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PubMed1998

Pediatric renal transplantation: indications and special considerations. A position paper from the Pediatric Committee of the American Society of Transplant Physicians.

Renal transplantation of children with chronic renal insufficiency (CRI) and end-stage renal disease (ESRD) appears to be the optimal form of renal replacement therapy. This report, which expresses the opinions of the nephrology members of the Pediatric Committee of the American Society of Transplant Physicians, discusses the indications for pediatric renal transplantation and identifies the unique aspects of caring for children with CRI and ESRD. Indications for pediatric renal transplantation include: 1) symptoms of uremia not responsive to standard therapy; 2) failure to thrive due to limitations in total caloric intake; 3) delayed psychomotor development; 4) hypervolemia; 5) hyperkalemia; and 6) metabolic bone disease due to renal osteodystrophy. The urgency and timing of renal transplantation in children must be considered in the context of a number of issues unique to children with CRI and ESRD such as delayed cognitive and educational performance, growth retardation, delayed puberty, etiology of ESRD, and timing of immunizations. In addition, these children frequently display various inherited and sporadic syndromes with multiorgan involvement requiring the expertise of a variety of pediatric subspecialists including the pediatric urologist, who plays a critical role in the evaluation of children with obstructive uropathy and other anomalies of the genito-urinary system. The advantages of a living-related donor are also delineated. The importance of adequate immunosuppression on graft function, early recognition of the signs and symptoms acute rejection, preventive strategies for minimizing the morbidity and mortality from viral infections in the post-transplant period, and the impact of transplantation on cognitive function, educational status, and catch-up growth are also discussed. To address these complex issues, transplant care of pediatric patients must be provided by a multidisciplinary team of pediatric health care professionals.

Child↗
PubMed1998

Renal transplantation in Down syndrome: a report of the North American Pediatric Renal Transplant Cooperative Study.

There are few published reports on renal transplantation in patients with Down syndrome and renal failure. By means of a questionnaire sent to participating renal centers of the North American Pediatric Renal Transplant Cooperative Study, this study identified 14 Down syndrome patients who received renal transplants between January 1987 and November 1995. There were 6 males and 8 females between the ages of 6 and 21 years. Of the group, 8 patients were Caucasian and 6 were of African American ethnicity. Four patients had a primary diagnosis of obstructive uropathy, two had hypoplastic/dysplastic renal disease, two had focal segmental glomerulosclerosis, two had a diagnosis of chronic glomerulonephritis and four patients had unspecified diagnoses. Eight patients received cadaver kidneys whilst the other six had a living related transplant from a parent or sibling. Only one patient had received a prior kidney transplant, ten patients were on dialysis at the time they were transplanted and 4 patients were preemptively transplanted. Standard immunosuppression with Cyclosporine, Imuran and Prednisone was used. In addition, nine patients received induction therapy at the time of transplantation. Follow-up data revealed that 5 grafts (35.7%) had failed, two as a result of rejection and three due to patient death. At the time of data cutoff there were 3 deaths, one due to viral infection and the other two secondary to cardio-pulmonary complications.

Adolescent↗
PubMed2000

Recommendations for the outpatient surveillance of renal transplant recipients. American Society of Transplantation.

Many complications after renal transplantation can be prevented if they are detected early. Guidelines have been developed for the prevention of diseases in the general population, but there are no comprehensive guidelines for the prevention of diseases and complications after renal transplantation. Therefore, the Clinical Practice Guidelines Committee of the American Society of Transplantation developed these guidelines to help physicians and other health care workers provide optimal care for renal transplant recipients. The guidelines are also intended to indirectly help patients receive the access to care that they need to ensure long-term allograft survival, by attempting to systematically define what that care encompasses. The guidelines are applicable to all adult and pediatric renal transplant recipients, and they cover the outpatient screening for and prevention of diseases and complications that commonly occur after renal transplantation. They do not cover the diagnosis and treatment of diseases and complications after they become manifest, and they do not cover the pretransplant evaluation of renal transplant candidates. The guidelines are comprehensive, but they do not pretend to cover every aspect of care. As much as possible, the guidelines are evidence-based, and each recommendation has been given a subjective grade to indicate the strength of evidence that supports the recommendation. It is hoped that these guidelines will provide a framework for additional discussion and research that will improve the care of renal transplant recipients.

