What is happening with hand transplants?

Première transplantation des deux mains : résultats à 18 mois

Background. The European double-blind, placebo-(PLA) controlled study of mycophenolate mofetil (MMF) for prevention of acute renal allograft rejection showed that MMF 2 and 3 g when added to a standard double-drug regimen of cyclosporine and corticosteroids significantly reduced the incidence of acute rejection/treatment failure at 6 months. Our study presents 3-year data for patient and graft survival, and safety in the MMF-treated patients. Methods. The trial included 491 patients who were randomly assigned to receive PLA (n=166), MMF 2 g (n=165), or MMF 3 g (n=160). Patients in the PLA group discontinued taking their PLA medication at 1 year posttransplantation; subsequently, they were followed-up only regarding patient and graft survival and the occurrence of malignancies. Results. The 3-year patient survival was 88.9, 92.7, and 91.8% in the PLA, MMF 2 g, and MMF 3 g groups, respectively. The 3-year graft survival (including death as a cause of graft loss) was 78, 84.8, and 81.2%, respectively. Acute allograft rejection was a principal cause of graft loss in all groups (PLA, 10.8%; MMF 2 g, 4.6%; MMF 3 g, 6.3%). Differences in 3-year graft loss rates (excluding death) and 95% confidence intervals for intent-to-treat comparisons of PLA versus MMF 2 g and 3 g, respectively, were 7.3% (1.1, 14.2) and 3.2% (−3.8, 10.1). This leads to a relative risk of graft loss of 0.55 in the MMF 2 g arm compared with the PLA arm. Acute allograft rejection had a major impact on graft loss at 3 years; 31.5% of patients with biopsy-proven acute rejection within 6 months of transplantation lost their graft by the end of 3 years. In contrast, only 6.6% who had no early acute rejection lost their graft by the end of the 3-year study period. Diarrhea, anemia, and leukopenia were the most common clinically relevant adverse events, occurring predominantly in the MMF 3 g group. Only one patient (MMF 3 g) developed cytomegalovirus tissue-invasive disease after the first year posttransplant. Over the 3-year posttransplant period, 12 patients developed malignancies (5 in the PLA group, 3 in the MMF 2 g group, and 4 in the MMF 3 g group). Conclusions. At 3 years posttransplantation, MMF was associated with 7.6% reduction in the incidence of graft loss (excluding death). These data indicate that MMF treatment not only results in a reduction of the incidence of acute rejections but also leads to reduction of late allograft loss.

An outbreak of 29 cases of Pneumocystis jirovecii pneumonia (PCP) occurred among renal and liver transplant recipients (RTR and LTR) in the largest Danish transplantation centre between 2007 and 2010, when routine PCP prophylaxis was not used. P. jirovecii isolates from 22 transplant cases, 2 colonized RTRs, and 19 Pneumocystis control samples were genotyped by restriction fragment length polymorphism and multilocus sequence typing analysis. Contact tracing was used to investigate transmission. Potential risk factors were compared between PCP cases and matched non-PCP transplant patients. Three unique Pneumocystis genotypes were shared among 19 of the RTRs, LTRs, and a colonized RTR in three distinct clusters, two of which overlapped temporally. In contrast, Pneumocystis control samples harbored a wide range of genotypes. Evidence of possible nosocomial transmission was observed. Among several potential risk factors, only cytomegalovirus viremia was consistently associated with PCP (P=0.03; P=0.009). Mycophenolate mofetil was associated with PCP risk only in the RTR population (P=0.04). We identified three large groups infected with unique strains of Pneumocystis and provide evidence of an outbreak profile and nosocomial transmission. LTRs may be infected in PCP outbreaks simultaneously with RTRs and by the same strains, most likely by interhuman transmission. Patients are at risk several years after transplantation, but the risk is highest during the first 6 months after transplantation. Because patients at risk cannot be identified clinically and outbreaks cannot be predicted, 6 months of PCP chemoprophylaxis should be considered for all RTRs and LTRs.

Perioperative management of high-risk corneal transplantation using basiliximab and mycophenolate mofetil

New immunosuppressive drugs such as anti-interleukin-2 receptor antibodies (aIL2R) and mycophenolate mofetil (MMF) have reduced the incidence of acute rejection after renal transplantation. Whether matching donor and recipient human leukocyte antigen (HLA) antigens is still relevant in patients receiving modern immunosuppression has been questioned. We retrospectively analyzed the incidence and risk factors of acute rejection during the first posttransplant year and the impact of acute rejection on long-term graft survival in a cohort of 208 renal transplant patients treated with aIL2R (basiliximab, n=166; daclizumab, n=42), calcineurin inhibitors (tacrolimus, n=180; cyclosporin, n=28), mycophenolate mofetil, and steroids. Graft and patient survival were calculated by the Kaplan-Meier method. Risk factors for acute rejection were analyzed by logistic regression modeling. Twenty-seven patients were treated for acute rejection (26 biopsy-proven) during the first posttransplant year. The Kaplan-Meier estimate of first-year acute rejection was 13.2%. The number of HLA mismatches (odds ratio [OR] 1.65 per HLA mismatch) and long periods of dialysis before transplantation (OR 3.1 for more than 4 years of dialysis) were the only independent risk factors for first-year acute rejection. First-year acute rejection was associated with a significant reduction in overall and death-censored graft survival at 5 years after transplantation. Although infrequent in patients receiving modern immunosuppressive drugs, acute rejection remains an important risk factor for graft loss after renal transplantation. Our results suggest that better HLA matching and shorter periods of dialysis before transplantation could reduce acute rejection rates and further improve outcomes under current immunosuppressive regimens.

