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Meta-Analysis
. 2013 Dec 2;2013(12):CD008842.
doi: 10.1002/14651858.CD008842.pub2.

Immunosuppressive T-cell antibody induction for heart transplant recipients

Luit Penninga  1 , Christian H Møller, Finn Gustafsson, Christian Gluud, Daniel A Steinbrüchel
Affiliations
Meta-Analysis

Immunosuppressive T-cell antibody induction for heart transplant recipients

Luit Penninga et al. Cochrane Database Syst Rev. .

Abstract

Background: Heart transplantation has become a valuable and well-accepted treatment option for end-stage heart failure. Rejection of the transplanted heart by the recipient's body is a risk to the success of the procedure, and life-long immunosuppression is necessary to avoid this. Clear evidence is required to identify the best, safest and most effective immunosuppressive treatment strategy for heart transplant recipients. To date, there is no consensus on the use of immunosuppressive antibodies against T-cells for induction after heart transplantation.

Objectives: To review the benefits, harms, feasibility and tolerability of immunosuppressive T-cell antibody induction versus placebo, or no antibody induction, or another kind of antibody induction for heart transplant recipients.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 11, 2012), MEDLINE (Ovid) (1946 to November Week 1 2012), EMBASE (Ovid) (1946 to 2012 Week 45), ISI Web of Science (14 November 2012); we also searched two clinical trial registers and checked reference lists in November 2012.

Selection criteria: We included all randomised clinical trials (RCTs) assessing immunosuppressive T-cell antibody induction for heart transplant recipients. Within individual trials, we required all participants to receive the same maintenance immunosuppressive therapy.

Data collection and analysis: Two authors extracted data independently. RevMan analysis was used for statistical analysis of dichotomous data with risk ratio (RR), and of continuous data with mean difference (MD), both with 95% confidence intervals (CI). Methodological components were used to assess risks of systematic errors (bias). Trial sequential analysis was used to assess the risks of random errors (play of chance). We assessed mortality, acute rejection, infection, Cytomegalovirus (CMV) infection, post-transplantation lymphoproliferative disorder, cancer, adverse events, chronic allograft vasculopathy, renal function, hypertension, diabetes mellitus, and hyperlipidaemia.

Main results: In this review, we included 22 RCTs that investigated the use of T-cell antibody induction, with a total of 1427 heart-transplant recipients. All trials were judged to be at a high risk of bias. Five trials, with a total of 606 participants, compared any kind of T-cell antibody induction versus no antibody induction; four trials, with a total of 576 participants, compared interleukin-2 receptor antagonist (IL-2 RA) versus no induction; one trial, with 30 participants, compared monoclonal antibody (other than IL-2 RA) versus no antibody induction; two trials, with a total of 159 participants, compared IL-2 RA versus monoclonal antibody (other than IL-2 RA) induction; four trials, with a total of 185 participants, compared IL-2 RA versus polyclonal antibody induction; seven trials, with a total of 315 participants, compared monoclonal antibody (other than IL-2 RA) versus polyclonal antibody induction; and four trials, with a total of 162 participants, compared polyclonal antibody induction versus another kind, or dose of polyclonal antibodies.No significant differences were found for any of the comparisons for the outcomes of mortality, infection, CMV infection, post-transplantation lymphoproliferative disorder, cancer, adverse events, chronic allograft vasculopathy, renal function, hypertension, diabetes mellitus, or hyperlipidaemia. Acute rejection occurred significantly less frequently when IL-2 RA induction was compared with no induction (93/284 (33%) versus 132/292 (45%); RR 0.73; 95% CI 0.59 to 0.90; I(2) 57%) applying the fixed-effect model. No significant difference was found when the random-effects model was applied (RR 0.73; 95% CI 0.46 to 1.17; I(2) 57%). In addition, acute rejection occurred more often statistically when IL-2 RA induction was compared with polyclonal antibody induction (24/90 (27%) versus 10/95 (11%); RR 2.43; 95% CI 1.01 to 5.86; I(2) 28%). For all of these differences in acute rejection, trial sequential alpha-spending boundaries were not crossed and the required information sizes were not reached when trial sequential analysis was performed, indicating that we cannot exclude random errors.We observed some occasional significant differences in adverse events in some of the comparisons, however definitions of adverse events varied between trials, and numbers of participants and events in these outcomes were too small to allow definitive conclusions to be drawn.