Ambulatory Care↗
PubMed2000

How the system functions. The roles of the United Network of Organ Sharing, the organ procurement and transplantation network, and the organ procurement organization in heart transplantation.

Have the limits for suitable recipient candidates for heart transplantation been exceeded? Does the current legislation and policy instituted at all levels, from DHHS to individual transplant programs, critically address the use of a dangerously limited resource? These and other questions must be the focus of future discussions regarding equitable and efficient heart transplantation in this country. The past has shown that many individuals working cooperatively within committees at federal and organizational levels have already made great strides in making organ transplantation a successful reality. Many factors influence the broadening gap between supply and demand. Each level of the system can make contributions that bring positive and creative solutions to old and new problems. Each team and committee must continue to demand representation from diverse, yet attentive, members to ensure that the specific needs of the thoracic organ recipients are properly reviewed and addressed. UNOS and its membership must continue to work together to meet the challenges of the growing acceptance of organ transplantation and the limited supply of donor organs. Continued efforts of politicians, health care professionals, and the general public must seek newer and more creative ways to manage the critical organ shortage and the ever-growing population of patients who seek heart transplantation as the only viable treatment option for their disease process. OPOs must continue their efforts to educate and promote organ donation and continue to work diligently toward increasing the pool of acceptable organ donors through improved patient management and the development of improved preservation and transport techniques. The transplant community must take the initiative to modify current legislation and to author new legislation to serve as better representors for the transplant patient population that desperately needs it.

Health Care Costs↗
PubMed2003

Kidney transplantation from living donors: comparison of results between related and unrelated donor transplants under new immunosuppressive protocols.

BACKGROUND: Recent advances in immunosuppressive therapy have led to a substantial improvement in the outcome of kidney transplantation. Living unrelated donors may become a source of additional organs for patients on the kidney waiting list. OBJECTIVES: To study the impact of the combination of calcineurin inhibitors and mycophenolate-mofetile, together with steroids, on outcomes of living related and unrelated transplants. METHODS: Between September 1997 and January 2000, 129 patients underwent living related (n = 80) or unrelated (n = 49) kidney transplant. The mean follow-up was 28.2 months. Immunosuppressive protocols consisted of MMF with cyclosporine (41%) or tacrolimus (59%), plus steroids. Patient and graft survival data, rejection rate, and graft functional parameters were compared between the groups. RESULTS: LUD recipients were older (47.8 vs. 33.6 years) with a higher number of re-transplants (24.5% vs. 11.2% in LRD recipients, P < 0.05). Human leukocyte antigen matching was higher in LRD recipients (P < 0.001). Acute rejection developed in 28.6% of LUD and 27.5% of LRD transplants (P = NS). Creatinine levels at 1, 2 and 3 years post-transplant were 1.6, 1.7 and 1.7 mg/dl for LRD patients and 1.5, 1.5 and 1.3 mg/dl for LUD recipients (P = NS). There was no difference in patient survival rates between the groups. One, 2 and 3 years graft survival rates were similar in LRD (91.3%, 90% and 87.5%) and LUD (89.8%, 87.8% and 87.8%) recipients. CONCLUSIONS: Despite HLA disparity, rejection and survival rates of living unrelated transplants under current immunosuppressive protocols are comparable to those of living related transplants.

Adult↗
PubMed2004

[Inadequate involvement of nephrologist/dialysis physicians in transplantation: based on the findings of a survey of transplant recipients].

