Charles G. Newstead

Diagnosis of post-transplant lymphoproliferative disorder in solid organ transplant recipients – BCSH and BTS Guidelines

A joint working group established by the Haemato‐oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Transplantation Society (BTS) has reviewed the available literature and made recommendations for the diagnosis and management of post‐transplant lymphoproliferative disorder (PTLD) in adult recipients of solid organ transplants. This review details the risk factors predisposing to development, initial features and diagnosis. It is important that the risk of developing PTLD is considered when using post transplant immunosuppression and that the appropriate investigations are carried out when there are suspicions of the diagnosis. These must include tissue for histology and computed tomography scan to assess the extent of disease. These recommendations have been made primarily for adult patients, there have been some comments made with regard to paediatric practice.

Management of post-transplant lymphoproliferative disorder in adult solid organ transplant recipients - BCSH and BTS Guidelines

A joint working group established by the Haemato‐oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Transplantation Society (BTS) has reviewed the available literature and made recommendations for the diagnosis and management of post‐transplant lymphoproliferative disorder in adult recipients of solid organ transplants. This review details the therapeutic options recommended including reduction in immunosuppression (RIS), transplant organ resection, radiotherapy and chemotherapy. Effective therapy should be instituted before progressive disease results in declining performance status and multi‐organ dysfunction. The goal of treatment should be a durable complete remission with retention of transplanted organ function with minimal toxicity.

Ondansetron therapy for uremic pruritus in hemodialysis patients

Pruritus is a distressing symptom affecting up to 90% of dialysis patients. Conventional treatment with antihistamines is often ineffective and may have unacceptable side effects. Serotonin (5-hydroxytryptamine type 3 [5-HT(3)]) is known to enhance pain perception and pruritic symptoms through receptors on sensory nerve endings. Antagonism of 5-HT(3) receptors may be of use in treating uremic pruritus. We randomly assigned 16 hemodialysis patients with persistent pruritus to treatment with the 5-HT(3)-receptor antagonist, ondansetron (8 mg), or placebo three times daily for 2 weeks each in a prospective, placebo-controlled, double-blind crossover study. Patients scored their intensity of pruritus daily on a 0-to-10 visual analogue scale (0 = no pruritus, 10 = maximal pruritus), and daily use of antihistamines as escape medication was recorded. The median daily pruritus score did not change significantly during active or placebo treatment (preondansetron, 5. 3; interquartile range [IQR], 3.4 to 6.3; during ondansetron, 3.9; IQR, 2.7 to 5.0; P = not significant; preplacebo, 3.7; IQR, 3.0 to 4. 6; during placebo, 3.6; IQR, 2.4 to 4.8; P = not significant). The median daily percentage of escape medication use decreased from 21% (IQR, 9 to 61) to 9% (IQR, 0 to 33) with ondansetron (P = not significant) and from 53% (IQR, 0 to 88) to 5% (IQR, 0 to 31) with placebo (P = not significant). There was no difference in predialysis biochemistry test results or dialysis efficacy during treatment phases. Ondansetron does not improve pruritus in hemodialysis patients. Use of antihistamines decreased with both ondansetron and placebo.

Acceptable Outcome After Kidney Transplantation Using Expanded Criteria Donor Grafts

Introduction. With the worldwide shortage of donors, extra lengths are ongoing to enlarge the donor pool. One means has been a greater use of “expanded criteria donor” (ECD) grafts. A major concern regarding ECD kidneys is poor long-term graft survival. The aims of this study were to determine whether ECD grafts, as defined by the United Network for Organ Sharing, had a negative impact on graft survival and to identify the principle donor and recipient factors that influenced graft survival in our patient cohort. Methods. We analyzed all deceased donor renal transplants in our unit from January 1995 to October 2005, in total 1053 transplants. Results. ECD grafts (United Network for Organ Sharing criteria) demonstrated higher rates of delayed graft function and higher early mean creatinine levels. However, there was no significant difference in 5-year graft survival. Multivariate analysis of our patient group identified donor hypertension and ischemic heart disease (IHD) as independent predictors of poor graft survival. Recipient age was significant on univariate but not on multivariate analysis. However, although younger recipients maintained acceptable 5-year graft survival despite donor hypertension, IHD, or a combination of both, these factors significantly reduced graft survival in older recipients. Conclusion. Although ECD grafts had slightly worse function, 5-year survival was comparable with standard grafts in all recipients. Donor hypertension, IHD, or a combination of both significantly reduced graft survival in older recipients, not evident in younger patients. We discuss the possible factors for improved outcome with ECD grafts in our patients and the implications of our patient analysis.