Authors' conclusions: This review shows that acute rejection might be reduced by IL-2 RA compared with no induction, and by polyclonal antibody induction compared with IL-2 RA, though trial sequential analyses cannot exclude random errors, and the significance of our observations depended on the statistical model used. Furthermore, this review does not show other clear benefits or harms associated with the use of any kind of T-cell antibody induction compared with no induction, or when one type of T-cell antibody is compared with another type of antibody. The number of trials investigating the use of antibodies against T-cells for induction after heart transplantation is small, and the number of participants and outcomes in these RCTs is limited. Furthermore, the included trials are at a high risk of bias. Hence, more RCTs are needed to assess the benefits and harms of T-cell antibody induction for heart-transplant recipients. Such trials ought to be conducted with low risks of systematic and random error.

PubMed Disclaimer

Conflict of interest statement

Luit Penninga: none known Christian H Møller: none known Finn Gustafsson: none known Christian Gluud: none known Daniel A Steinbrüchel: none known

Figures

1
1
Study flow diagram
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
4
4
Interleukin‐2 receptor antagonist induction versus no induction: mortality: trial sequential analysis of the effect of interleukin‐2 receptor antagonist induction versus no induction on mortality based on four trials with 576 participants. The diversity adjusted required information size (DARIS) of 11138 participants was calculated based on type I error of 5%, type II error of 20%, risk reduction of 20%, and information size was adjusted for diversity (0%). The cumulative Z‐curve does not cross trial sequential alpha and beta spending monitoring boundaries, and required information size was not reached.
5
5
Interleukin‐2 receptor antagonist induction versus no induction: acute rejection: trial sequential analysis of the effect of interleukin‐2 receptor antagonist induction versus no induction on acute rejection based on four trials with 576 participants. The diversity adjusted required information size (DARIS) of 4707 participants was calculated based on type I error of 5%, type II error of 20%, risk reduction of 20%, and information size was adjusted for diversity (80%). The cumulative Z‐curve does not cross trial sequential alpha and beta spending monitoring boundaries, and required information size was not reached.
6
6
Interleukin‐2 receptor antagonist induction versus no induction: infection: trial sequential analysis of the effect of interleukin‐2 receptor antagonist induction versus no induction on infection based on three trials with 545 participants. The diversity adjusted required information size (DARIS) of 1255 participants was calculated based on type I error of 5%, type II error of 20%, risk reduction of 20%, and information size was adjusted for diversity (6%). The cumulative Z‐curve does not cross trial sequential alpha spending monitoring boundary, and required information size was not reached. However, the cumulative Z‐curve reaches the area of futility (trial sequential beta spending monitoring boundary), hence we can reject a difference of 20% of more between the groups regarding infection.
1.1
1.1. Analysis
Comparison 1 Antibody induction versus no induction, Outcome 1 Mortality.
1.2
1.2. Analysis
Comparison 1 Antibody induction versus no induction, Outcome 2 Acute rejection.
1.3
1.3. Analysis
