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The Host Response to Grafts and Transplantation Immunology
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Antilymphocyte globulin is a purified preparation of antibodies raised to lymphocytes. These antibodies interfere with immune responses by causing lymphocytes to be destroyed by complement-mediated lysis or by phagocytes of the reticuloendothelial system. Patients will become sensitized to these antibodies, since being made in horses, they are foreign proteins. Patients quickly generate neutralizing antibodies, making therapy with antilymphocyte globulin or monoclonal antibodies ineffective.
The lymphoreticular system and bone marrow
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Treatment is supportive in the early part of the disease, with transfusion of red cells and platelets. Good results may be seen with androgens and anti-lymphocyte globulin. In younger patients, bone marrow transplantation has a fairly high success rate.
Autologous Stem Cell Transplantation in Animal Models of Autoimmune Diseases
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Those considerations clearly emphasize the need for more specific and less toxic conditioning. Anti-lymphocyte antibodies (ATG (anti-T cell globulin) and ALG (anti-lymphocyte globulin)) are currently used as part of the conditioning regimen in clinical protocols of autologous BMT for MS35 and JCA.36 ALS (anti-lymphocyte serum) was previously shown to protect against allogeneic GvHD in mice and monkeys even when administered before the bone marrow.37,38 These observations suggest that for conditioning of AD patients, it is best to inject the last dose of ATG 24 hours or shorter before the stem cell reinfusion. It may then react with residual lymphocytes in the recipient as well as with lymphocytes that are introduced with the graft.38 Unfortunately, the merits of ATG and its optimal application in conditioning for AD could not be investigated properly in animal models so far. The available polyclonal anti-lymphocyte antibodies against rat T lymphocytes cross-reacted with hematopoietic stem cells, which precluded reliable dose finding and made extrapolations to the clinical antibodies very difficult. In view of the experience with current ATG preparations, there is no doubt that highly specific anti-human T cell monoclonal antibodies, especially if specificity against autoreactive cells could be achieved, would be a great asset for current conditioning regimens.
Is it time to reconsider prophylactic antimicrobial use for hematopoietic stem cell transplantation? a narrative review of antimicrobials in stem cell transplantation
Published in Expert Review of Anti-infective Therapy, 2021
Dilshad Jahan, Ed Peile, Md Arif Sheikh, Salequl Islam, Sharlene Parasnath, Paras Sharma, Katia Iskandar, Sameer Dhingra, Jaykaran Charan, Timothy Craig Hardcastle, Nandeeta Samad, Tajkera Sultana Chowdhury, Siddhartha Dutta, Mainul Haque
Immunosuppressive agents such as cyclophosphamide, antilymphocyte globulin (ALG), ATG, or procarbazine (PCB) remain the mainstay for the treatment options to control GVHD in Allo-HSCT [76,77]. Although immunosuppressive drugs have both benefits and harms in correlated transplant diseases [78], excessive immunosuppression augments the probabilities of infection and relapse following HSCT [67,78,79]. Multiple countries around the globe adopted ATG for the management of GVHD in HSCT [80,81]. Whilst it is known that excessive ATG dosing enhances the probability of microbial disease, there is currently no research-based definition of optimal dosing. Several groups advise dosing schedules of 6–10 mg/kg ATG for HSCT management [82,83]. Additionally, it has been observed that even with ATG administration to prevent GVHD, especially among haploidentical Allo-HSCT, the risk of recurrence is not minimized for patients with refractory hematologic malignancies [84–86]. Further research is essential to establish the ideal dose of ATG to avert GVHD and, consequently, lower the frequency of relapsing malignancies and post-transplantation microbial infections.
A comparative study of porcine antihuman lymphocyte globulin versus antithymocyte globulin-fresenius in an allogeneic hematopoietic cell transplantation conditioning regimen for severe aplastic anemia
Published in Hematology, 2021
Yanming Zhang, Limin Liu, Yejun Si, Miao Miao, Huiying Qiu, Xiaowen Tang, Yue Han, Chengcheng Fu, Zhengming Jin, Suning Chen, Aining Sun, Depei Wu
In previous studies, improved survival after transplantation was shown for both MRD and alternative donors in children and adults. Improved outcomes may have been a consequence of changes in graft-versus-host disease (GVHD) prophylaxis, changes in conditioning regimens, better donor selection, and a larger use of ATG. Conditioning regimens for HSCT in SAA with ATG led to better survival associated with a lower risk of grade II − IV acute GVHD (aGVHD) [23,24]. There are different species of animals utilized to produce ATG, and the available sources currently include horse ATG (h-ATG) and rabbit ATG (r-ATG). Two different r-ATG formulations, thymoglobulin-ATG (ATG-T) and fresenius-ATG (ATG-F) (Fresenius Biotech GmbH, Germany), are usually employed as prophylaxis for GVHD [25]. ATG-T use resulted in fewer adverse effects compared with ATG-F, and similar clinical outcomes were observed in patients undergoing HSCT, suggesting that ATG-T has stronger immunosuppressive activity than ATG-F [26–29]. On the other hand, HSCT with ATG remain to be a heavy financial burden for SAA patients even in Western countries. Anti-human T lymphocyte porcine immunoglobulin (p-ALG) (Wuhan Institute of Biological Products, China, State Medical Permit No. S10830001) was approved by the Sino Food and Drug Administration (SFDA) in 2004. It is commonly used in China to treat people with SAA due to its similar efficacy and safety as rabbit ATG; because of its lower cost (p-ALG costs only about 40% of the cost of rabbit ATG), it is widely used as a first-line therapy against acquired SAA in China [30,31].
Small PNH clones detected by fluorescent aerolysin predict a faster response to immunosuppressive therapy in patients with severe aplastic anaemia
Published in Hematology, 2020
Xiang Ren, Xingxin Li, Jiali Huo, Yahong You, Jinbo Huang, Yingqi Shao, Meili Ge, Zhendong Huang, Jing Zhang, Min Wang, Peng Jin, Neng Nie, Yizhou Zheng
Currently, anti-thymocyte globulin or anti-lymphocyte globulin (ATG or ALG) in combination with cyclosporine A (CyA) still consist a gold standard of immunosuppressive therapy (IST) for the majority of patients who are not candidates for haematopoietic stem cell transplantation (HSCT) [2–4]. However, this intense IST leads to haematologic responses in just about two-thirds of patients [4,5]. It’s desirable that treatment for AA by IST has improved, especially when eltrombopag was added to initial standard IST [6]. But when considering the rest of the patients who may not benefit well from IST, the treatment regimen is still not perfect, and in other words, the long-term results of IST are still poorly predictive in unselected cohorts. It might be valuable to identify patients who are not likely to benefit from IST, thus allowing IST to be avoided in favour of pursuing alternative approaches such as unrelated matched HSCT.