Abstract
Antithymocyte globulin (ATG) is commonly used in allogeneic haematopoietic stem cell transplantation (HSCT). Little information is available, however, as to the optimal protocol for use and the side-effects occurring if ATG is administered in high daily doses (10–30 mg/kg). We report our experience with ATG Fresenius (ATG-F) in conditioning for allogeneic HSCT. During a period of 3 days, 47 patients received doses between 10 and 30 mg/kg either over 4 h preceded by 1–1.5 mg/kg prednisolone 30 min before the start of ATG-F (protocol A) or alternatively, over 12 h with 3–4 mg/kg prednisolone being administered before and 6 h after start of ATG (protocol B). During treatment with ATG-F, the side-effects observed included inflammation, disseminated intravascular coagulation, hyperdynamic circulation and renal dysfunction. Although these complications caused substantial morbidity, they were reversible within a few days. Side-effects were significantly more severe in patients treated according to protocol A than in those treated according to protocol B. As prolonged infusion of ATG-F does not reduce T cell clearance due to the long half-life of ATG-F, and since less cytokine release during conditioning might have beneficial long-term effects, we recommend administering ATG-F over 12 h preceded by high-dose steroid treatment.
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References
Kolb HJ, Thierfelder S, Baumann P, Balk O . Conditioning recipients of hematopoietic cells with antilymphocyte serum (ALS) and partial irradiation Rev Europ Etudes Clin Biol 1971 16: 810 814
Kolb HJ, Storb R, Graham TC et al. Antithymocyte serum and methotrexate for control of graft-versus-host disease in dogs Transplantation 1973 16: 17 23
Fresenius HemoCare Immune Therapy GmbH, Gräfelfing, Germany. ATG-Fresenius S. Gebrauchsinformation und Fachinformation
Glucksberg H, Storb R, Fefer A et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors Transplantation 1974 18: 295 304
Reinhart K, Karzai W, Meisner M . Procalcitonin as a marker of the systemic inflammatory response to infection Intens Care Med 2000 26: 1193 1200
Grosse-Wilde H, Jakubowski HD, Eigler FW, Kuwert EK . In vitro immunoresponsiveness in recipients of cadaveric renal allografts during ATG therapy Proc Eur Dial Transplant Assoc 1981 18: 481 485
Eiermann TH, Lambrecht P, Zander AR . Monitoring antithymocyte globulin (ATG) in bone marrow recipients Bone Marrow Transplant 1999 23: 779 781
Frickhofen N, Heit W, Raghavachar A et al. Immunosuppressive therapy in panmyelopathy. Experiences with various forms of therapy in 42 patients Deut Med Wochenschr 1987 112: 535 541
Titiz MI, Turkmen F, Yegenaga I et al. Abdominal pain that mimics acute appendicitis caused by an ATG overdose in a kidney transplant recipient Transplant Int 1994 7: 385
Hoffman T, Tripathi AK, Lee YL et al. Stimulation of human monocytes by anti-CD3 monoclonal antibody: induction of inflammatory mediator release via immobilization of Fc receptor by adsorbed immunoglobulin and T-lymphocytes Inflammation 1992 16: 571 585
Holler E, Kolb HJ, Mittermüller J et al. Modulation of acute graft-versus-host disease after allogeneic bone marrow transplantation by tumor necrosis factor alpha (TNF alpha) release in the course of pretransplant conditioning: role of conditioning regimens and prophylactic application of a monoclonal antibody neutralizing human TNF alpha (MAK 195F) Blood 1995 86: 890 899
Rosenbloom AJ, Pinsky MR, Bryant JL et al. Leukocyte activation in the peripheral blood of patients with cirrhosis of the liver and SIRS. Correlation with serum interleukin-6 levels and organ dysfunction JAMA 1995 274: 58 65
Vervloet MG, Thijs LG, Hack CE . Derangements of coagulation and fibrinolysis in critically ill patients with sepsis and septic shock Semin Thromb Hemost 1998 24: 33 44
Lee WL, Downey GP . Coagulation inhibitors in sepsis and disseminated intravascular coagulation Intens Care Med 2000 26: 1701 1706
Chatenoud L, Legendre C, Ferran C et al. Corticosteroid inhibition of the OKT3-induced cytokine-related syndrome-dosage and kinetics prerequisites Transplantation 1991 51: 334 338
Buttgereit F, Wehling M, Burmester GR . A new hypothesis of modular glucocorticoid actions: steroid treatment of rheumatic diseases revisited Arthritis Rheum 1998 41: 761 767
Cronin L, Cook DJ, Carlet J et al. Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature Crit Care Med 1995 23: 1430 1439
Pinsky MR, Vincent JL, Deviere J et al. Serum cytokine levels in human septic shock. Relation to multiple-system organ failure and mortality Chest 1993 103: 565 575
Thijs LG, Hack CE . Time course of cytokine levels in sepsis Intens Care Med 1995 21: S258 S263
Sorensen JB, Andersen MK, Hansen HH . Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in malignant disease J Intern Med 1995 238: 97 110
Assicot M, Gendrel D, Carsin H et al. High serum procalcitonin concentrations in patients with sepsis and infection Lancet 1993 341: 515 518
AlNawas B, Krammer I, Shah PM . Procalcitonin in diagnosis of severe infections Eur J Med Res 1996 1: 331 333
Brunkhorst FM, Eberhard OK, Brunkhorst R . Discrimination of infectious and noninfectious causes of early acute respiratory distress syndrome by procalcitonin Crit Care Med 1999 27: 2172 2176
Sachse C, Machens HG, Felmerer G et al. Procalcitonin as a marker for the early diagnosis of severe infection after thermal injury J Burn Care Rehabil 1999 20: 354 360
Schwenger V, Sis J, Breitbart A, Andrassy K . CRP levels in autoimmune disease can be specified by measurement of procalcitonin Infection 1998 26: 274 276
Sabat R, Hoflich C, Docke WD et al. Massive elevation of procalcitonin plasma levels in the absence of infection in kidney transplant patients treated with pan-T-cell antibodies Intens Care Med 2001 27: 987 991
Holler E, Kolb HJ, Moller A et al. Increased serum levels of tumor necrosis factor alpha precede major complications of bone marrow transplantation Blood 1990 75: 1011 1016
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Pihusch, R., Holler, E., Mühlbayer, D. et al. The impact of antithymocyte globulin on short-term toxicity after allogeneic stem cell transplantation. Bone Marrow Transplant 30, 347–354 (2002). https://doi.org/10.1038/sj.bmt.1703640
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DOI: https://doi.org/10.1038/sj.bmt.1703640
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