Comparison 1 Antibody induction versus no induction, Outcome 3 Infection.
1.4
1.4. Analysis
Comparison 1 Antibody induction versus no induction, Outcome 4 Cytomegalovirus infection.
1.5
1.5. Analysis
Comparison 1 Antibody induction versus no induction, Outcome 5 Post‐transplantation lymphoproliferative disorder.
1.6
1.6. Analysis
Comparison 1 Antibody induction versus no induction, Outcome 6 Cancer.
1.7
1.7. Analysis
Comparison 1 Antibody induction versus no induction, Outcome 7 Adverse events.
1.8
1.8. Analysis
Comparison 1 Antibody induction versus no induction, Outcome 8 Chronic allograft vasculopathy.
1.9
1.9. Analysis
Comparison 1 Antibody induction versus no induction, Outcome 9 Renal failure requiring chronic dialysis.
1.10
1.10. Analysis
Comparison 1 Antibody induction versus no induction, Outcome 10 Serum creatinine.
1.11
1.11. Analysis
Comparison 1 Antibody induction versus no induction, Outcome 11 Hypertension.
2.1
2.1. Analysis
Comparison 2 Interleukin‐2 receptor antagonist (IL‐2 RA) versus no induction, Outcome 1 Mortality.
2.2
2.2. Analysis
Comparison 2 Interleukin‐2 receptor antagonist (IL‐2 RA) versus no induction, Outcome 2 Acute rejection.
2.3
2.3. Analysis
Comparison 2 Interleukin‐2 receptor antagonist (IL‐2 RA) versus no induction, Outcome 3 Infection.
2.4
2.4. Analysis
Comparison 2 Interleukin‐2 receptor antagonist (IL‐2 RA) versus no induction, Outcome 4 Cytomegalovirus infection.
2.5
2.5. Analysis
Comparison 2 Interleukin‐2 receptor antagonist (IL‐2 RA) versus no induction, Outcome 5 Post‐transplantation lymphoproliferative disorder.
2.6
2.6. Analysis
Comparison 2 Interleukin‐2 receptor antagonist (IL‐2 RA) versus no induction, Outcome 6 Cancer.
2.7
2.7. Analysis
Comparison 2 Interleukin‐2 receptor antagonist (IL‐2 RA) versus no induction, Outcome 7 Adverse events.
2.8
2.8. Analysis
Comparison 2 Interleukin‐2 receptor antagonist (IL‐2 RA) versus no induction, Outcome 8 Hypertension.
3.1
3.1. Analysis
Comparison 3 Interleukin‐2 receptor antagonist (IL‐2 RA) versus monoclonal antibody, Outcome 1 Mortality.
3.2
3.2. Analysis
Comparison 3 Interleukin‐2 receptor antagonist (IL‐2 RA) versus monoclonal antibody, Outcome 2 Acute rejection.
3.3
3.3. Analysis
Comparison 3 Interleukin‐2 receptor antagonist (IL‐2 RA) versus monoclonal antibody, Outcome 3 Infection.
3.4
3.4. Analysis
Comparison 3 Interleukin‐2 receptor antagonist (IL‐2 RA) versus monoclonal antibody, Outcome 4 Cytomegalovirus infection.
3.5
3.5. Analysis
Comparison 3 Interleukin‐2 receptor antagonist (IL‐2 RA) versus monoclonal antibody, Outcome 5 Post‐transplantation lymphoproliferative disorder.
3.6
3.6. Analysis
Comparison 3 Interleukin‐2 receptor antagonist (IL‐2 RA) versus monoclonal antibody, Outcome 6 Cancer.
3.7
3.7. Analysis
Comparison 3 Interleukin‐2 receptor antagonist (IL‐2 RA) versus monoclonal antibody, Outcome 7 Adverse events.
4.1
4.1. Analysis
Comparison 4 Interleukin‐2 receptor antagonist (IL‐2 RA) versus polyclonal antibody, Outcome 1 Mortality.
4.2
4.2. Analysis
Comparison 4 Interleukin‐2 receptor antagonist (IL‐2 RA) versus polyclonal antibody, Outcome 2 Acute rejection.
4.3
4.3. Analysis
Comparison 4 Interleukin‐2 receptor antagonist (IL‐2 RA) versus polyclonal antibody, Outcome 3 Infection.
4.4
4.4. Analysis
Comparison 4 Interleukin‐2 receptor antagonist (IL‐2 RA) versus polyclonal antibody, Outcome 4 Cytomegalovirus infection.
4.5
4.5. Analysis
Comparison 4 Interleukin‐2 receptor antagonist (IL‐2 RA) versus polyclonal antibody, Outcome 5 Post‐transplantation lymphoproliferative disorder.
4.6
4.6. Analysis
Comparison 4 Interleukin‐2 receptor antagonist (IL‐2 RA) versus polyclonal antibody, Outcome 6 Cancer.
