R Y Calne

Singapore General Hospital, Tumasik, Singapore

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Publications (402)3276.47 Total impact

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    ABSTRACT: To outline the rationale of powerful depleting induction therapy with alemtuzumab and minimal maintenance immunosuppression after organ transplantation. The original observations in principle have been confirmed by many independent centres. Follow-up of the 'prope tolerance' protocol has confirmed a low incidence of rejection, infection and post transplant lymphoproliferative disorder (PTLD). Especially, encouraging results were obtained in African-Americans. There were few side effects and the regimen was well tolerated by patients. Treg cells were observed in the circulation, which could be an important factor in the mechanisms of graft acceptance using a prope tolerance regimen. There was a considerable reduction in the costs of the transplantation procedure. It is suggested that this minimalisation of maintenance immunosuppression is the best therapy currently available that we can offer to our patients.
    No preview · Article · Jun 2011 · Current opinion in organ transplantation
  • Roy Calne

    No preview · Article · Apr 2009 · The Lancet
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    R Y Calne
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    ABSTRACT: The early days of liver transplantation were exciting, demanding, subject to terrible disappointments and sadness but occasional elation, and a gradual understanding of the factors necessary to achieve a satisfactory operation. In addition, care of an extremely sick patient, the management of the disease, especially if it was infectious or malignant, and the support of the relatives and the transplant team, required a group of loyal, dedicated and above all optimistic members who could see through the repeated unhappy outcomes that eventually most of the problems would be solved. This in fact has come to pass.
    Preview · Article · Oct 2008 · American Journal of Transplantation
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    ABSTRACT: Abstract The efficacy and safety of an FK 506-compared to a cyclosporin A based immunosuppression regimen was examined in liver recipients who underwent transplantation for fulminant hepatic failure in the European FK 506 liver study. A consistent trend towards improved patient and graft survival noted in the FK 506-treated patients was apparent from the first postoperative week (e. g. patient survival: day 7, 95.5% vs. 82.1% and month 6, 72.7% vs. 60.7%). Acute (in particular intractable) rejection was less frequent in the FK 506 group (e. g. cumulative intractable rejection rate at 6 months, 6.2% vs. 22.6%). In a single centre (Kings College Hospital), 17 patients were studied in more detail. The FK 506 treatment group had improved graft function, lower steroid requirments and episodes of infection. Accompanying these benefits, apache 111 and TISS scores were lower in this group in the early posttransplant period. Intensive care discharge was earlier and both treatment groups experienced similar toxicity.
    No preview · Article · Jun 2008 · Transplant International
  • RY Calne · K O Lee

