Islet-after-failed-pancreas and pancreas-after-failed islet transplantation: Two complementary rescue strategies to control diabetes

For selected patients with type 1 diabetes, β-cell replacement is the treatment of choice, either by islet transplantation (ITX) or whole pancreas transplantation (PTX). When either modality fails, current practice is to consider retransplantation, or return to exogenous insulin. We investigate outcomes with PTX after failed ITX (PAI), and ITX after failed PTX (IAP). All patients receiving PAI or IAP at a single institution were identified. Donor and recipient variables were documented, including transplant outcomes analyzed for insulin requirement and metabolic control. Five subjects were listed for PAI, and 2 received transplants. Of the 4 listed for IAP, 3 have received transplants. The mean waitlist time was 4.5 ± 4.1 y for PAI and 0.35 ±0 .4 y for IAP (p = 0.08). Metabolic control was excellent after PAI, with 2/2 insulin-independent. After IAP, 1/2 achieved insulin independence and good metabolic control after 2 islet infusions. The third could not receive 2^nd infusion and presented c-peptide levels < 0.1 nmol/L. Both strategies are feasible. The outcomes after PAI in our center must be offset by much longer waitlist time due to the sensitization status of these patients. Data from multicentre experience will allow more robust comparative outcomes to be made, the current observations being restricted to a limited patient set.     

Islet-after-failed-pancreas and pancreas-after-failed islet transplantation: Two complementary rescue strategies to control diabetes

For selected patients with type 1 diabetes, β-cell replacement is the treatment of choice, either by islet transplantation (ITX) or whole pancreas transplantation (PTX). When either modality fails, current practice is to consider retransplantation, or return to exogenous insulin. We investigate outcomes with PTX after failed ITX (PAI), and ITX after failed PTX (IAP). All patients receiving PAI or IAP at a single institution were identified. Donor and recipient variables were documented, including transplant outcomes analyzed for insulin requirement and metabolic control. Five subjects were listed for PAI, and 2 received transplants. Of the 4 listed for IAP, 3 have received transplants. The mean waitlist time was 4.5 ± 4.1 y for PAI and 0.35 ±0 .4 y for IAP (p = 0.08). Metabolic control was excellent after PAI, with 2/2 insulin-independent. After IAP, 1/2 achieved insulin independence and good metabolic control after 2 islet infusions. The third could not receive 2^nd infusion and presented c-peptide levels < 0.1 nmol/L. Both strategies are feasible. The outcomes after PAI in our center must be offset by much longer waitlist time due to the sensitization status of these patients. Data from multicentre experience will allow more robust comparative outcomes to be made, the current observations being restricted to a limited patient set.     

Non-composite combined liver and intestinal allotransplantation

Introduction Small bowel transplantation has been the optimal choice for patients with irreversible intestinal failure. Advances in total parenteral nutrition (TPN) have allowed patients with short bowel syndrome to survive, but the long-term effects are often complicated by intestinal failure. As a result, many candidates for intestinal transplantation have concomitant cholestatic liver damage. Thus, simultaneous liver and intestinal transplantation is required.[1-5] Herein we present a cas…     

Heart-lung transplantation

Heart-lung transplantation itself is not a particularly difficult operation technically. It is the setting in which this procedure is performed which is difficult. The three issues of importance in a successful outcome are appropriate harvest of the heart-lung bloc from the donor, careful explant of the heart and lungs of the recipient, and finally the implant of the heart-lung bloc into the recipient. None of this requires extraordinary technical skill, but does require careful coordination and planning as well as adhering to some fundamental principles. One of the major pitfalls encountered is bleeding related to the explant procedure. Another is graft failure related to harvest and/or the implant procedure. The third is injury to either the phrenic nerve(s) or the left recurrent laryngeal nerve related to the explant procedure. Heart-lung transplantation is a major investment in resources of all sorts including financial, personnel, as well as the organs themselves. It is absolutely imperative that this procedure be performed only by experienced surgeons in centers with established expertise.     