4.7
4.7. Analysis
Comparison 4 Interleukin‐2 receptor antagonist (IL‐2 RA) versus polyclonal antibody, Outcome 7 Adverse events.
4.8
4.8. Analysis
Comparison 4 Interleukin‐2 receptor antagonist (IL‐2 RA) versus polyclonal antibody, Outcome 8 Chronic allograft vasculopathy.
5.1
5.1. Analysis
Comparison 5 Monoclonal antibody versus polyclonal antibody, Outcome 1 Mortality.
5.2
5.2. Analysis
Comparison 5 Monoclonal antibody versus polyclonal antibody, Outcome 2 Acute rejection.
5.3
5.3. Analysis
Comparison 5 Monoclonal antibody versus polyclonal antibody, Outcome 3 Infection.
5.4
5.4. Analysis
Comparison 5 Monoclonal antibody versus polyclonal antibody, Outcome 4 Cytomegalovirus infection.
5.5
5.5. Analysis
Comparison 5 Monoclonal antibody versus polyclonal antibody, Outcome 5 Post‐transplantation lymphoproliferative disorder.
5.6
5.6. Analysis
Comparison 5 Monoclonal antibody versus polyclonal antibody, Outcome 6 Cancer.
5.7
5.7. Analysis
Comparison 5 Monoclonal antibody versus polyclonal antibody, Outcome 7 Adverse events.
5.8
5.8. Analysis
Comparison 5 Monoclonal antibody versus polyclonal antibody, Outcome 8 Serum creatinine.
6.1
6.1. Analysis
Comparison 6 Anti‐thymocyte globulin (ATG) versus anti‐lymphocyte globulin (ALG), Outcome 1 Mortality.
6.2
6.2. Analysis
Comparison 6 Anti‐thymocyte globulin (ATG) versus anti‐lymphocyte globulin (ALG), Outcome 2 Infection.
6.3
6.3. Analysis
Comparison 6 Anti‐thymocyte globulin (ATG) versus anti‐lymphocyte globulin (ALG), Outcome 3 Adverse events.
7.2
7.2. Analysis
Comparison 7 High‐dose anti‐thymocyte globulin (ATG) versus standard‐dose, Outcome 2 Acute rejection.
7.3
7.3. Analysis
Comparison 7 High‐dose anti‐thymocyte globulin (ATG) versus standard‐dose, Outcome 3 Infection.
7.4
7.4. Analysis
Comparison 7 High‐dose anti‐thymocyte globulin (ATG) versus standard‐dose, Outcome 4 Cytomegalovirus infection.
7.5
7.5. Analysis
Comparison 7 High‐dose anti‐thymocyte globulin (ATG) versus standard‐dose, Outcome 5 Post‐transplantation lymphoproliferative disorder.
7.6
7.6. Analysis
Comparison 7 High‐dose anti‐thymocyte globulin (ATG) versus standard‐dose, Outcome 6 Cancer.
7.7
7.7. Analysis
Comparison 7 High‐dose anti‐thymocyte globulin (ATG) versus standard‐dose, Outcome 7 Adverse events.
7.8
7.8. Analysis
Comparison 7 High‐dose anti‐thymocyte globulin (ATG) versus standard‐dose, Outcome 8 Chronic allograft vasculopathy.
7.9
7.9. Analysis
Comparison 7 High‐dose anti‐thymocyte globulin (ATG) versus standard‐dose, Outcome 9 Renal failure requiring chronic dialysis.
7.10
7.10. Analysis
Comparison 7 High‐dose anti‐thymocyte globulin (ATG) versus standard‐dose, Outcome 10 Mortality.
8.1
8.1. Analysis
Comparison 8 RATG‐Thymoglobulin versus RATG‐Fresenius, Outcome 1 Mortality.
8.2
8.2. Analysis
Comparison 8 RATG‐Thymoglobulin versus RATG‐Fresenius, Outcome 2 Acute rejection.
8.3
8.3. Analysis
Comparison 8 RATG‐Thymoglobulin versus RATG‐Fresenius, Outcome 3 Infection.
8.4
8.4. Analysis
Comparison 8 RATG‐Thymoglobulin versus RATG‐Fresenius, Outcome 4 Cytomegalovirus infection.
8.5
8.5. Analysis
Comparison 8 RATG‐Thymoglobulin versus RATG‐Fresenius, Outcome 5 Post‐transplantation lymphoproliferative disorder.
8.6
8.6. Analysis
Comparison 8 RATG‐Thymoglobulin versus RATG‐Fresenius, Outcome 6 Cancer.
8.7
8.7. Analysis
Comparison 8 RATG‐Thymoglobulin versus RATG‐Fresenius, Outcome 7 Adverse events.
8.8
8.8. Analysis
Comparison 8 RATG‐Thymoglobulin versus RATG‐Fresenius, Outcome 8 Chronic allograft vasculopathy.
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Update of

