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Allogeneic peripheral blood stem cell transplantation in patients with advanced hematologic malignancies: a retrospective comparison with marrow transplantation.

Allogeneic peripheral blood stem cell (PBSC) transplants from HLA-identical siblings were performed in 37 patients with advanced hematologic malignancies. Outcomes were compared to a historical group of 37 similar patients with advanced hematologic malignancies receiving bone marrow (BM) transplants from HLA-identical donors. The PBSC group and historical BM group were well matched for diagnosis, disease stage, age, and graft-versus-host disease (GVHD) prophylaxis. Patients received PBSC transplants between 1993 to 1995 while BM patients were treated between 1989 to 1994. Engraftment, measured by the time to reach a peripheral neutrophil count > 500/L and platelet count > 20,000/microL without transfusions, occurred on days 14 and 11 in the patients transplanted with PBSC compared to days 16 and 15 in the patients receiving BM (P = .00063, .00014). The PBSC group required a median of 8 U of red blood cells and 24 U of platelets compared to 17 U of red blood cells and 118 U of platelets for BM transplant recipients (P = .0005, .0001). The estimated risks of developing grades 2 to 4 acute GVHD were 37% for the PBSC group and 56% for the BM group (P = .18), while the estimated risks of grades 3 to 4 acute GVHD were 14% for the PBSC group and 33% for the BM group, P = .05). Chronic GVHD occurred in 7 of 18 evaluable patients receiving PBSC and 6 of 23 evaluable patients receiving BM, P = .5. The estimated risks of transplant-related mortality at 200 days were 27% versus 45% (P = .33) relapse were 70% versus 53% (P = .27) and of overall survival were 50% and 41% (P = .39) for patients transplanted with PBSC or BM, respectively. This retrospective comparison suggests that compared to marrow transplantation from HLA-identical donors, allogeneic PBSC transplantation from HLA-identical donors is associated with faster engraftment, fewer transfusions, and no greater incidence of acute or chronic GVHD.

Adult↗

[Allogenic bone marrow transplantation versus autograft in acute lymphoblastic leukemia, in second remission in 113 children. Results of the Grupo Español de Transplante de Medula Niños (GETMON)].

PURPOSE: Using the data from the GETMON ("Grupo Español de Trasplante de Medula Osea en Niños") we carried out a retrospective analysis of the results of allogeneic bone marrow transplantation (alloBMT) compared to autologous bone marrow transplantation (ABMT) in 113 paediatric patients with acute lymphoblastic leukaemia (ALL) in second remission. Transplants were performed by the following centers, from April 1983 to December 1991: H. Vall d'Hebrón and H. Sant Pau from Barcelona, H. Ramón y Cajal and H. Niño Jesús from Madrid and H. Marqués de Valdecilla from Santander. PATIENTS AND METHODS: The study included 113 patients between the ages of two and 16 years with ALL in second remission at marrow transplant. Fifty-six underwent alloBMT and 57 ABMT. Both groups were homogeneous with respect to age, sex, immunophenotype, duration of first remission, risk at diagnosis, percentage of early and late relapses, percentage with marrow or extramedullary relapse prior to transplant, time interval from attainment of second remission to transplant, and conditioning regimens applied for marrow transplant, with predominance of chemoradiotherapy in both. RESULTS: Haematologic recovery was observed to be faster in alloBMT than in ABMT. A granulocyte count > 0.5 x 10(9)/l was reached in alloBMT patients in a median of 19 days and in ABMT patients in a median of 25 days (p < 0.001). Early procedure-related death after ABMT occurred only in one patient (1.75%) and was caused by hepatic veno-occlusive disease. In the alloBMT group, the incidence was 25%. GVHD and infection were the most common causes. Actuarial DFS for alloBMT was 38.8 +/- 6.7% at 8.5 years versus 29.2 +/- 6.5% at 4.5 years for ABMT, p = NS. No significant differences of actuarial DFS were found between alloBMT or ABMT in patients according to leukocyte count and risk at diagnosis, neither with first remission duration, nor with remission duration at transplant. A separate analysis of actuarial DFS for each group shows that in ABMT group DFS was significantly greater in patients who had presented a late relapse (> 30 months) 61.1 +/- 13.8%, than those who had presented an early relapse (< 30 months) 18.3 +/- 6.5% (p < 0.005). Probability of relapse was significantly greater in ABMT (70%) compared to alloBMT (46%) (p < 0.025). Transplant offers a better DFS in extramedullary relapses compared to isolated or combined bone marrow relapses: 71.4 +/- 17.1% with alloBMT and 38.1 +/- 14.7% with ABMT (p = NS). CONCLUSIONS: In our experience we observed a better DFS with alloBMT compared with ABMT, overcoat in early relapses, but without significant difference. A higher relapse rate in ABMT group is partially compensated by more early deaths in alloBMT offers a few survival possibilities in patients with medullary relapses whose first remission lasted less than 30 months.

Adolescent↗

Diastolic dysfunction coincides with early mild transplant rejection: in situ measurements in a heterotopic rat heart transplant model.

