Unrelated donor bone marrow transplantation for Fanconi anemia

This paper describes the approach taken at the University of Queensland to broaden the scope of curriculum design to involve rural general practitioners, medical students and rural health care consumers. A form of nominal group process in serial telephone teleconferences was used, with a group of rural general practitioners, to develop and pilot curriculum content, learning strategies and assessment methods. Medical students assisted in the evaluation of the curriculum and representatives of rural organisations were consulted about the value of hosting medical students in rural communities. The three groups made significant contributions to the project. The results will be trialed for the entire year 6 cohort (240 students) in 1995 and will form the basis of the planned rural practice term in the new graduate course.     

Unrelated donor marrow transplantation for chronic myelogenous leukaemia

Between January 1989 and July 1995 the search for an unrelated donor (UD) was started for 379 consecutive Italian patients with Philadelphia positive (Ph+) chronic myelogenous leukaemia (CML). 89 (23%) were transplanted. The overall probability of transplant before and after December 1991 was 16% and 49%, respectively (P=0.0001), and average interval between search activation and graft was 23 months and 13 months, respectively (P=0.0001). Disease-free survival (DFS) following 60 consecutive transplants performed before February 1996 was 41.5% at 48 months and was 64% for patients grafted after January 1993. In univariate analysis, five variables had a favourable effect on DFS: year of bone marrow transplantation (BMT) after 1993 (P=0.0002), HLA-DRB1 donor/recipient (D/R) match (P=0.0006), total body irradiation (TBI) containing regimen (P=0.0006), graft-versus-host disease (GvHD) prophylaxis including 'early' cyclosporin before the transplant, and a marrow cell dose > 3 x 10(8)/kg of recipient body weight (P=0.04). Multivariate analysis confirmed that HLA identity (P=0.006), TBI-containing regimen (P=0.0001) and 'early cyclosporin' (P=0.04) were associated with higher DFS. Transplant-related mortality (TRM) was 67% in patients grafted before January 1993 and 30% in patients grafted subsequently (P=0.002). Multivariate analysis confirmed DRB1 identity (P=0.03) and TBI-containing regimen (P=0.0005) to be independent factors predictive of low TRM. This suggests that the outcome of patients transplanted from an HLA DRB1 matched donor, after a TBI-containing preparative regimen, is similar to results recently reported in patients transplanted from geno-identical siblings. These results indicate that the search should be initiated at diagnosis for patients < 45 years of age and UD BMT should be considered early in the disease course for those with an available DRB1-matched unrelated donor.     

Related donor liver transplant for veno-occlusive disease following T-depleted unrelated donor bone marrow transplantation

The results of a study of Inter-Alpha-Trypsin Inhibitor (ITI) polymorphism in 281 blood samples are reported in this paper. These samples were taken from healthy individuals of both sexes, unrelated and resident in the Province of Cadiz. The frequency of ITI*1 was 0.617 and of ITI*2 was 0.383. The probability of exclusion in paternity testing was 0.18.     

The importance of non-heart-beating donor kidneys in reducing the organ shortage

The serum concentrations of calcitonin (CT) and sublemmal granule numerical density in the thyroid C-cell basal polus cytoplasm were measured in guanethidine-sympathectomized rats aged 2 weeks. Based on the previously proposed procedure [Krasnoperov et al. 1997], the confidence interval of endogenous CT bioavailability was found to be 52-100% (p > or = 0.95). It significantly differed from the similar control parameter (73-100%). The findings suggest that it cannot be excluded that unlike normal animals, sympathectomized 2-week rats may have CT retention at the transinterstitial and/or transmural stages of hemato-C-cellular mass-transfer.     