The number of kidney transplantations(KTx) performed annually in Japan remains small even after enactment of the "Organ Transplant" law. One of the reasons for this paucity of KTx might be because most nephrologists or dialysis physicians who provide medical care to potential transplant candidates have little knowledge of KTx and are seldom involved in the care of recipients and donors. The extent to which Japanese physicians participate in KTx has not been well studied. We sent questionnaires to the 212 kidney transplant recipients who have received an allograft at Tokyo Women's Medical University and conducted a survey to examine the extent to which nephrologists or dialysis physicians are involved in KTx. There were 149 recipients, consisting of 95 males and 54 females with an average age of 46.5 years, who responded to the questionnaire. Only 23% of the patients had considered KTx before dialysis access placement. Lack of information on KTx was suspected for this delay in considering KTx. In fact, only 18% of patients were informed about KTx by their nephrologists before starting dialysis and as many as 49% did not receive any information at all. Forty-eight percent of the patients were not provided with the information even on registration for a cadaveric transplant list by their physicians. Only 20% of the patients received some information about KTx through their nephrologists. On the other hand, nearly 100% of patients think it is essential for nephrologists or dialysis physicians to provide information on KTx especially before the initiation on dialysis access. In addition, almost all of the patients would prefer nephrologists or a dialysis physician to participate in the care of transplant patients from the stage of preoperative evaluation through the post-transplant follow-up period. In conclusion, nephrologists or dialysis physicians have not provided information on KTx to their patients appropriately and most of the transplant recipients expect them to participate in KTx. Nephrologists and dialysis physicians need fundamental knowledge about KTx so that they can provide appropriate information to patients with end-stage renal disease.

Clinical Competence↗
PubMed2004

[Advantages of living donor kidney transplantation; possibilities in the national transplantation program].

The review paper summarizes the advantages of the living donor kidney transplantation aiming that this kind of activity should get more support in Hungary. It is a general phenomenon overall the world, that there is no more possibility to increase the number of cadaver transplantations, and the outcome of them is also worsening because of the accumulation of aged patients with long time period of dialysis treatment. The paper points out the better results of living donor kidney transplantation underlining that the kidney long term survival, in general, is 10% over the cadaver kidney survival with significant less complication. The indication of living related and unrelated donor kidney transplantation is reported and the harmless of donor kidney removal demonstrated. An important part of the review contains the ethical, legal and social issue of the living donation, moreover, its economical benefit. It shows that in certain countries the living donation becomes in the forefront of the transplantation activity, which demonstrates from statistical point of view the overall benefit in comparison to cadaver transplantation. Based on the experience of those countries, which are performing this type of transplantation for a long time ago recommendation is given what should be the methodology to increase the activity in this field of transplantation.

Altruism↗
PubMed2005

[Kidney transplant survival rates and surgical complications in kidney transplants in children; experiences in the Emma Children's Hospital AMC].

OBJECTIVE: To describe surgical complications, and patient and kidney transplant survival rates in children who have had a kidney transplant. DESIGN: Retrospective. METHOD: Data were analysed concerning the children who had been treated with a renal transplantation in the period 1985-2001 because of terminal renal insufficiency in the Emma Children's Hospital of the Academic Medical Centre in Amsterdam, The Netherlands, with arbitrary end date October 7, 2002. RESULTS: In the study period, 55 primary kidney transplantations were performed on 24 girls and 31 boys. 13 living related and 42 post mortem transplantations were performed. The extra-peritoneal approach was performed in all recipients. Up to October 7, 2002, 14 surgical complications (25%) developed: 4 cases of renovascular thrombosis, 4 urinary leakages, 6 urethral strictures, 1 urethral necrosis, 5 haematomas and 3 lymphoceles. 6 patients lost their grafts due to surgical complications (11%); 4 due to thrombosis, 1 due to urethral necrosis and 1 due to haemorrhage or haematoma. Due to hypertension secondary to the underlying kidney disease 2 patients died within one year after transplantation from hypertensive encephalopathy and cerebral bleeding respectively. The one- and five-year graft survival was 83% and 74% for living related transplantations respectively, and for post mortem transplantations 78% and 68% respectively. The main causes of graft loss were chronic rejection (9/21; 43%), acute rejection (4/21; 19%), thrombosis (4/21; 19%) and surgical complications (2/21; 10%). Primary nonfunction was the only factor with a negative prognostic value for graft survival.

Adolescent↗
PubMed1987

Current status of allogeneic bone marrow transplantation in leukemia: a report from the International Bone Marrow Transplant Registry.

