 6 (IL-6) may play an important role in DSA generation and cAMR...
September 2017: American Journal of Transplantation
Nathalie Balandraud, Gaetan Texier, Emmanuel Massy, Olivier Muis-Pistor, Marielle Martin, Isabelle Auger, Marie-Caroline Guzian, Sandrine Guis, Thao Pham, Jean Roudier
BACKGROUND: Epstein-Barr Virus (EBV) is a widely disseminated lymphotropic herpes virus implicated in benign and malignant disorders. In transplant patients, immunosuppressive drugs (cyclosporine) diminish control of EBV replication, potentially leading to lymphoproliferative disorders (LPD). Rheumatoid arthritis (RA) patients have impaired control of EBV infection and have EBV load ten times higher than controls. As post transplant patients, patients with RA have increased risk of developing lymphomas...
2017: PloS One
Brandon R Shank, Bryan Do, Adrienne Sevin, Sheree E Chen, Sattva S Neelapu, Sandra B Horowitz
Patients with B-cell hematologic malignancies who progress through first- or second-line chemotherapy have a poor prognosis. Early clinical trials with autologous anti-CD19 chimeric antigen receptor (CAR) T cells have demonstrated promising results for patients who have relapsed or refractory disease. Lymphodepleting conditioning regimens, including cyclophosphamide, fludarabine, pentostatin, bendamustine, interleukin-2, and total body irradiation, are often administered before the infusion of CAR T cells, allowing for greater T-cell expansion...
March 2017: Pharmacotherapy
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