    No preview · Article · Sep 2007 · The Lancet
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    ABSTRACT: RACIONAL: A maior indicação do transplante de pâncreas ou de ilhotas de Langerhans é o diabetes mellitus do tipo I. O processo deve suprir as necessidades de insulina, mantendo os níveis glicêmicos dentro da normalidade OBJETIVOS: Estudar o alotransplante de ilhotas de Langerhans no fígado de ratos Lewis (RT11), tendo como doadores de ilhotas ratos Wistar (RT1u). No grupo controle (n = 8) injetava-se, no timo, solução de Hanks e no grupo de estudo(n = 8), células não-parenquimatosas hepáticas MATERIAL E MÉTODOS: No grupo controle com o método de separação e purificação das ilhotas de Langerhans obteve-se 3.637 ± 783,3 ilhotas com pureza de 85 ± 3,52%. No grupo de estudo obteve-se 3.270 ± 770 ilhotas de Langerhans com pureza de 84,25 ± 2,76% e com o método de isolamento e purificação das células não-parenquimatosas hepáticas obteve-se 2 x 106 células RESULTADOS: No grupo controle, o transplante de 3.637 ± 783,3 ilhotas de Langerhans no fígado, quase normalizou a glicemia que chegou a 17,95 ± 5,33 mmol/L no 2º dia do pós-operatório (diferença significante com relação ao pré-operatório). Do pós-operatório imediato até o 8º dia do pós-operatório a glicemia não se elevou significativamente, porém a partir do 10º dia do pós-operatório houve aumento significativo deste parâmetro, o que pode ser compatível com rejeição aguda do enxerto. No grupo de estudo, o transplante de 3.270 ± 770 ilhotas de Langerhans no fígado, quase normalizou a glicemia que chegou a 17,95 ± 5,33 mmol/L no 2º dias do pós-operatório (diferença significante com relação ao pré-operatório). Do 4º ao 10º pós-operatório a glicemia elevou-se significativamente, o que pode ser compatível com quadro de rejeição aguda do enxerto e certamente precoce CONCLUSÃO: A inoculação de células alogênicas apresentadoras de antígenos (células não-parenquimatosas hepáticas) no timo de ratos imunossuprimidos e diabéticos, antes do alotransplante de ilhotas de Langerhans no fígado, ao contrário de inibir a reação do receptor contra o enxerto, prolongando a sobrevida média das ilhotas e, possivelmente, levando ao estado de tolerância imunológica, induziu ao processo de rejeição aguda precoce.
    Preview · Article · Dec 2006 · Arquivos de Gastroenterologia
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    H-S Eng · Z Mohamed · R Calne · C C Lang · MA Mohd · W-T Seet · S-Y Tan
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    ABSTRACT: Cyclosporine is a substrate of cytochrome P-450 3A (CYP3A) subfamily of enzymes and characterized by a narrow therapeutic range with wide interindividual variation in pharmacokinetics. A few single-nucleotide polymorphisms detected in CYP3A genes have been shown to correlate significantly with the CYP3A protein expression and activity. We therefore postulated that these polymorphisms could be responsible for some of the interindividual variation in cyclosporine pharmacokinetics. The objective of our study is to determine correlation if any between single-nucleotide polymorphisms of CYP3A5 and CYP3AP1 on cyclosporine dose requirement and concentration-to-dose ratio in renal allograft recipients. Cyclosporine-dependent renal allograft recipients were genotyped for CYP3A5 A6986G and CYP3AP1 G-44A. The cyclosporine dosages prescribed and the corresponding cyclosporine trough levels for each patient were recorded so that cyclosporine dose per weight (mg/kg/day) and concentration-to-dose ratio (C(0)/D, whereby C(0) is trough level and D is daily dose per weight) could be calculated. A total of 67 patients were recruited for our study. The dose requirement for 1, 3, and 6 months post-transplantation ranged 2.3-11.4, 1.0-9.0, and 1.4-7.2 mg/kg/day, respectively. Patients with *1*1*1*1 (n=5) CYP3A5- and CYP3AP1-linked genotypes needed higher dose of cyclosporine compared to patients with *1*3*1*3 (n = 27) and *3*3*3*3 (n = 33) linked genotypes in months 3 and 6 post-transplantation (P < 0.016). The identification of patients with *1*1*1*1 by CYP3A5 and CYP3AP1 genotyping may have a clinically significant and positive impact on patient outcome with reduced rejection rate by providing pretransplant pharmacogenetic information for optimization of cyclosporine A dosing.
    Full-text · Article · May 2006 · Kidney International
  • R. Y. Calne