Utilization of bone marrow transplantation as a therapeutic modality continues to increase. During the 32 years between 1955 and 1986 more than 15,000 patients received allogeneic transplants; more than 50% of these were performed in the 3 years, 1984 to 1986. Transplantation is an effective therapy for acute leukemias; in some instances it is the preferred treatment. In chronic myelogenous leukemia, aplastic anemia, and some genetic and immune deficiency diseases, bone marrow transplantation provides the only possibility for cure. Bone marrow transplantation is investigational in other conditions and is associated with substantial problems such as graft-vs-host disease, interstitial pneumonitis, and the requirement for an HLA-identical donor. Recently an increasing number of transplants have been performed using HLA partially or fully matched related or unrelated donors with some success. The development of AGVHD and interstitial pneumonitis can to some extent be predicted by risk factor assessment. AGVHD can be prevented by depletion of T cells from the donor bone marrow but this is associated with an increased risk of graft rejection and leukemia relapse. Interstitial pneumonitis can be modified by prophylaxis with CMV immune globulin and by the use of CMV-negative blood donors. In this report we summarized data from the International Bone Marrow Transplant Registry concerning allogeneic bone marrow transplantation in leukemia.

Bone Marrow Transplantation↗
PubMed1982

Urinary enzyme excretion by renal-transplant recipients in relation to interval after transplantation.

We determined the urinary excretion of the enzymes aminopeptidase (EC 3.4.11.2), alkaline phosphatase (EC 3.1.3.1), gamma-glutamyltransferase (EC 2.3.2.2), and N-acetyl-beta-glucosaminidase (EC 3.2.1.30) in two groups of renal-transplant recipients at different times after transplantation (1.8 months and 52 months, respectively). Both groups of patients showed a higher rate of enzyme excretion than did a reference group of healthy persons. More aminopeptidase and N-acetyl-beta-glucosaminidase were excreted during the early period after transplantation than later. The time-dependence of urinary enzyme excretion was confirmed in six renal-transplant recipients studied during the course of 15 months after transplantation. There was a general correlation between the extent of urinary enzyme excretion and both the time after transplantation and the daily dose of prednisolone. Therefore, it is necessary to take into account this influence on the extent of urinary enzyme in renal-transplant recipients if urinary enzyme excretion is used as an indicator of renal disorder and especially as an early predictor of transplant rejection.

Acetylglucosaminidase↗
PubMed1994

Survival and functional outcome after single and bilateral lung transplantation. Loyola Lung Transplant Team.

BACKGROUND: The experience at Loyola University Chicago was retrospectively reviewed to evaluate survival and functional outcome after single lung transplantation (SLT) and bilateral lung transplantation (BLT). METHODS: Ninety patients underwent lung transplantation at Loyola University Chicago between April 1990 and December 1993. Mean age was 45 years (range, 13 to 66 years). Fifty percent were male. Pre-lung transplant pulmonary diseases were as follows: emphysema and/or chronic obstructive pulmonary disease in 43 patients, pulmonary fibrosis in 13, cystic fibrosis in 14, pulmonary hypertension in eight, repeated transplantation for obliterative bronchiolitis in four, bronchiectasis in two, bronchoalveolar cell carcinoma in two, sarcoidosis in one, primary obliterative bronchiolitis in one, histiocytosis X in one, and lymphangiomyomatosis in one. Fifty-seven patients underwent SLT, and 33 had BLT. Maintenance immunosuppression medications consisted of cyclosporine, azathioprine, and prednisone. RESULTS: Perioperative complications were as follows: seven of 33 patients bled after BLT, and two of 57 bled after SLT. Bronchial complications were found in six of 66 (9%) BLT anastomoses and eight of 57 (14%) SLT anastomoses. Nine operative deaths occurred in SLT patients: six from allograft failure, one from infection, one from intrapulmonary hemorrhage, and one from bronchial dehiscence. Only two patients died in the perioperative period after BLT and that was of infection. Three late deaths occurred after BLT, all as a result of infection; 13 recipients died late after SLT: five of infection, four patients from lymphoma, two of pancreatitis, one of tension pneumothorax, and one of pulmonary embolism. For the entire patient population the actuarial 1- and 2-year survival rates were 72% and 68%, respectively. One-year survival rates were significantly better for patients undergoing lung transplantation for obstructive and nonrestrictive lung diseases than those of patients undergoing lung transplantation for vascular or restrictive pulmonary disease. Recipients of BLT had a trend toward better survival than recipients of SLT. Lung function 6 months after transplantation measured by forced expiratory volume in 1 second was significantly better in BLT than SLT, 71% of predicted versus 54%. CONCLUSIONS: Patients who undergo BLT have significantly better postoperative pulmonary function than those who undergo SLT. On the basis of the study there was a trend toward better survival with BLT.

