异体骨髓移植/脐血移植/造血干细胞移植/重型再障ATG应用指南（英语版）

Anti-Human thymocyte globulin (ATG) Administration Guidelines for Allogeneic Transplantation and Severe Aplastic Anemia

Introduction      Horse anti-thymocyte globulin (H-ATG) is a gamma globulin protein obtained from hyperimmune serum of horses immunized with human thymus lymphocytes. It is an antilymphocytic immunosuppressant which alters the function of T-cell (thymus dependent) lymphocytes. It is used as a preparative drug for marrow transplant, immunosuppressive therapy in aplastic anemia, and GVHD treatment.郑州大学一附院血液内科万鼎铭

Dosage               Usual ATG dosage for GVHD treatment is 15mg/kg every other day times 6 doses. ATG doses are specified in each protocol. Use adjusted ideal body weight for markedly obese patients.

Skin tests          Perform skin tests prior to first dose of ATG.

Anaphylaxis precaution      During the administration of the skin test, have diphenhydramine (苯海拉明50mg I.V.) and epinephrine 1:1000 (肾上腺素1ml) available at the bedside in case of allergic reaction.

Administration of skin test      Skin tests should be performed by P.A.(physician"s assistant) or M.D.(medical doctors) and reaction confirmed with them. Two intradermal tests are routinely done. Both are administered at the same time and reactions noted. To prepare:

1. Control: Use 0.1 ml of NS.

2. Horse ATG: A 1:1000 dilution is used for skin testing (0.1 ml/test)

Mark test sites NS or ATG with pen. The patient and specifically the skin test should be observed at one hour after intradermal injection. A local reaction of 10 mm or greater with a wheal or erythema, or both, with or without pseudopod formation and itching or a marked local swelling should be considered a positive test. Allergic reactions such as anaphylaxis have occurred in patients whose skin test in negative. In the presence of a locally positive skin test to ATG, serious consideration to alternative forms of therapy should be given. A positive test shall be noted if any of the following is present: ①Systemic reaction    Urticaria; Generalized itching or rash; Tachycardia; Dyspnea; Hypotension; Anaphylaxis (shock) ②Local reaction    Local symptoms (observe 1 hour): Induration (wheal) and/or erythema more than 10 mm with pseudopod formation and itching to ATG or marked local swelling of the extremity ③Positive reaction    Patients with a positive skin test or systemic reaction should not receive ATG unless approved by the attending physician or principal investigator.

Preparation of ATG   Horse ATG is manufactured in 250mg/5ml vials. ATG, once diluted, is physically and chemically stable for up to 24 hours at concentrations of up to 4 mg/ml in NS, ½NS, D5¼NS and D5½NS. The use of high-flow veins will minimize the occurrence of phlebitis and thrombosis. If a peripheral vein is being used, a dilution of 1 mg/ml should be used to prevent phlebitis. Dilution is D5W is not recommended as low salt concentrations can cause precipitation. Highly acidic solutions can also contribute to physical instability over time. Diluted ATG should be stored in the refrigerator if prepared prior to the time of infusion. The total time in dilution should not exceed 24 hours (including infusion time).

ATG administration     Horse ATG should be administered alone and not run piggyback with any other solution. Always use a filter (in-line) when administering ATG to the patient (i.e. 1 micron).

Infusion schedule        Epinephrine 1:10000, diphenhydramine 50mg I.V. and hydrocortisone 100mg I.V. should be at bedside. In order to assess potential toxicity, a gradually increasing dose rate is recommended for the initial infusion, e.g. 50mg ATG over 1 hour, 100 mg ATG over the next hour. Remaining calculated dose can be infused over 4-10 hours as tolerated by patient. Initial infusion aliquots proportionate to dose should be estimated for pediatric patients. For patients receiving ATG as part of conditioning, 1 mg/kg of methylprednisolone should be given before every dose.

Toxicities and treatments

Major toxicity    Any toxicity considered by the physician to be a major threat to the patient mandates discontinuation of the ATG.

Chills and Fever   Chills and fever commonly occur in patients receiving ATG. Minor toxicities can usually be managed by symptomatic treatment and temporary slowing of the infusion. If during infusion the patient develops fever and/or chills, (s)he should be medicated with diphenhydramine 25-50mg I.V. (pediatric 1 mg/kg) and an antipyretic, e.g. acetaminophen (对乙酰氨基酚，扑热息痛), 300-600mg (pediatric 10-15 mg/kg) p.o. q6-8 hours prn. For severe fever and chills meperidine (哌替啶) 25-50 mg (pediatric 1 mg/kg) I.V. q 4-6 hours prn may also be required.

Purities           Itching and erythema occasionally develop. Symptoms are generally controlled with diphenhydramine.

Respiratory distress  Respiratory distress may be a sign of anaphylaxis. Infusion should be discontinued. If reaction persists, diphenhydramine, epinephrine and/or hydrocortisone should be administered. Pain is chest, flank or back may be a sign of anaphylaxis or hemolysis. Infusion should be discontinued.

Hypotension            Hypotension occurs rarely and may be a sign of anaphylaxis. Discontinue infusion and treat accordingly.

Serum sickness       Syndrome of fevers, arthralgias, fluid weight gain, and rash may occur. Treat with steroids.

Phlebitis             Can be caused by infusion of ATG through peripheral veins. This can be avoided by infusion of ATG into a high flow vein.