Allogeneic bone marrow transplantation for systemic AL amyloidosis

Low-intensity chemotherapy is ineffective in most patients with AL amyloidosis, probably because clinical benefit requires regression of the amyloid deposits, and this occurs only very gradually after the underlying plasma cell dyscrasia has been suppressed. We report the first successful allogeneic bone marrow transplant (allo-BMT) for AL amyloidosis, which after 3 years was associated with complete clinical recovery. This supports the idea that there may be a brief window of opportunity in patients with AL amyloidosis during which dose-intensive chemotherapy is feasible and most likely to produce clinical benefit.     

肾移植超急性排斥反应64例分析

目的：对肾移植超急性排斥反应（ＨＡＲ）的发生机制、危险因素、诊断与鉴别诊断、预防及处理进行分析。方法：１９７８年６月￣１９９７年１２月施行同种异体肾移植１５００例，发生ＡＨＲ６４例（４．２７％）。结果：除１例对症处理外，其余移植肾均于术中或术后短期予以摘除，对１５例在短期内作了再次移植，１０例（６６．７％）取得成功。结论：ＨＡＲ是一种严重的不可逆性体液排斥反应，目前对其治疗尚无良策，一旦发生应尽早     

Hepatitis B in transplantation

Hepatitis B has been a major challenge within the field of transplantation over the past few decades. Due to aggressive recurrence post‐transplant, patients with hepatitis B have been excluded from the benefits of both solid organ and bone marrow transplants. Progress has been made, however, through an improved understanding of the biology of hepatitis B and the development of new antiviral strategies that can reliably suppress the virus. Patients with hepatitis B are now candidates for transplantation in an increasing number of circumstances. Careful pre‐transplant evaluation is mandatory, together with a tailored antiviral regimen depending on the replicative status of the virus and the organ being transplanted. Minimizing steroid dose following transplantation is an important part of the strategy to reduce the risk of viral reactivation. Lamivudine has been an important development and it has assumed an increasing role in the management of these patients. As additional antivirals are developed, increasingly effective drug combinations will prevent viral recurrence as well as the emergence of drug‐resistant mutants, which plagues the use of single agents. It is a rapidly evolving field and there is every reason for continued optimism.     

Paediatric haematologists’ attitudes regarding haematopoietic cell transplantation as treatment for sickle cell disease

Beginning early in childhood, patients with sickle cell disease [SCD; a group of genetic haemoglobin disorders characterized by the sickle or HbS mutation (HBB E7V)] are at risk of life-threatening and debilitating health events. Despite the high morbidity and mortality of this disease, haematopoietic cell transplantation (HCT), a curative therapy for SCD, remains underutilized. A variety of factors, including the limited availability of suitable donors, play a role in this trend, but do not fully explain the low frequency with which this therapy is employed. The objective of this study was to identify paediatric haematologists’ attitudes about HCT as a treatment option for SCD, and to describe the impact of these attitudes on their practices of discussing HCT with families of children affected by this disease. A nationwide survey of paediatric haematologists in the United States was conducted between February and May 2016. Two hundred and eighty-seven surveys were included in the final analysis (response rate 20%). On average, respondents reported informing 42% of families about HCT as a treatment option (N = 248, 95% confidence interval: 38–46). Clinician attitudes about the cost and safety of HCT were associated with practices of discussing this therapy with families. These findings suggest that clinician attitudes and referral practices may play a role in the underutilization of this therapy in the SCD population.     