Adolescent↗
PubMedDate not supplied

Segmental flow-resistance relationship in pulmonary lobar transplantation: possibility for donor lobe evaluation in pediatric lung transplantation.

Pulmonary lobar transplantation is an option for pediatric lung transplantation, and it has the potential of extended applications. We compared the relationship between segmental blood flow and segmental vascular resistance of the pulmonary lobe with that of the transplanted single lung. Eight of 14 puppies received a left upper pulmonary lobe from double-weighed adult dogs, and the other six puppies received a left lung from puppies. All recipient dogs were treated with oral cyclosporine (15 mg/kg/day) and intramuscular prednisolone (1.0 mg/kg/day), after the operation. Pulmonary arterial and left atrial pressures and segmental flow of the lungs were measured at rest and while the inferior vena cava or right pulmonary artery was clamped, before and 1 hour and 2 weeks after lung transplantation. Vascular resistance of the lung segment was calculated at each hemodynamic state. Segmental resistance of the lung at rest significantly increased from pretransplantation to 1 hour after transplantation (pulmonary lobe group, 2211 +/- 42 to 2555 +/- 61 dyne.sec.cm-5; single lung group, 2126 +/- 56 to 2557 +/- 72 dyne.sec.cm-5) and recovered 2 weeks after transplantation in both groups. However, by means of partial clamp of the right pulmonary artery, segmental resistances of 1 hour after transplantation pulmonary lobe (2248 +/- 37 dyne.sec.cm-5), and single lung (2206 +/- 34 dyne.sec.cm-5) at the same segmental flow of the pretransplantation state (310 to 320 ml/min) were equivalent to those of the pretransplantation lungs. There was no significant difference in the segmental resistance at any segmental flow between the pulmonary lobe and single lung before and after lung transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Pretransplantation risk factors for death after heart transplantation: a multiinstitutional study. The Transplant Cardiologists Research Database Group.

Risk factors for death after heart transplantation were identified by analyzing the total primary heart transplantation experience (n = 911) among 25 institutions from January 1, 1990, through June 30, 1991. Overall actuarial survival was 93% at 1 month and 84% at 12 months. The hazard function for death was highest early after heart transplantation and fell rapidly over the first 6 months, with a gradually declining hazard thereafter. The two most common causes of death were infection (n = 29) and early graft failure (n = 28), accounting for 45% of the overall deaths. By multivariable analysis, risk factors for death during the study period included very young recipient age (p = 0.004), advanced age (p = 0.009), ventilator support at time of transplantation (p = 0.09), abnormal renal function (p = 0.1), lower pretransplantation cardiac output (p = 0.009), higher pulmonary vascular resistance in children (p = 0.006), longer donor ischemic time (p = 0.001), older donor age (p = 0.001), and donor and recipient not both blood type O (p = 0.009). The recipient age effect was greatest in patients under 5 years of age (1-year survival rate 68% versus 85% for all others, p = 0.002). Patients aged 60 years and older had a 1-year survival rate of 81%. Patients who were ventilator dependent at transplantation fared especially poorly, with a 3-month survival rate of 65%. Transplantation of a blood group O heart into a non-O recipient had a somewhat lower 1-year survival rate than did blood group O into an O recipient (82% versus 88%, p = 0.06). The adverse effect of a longer ischemic time was most notable after 4 hours (1-month survival rate 71% for more than 4 hours versus 85% for less than 4 hours, p = 0.0003). Inference: These multiinstitutional-derived risk factors for early-term death after heart transplantation may help improve patient and donor selection and focus further scientific investigations to increase the safety of heart transplantation.

Actuarial Analysis↗
PubMed1996

Organ Procurement Organization and transplant center effects on cadaver renal transplant outcomes.