    No preview · Article · Apr 2006 · Immunological Reviews
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    ABSTRACT: [corrected] The major indication for pancreas or islet transplantation is diabetes mellitus type I. This process has to supply the insulin necessity keeping glucose under control We studied allogenic islet transplantation on the rat liver, Wistar (RT1u) to Lewis (RT1(1)) as a recipient. Control group (n = 8) and nonparenchymal cell group (n = 8) respectively with injection of Hanks solution and nonparenchymal cells in the thymus before islet transplantation. With the method of isolation and purification of the islets we obtained both in the control group 3.637 +/-783,3 islets with purity of 85 +/- 3,52% and nonparenchymal cell group 3.270 +/- 770 islets with purity of 84,25 +/- 2,76%. The nonparenchymal cells were retrieved from the liver and we obtained 2 x 106 cells. Diabetes was induced by i.v. streptozotocin Control group the transplantation of 3.637 +/- 783,3 islets in the rat liver normalized glucose test, 7,21 +/- 0,57 mmol/L in the 2nd postoperative day. Acute rejection came in the 6th postoperative day with significantly increase of glucose test in nonparenchymal cell group, the transplantation of 3.270 +/- 770 islets in the rat liver, almost normalized the glucose test was 17,95 +/- 5,33 mmol/L in the 2nd postoperative day. From the 4th postoperative day to 10th postoperative day. The glucose test increase significantly showing an early acute rejection The injection of nonparenchymal cells in the thymus before allogenic islet transplantation in the rat liver lead to an early acute rejection.
    Preview · Article · Jan 2006 · Arquivos de Gastroenterologia
  • Roy Calne
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    ABSTRACT: Purpose of review: Alemtuzumab (Campath 1H) is a powerful lympholytic monoclonal antibody, which is only effective against human lymphocytes. It has been used in a number of autoimmune diseases and has had especially good results in the management of chronic lymphatic leukemia. Recent findings: Recent studies and clinical trials have defined optimal modes of administration of the antibody. The principle is to give one or two doses to the patient in the perioperative part of the organ transplant as a preemptive strike. T and B lymphocytes are banished from the circulation for approximately 1 month. Advantage is taken of this period of relative immuno-incompetence to establish maintenance immunosuppression at a very low dose. Half the normal dose of one calcineurin inhibitor is sufficient to maintain good organ function without the need for conventional immunosuppression. In particular corticosteroids can be avoided in most patients. This contributes to a good quality of life. The protocol is much cheaper than conventional immunosuppression and long-term follow-up has given encouraging results. Summary: A monoclonal antibody that targets the lymphocyte surface antigen CD52 was recently developed for use in humans. In clinical trials the antibody was shown to have striking effects on lymphocytes being responsible for a drastic reduction in lymphocyte numbers within the very first few hours after infusion. Lymphocyte depletion is maintained for several weeks despite only two doses of the antibody being administered. This affords maintenance immunosuppressive regimen in which significantly less drugs are used, which results in better tolerability and less costs.
    No preview · Article · Nov 2005 · Current Opinion in Organ Transplantation
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    Roy Calne
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    ABSTRACT: I have attempted to summarize the progress that has been made in organ transplantation in the past 50 years since the first identical twin transplant. For those who have worked long in this area its success has been remarkable. We currently expect patients to survive the operation and more than 90% of the graft to be functioning at a year with the half-life of the graft beyond 10 years, with some patients surviving into the fifth decade after kidney transplantation with grafts from unrelated donors and the fourth decade for liver transplants. Now the main stumbling block is shortage of organ donors and this is unlikely to be solved easily. There has been a considerable increase in donations from living volunteers and also the worry of immoral and illegal practices. In the future, we can expect considerable advances in immunosuppression with more effective, less toxic drugs and in some patients induction therapy that may approach tolerance so that no maintenance therapy will eventually be needed. Cell transplantation is likely to be developed as treatment for the clinic in the next 5-10 years, but developments of transplantation from animal to man still remains unsolved and unlikely to be successful in the clinic in the near future.
    Preview · Article · Oct 2005 · Philosophical Transactions of The Royal Society B Biological Sciences
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    ABSTRACT: A randomized, multicenter, controlled trial was undertaken to evaluate the safety and efficacy of Alemtuzumab, a powerful lytic agent for both T and B lymphocytes, in the prophylaxis of rejection in renal transplantation (RTx). Thirty patients were randomized to receive Alemtuzumab together with low-dose cyclosporine (CsA) monotherapy (CAMPATH, n = 20) or to full doses of CsA with azathioprine and corticosteroids (Standard, n = 10). CsA was administered at doses to achieve whole-blood trough CsA levels of 90 to 110 ng/mL and 180 to 225 ng/mL in CAMPATH and Standard groups, respectively. Per protocol, CsA trough levels were lower in patients assigned to CAMPATH post-RTx (median trough level of 119 vs. 166 ng/mL at 6 months, CAMPATH vs. Standard; 95% confidence interval, -92 to -34). At 6 months post-RTx, serum creatinine, graft and patient survivals, incidence of biopsy proven acute rejection (25% vs. 20%, CAMPATH vs. Standard), overall treatment failure, and severe and moderate infections were comparable. Whereas all patients receiving Standard therapy required maintenance corticosteroids at 6 months, of the 17 of 20 patients with functioning grafts in CAMPATH, 15 (88%, 95% confidence interval, 53%-97%) were steroid free. These results suggest that Alemtuzumab is an effective induction agent that permits low-dose steroid-free immunosuppression in RTx.
    No preview · Article · Oct 2005 · Transplantation
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    Roy Calne
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    ABSTRACT: For 30 years there has been experimental work aimed at transplanting islets for the treatment of diabetes with a view to curing the disease and preventing the secondary complications. Many technical difficulties were experienced, first in isolating the islets without damaging them, and second in finding a suitable place to inject them, but until recently the results of a vascularized pancreas transplant have been superior to islet transplantation. In 2000, the group in Edmonton, headed by Shapiro, published encouraging results using a different immunosuppression in transplanting patients earlier in the course of their disease than had been attempted previously. The results were excellent at a year and good at 2 years in patients with Type I diabetes, however there was the rather worrying attrition at five years. Nevertheless, the Edmonton observations were proof of concept and have intensified interest in treating diabetes and other diseases where a specific protein synthesis was required by cell transplantation and/or genetic engineering. The recent interest in embryonic stem cells extenuated these efforts and progress is being made in defining the difficulties, which are greater than most workers would have predicted. In this review, the subject is discussed explaining where progress needs to be made in order to provide treatment that would be of value to patients.
    Preview · Article · Oct 2005 · Philosophical Transactions of The Royal Society B Biological Sciences
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    ABSTRACT: Background. A randomized, multicenter, controlled trial was undertaken to evaluate the safety and efficacy of Alemtuzumab, a powerful lytic agent for both T and B lymphocytes, in the prophylaxis of rejection in renal transplantation (RTx). Methods. Thirty patients were randomized to receive Alemtuzumab together with low-dose cyclosporine (CsA) monotherapy (CAMPATH, n=20) or to full doses of CsA with azathioprine and corticosteroids (Standard, n=10). CsA was administered at doses to achieve whole-blood trough CsA levels of 90 to 110 ng/mL and 180 to 225 ng/mL in CAMPATH and Standard groups, respectively. Results. Per protocol, CsA trough levels were lower in patients assigned to CAMPATH post-RTx (median trough level of 119 vs. 166 ng/mL at 6 months, CAMPATH vs. Standard; 95% confidence interval, -92 to -34). At 6 months post-RTx, serum creatinine, graft and patient survivals, incidence of biopsy proven acute rejection (25% vs. 20%, CAMPATH vs. Standard), overall treatment failure, and severe and moderate infections were comparable. Whereas all patients receiving Standard therapy required maintenance corticosteroids at 6 months, of the 17 of 20 patients with functioning grafts in CAMPATH, 15 (88%, 95% confidence interval, 53%-97%) were steroid free. Conclusion. These results suggest that Alemtuzumab is an effective induction agent that permits low-dose steroid-free immunosuppression in RTx.
    No preview · Article · Sep 2005 · Transplantation
  • Roy Calne

