This medical condition has either been superseded or has become inactive
| Specific Conditions |
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| Indication for Ig Use |
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| Level of Evidence | Clear evidence of benefit (Category 1) |
| Description and Diagnostic Criteria |
Transplant rejection occurs when a recipient’s immune system attacks a transplanted organ or tissue. Despite the use of immunosuppressants, one or more episodes of rejection can occur after transplantation. Both cellular and humoral (antibody-mediated) effector mechanisms can play a role. The presence and pattern of rejection need to be established by biopsy. Laboratory tests to assess the presence and strength of antibodies to the donor antigens can provide additional useful information. Clinical assessment, blood tests, ultrasound and nuclear imaging are used primarily to exclude other causes of organ dysfunction. Acute cellular rejection occurs in 15–30% of renal transplants and is responsive to steroids in more than 90% of cases. When rejection is steroid resistant, intravenous immunoglobulin (IVIg) is a safer therapy than anti-T cell antibody therapy, with equal efficacy. Antibody-mediated rejection (AbMR) occurs in 5–10% of renal transplants that have been performed with a compatible cross match. Before the use of IVIg and plasma exchange, AbMR failed to respond adequately to therapy in most cases. Additionally, complications from therapy were severe and sometimes fatal. AbMR responds to IVIg with or without plasma exchange in more than 85% of patients. |
| Justification for Evidence Category |
A randomised controlled trial (RCT) enrolling adult patients with end-stage renal disease (ESRD) who were highly sensitised to human leucocyte antigen (HLA) found that IVIg was better than placebo in reducing anti-HLA antibody levels in highly sensitised patients with ESRD (followed for two years after transplant), and that transplant rates were improved with IVIg therapy (Jordan et al 2004). Multiple case series have been reported in the literature, indicating efficacy in (acute) antibody-mediated rejection, and recommended by a consensus conference (Takemoto et al 2004). Jordan et al (2003) combined data from seven renal transplant recipients and three heart transplant recipients with steroid-resistant combined antibody-mediated and cellular rejection. All patients in this series were successfully treated with high-dose IVIg. A small RCT of transplanted patients with a five-year follow-up period showed that IVIg was as effective as OKT3 monoclonal antibodies in the treatment of steroid-resistant rejection (survival rate at two years was 80% in both groups), but that IVIg generated fewer side effects (Casadei et al 2001). |
| Qualifying Criteria for Ig Therapy |
Pre-transplantation where an antibody or antibodies prevent transplantation (donor-specific anti-human leukocyte antigen [HLA] antibody/ies and/or anti-blood group antibody).
Post-transplantation to treat biopsy proven cellular rejection unresponsive to steroids - or acute antibody mediated rejection.
AND
For prevention and/or treatment of rejection where other therapies are contraindicated or pose a threat to the graft or patient.
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| Review Criteria for Assessing the Effectiveness of Ig Use |
Pre-transplantation where an antibody or antibodies prevent transplantation (donor-specific anti-human leukocyte antigen [HLA] antibody/ies and/or anti-blood group antibody).
Clinical effectiveness of Ig therapy may be demonstrated by:
Post-transplantation to treat biopsy proven cellular rejection unresponsive to steroids - or acute antibody mediated rejection.
Clinical effectiveness of Ig therapy may be demonstrated by:
For prevention and/or treatment of rejection where other therapies are contraindicated or pose a threat to the graft or patient.
Clinical effectiveness of Ig therapy may be demonstrated by:
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| Dose |
Pre-transplantation where an antibody or antibodies prevent transplantation (donor-specific anti-human leukocyte antigen [HLA] antibody/ies and/or anti-blood group antibody).
When IVIg is used alone, further doses may be warranted two to four weeks after initial therapy, depending on clinical response and/or biopsy findings. The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient. Dosing above 1 g/kg per day is contraindicated for some IVIg products. Refer to the current product information sheet for further information. Post-transplantation to treat biopsy proven cellular rejection unresponsive to steroids - or acute antibody mediated rejection.
When IVIg is used alone, further doses may be warranted two to four weeks after initial therapy, depending on clinical response and/or biopsy findings. The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient. Dosing above 1 g/kg per day is contraindicated for some IVIg products. Refer to the current product information sheet for further information. For prevention and/or treatment of rejection where other therapies are contraindicated or pose a threat to the graft or patient.