Indo-asian experience of renal transplantation in Yorkshire: Results of a 10-year survey

Background. There is a significant Indo-Asian community in Yorkshire. The rate of end-stage renal failure is disproportionately high in this ethnic group. There have not been any large studies of this ethnic minority’s access to and outcome after cadaveric renal transplantation. Methods. Three local cohorts were studied: 846 adult patients (9.1% Asian) who started renal replacement therapy 1990–1994, 822 adult patients (11.4% Asian) registered on the transplant waiting list 1985–1994; and 608 adult patients (8.6% Asian) transplanted 1985–1994. Results. At 1 year from the start of dialysis, 34% of Asian and 31% of non-Asian patients were registered onto the waiting list. After adjustment for age in a multifactorial model, Asian patients were less likely to be listed (relative risk, 0.68), although this did not reach statistical significance (P =0.06). There was a significant difference in graft rate between the groups: at 3 years 72% of non-Asians versus 55% of Asians had been transplanted from the waiting list (P <0.001). For those transplanted, HLA matching was superior for white patients: 34% versus 20% of pairings achieved a 000 mismatched or favorably matched graft (P <0.05). Transplant survival at 5 years was 71% in the non-Asian and 58% in the Asian patients (P =0.07). Asian cadaveric donation was identified in 2 of 608 transplants during a 10-year period. Conclusion. Asian patients gained access to the transplant waiting list at a similar rate to the non-Asian white majority. Because of difficulties with HLA matching, Asian patients were significantly disadvantaged in receiving a transplant once listed, and there was a trend towards reduced posttransplant survival. Cadaveric donation was uncommon from within the Asian community; the reasons for which are likely to be complex.

Intravenous immunoglobulin-induced panel reactive antibody A reduction: Not all preparations are created equal

Background. Use of intravenous (IV) immunoglobulin (Ig) to obtain panel reactive antibody (PRA) A reduction in sensitized patients has been widely reported. Because no IVIg preparation is formulated specifically for this purpose, the authors have sought to determine whether, through laboratory testing, they could guide the rational choice of product for clinical use. Methods. Using a flow cytometric approach, the authors have quantitatively determined the capacity of 22 different IVIg preparations to cause PRA reduction. Results. IVIg preparations showed considerable variability in their individual capacity to reduce serum PRA. Protein-A pretreatment of IVIg preparations was found to reduce their capacity to cause PRA reduction. Conclusion. Laboratory screening of IVIg preparations provides a rational basis for the selection of product for administration to patients in whom the aim is to produce a PRA reduction. Experiments involving protein-A treatment of IVIg preparations indicate that immunoglobulin G is the principal factor involved in the abrogation of serum reactivity.

Alemtuzumab (Campath-1H)-Induced Coagulopathy in Renal Transplantation

1. Tan HP, Donaldson J, Ellis D, et al. Pediatric living donor kidney transplantation under alemtuzumab pretreatment and tacrolimus monotherapy: 4-year experience. Transplantation 2008; 86: 1725. 2. Calne R, Friend P, Moffatt S, et al. Prope tolerance, perioperative campath 1H, and low-dose cyclosporin monotherapy in renal allograft recipients. Lancet 1998; 351: 1701. 3. Chakrabarti P, Wong HY, Scantlebury VP, et al. Outcome after steroid withdrawal in pediatric renal transplant patients receiving tacrolimus-based immunosuppression. Transplantation 2000; 70: 760.

Elective withdrawal of cyclosporin following renal transplantation: A single centre experience

SUMMARY: Withdrawal of cyclosporin in the early post‐transplant period may provoke acute graft dysfunction, although the reported incidence is variable. We have reviewed our experience of 212 renal transplant recipients to determine the incidence of early post‐withdrawal acute graft dysfunction and examine which factors predict it. Gender, age at initiation of withdrawal, timing and duration of withdrawal, pre‐withdrawal immunosuppression, doses of prednisolone and azathioprine at initiation of withdrawal and, during the first 6 months post witfidrawal, episodes of prior acute transplant rejection, human leucocyte antigen match and previous renal transplantation were considered. In classifying acute graft dysfunction, a 50% increase in serum creatinine from baseline was taken as a minimum criterion, and additional evidence (biopsy, fine needle aspirate, response to immunotherapy) was sought for evidence of a link with cyclosporin withdrawal. Acute graft dysfunction was documented in 28 (13.2%) patients, 26 episodes occurring within 4 months of completion of cyclosporin withdrawal. the mean time interval from transplantation to initiation of withdrawal was significantly shorter in this group (239 vs 299 days, P < 0.02). the median withdrawal period was of similar duration in the groups with and without acute dysfunction, but for the subgroup of patients previously on triple therapy (cyclosporin, prednisolone and azathioprine, n= 78), withdrawal had occurred more rapidly in those with dysfunction (25 vs 67 days, P < 0.05). None of the remaining variables that were considered had a significant effect on outcome, although subgroups tended to be small. Cyclosporin withdrawal may be safer if delayed until after the first post‐transplant year with gradual dose reduction over a period of months.

Increased transplant opportunity following improved definition of patient sensitisation

Purpose – The paper is targeted to health service management teams as an aid to understanding the relationship between investment in process redesign in a clinical laboratory environment and improved quality of service/increased clinical activity.Design/methodology/approach – An audit of the units serum screening capability was performed against the standards of the current UK allocation scheme for cadaveric kidneys. Based on findings of this audit the laboratorys serum screening protocol was redesigned involving development of a new testing strategy and introduction of novel methods. A concurrent review of the effects of this initiative in terms of cadaveric kidney offers received/transplant numbers was undertaken and a cost‐benefit analysis made.Findings – An improved eligibility of the patient cohort for cadaveric kidney offers was obtained together with a reduced unexpected positive crossmatch rate. These factors have together contributed to an increase in transplant numbers at the centre. Significa...