1. A majority of transplant centers had significant improvements in cadaver donor kidney graft survival rates since 1991. A 10% or greater increase in one-year graft survival rates was reported by 36 of 128 large transplant centers. 2. When transplants were grouped according to the organ procurement agency that procured the kidney, large variations in one-year graft survival rates among 65 OPOs were noted. The "OPO effect" was of a magnitude similar to that of the "center effect" when analyzed separately. 3. Fourteen OPOs with the lowest graft survival rates procured a significantly higher fraction of kidneys from older, hypertensive or Black donors and donors whose deaths were not from motor vehicle accidents. Transplants were more often given to Black recipients, and kidneys were less frequently shared compared with 15 OPOs with the highest graft survival rates. 4. Significantly higher proportions of non-Black donors and recipients, patients with no activity limitation at the time of listing, patients working fulltime at the time of transplantation, and patients on dialysis less than one year were more frequently transplanted at 21 centers with excellent one-year graft survival rates compared with centers in groups with poorer results. 5. Increased numbers of mismatched HLA-B,DR antigens were detrimental to graft survival at centers with good or fair one-year graft survival rates, but had a minimal effect at centers with excellent results. 6. The OPO effect on graft survival rates was significantly associated with the center effect. Kidneys procured by OPOs associated with low graft survival rates and transplanted at centers with low graft survival rates resulted in the worst graft outcome. Interestingly, kidneys procured by OPOs associated with high graft survival rates, but transplanted by centers with low graft survival rates had better outcomes than kidneys from OPOs with lower graft survival rates. 7. Based on univariate analyses, the center and OPO effects ranked third and fifth among 16 significant factors. However, after adjusting for these 16 potentially confounding variables using a multivariate Cox regression model, the differences between the best and worst center and OPO groups were the fourth and eleventh most detrimental risk factors on graft outcome, respectively.

Adolescent↗
PubMed1997

Cytomegalovirus immune globulin (CMVIG) prophylaxis is associated with increased survival after orthotopic liver transplantation. The Boston Center for Liver Transplantation CMVIG Study Group.

Cytomegalovirus (CMV) causes considerable morbidity and mortality in orthotopic liver transplant (OLT) recipients. Several prophylactic strategies against CMV have been studied in solid organ transplant recipients, including cytomegalovirus immune globulin (CMVIG). We examined the effect of CMVIG prophylaxis on first-year and long-term survival after liver transplantation. Data were analysed for 162 OLT recipients from four transplant centers in Boston who participated in two CMVIG prophylaxis trials. Ninety patients received CMVIG (median follow-up 5.6 yr), and 72 patients received placebo (median follow-up 5.4 yr). CMVIG prophylaxis was shown to be associated with increased first-year (86% vs. 72%, p = 0.029) and long-term (68% vs. 54%, p = 0.055) survival. The distribution of baseline characteristics including donor and recipient demographics, donor CMV serostatus, United Network for Organ Sharing (UNOS) status, pre-transplant renal and liver function tests, transplantation surgical time, number of units of blood products administered during transplantation, primary immunosuppressive regimen, use of solumedrol or antilymphocyte therapy for induction of immunosuppression or treatment of rejection, and surgical complications was similar for CMVIG and placebo recipients. CMVIG recipients were more likely to have primary biliary cirrhosis than placebo recipients (21% vs. 8%, p = 0.025). Using a Cox proportional hazards multivariate model to control for pre-transplant liver disease, CMVIG was shown to be independently associated with increased first-year survival (p = 0.042); a trend toward association with increased long-term survival (p = 0.098) was also shown. These data support that CMVIG prophylaxis, beyond its proven efficacy in decreasing the incidence of severe CMV-associated disease, is associated with increased survival when used prophylactically in OLT recipients.

Adolescent↗
PubMed2002

Maternal-fetal relationship, natural chimerism and bilateral transplantation tolerance as the basis for non-myeloablative stem cell transplantation.