Hand and upper extremity transplantation offers a promising reconstructive solution for select patients lacking a functional upper limb. For such an endeavor, it is imperative that multiple medical and surgical specialties and teams work in concert to achieve a common goal. Sixteen years from the first successful hand transplantation, the number of centers performing or planning to perform hand transplantation worldwide has increased considerably. This procedure may become the standard of care for properly selected patients in the not-too-distant future. To facilitate this transition, unified protocols are required. In this manuscript, we focus on the donor limb procurement process, including the sequence of events, logistics, and inter-specialty team interaction. Through review of the current literature, we acknowledge and address possible variations, and provide an illustrative overview of the operation. It is important that all members involved in this procedure, including the Organ Procurement Organization (OPO), solid organ procurement teams, and donor hospital staff, are aware of this process. Opportunities for future research in this field are further discussed.

Bilateral hand transplantation: Bone healing under immunosuppression with tacrolimus, mycophenolate mofetil, and prednisolone

P031 Role of donor specific antibody (DSA) in hand transplantation

Liver transplantation for hepatitis C virus (HCV) non-viremic recipients with HCV viremic donors.

Since May 2002, all groups performing hand transplantations have supplied information to the International Registry on Hand and Composite Tissue Transplantation (IRHCCT). The analysis of all cases with follow-up information up to September 2007 is presented here. From September 1998 to September 2007, 38 hands (18 unilateral and 10 bilateral hand transplantations) and two digits have been reported to IRHCTT, for a total of 30 patients with a follow-up period ranging from 6 months to 9 years. They were 28 males and two females, median age of 34 years. Time since hand loss ranged from 2 months to 34 years and in 50% of cases the level of amputation was at wrist level. Immunosuppressive therapy included tacrolimus, mycophenolate mofetil, rapamycin, and steroids; polyclonal or monoclonal antibodies were used for induction. Topical immunosuppression was also employed in several cases. Patient survival was 100%. Graft survival was 100% at 1 and 2 years. Except for the Chinese patients, current graft survival is 95.6% and cause of graft loss was always no compliance to the treatment. Acute rejection episodes occurred in 85% of the patients within the first year and they were reversible in all compliant patients. Side-effects included opportunistic infections and metabolic complications. All patients developed protective sensibility, 90% of them developed tactile sensibility, and 72% also a discriminative sensibility. Motor recovery enabled patients to perform most daily activities. Hand transplantation is feasible with a high success rate and satisfactory functional outcome.

Effect of Prophylaxis With Low-Dose Anti-Thymocyte Globulin on Prevention of Acute Kidney Allograft Rejection

Objective To retrospectively analyze the clinical management and follow-up of 13 recipients with survival of over ten years after cardiac transplantation. Methods Thirteen male recipients underwent orthotopic heart transplantation between August 1995 and June 2001 in our center and received standard immunosuppressive therapy protocols (8 cases) or induction therapy protocols (5 cases). Cyclosporine, azathioprine or mycophenolate mofetil, and prednisolone were applied as maintenance immunosuppressive regimens. Six recipients switched from azathioprine to mycophenolate mofetil when mycophenolate mofetil was available. Perioperative complications were prevented and treated. After operation, the recipients were followed up regularly to set up personnel long-term follow-up files. The incidence of acute rejection (AR) and (cardiac allograft vasculopathy (CAV) was monitored. Results The 13 survived recipients accounted for 48. 1 % of the total number in the corresponding period (13/27). All survivals recovered well and had a good quality of life. The recent (1 year) complications included acute allograft rejection (3 cases), infection (4 cases), renal insufficiency (3 cases), allograft right ventricular dysfunction (5 cases), post-transplant diabetes (2 cases) and liver dysfunction (5 cases). The long-term (1 year later) complications included acute allograft rejection (2 cases), CAV (2 cases), hypercholesterolemia (5 cases), hypertension (4 cases), hyperuricemia (10 cases) and chronic renal impairment (3 cases). One hepatitis B virus carrier died of liver cancer 13 years after transplantation. Conclusion The long-term survival of cardiac allograft recipients is closely associated with psychological state, financial condition, compliance and follow-up medical system, while the sociological and environmental factors may play important roles. Key words: Heart transplantation; Survival; Follow-up studies