    No preview · Article · Aug 2005 · Transplantation
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    R Calne
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    ABSTRACT: Organ transplantation has developed in the past 50 years from a primitive therapeutic attempt to an accepted and much sought after form of treatment. During the same period, bone marrow transplantation, a form of cell transplantation, also has become established with similar successes provided the donor and recipient are well matched. The next challenges in transplantation are to overcome the donor shortage and to devise new ways of treating diseases that at present have unsuccessful management. The transplantation of cells programmed to produce essential proteins is an important goal, especially if the cells were autologous, for example, adult stem cells persuaded to produce insulin and act as surrogate beta cells. In this short article, I have reviewed some of the progress and difficulties of cell transplantation, which is currently a popular and intense area of research worldwide.
    Preview · Article · Jul 2005 · Transplantation Proceedings
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    ABSTRACT: Alemtuzumab is a powerful lymphocyte depleting antibody currently being evaluated in solid organ transplantation. This paper describes 5-year results of a single center study of alemtuzumab as induction in renal transplantation. Thirty-three renal transplant recipients received 20mg alemtuzumab on day 0 and 1, followed by half-dose cyclosporin monotherapy (trough concentration 75–125 ng/mL) from day 3. They were compared in a retrospective contemporaneous-controlled manner with 66 kidney transplant recipients transplanted in the same period and center who received conventional immunosuppression with cyclosporin, azathioprine and prednisolone. In the alemtuzumab group 12% of recipients died compared to 17% in the control group (p = 0.48); likewise graft loss was similar in both groups (21% vs. 26%, respectively, p = 0.58). Incidence of acute rejection was also comparable at 5 years (31.5% vs. 33.6%), although the pattern of rejection was different with 14% patients in the alemtuzumab group experiencing rejection over 1 year post-transplant compared to none in the control group. There was no significant difference between groups in terms of infection or serious adverse events. While acknowledging the limitations of a relatively small single-center study, results suggest that alemtuzumab induction allowed satisfactory long-term patient and graft survival equivalent to that seen with standard triple immunosuppression, while avoiding steroid therapy.
    Full-text · Article · Jul 2005 · American Journal of Transplantation
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    ABSTRACT: RACIONAL: A maior indicação do transplante de pâncreas ou de ilhotas de Langerhans é o diabetes mellitus do tipo I. O processo deve suprir as necessidades de insulina, mantendo os níveis glicêmicos dentro da normalidade. OBJETIVOS: Estudou-se o alotransplante de ilhotas de Langerhans no fígado de ratos Lewis, tendo como doadores de ilhotas ratos Wistar. No grupo controle (n = 8) injetava-se, no timo, solução de Hanks e no grupo de estudo (n = 9), células dendríticas. MATERIAL E MÉTODOS: No grupo controle com o método de separação e purificação das ilhotas de Langerhans obteve-se 3637 ± 783,3 ilhotas com pureza de 85% ± 3,52%. No grupo de estudo obteve-se 3268 ± 378 ilhotas de Langerhans com pureza de 87% ± 4,47% e com o método de isolamento e purificação das células dendríticas do baço obteve-se 3,34 x 105 ± 1,16 células. RESULTADOS: No grupo controle, o transplante de 3637 ± 783,3 ilhotas de Langerhans no fígado, normalizou a glicemia que chegou a 7,21 ± 0,57 mmol/L no segundo pós-operatório (diferença significativa com relação ao pré-operatório). Do pós-operatório imediato até o 8º pós-operatório a glicemia não se elevou significativamente, porém a partir do 10º pós-operatório houve aumento significativo deste parâmetro, o que pode ser compatível com rejeição aguda do enxerto. No grupo de estudo, o transplante de 3258 ± 378 ilhotas de Langerhans no fígado, normalizou a glicemia, que chegou a 9,3 ± 2,85 mmol/L no segundo pós-operatório (diferença significativa com relação ao pré-operatório). Do 4º ao 10º pós-operatório, a glicemia elevou-se significativamente, o que pode ser compatível com quadro de rejeição aguda do enxerto e certamente precoce. CONCLUSÃO: A inoculação de células alogênicas apresentadoras de antígenos (células dendríticas) no timo de ratos imunossuprimidos e diabéticos, antes do alotransplante de ilhotas de Langerhans no fígado, ao contrário de inibir a reação do receptor contra o enxerto, prolongando a sobrevida média das ilhotas e, possivelmente, levando ao estado de tolerância imunológica, induziu ao processo de rejeição aguda precoce.
    Preview · Article · Mar 2005 · Arquivos de Gastroenterologia
  • Roy Calne