References

References to studies included in this review

Balk 1992 {published data only}
    1. Balk AH, Meeter K, Simoons ML, Brouwer RM, Zondervan PE, Mochtar B, et al. Polyclonal versus monoclonal rejection prophylaxis after heart transplantation: a randomised study. Transplantation International 1992;5 Suppl 1:S476‐9. - PubMed
Beniaminovits 2000 {published data only}
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Kobashigawa 1993 {published data only}
    1. Kobashigawa JA, Stevenson LW, Brownfield E, Moriguchi JD, Kawata N, Hamilton M, et al. Does short‐course induction with OKT3 improve outcome after heart transplantation? A randomized trial. Journal of Heart and Lung Transplantation 1993;12(2):205‐8. - PubMed
Kormos 1990 {published data only}
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    1. Kormos RL, Armitage JM, Dummer JS, Miyamoto Y, Griffith BP, Hardesty RL. Optimal perioperative immunosuppression in cardiac transplantation using rabbit antithymocyte globulin. Transplantation 1990;49(2):306‐11. - PubMed
    1. Kormos RL, Herlan DB, Armitage JM, Stein K, Kaufman C, Zeevi A, et al. Monoclonal versus polyclonal antibody therapy for prophylaxis against rejection after heart transplantation. Journal of Heart Transplantation 1990;9(1):1‐9. - PubMed
Macdonald 1993 {published data only}
    1. Macdonald PS, Mundy J, Keogh AM, Chang VP, Spratt PM. A prospective randomized study of prophylactic OKT3 versus equine antithymocyte globulin after heart transplantation‐‐increased morbidity with OKT3. Transplantation 1993;55(1):110‐6. - PubMed
Mattei 2007 {published data only}
    1. Boissonnat P, Sebbag L, French Heart Nausicaa Study Grp. Less infectious deaths with basiliximab (Simulect (R)) over antihymocyte globulin (Thymoglobuline (R)) induction therapy in heart transplantation: Results of nausicaa, a national multicentre prospective randomized study. 2005; Vol. 5:386.
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Mehra 2005 {published data only}
    1. Mehra MR, Zucker MJ, Wagoner L, Michler R, Boehmer J, Kovarik J, et al. A multicenter, prospective, randomized, double‐blind trial of basiliximab in heart transplantation. Journal of Heart and Lung Transplantation 2005;24(9):1297‐304. - PubMed
Menkis 1992 {published data only}
    1. Menkis AH, Powell AM, Novick RJ, McKenzie FN, Kostuk WJ, Pflugfelder PW, et al. A prospective randomized controlled trial of initial immunosuppression with ALG versus OKT3 in recipients of cardiac allografts. Journal of Heart and Lung Transplantation 1992;11(3 Pt 1):569‐76. - PubMed
Mullen 2005 {published data only}
    1. Mullen JC, Dueck A, Bentely MJ, Modry DL, Wang SH, Burton JR, et al. A randomized control trial of daclizumab versus anti‐thymocyte globulin induction for heart transplantation. Journal of Heart and Lung Transplantation 2005;24(2):143.
Schnetzler 2002 {published data only}
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Segovia 2006 {published data only}
    1. Segovia J, Rodriguez‐Lambert JL, Crespo‐Leiro MG, Almenar L, Roig E, Gomez‐Sanchez MA, et al. A randomized multicenter comparison of basiliximab and muromonab (OKT3) in heart transplantation: SIMCOR study. Transplantation 2006;81(11):1542‐8. - PubMed
van Gelder 1996 {published data only}
    1. Wabbijn M, Balk AH, Domburg RT, Vantrimpont PJ, Riemsdijk I, Baan CC, et al. Ten‐year follow‐up of recipients of a kidney or heart transplant who received induction therapy with a monoclonal antibody against the interleukin‐2 receptor. Experimental and Clinical Transplantation 2004;2(1):201‐7. - PubMed
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van Gelder 2004 {published data only}
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Wollenek 1989 {published data only}
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References to studies excluded from this review