Immunosuppression therapy in lung transplantation (LTX) remains unsatisfactory due to a high incidence of infection and frequent acute rejection (AR), leading to early onset of the bronchiolitis obliterans syndrome (BOS). The long-term success of LTX is limited by BOS, associated with marked morbidity and mortality. The strongest risk factor for BOS is frequent AR. Decreasing frequent AR episodes might lead to improved long-term survival following LTX. Despite the introduction of many novel agents, the basis of currently applied protocols remains a calcineurin inhibitor, that is, cyclosporine/tacrolimus (TAC). Eighty-two lung recipients received oral-only administered immunosuppression with oral TAC, mycophenolate mofetil (MMF) and intravenous (IV) methylprednisolone as introduction 2h prior to skin incision. Intra-operatively, patients received additional methylprednisolone prior to unclamping the pulmonary arteries. Postoperatively oral TAC/MMF and prednisolone were continued and trough levels closely monitored (target 8-12 ng ml(-1)). Pulmonary function tests were performed frequently and daily after discharge by means of a self-measuring device (daily forced expiratory volume in 1s (FEV(1))) as the major part of a close follow-up and monitoring programme. Trans-bronchial biopsies were rarely performed. Patient data were collected prospectively and stored in transplantation registries. LTX survival was analysed according to the Kaplan-Meier method. The follow-up of the LTX patients through frequent ambulatory care unit visits and close monitoring of the immunosuppressive regimen and the medication response was 100% complete. The mean duration of observation per patient was 1.8 + or - 1.7 years (median 1.4, range: 0.0-6.4 years) and this study included 176.5 patient-related years of follow-up. The 1-, 3- and 5-year survival following LTX was 70%, 60% and 55%, respectively. Eight patients (10%) underwent high-dose intravenous (IV) bolus methylprednisolone treatment and taper for AR. Two additional patients developed BOS more than 4 years following LTX. The AR- and BOS-related mortality was 0% within the 7-year interval of LTX. Alterations in FEV(1) were associated with significant anastomotic airway and infectious complications, requiring frequent bronchoscopic interventions, stenting and laser therapy as well as frequent IV antibiotic treatment. The 30-day and in-hospital mortality of 19.5% was markedly related to primary graft failure and viral infection. Long-term survival was limited predominantly by cytomegalovirus (CMV) infection and sepsis. Our results suggest that a standard immunosuppressive regimen of TAC and MMF orally administered and introduced prior to skin incision for LTX surgery and maintained long-term might reduce the incidence of acute and chronic rejection. Viral infections and not BOS seemed to be the limiting factor of long-term survival.

The safety and efficacy of daclizumab (1 mg/kg/dose every 14 d for five doses) has been established in kidney and heart transplant recipients. Alternative dosing regimens based on pharmacokinetic simulation and limited clinical trials are being investigated. The purpose of this ongoing multicenter study is to determine the safety and efficacy of two dosing regimens of daclizumab as an adjunctive immunosuppressive agent compared with no antibody induction in simultaneous kidney-pancreas transplant (SKPT) recipients receiving tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids as primary immunosuppression. This is an interim report of a multicenter, prospective, open-label, randomized study with a target enrolment of 290 patients. Eligible SKPT patients were randomized to one of three groups: daclizumab 1 mg/kg/dose every 14 d for five doses (Group I), daclizumab 2 mg/kg/dose every 14 d for two doses (Group II), and no antibody induction (Group III). The primary endpoint of the study is a composite of the incidence of presumed or biopsy-proven kidney or pancreas rejection, graft loss, or death within the first 6 months post-transplantation. A total of 166 patients were randomized into the three groups [Group I (n = 70), Group II (n = 74), Group III (n = 22)]. Demographic and transplant characteristics were similar among the groups. At a minimum follow-up of 3 months, patient, kidney and pancreas graft survival rates were similar among the three groups. However, the rates of acute renal allograft rejection were 18% (Group I), 8% (Group II), and 36% (Group III), p < 0.05. The probabilities of either kidney or pancreas allograft rejection were 22% (Group I), 8% (Group II), and 38% (Group III). At 3 months, the actuarial event-free survival (no acute rejection, allograft loss, or death) rates were 67, 81 and 50% in Groups I, II, and III, respectively. There were no differences in the incidence of infectious complications among the groups and no serious adverse events associated with daclizumab were observed. The two-dose regimen (Group II) appears to be as effective as the five-dose regimen (Group I) in preventing acute rejection after SKPT and is associated with the lowest acute rejection rates and the highest rate of event-free survival (no rejection or graft loss). However, the benefits of daclizumab compared with no antibody induction await larger sample size accrual.

18-month outcomes of heterologous bilateral hand transplantation in a child: a case report