Impact of the Hospital Coordinator Program on obtaining kidneys for renal transplantation

Limited organ supply is currently the major obstacle to the transplantation programs around the world. As an alternative to increase the organ donation rate, we undertook a preliminary transplant coordinator program study, during a 6 month period, in five public hospitals, as part of the National Transplant Program of the Centro Nacional de Diálisis y Trasplante. The primary objective of the Transplant Coordinator Program was donor detection and organ procurement, along with education of the community. Forty five predonors were detected, with an average age of 25.8 +/- 1.6 years, of these, 36 were men (80%). None of them was a voluntary donor. The most frequent diagnoses were cranial trauma in 57.8% and stroke in 22.2% Forty two percent (42.3%) of the predonors were detected in the emergency room, 33.3% in intensive care units and 24.4% in the surgery recovery room. The conversion rate of predonors to donors were 29%. The main causes for not conversion of predonors into donors were: family refusal 44%, sepsis 13%, cardiac arrest 13%, and reduced renal function 6%. In conclusion, the Transplant Coordinator Program allows to increase the predonor detection and gives good information for adequate management of donor and public educational campaign about the subject.     

The donor stage of orthotopic liver transplantation

First clinical experience of the harvesting (donor) stage of orthotopic transplantation of the liver in Russia is represented. During 5-year period in National Research Center of Surgery RAMS 16 orthotopic transplantations of the liver were carried out. Surgical modes of harvesting of the donor liver are detailed ("standard" and "fast"), the regimes and methods of preservation of the liver were determined. The influence of various parameters on function of the graft in postoperative period was established. Adequate selection of donors, correct and proper choice of donor-recipient pair, limited time of preservation allow to decrease the number of graft function failure and to eliminate primarily nonfunctioning grafts.     

Unrelated donor bone marrow transplantation for children with acute leukemia

PURPOSE: To test the use of unrelated donor bone marrow transplantation (URD BMT) to cure children with high-risk acute leukemias. PATIENTS AND METHODS: Between June 1985 and December 1994, 50 children with acute leukemia (15 acute myelogenous leukemia [AML], 35 acute lymphoblastic leukemia [ALL]; 22 greater than second complete remission [CR]) received BMT from a URD at the University of Minnesota. Ages ranged from 0.9 to 17.5 years (median, 8.8). Median follow-up is 2.1 years (range, 1 to 7.3). Thirty patients (60%) received bone marrow fully matched at HLA-A,B and DRB1; 20 (40%) received bone marrow with a major or minor mismatch at a single HLA-A or B locus. RESULTS: The median time to neutrophil engraftment was day 24 (range, 14 to 42 days) in those receiving matched and day 25 (range, 15 to 32 days) in those receiving mismatched marrow (P = .35). The incidence of grades III to IV graft-versus-host disease (GVHD) was 23% (95% confidence interval [CI], 7% to 39%) in matched and 32% (95% CI, 8% to 52%) in HLA-mismatched patients (P = .57). The incidence of chronic GVHD was 50% (95% CI, 28% to 72%) in matched and 57% (95% CI, 23% to 91%) in mismatched patients (P = .80). Disease-free survival for patients with ALL is 37% (95% CI, 21% to 53%) at 1 year and 30% (95% CI, 15% to 46%) at 2 years; for patients with AML, 53% (95% CI, 28% to 78%) at 1 year and 33% (95% CI, 6% to 60%) at 2 years. CONCLUSION: URD BMT is an effective treatment for children with poor-prognosis acute leukemia and should be considered for all high-risk patients. Early referral of patients is strongly recommended.     

Deciding eligibility for transplantation when a donor kidney becomes available

The expectation of transplant success for some patient/donor-kidney matches can be so low that transplantation is not considered an option. The issue may be framed as deciding the minimum expectation of transplant success that would justify a patient's eligibility for transplantation with an available donor kidney. If the minimum is set too high, the patient will be eligible for very few donor kidneys and will wait excessively for transplantation. If the minimum is set too low, the patient has a greater risk of graft failure once transplantation has been done. A decision model calculates the minimum predicted one-year graft survival rate that would determine eligibility for an available donor kidney, with the goal of maximizing quality-adjusted life expectancy. The minimum predicted one-year graft survival rate depends on the patient's health and demographic characteristics and attitudes about quality of life with kidney-replacement therapies. Graft survival rates and quality-adjusted life expectancies may increase by as much 6.7% and 1.6 months, respectively, with only a slight increase (< 0.4 months) in the quality-adjusted waiting time until transplantation.     