When IVIg is used alone, further doses may be warranted two to four weeks after initial therapy, depending on clinical response and/or biopsy findings. The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient. Dosing above 1 g/kg per day is contraindicated for some IVIg products. Refer to the current product information sheet for further information. |
| Bibliography |
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| Ahsan, N & Shah, KV 2002, ‘Polyomaviruses: an overview’, Graft, vol. 5, pp. S9–18. Biotext 2004, ‘Summary data on conditions and papers’, in A systematic literature review and report on the efficacy of intravenous immunoglobulin therapy and its risks, commissioned by the National Blood Authority on behalf of all Australian Governments, pp. 86–7. Available from: http://www.nba.gov.au/pubs/pdf/report-lit-rev.pdf Casadei, DH, del C Rial, M, Opelz, G, et al 2001, ‘A randomised and prospective study comparing treatment with high-dose intravenous immunoglobulin with monoclonal antibodies for rescue of kidney grafts with steroid-resistant rejection’, Transplantation, vol. 71, no. 1, pp. 53–8. Conti, DJ, Freed, BM, Gruber, SA, et al 1994, ‘Prophylaxis of primary cytomegalovirus disease in renal transplant recipients. A trial of gancyclovir vs. immunoglobulin’, Archives of Surgery, vol. 129, no. 4, pp. 443–7. Frommer, M & Madronio, C 2006, The use of intravenous immunoglobulin in Australia. A report for the National Blood Authority, Part B: systematic literature review, Sydney Health Projects Group, University of Sydney, Sydney, pp. 18–20. Jordan, SC, Tyan, D, Stablein, D, et al 2004, ‘Evaluation of intravenous immunoglobulin as an agent to lower allosensitisation and improve transplantation in highly sensitized adult patients with end-stage renal disease: report of the NIH IG02 trial’, Journal of the American Society of Nephrology, vol. 15, no. 12, pp. 3256–62. Jordan, SC, Vo, A, Bunnapradist, S, et al 2003, ‘Intravenous immune globulin treatment inhibits cross match positivity and allows for successful transplantation of incompatible organs in living-donor and cadaver recipients’, Transplantation, vol. 76, no. 4, pp. 631–6. Jordan, SC, Vo, AA, Tyan, D, et al 2005, ‘Current approaches to treatment of antibody-mediated rejection’, Pediatric Transplantation, vol. 9, no. 3, pp. 408–15. Lian, M, Chan, W, Slavin, M, et al 2006, ‘Miliary tuberculosis in a Caucasian male transplant recipient and the role of intravenous immunoglobulin as an immunosuppressive sparing agent’, Nephrology (Carlton), vol. 11, no. 2, pp. 156–8. Luke, PP, Scantlebury, VP, Jordan, ML, et al 2001, ‘Reversal of steroid- and anti-lymphocyte antibody-resistant rejection using intravenous immunoglobulin (IVIg) in renal transplant recipients’, Transplantation, vol. 72, no. 3, pp. 419–22. Moger, V, Ravishankar, M, Sakhuja, V, et al 2004, ‘Intravenous immunoglobulin: a safe option for treatment of steroid-resistant rejection in the presence of infection’, Transplantation, vol. 77, no. 9, pp. 1455–6. Orange, JS, Hossny, EM, Weiler, CR, et al 2006, ‘Use of intravenous immunoglobulin in human disease: a review of primary evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology’, Journal of Allergy and Clinical Immunology, vol. 117, no. 4, pp. S525–53. Peraldi, MN, Akposso, K, Haymann, JP, et al 1996, ‘Long-term benefit of intravenous immunoglobulins in cadaveric kidney retransplantation’, Transplantation, vol. 62, no. 11, pp. 1670–3. Puliyanda, D, Radha, RK, Amet, N, et al 2003, ‘IVIg contains antibodies reactive with polyoma BK virus and may represent a therapeutic option for BK nephropathy’, American Journal of Transplantation, vol. 3, suppl. 4, p. 393. Sonnenday, CJ, Warren, DS, Cooper, MC, et al 2004, ‘Plasmapheresis, CMV hyperimmune globulin, and anti-CD20 allow ABO-incompatible renal transplantation without splenectomy’, American Journal of Transplantation, vol. 4, pp. 1315–22. Takemoto, SK, Zeevi, A, Feng, S, et al 2004, ‘National conference to assess antibody-mediated rejection in solid organ transplantation’, American Journal of Transplantation, vol. 4, no. 7, pp. 1033–41. Tydén, G, Kumlien, G, Genberg, H, et al 2005, ‘ABO incompatible kidney transplantations without splenectomy, using antigen-specific immunoadsorption and rituximab’, American Journal of Transplantation, vol. 5, no. 1, pp. 145–8. UK National Kidney Federation 2002, ‘Transplant’. Available from: http://www.kidney.org.uk/Medical-Info/transplant.html#rej [cited 7 Dec 2007]. |