Bone marrow transplantation (BMT) which represents an important clinical tool for treatment of patients with a wide variety of malignant and non-malignant diseases, however, the procedure is associated with procedure-related toxicity and mortality as well as unavoidable late complications. Many of the undesirable consequences of BMT are caused directly or indirectly by the intensive conditioning administered during the pre-transplant period. However, if the main goal of the BMT procedure is to enable immunotherapy by alloreactive donor lymphocytes, the conditioning prior to BMT needs to be reconsidered, because transplantation tolerance across major histocompatibility complex (MHC) occurs spontaneously in nature, as evidenced by the fact that pregnant females do not reject their conceptus. In fact, as shown by Owens in the 1940s, placental parabiosis in utero leads to permanent mixed chimerism and bilateral transplantation tolerance. These observations followed by experiments carried out in the 1950s by Billingham et al. suggested that infusion of parental stem cells into neonates with no exogenous immunosuppressive treatment resulted in mixed chimerism and permanent transplantation tolerance to donor alloantigens. Thus, a window of opportunity provided shortly after delivery, was sufficient for induction of tolerance without the need for heavy conditioning. Tolerant recipients were shown to be chimeras with only a small proportion of donor cells. However, without corroborating evidence that transplantation tolerance could be intentionally induced, the approach could not be applied in clinical practice for immunocompetent recipients. Starting in 70s, we documented the feasibility of establishing bilateral transplantation tolerance by mixed chimerism following non-myeloablative conditioning in immu. nologically mature recipients across MHC in mice, rats and dogs. Several studies have shown that reduced intensity conditioning can be very useful for immunoregulation whereas more intensive the pre-grafting immunosuppression resulted in more aggressive the GVHD. These and other findings suggested that lower intensity conditioning may be sufficient for engraftment of donor stem cells, thus suggesting that immunosuppression without myeloablation may be sufficient for prevention of allograft rejection. Following engraftment of donor stem cells, donor lymphocytes infused with bone marrow or mobilized blood stem cells can eradicate residual hematopoietic cells of host origin, occasionally non-hematopoietic tumor cells of host origin as well. Whenever indicated, donor lymphocytes infusion (DLI) can be used at a later stage post BMT to eradicate residual malignant cells of host origin or for the treatment of residual or recurrent disease. Taken together, ongoing clinical studies suggest that high-dose, myeloablative chemoradiotherapy, could be safely replaced with non-myeloablative conditioning (NST).

Animals↗
PubMed1998

Faster engraftment but no reduction in infectious complications after peripheral blood stem cell transplantation compared to autologous bone marrow transplantation.

Patients who receive transplants of autologous peripheral stem cells have a shorter duration of neutropenia than patients who receive autologous bone marrow transplants. There is conflicting evidence regarding the risk of infections. A retrospective analysis on 123 patients who received transplants of either autologous bone marrow or peripheral blood stem cells for multiple myeloma or breast cancer was performed to study whether this shorter duration of neutropenia can influence the risk of and the severity of infection. Patients who underwent peripheral blood stem cell transplantation (PBSCT) had faster engraftment than the group treated with autologous bone marrow transplantation (ABMT). Furthermore, the requirement for transfusions of red blood cells and platelets was a reduced. The number of days needed in hospital was significantly lower in PBSCT patients. No reduction in the frequency of infectious complications was found in PBSCT as compared with ABMT patients, but the numbers of days with fever and with antibiotic treatment were significantly lower in the PBSCT patients. Breast cancer patients had significantly faster engraftment but no fewer infectious complications than myeloma patients, regardless of the type of transplantation. Significantly lower numbers of clinically verified infections were found in the group of patients receiving colony-stimulating factors (CSF) after transplantation even though there was no difference in the duration of neutropenia. The need for antibiotic treatment was also significantly less in the group treated with CSF.

Adult↗
PubMed2026

Trimethoprim/sulfamethoxazole-triggered drug-induced hypersensitivity syndrome in an HLA B*13:01-positive kidney transplant recipient: a case report with implications for HLA-severe cutaneous adverse reaction associations in transplant care.

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe cutaneous adverse reaction (SCAR) with a reported mortality rate of approximately 2-10%. DIHS/DRESS typically develops 2-8 weeks after exposure to an offending drug. An important focus of contemporary SCAR research is the growing evidence that specific human leukocyte antigen (HLA) alleles confer a markedly increased risk of drug-specific hypersensitivity reactions. We report a case of a kidney transplant recipient who developed DIHS/DRESS after prolonged trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis and carried the HLA-B13:01 allele. HLA-B13:01 is a strong genetic risk factor for TMP/SMX-induced DIHS/DRESS, particularly in Southeast Asian populations. Herein, we highlight the potential clinical relevance of pre-transplant HLA typing in predicting SCAR risk in transplant recipients. TMP/SMX-associated DIHS/DRESS may be under-recognized in transplant settings, where awareness of HLA-associated risk remains limited despite robust evidence from non-transplant populations. Transplant clinicians should be aware that DIHS/DRESS can occur outside the typical latency period, especially during immunosuppressant tapering, highlighting the need to integrate pharmacogenomic risk assessments into transplant care.

Humans↗