When should expanded criteria donor kidneys be used for single versus dual kidney transplants?

BACKGROUND: To increase the utilization of cadaveric donor kidneys, we have recently expanded our acceptable criteria to include aged donors (frequently with a history of hypertension), by selectively using both donor kidneys (dual transplant) into a single recipient. METHODS: To define when these expanded criteria donor (ECD) kidneys should be used as a single versus a dual kidney transplant, we retrospectively reviewed 52 recipients of ECD kidneys that had been turned down by all other local centers between 1/1/95 and 11/15/96. Fifteen patients received dual transplants, whereas the remaining 37 received single kidneys. Of the dual kidney recipients, 14 of 15 ECD were > or = 59 years of age, 10 of 15 were hypertensive, and 9 of 15 were both. Of the single recipients, 11 of 37 ECD were > or = 59 years of age, 11 of 37 were hypertensive, and 7 of 37 were both. All patients received cyclosporine-based triple-drug therapy. We compared seven donor (D) and sixteen recipient outcome variables in single versus dual kidney transplants as subgrouped by: (1) donor admission creatinine clearance (D-AdC(Cr)) < 90 ml/min; (2) D-age > or = 59 years; and (3) cold storage (Cld Stg) < or > 24 hr. RESULTS: In the group with D-AdC(Cr) < 90, there was a significantly higher incidence of delayed graft function (DGF) in single versus dual recipients (9 of 20 [45%] vs. 1 of 11 [9%]; P=0.04) and worse early graft function based upon mean serum creatinine at 1 and 4 weeks (5.3+/-3.3 and 2.8+/-2.0 vs. 1.7+/-0.6 and 1.4+/-0.5 mg] dl; P<0.05). In the group with D-age > or = 59, recipients of single kidneys had significantly higher mean serum creatinine at 1, 4, and 12 weeks versus recipients of dual kidneys (5.1+/-3.3, 3.4+/-2.1, 2.8+/-1.5 versus 2.8+/-2.5, 1.5+/-0.6, 1.6+/-0.5 mg/dl; P<0.05). Cld Stg time also had an impact on DGF and early outcome. Recipients of dual kidneys stored less than 24 hr had a significantly lower incidence of DGF versus single kidneys stored more than 24 hr (10% vs. 46%; P<0.05) and better early graft function based on mean serum creatinine at 1, 4, and 12 weeks (1.9+/-0.8, 1.3+/-0.4, 1.5+/-0.2 vs. 6.6+/-3.4, 3.0+/-1.6, 2.9+/-1.9 mg/dl; P<0.05). The overall 1-year patient and graft survivals were 96% and 81% vs. 93% and 87% (P=NS) in recipients of single ECD versus dual ECD kidneys. CONCLUSIONS: In conclusion, we believe that kidneys from ECD with D-AdC(Cr) < 90 ml/min and D-age > or = 59 should be used as dual kidney transplants, keeping the Cld Stg time at < 24 hr to minimize the effect of Cld Stg on early graft function.     

Impact of extreme donor age on the outcome of living-related donor kidney transplantation

Eosinophil cationic protein (ECP) in sputum may be used to estimate the severity of bronchial inflammation and obstruction in asthmatics as well as to monitor asthma drug therapy. For this purpose, standardized processing of sputum is important. The aim of our study was to determine whether time and temperature influence the ECP concentration in the sputum of asthmatics. The samples of induced sputum obtained from 12 patients with stable asthma were homogenized using ultrasonification, and centrifuged. Supernatants were evenly divided and stored for 1, 6, 24 or 72 h at either 4 or 25 degrees C, then frozen at -80 degrees C. The ECP concentrations were determined using fluoroimmunoassay and compared with the immediately frozen samples. After storing at 4 degrees C, the ECP levels at the four time points were 101.2, 96.0, 98.2 and 90.6% of the initial concentration, respectively. When sputum specimens were stored at 25 degrees C, ECP levels decreased to 96.1, 94.4, 90.7 and 87.7%, respectively. The influence of time on ECP concentrations in sputa was statistically significant (p=0.02). A significant temperature effect was found when comparing the specimens stored at 4 degrees C with those at 25 degrees C (p=0.03). Looking at individual time points, a significant decrease in ECP concentration was only seen at 25 degrees C after 24 and 72 h. We conclude that eosinophilic cationic protein in the sputum of asthmatics decreases in a time- and temperature-dependent process. If sputa cannot be processed after obtaining the specimens, they should be stored in a refrigerator at 4 degrees C, until eosinophilic cationic protein is measured.     