Adamson 1998 {published data only}
    1. Adamson R, Obispo E, Dychter S, Dembitsky W, Moreno‐Cabral R, Jaski B, et al. Long‐term outcome with the use of OKT3 induction therapy in heart transplant patients: a single‐center experience. Transplantation Proceedings 1998;30(4):1107‐9. - PubMed
Almenar 2005 {published data only}
    1. Almenar L, Garcia‐Palomar C, Martinez‐Dolz L, Chamorro C, Moro J, Zorio E, et al. Influence of induction therapy on rejection and survival in heart transplantation. Transplantation Proceedings 2005;37(9):4024‐7. - PubMed
Carlsen 2005 {published data only}
    1. Carlsen J, Johansen M, Boesgaard S, Andersen CB, Arendrup H, Aldershvile J, et al. Induction therapy after cardiac transplantation: a comparison of anti‐thymocyte globulin and daclizumab in the prevention of acute rejection. Journal of Heart and Lung Transplantation 2005;24(3):296‐302. - PubMed
Chien 2000 {published data only}
    1. Chien NC, Lin FL, Chou NK, Hsu RB, Wang SS, Chu SH, et al. Rabbit antithymocyte globulin induction immunosuppression in heart transplantation. Transplantation Proceedings 2000;32(7):2380‐2. - PubMed
Chin 2005 {published data only}
    1. Chin C, Pittson S, Luikart H, Bernstein D, Robbins R, Reitz B, et al. Induction therapy for pediatric and adult heart transplantation: comparison between OKT3 and daclizumab. Transplantation 2005;80(4):477‐81. - PubMed
Chou 2008 {published data only}
    1. Chou NK, Wang SS, Chen YS, Yu HY, Chi NH, Wang CH, et al. Induction immunosuppression with basiliximab in heart transplantation. Transplantation Proceedings 2008;40(8):2623‐5. - PubMed
Costanzo‐Nordin 1989 {published data only}
    1. Costanzo‐Nordin MR, O'Sullivan EJ, Hubbell EA, Zucker MJ, Pifarre R, McManus BM, et al. Long‐term follow‐up of heart transplant recipients treated with murine antihuman mature T cell monoclonal antibody (OKT3): the Loyola experience. Journal of Heart Transplantation 1989;8(4):288‐95. - PubMed
Delgado 2005 {published data only}
    1. Delgado DH, Miriuka SG, Cusimano RJ, Feindel C, Rao V, Ross HJ. Use of basiliximab and cyclosporine in heart transplant patients with pre‐operative renal dysfunction. Journal of Heart and Lung Transplantation 2005;24(2):166‐9. - PubMed
Flaman 2006 {published data only}
    1. Flaman F, Zieroth S, Rao V, Ross H, Delgado DH. Basiliximab versus rabbit anti‐thymocyte globulin for induction therapy in patients after heart transplantation. Journal of Heart and Lung Transplantation 2006;25(11):1358‐62. - PubMed
Hegewald 1989 {published data only}
    1. Hegewald MG, O'Connell JB, Renlund DG, Lee HR, Burton NA, Karwande SV, et al. OKT3 monoclonal antibody given for ten versus fourteen days as immunosuppressive prophylaxis in heart transplantation. Journal of Heart Transplantation. UNITED STATES, 1989; Vol. 8, issue 4:303‐9. - PubMed
Kirklin 1990 {published data only}
    1. Kirklin JK, Bourge RC, White‐Williams C, Naftel DC, Thomas FT, Thomas JM, et al. Prophylactic therapy for rejection after cardiac transplantation. A comparison of rabbit antithymocyte globulin and OKT3. Journal of Thorac and Cardiovascular Surgery 1990;99(4):716‐24. - PubMed
Koch 2005 {published data only}
    1. Koch A, Daniel V, Dengler TJ, Schnabel PA, Hagl S, Sack FU. Effectivity of a T‐cell‐adapted induction therapy with anti‐thymocyte globulin (Sangstat). Journal of Heart and Lung Transplantation 2005;24(6):708‐13. - PubMed
Laufer 1989 {published data only}
    1. Laufer G, Laczkovics A, Wollenek G, Schreiner W, Sochor H, Holzinger C, et al. Impacts of low‐dose steroids and prophylactic monoclonal versus polyclonal antibodies on acute rejection in cyclosporine‐ and azathioprine‐immunosuppressed cardiac allografts. Journal of Heart Transplantation 1989;8(3):253‐61. - PubMed
Petrikovits 2005 {published data only}
    1. Petrikovits E, Bedanova H, Necas J, Studenik P, Cerny J. Daclizumab in the induction phase of immunosuppression in heart transplant recipients. Annals of Transplantation 2005;10(3):5‐10. - PubMed
Pham 2010 {published data only}
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