Safety and Efficacy of Alemtuzumab in Pediatric Intestinal Transplantation

Intraoperatively, it is our impression that Alemtuzumab may predispose to mild coagulopathy. Therefore, we have elected to administer steroids, and withhold Alemtuzumab in the operating room for all small bowel transplant recipients.

• Premedication with acetaminophen 10 mg/kg orally + diphenhydramine 1 mg/kg intravenously + methylprednisolone 2 mg/kg, intravenously will occur 30 minutes before Alemtuzumab administration.
• Steroids up to 10 mg/kg as bolus will be administered intravenously in the operating room prior to reperfusion of the allograft followed by decreasing amounts of low-dose steroids post-transplant.

Day 1 post-transplant: up to 5 mg/kg can be given Day 2 post-transplant: up to 4 mg/kg can be given Day 3 post-transplant: up to 3 mg/kg can be given Day 4 post-transplant: up to 2 mg/kg can be given Day 5 post-transplant: up to 1 mg/kg can be given

Maintenance steroids are tapered thereafter by switching to equivalent amounts of oral prednisone, as soon as ileus results and oral intake intake is possible. By the end of the first month, all patients receive no more than 2.5-5 mg/day of prednisone. This amount is exceeded only if rejection occurs. Long-term prednisone usage may be elected in patients re-transplanted for chronic rejection.

• A single dose of Alemtuzumab 0.4-0.5 mg/kg will be given intravenously slowly post-operatively. Total dose will not exceed 30 mg.

Procedures:

• Tacrolimus will be initiated at 0.01 mg per kg body weight orally. If biopsy-proven rejection does not occur, Tacrolimus will be titrated to whole blood concentrations:

Month 1: 15-20 ng/ml Months 2-3: 10-15 ng/ml Month 4-6: 8-10 ng/ml Months 6-12: 5-10 ng/ml

• This minimization protocol will be delayed by 3 months if biopsy proven acute cellular rejection occurs. At the event of rejection, Tacrolimus minimization and steroids sparing will be discontinued and standard immunosuppression will be instituted. For example, if rejection occurs, Tacrolimus is increased to month 1 levels of 15-20 ng/ml, and steroids added to the regimen. Steroids will be reduced or eliminated within 3 months of rejection, and tacrolimus minimization resumed as described above. These levels of Tacrolimus are our standards of care in the event of rejection. Current immunosuppressive protocols at our center include rabbit anti-human thymocyte globulin (rATG) with Tacrolimus monotherapy, or Tacrolimus + steroid without induction.
• Laboratory tests per clinical protocol. The clinical standard of care will be followed in performing post-Tx monitoring labs consisting of complete blood count with differential count, serum sodium, potassium, chloride, bicarbonate, BUN, creatinine and glucose, and liver function tests consisting of Total bilirubin, aspartate alanine transaminase (ALT), aspartate glutamine transaminase (AST), and glutamyl galactosyl transaminase (GGT), and TAC whole blood concentrations. These laboratory tests are performed at least weekly in the first and second months, twice monthly in month 3, and monthly thereafter to the sixth month. The extra 1 to 11 ml needed for pharmacodynamic and pharmacogenomic studies is discussed further in items 5 and in Table 1.
• Surveillance intestinal allograft biopsies will be performed per clinical surveillance protocol-twice weekly in the first month, weekly in the second month, two-weekly in the third month, and at least monthly thereafter until the end of the 6th month, and at least annually thereafter. Surveillance biopsies are done because no blood test exists to indicate intestinal allograft dysfunction.

Inclusion criteria

• Age 0-25 years
• male and female
• Primary intestine transplantation, repeat intestine transplantation, and intestine transplantation in the setting of a previous or simultaneous liver transplantation

Exclusion criteria

• documented non-compliance
• known hypersensitivity to egg protein
• pregnancy
• malignancy
• hepatitis C and B defined as anti-HCV antibody positive, and anti-Hepatitis B surface antigen or Hepatitis B core antibody positive or HBV DNA positive.