    No preview · Article · Feb 2005 · Xenotransplantation
  • R Y Calne
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    ABSTRACT: This is a short review of tolerance from the point of view of the clinician. Various examples of tolerance occurring in patients and animal models that relate to the clinical experience are described. It is suggested that there may be different mechanisms by which tolerance is achieved, but, from the patient's point of view operational, tolerance is the goal whereby, after a short induction procedure, the patient will maintain good function in the grafted organ indefinitely without maintenance immunosuppression. It is pointed out that such a goal may be difficult to achieve with any given protocol due to the enormous variation between donors and recipients of organ grafts of tissue matching, innate immune reactivity, and susceptibility to disturbance of a tolerant state by infections or allergic reactions. Thus, the case is made for prope or almost tolerance in which graft acceptance is maintained by a low, nontoxic dosage of maintenance immunosuppression which may not be required indefinitely.
    No preview · Article · Feb 2005 · International Immunopharmacology

Publication Stats

12k Citations
3,276.47 Total Impact Points

Institutions

  • 2005
    • Singapore General Hospital
      • Department of Renal Medicine
      Tumasik, Singapore
  • 1969-2005
    • University of Cambridge
      • • Department of Surgery
      • • Department of Radiology
      Cambridge, England, United Kingdom
  • 1999
    • Dalhousie University
      • Department of Surgery
      Halifax, Nova Scotia, Canada
  • 1997
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
  • 1988-1997
    • The Peninsula College of Medicine and Dentistry
      • Child Health Group
      Plymouth, England, United Kingdom
    • Papworth Hospital NHS Foundation Trust
      Papworth, England, United Kingdom
  • 1996
    • The Prince Charles Hospital (Queensland Health)
      Brisbane, Queensland, Australia
  • 1993
    • Chulalongkorn University
      • Department of Surgery
      Siayuthia, Bangkok, Thailand
  • 1990
    • The Kings College
      Cambridge, Massachusetts, United States
  • 1974-1988
    • King's College London
      • Department of Immunobiology
      Londinium, England, United Kingdom
  • 1982
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany
  • 1977
    • British Medical Journal
      Londinium, England, United Kingdom
  • 1971
    • Middlesex Hospital
      मिडलटाउन, Connecticut, United States
  • 1970
    • St George's, University of London
      Londinium, England, United Kingdom
  • 1968
    • Cambridge Eco
      Cambridge, England, United Kingdom