R Y Calne

University of Cambridge, Cambridge, ENG, United Kingdom

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Publications (398)3009.92 Total impact

  • [Show abstract] [Hide abstract]
    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.
    Current opinion in organ transplantation 06/2011; 16(4):353-8. · 3.27 Impact Factor
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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.
    Transplant International 06/2008; 7(S1):64 - 69. · 3.16 Impact Factor
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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.
    Kidney International 05/2006; 69(10):1858-64. · 8.52 Impact Factor
  • Arquivos De Gastroenterologia. 01/2006; 43(4).
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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.
    Arquivos de Gastroenterologia 01/2006; 43(4):321-7.
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    ABSTRACT: Of 9 patients who survived the immediate postoperative period after hepatic transplantation, 6 later died from infection. Pulmonary infection was the major problem. Biliary infection related to bile fistulas may be less in the future with the improved technique of a cholecystdochostomy which was carried out in the last 2 patients. Frequent bacteriaemias were noted and the organisms were often the same as those found in the bile. Most infections were thought to be autogenous. Cytomegalovirus infection occurred in 6 patients, but in none was there evidence that the virus did harm. Broad-spectrum antibiotic therapy was freely used in the earlier patients but was often followed by superinfection with resistant organisms and fungi. The present policy is not only to use antibiotics sparingly but to rely on narrow-spectrum drugs wherever possible.
    British Journal of Surgery 12/2005; 57(4):280 - 284. · 4.84 Impact Factor
  • 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.
    Current Opinion in Organ Transplantation 11/2005; 10(4):261-264. · 3.27 Impact Factor
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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.
    Transplantation 10/2005; 80(6):765-74. · 3.78 Impact Factor
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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.
    Philosophical Transactions of The Royal Society B Biological Sciences 10/2005; 360(1461):1797-801. · 6.23 Impact Factor
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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.
    Philosophical Transactions of The Royal Society B Biological Sciences 10/2005; 360(1461):1769-74. · 6.23 Impact Factor
  • Roy Calne
    Transplantation 08/2005; 80(1):6-7. · 3.78 Impact Factor
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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 20 mg 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.
    American Journal of Transplantation 07/2005; 5(6):1347-53. · 6.19 Impact Factor
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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.
    Transplantation Proceedings 07/2005; 37(5):1979-83. · 0.95 Impact Factor
  • Roy Calne
    Xenotransplantation 02/2005; 12(1):5-6. · 2.57 Impact Factor
  • Transplantation 01/2005; 80(6):765-774. · 3.78 Impact Factor
  • Arquivos De Gastroenterologia. 01/2005; 42(1).
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    ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.
    Transplantation 07/2004; 78(2):55-56. · 3.78 Impact Factor
  • R Calne
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    ABSTRACT: In this short review I show how cyclosporine fits into the broader picture of immunosuppression for organ allografting. Before cyclosporine there were some good results, particularly in kidney grafting, but also a failure rate of 50% of grafts by 1 year. Cyclosporine changed the graft survival of 1 year to 80%, although at 10 years the graft survival was little different from patients treated with azathioprine and steroids. Nevertheless, many patients achieved good function in their kidneys when treated with cyclosporine; these patients would have lost the kidneys under the old regimen. The cause of the late failure in patients treated with cyclosporine was predominantly nephrotoxicity due to the calcineurine inhibition, damaging the kidneys. Now that this is better understood and new drugs are available, many regimens have been tried but cyclosporine remains an important tool for the clinician in the treatment of patients with organ allografts.
    Transplantation Proceedings 04/2004; 36(2 Suppl):13S-15S. · 0.95 Impact Factor
  • Transplantation 01/2004; 78. · 3.78 Impact Factor
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    ABSTRACT: In 1996 two transplantation centres in the UK were commissioned by the National Specialist Commissioning Advisory Group for England and Wales to assess small intestinal transplantation in adults. The joint experience of the two centres is presented. Patients with irreversible small intestinal failure and complications of parenteral nutrition, and those with abdominal disease requiring extensive visceral resection, were assessed as candidates and where appropriate listed for surgery. Thirty-six patients were assessed for small intestinal transplantation and, of these, 14 underwent surgery. Twelve patients survived the transplantation procedure. Of these, seven patients were alive at 1 year, five at 3 years and three at 5 years. Three patients remain alive. Patient and graft survival improved with experience; the 1-year survival rate improved in the last 4 years of this experience from 43 to 57 per cent, and the 3-year survival rate from 29 to 43 per cent. Small intestinal transplantation is associated with a high mortality rate but may benefit carefully selected patients in whom conservative management is likely to carry a greater mortality rate.
    British Journal of Surgery 07/2003; 90(6):723-7. · 4.84 Impact Factor

Publication Stats

9k Citations
3,009.92 Total Impact Points

Institutions

  • 1969–2011
    • University of Cambridge
      • • Department of Surgery
      • • Department of Pathology
      Cambridge, ENG, United Kingdom
  • 1988–2008
    • The Peninsula College of Medicine and Dentistry
      Plymouth, England, United Kingdom
  • 2005
    • St George's Hospital
      Christchurch, Canterbury Region, New Zealand
    • Singapore General Hospital
      • Department of Renal Medicine
      Tumasik, Singapore
  • 1988–2005
    • King's College London
      • Department of Immunobiology
      Londinium, England, United Kingdom
  • 2003
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 1998–2002
    • Biomedical primate research centre
      • Department of Immunobiology
      Rijswijk, South Holland, Netherlands
  • 1999
    • Dalhousie University
      • Department of Surgery
      Halifax, Nova Scotia, Canada
  • 1995
    • Chulalongkorn University
      • Department of Surgery
      Bangkok, Bangkok, Thailand
  • 1994
    • Freie Universität Berlin
      Berlín, Berlin, Germany
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
    • Universität Heidelberg
      • Department of Spine Surgery
      Heidelberg, Baden-Wuerttemberg, Germany
  • 1989
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom
  • 1982
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany
  • 1977
    • British Medical Journal
      Londinium, England, United Kingdom