Experimental transplantation of size-reduced, adult kidneys into pediatric recipients

BACKGROUND: Renal transplantation in infants is frequently complicated by graft thrombosis and accelerated rejection reactions. We herein tested the hypothesis that the amount of blood required to sustain normal perfusion of an adult renal allograft transplanted into a pediatric recipient would surpass the cardiac output and aortic blood flow of the recipient and that the ensuing low flow in full-size grafts (FSG) would induce a release of thrombogenic substances. METHODS: In a porcine renal transplant model, adult FSG were transplanted into pediatric recipients. Macro- and microhemodynamic as well as metabolic data were recorded. Surgically size-reduced grafts (RSG) served as controls. RESULTS: Donor weight was 55.1+/-4.8 kg and 9.6+/-0.9 kg for recipients. FSG weight was 122+/-16 g and 65+/-14 g for RSG. Blood flow in donor kidneys was 20% higher than the infrarenal aortic blood flow of recipients. After reperfusion, mean arterial pressure in recipients of FSG but not RSG dropped to 64 mmHg, despite an increase in cardiac output by 60%. FSG but not RSG were polyuric and proteinuric. The release of endothelin and thromboxane B2 into the circulation was higher from FSG when compared with RSG (P<0.05 for endothelin after 60 min; NS for thromboxane B2). CONCLUSIONS: After transplantation of FSG into pediatric recipients, the macrohemodynamic limitations of the recipient cause microcirculatory disturbances in the graft, which contribute to the release of vasoconstrictive and prothrombotic substances and an impaired early graft function. Some of those effects can be ameliorated by surgically size reducing the renal graft.     

Frozen section evaluation of donor livers before transplantation

Frozen section examination was performed on 385 donor livers before transplantation. Exclusion criteria were applied to the donor livers examined to exclude potentially dysfunctional livers. The exclusion criteria included the following: severe macrovesicular steatosis, ischemic necrosis, prominent chronic portal inflammation, prominent periductular fibrosis, granulomatous inflammation, bridging fibrosis, and malignancy. Twenty-seven of the 385 donor livers examined were excluded before transplantation. The following histologic features were present in the excluded livers: severe steatosis (22), ischemic necrosis (2), portal inflammation (1), and periductular fibrosis (2). Steatosis was present in 51 of the 385 (13.25%) organs examined, including 22 of the donor organs excluded before transplantation. Twenty-nine livers with mild to moderate steatosis were implanted into size and blood type-matched recipients. Indicators of allograft function (prothrombin time and bilirubin) and damage (aspartate aminotransferase and alanine aminotransferase) were measured daily for the first 10 days after transplant. There was no statistically significant difference between the group of nonfat livers and donor livers containing mild steatosis. Statistically significant higher posttransplant serum alanine aminotransferase and prothrombin time levels were present in the patients with livers implanted with mild versus moderate steatosis. The 1-year survival rate for patients receiving fatty versus nonfatty donor livers was not statistically different (Kaplan-Meier, P = 0.592). No significant differences were found in the clinical and laboratory characteristics of donors whose organs were implanted compared with the clinical and laboratory characteristics of donors whose organs were excluded. The primary nonfunction rate after applying the exclusion criteria was 1.4%, which is a significant decrease compared with our primary nonfunction rate of 8.5% before using frozen section examination. Frozen section examination is useful in excluding donor organs which may become dysfunctional after transplantation.