Single versus tandem high‐dose melphalan followed by autologous blood stem cell transplantation in multiple myeloma: long‐term results from the phase III GMMG‐HD2 trial

The prospective, randomized phase III trial GMMG‐HD2 aimed at demonstrating non‐inferiority of single (Arm A) versus tandem (Arm B) high‐dose melphalan followed by autologous transplantation (HDM/ASCT) with regard to 2‐year event‐free survival (EFS) in newly‐diagnosed multiple myeloma (MM) and included 358 evaluable patients [Intention‐to‐treat population, (ITT), single/tandem HDM/ASCT: n = 177/181]. After a median follow‐up of more than 11 years, non‐inferiority of single versus tandem HDM/ASCT was demonstrated using the planned non‐inferiority threshold of 15% of the 2‐year EFS rate. Neither EFS (P = 0·53) nor overall survival (OS) (P = 0·33) differences were observed in the ITT population. In the tandem arm, 26% (n = 47/181) of patients refused a second HDM/ASCT due to non‐medical reasons. A per‐protocol (PP) analysis, including patients who received the intervention (single/tandem HDM/ASCT: n = 156/93) and patients who did not receive a second HDM/ASCT due to medical reasons (12%, n = 22/181), did not yield differences in EFS (P = 0·61) or OS (P = 0·16). In the ITT and PP set of the tandem arm, the rates of complete responses increased from first to second HDM/ASCT (both P = 0·04). Ten‐year OS for the entire ITT was 34% (95% confidence interval: 29–40%). OS after first relapse was significantly shortened in the tandem arm (P = 0·04). In this study single HDM/ASCT was non‐inferior to tandem HDM/ASCT in MM.     

Outcomes in partial liver transplantation: deceased donor split-liver vs. live donor liver transplantation

BackgroundOrgan shortage has resulted in greater emphasis on partial liver transplantation (PLT) as an alternative to whole-organ liver transplantation.MethodsThis study was conducted to assess outcomes in PLT and to compare outcomes of deceased donor split-liver transplantation (DD-SLT) and live donor liver transplantation (LDLT) in adults transplanted in the USA using data reported to the United Network for Organ Sharing in the era of Model for End-stage Liver Disease (MELD) scores.ResultsBetween 2002 and 2009, 2272 PLTs were performed in the USA; these represented 5.3% of all liver transplants carried out in the country and included 557 (24.5%) DD-SLT and 1715 LDLT (75.5%) procedures. The most significant differences between the DD-SLT and LDLT groups related to mean MELD scores, which were lower in LDLT recipients (14.5 vs. 20.9; P < 0.001), mean recipient age, which was lower in the LDLT group (50.7 years vs. 52.8 years; P < 0.001), and mean donor age, which was lower in the DD-SLT group (23.0 years vs. 37.3 years; P < 0.001). Allograft survival was comparable between the two groups (P= 0.438), but patient survival after LDLT was better (P= 0.04). In Cox regression analysis, LDLT was associated with better allograft (hazards ratio [HR]= 0.7, 95% confidence interval [CI] 0.630–0.791; P < 0.0001) and patient (HR = 0.6, 95% CI 0.558–0.644; P < 0.0001) survival than DD-SLT.ConclusionsPartial liver transplantation represents a potentially underutilized resource in the USA. Despite the differences in donor and recipient characteristics, LDLT is associated with better allograft and patient survival than DD-SLT. A different allocation system for DD-SLT allografts that takes into consideration cold ischaemia time and recipient MELD score should be considered.     

Tolerance and chimerism and allogeneic bone marrow/stem cell transplantation in liver transplantation

The liver has particular tolerogenic properties that allow its spontaneous acceptance in some animal species.Liver structure is considered to favor a tolerogenic environment.The peripheral tolerance mechanisms also play a role in spontaneous tolerance to liver graft.In a clinical setting,the main challenge nowadays facing liver transplantation is minimization of immunosuppression with the goal of donor-specific tolerance.Mechanisms involved in tolerance to transplanted organs are complex and partly unknown.A significant mechanism in tolerance induction is chimerism.Chimerism can be induced through transplantation of allogeneic donor bone marrow/stem cells under appropriate host conditioning.This review focuses on the tolerance mechanisms in liver transplantation and highlights the role of chimerism and allogeneic bone marrow/stem cell transplantation in tolerance development.