BACKGROUND: Diastolic dysfunction seen in early clinical transplant rejection has been difficult to demonstrate in experimental rodent models because of the inability to make sensitive in situ measurements of systolic and diastolic functions. We have developed a heterotopic heart transplant model with Fisher 344 and ACI rats (without immunosuppression), where in situ measurements of diastolic and systolic functions were made sequentially (daily) by use of an implanted left ventricular balloon. METHODS: Syngeneic and allogeneic heterotopic heart transplants were performed. In situ function was determined by varying balloon volume to measure the developed pressure, the rates of pressure rise (+dp/dt) and pressure fall (-dp/dt), diastolic pressure-volume relationship, and the time constant of diastolic relaxation (tau). These results were compared with function measurements in transplanted hearts that were excised and perfused in a Langendorff mode (ex vivo) during the same posttransplantation period. RESULTS: Histologic examination revealed that at day 3 after transplantation, allografts showed mild lymphocytic infiltration indicative of mild or early rejection, and by day 5, there was severe rejection with myocyte necrosis. By day 3, the slope of the diastolic pressure-volume relationship (ie, left ventricular stiffness) was significantly higher in allografts as compared with isografts (436 +/- 96 vs 177 +/- 26 mm Hg/mL, p < .05). Similarly, tau was significantly longer in allografts by day 3 after transplantation. Developed pressure and +dp/dt became significantly lower in allografts beginning on day 6. Function measurements made in the isolated perfused ex vivo hearts yielded the same results at day 3 after transplantation as the in situ group of hearts. CONCLUSION: Using a chronically implanted left ventricular balloon, we have developed a heterotopic heart transplant model where sensitive measurements of systolic and diastolic functions can be made. With this preparation, the early changes in the diastolic dysfunction seen clinically can be reproducibly detected. Thus this model may be useful to study mechanisms and interventions during early transplant rejection.

Animals↗

Early and late invasive pneumococcal infection following stem cell transplantation: a European Bone Marrow Transplantation survey.

Streptococcus pneumoniae (S. pneumoniae) may cause severe and lethal infections months and years following stem cell transplantation (SCT). In a prospective survey over a 3.5-year period, we assessed the incidence, risk factors and outcome for invasive pneumococcal infection (IPI) following SCT. Fifty-one episodes of IPI were reported: 43 episodes after bone marrow transplantation (BMT) and 8 after peripheral blood stem cell transplantation (PBSCT); 35 after allogeneic SCT and 16 after autologous SCT. Seven IPI episodes, all bacteraemias, were defined as early, occurring 1-35 d (median 3 d) post transplantation. Forty-four episodes were defined as late (> or = 100 d post SCT), occurring 4 months to 10 years (median 17 months) post transplantation. The incidences of early and late IPI were 2.03/1000 and 8.63/1000 transplantations respectively (P = 0.001). A higher incidence of late IPI was observed after BMT than after PBSCT (10.99 versus 3.23/1000; P < 0.01) and after allogeneic versus autologous SCT (12.20 versus 4.60/1000; P < 0.01). There was a higher estimated incidence of IPI in allogeneic patients with than in those without graft-versus-host disease (GVHD) (18.85 versus 8.25/1000; P = 0.015). The mortality rate was 20%, including 2/7 of early and 8/44 of late IPI. S. pneumoniae is a rare but important complication during the aplastic phase after SCT. In conclusion, S. pneumoniae is a significant cause of morbidity late post-transplantation, especially in allogeneic patients, and particularly those with GVHD. The high IPI mortality rate, both early and late post-transplantation, requires preventive approaches, mainly effective immunization.

Adolescent↗

Results of transplanting developing third molars as part of orthodontics space management. Part 2: results following the orthodontic treatment of transplanted developing third molars in cases of aplasia and premature loss of teeth with atrophy of the alveolar process.

MATERIAL AND METHODS: The aim of this study was to assess the effects of atrophy of the alveolar process and subsequent orthodontic treatment on the transplantation results of developing third molars. The material consisted of 35 teeth transplanted to an atrophied alveolar process. 19 of these teeth were treated orthodontically subsequent to transplantation. The control group consisted of 61 developing molars transplanted to a new extraction socket. The transplanted teeth were followed up clinically and radiographically for a mean period of 3.2 years. RESULTS: The success rate was 85% for transplants to new extraction sockets and 84% for transplants to atrophied jaw sections with subsequent orthodontic treatment. In contrast, transplants to atrophied jaw sections without subsequent orthodontic treatment showed a significantly (p < or = 0.001) lower success rate of only 37.5%. These poorer results were due to persistent infraocclusion and ankylosis. CONCLUSIONS: Even in cases with atrophy of the alveolar process, a transplantation with subsequent orthodontic treatment represents a promising treatment concept, whereas teeth without subsequent orthodontic treatment showed a lower success rate. Orthodontic tooth movement had no negative effect on the healing rates of transplanted developing third molars.

Adolescent↗

Neural transplantation in the spinal cord of adult rats. Conditions, survival, cytology and connectivity of the transplants.

Embryonic neural tissues of various types were transplanted into the intact, completely transected, and partially transected spinal cords of adult rats. The host animals were killed 4-6 months after the surgery, and the spinal cords and transplants examined. The best results were obtained when embryonic neocortical tissues obtained from 16-day rat embryos were used for transplantation into host animals that had been subjected to partial sectioning of the spinal cord. Use of other types of neural tissue, or transplantation of tissues into the intact or completely severed spinal cords was not successful. The successful neocortical transplants had survived, grown, differentiated, and established anatomical integration with the host spinal cords. The anatomical integration was established through an interface with the host spinal cord along the basal aspect. Along the lateral aspect glial scar tissue was present separating the transplants from the spinal cord parenchyma. The transplants contained well-differentiated and normal-looking neurons. They received afferents from the spinal cord only through the interface and not through the glial scar formations. The findings indicated that it is possible to transplant embryonic neocortical tissues into the spinal cords of the adult animals that become integrated with the spinal cord parenchyma. The axonal fibers in the adult spinal cord appear capable of regeneration and growing into the transplants only when an appropriate neural milieu, in the form of a healthy and viable interface, is available. In its absence the severed axons of the adult spinal cord do not grow into the neural transplants.

Animals↗

Long-term peritoneal dialysis before transplantation and intra-abdominal infection after simultaneous pancreas-kidney transplantations.

OBJECTIVE: To investigate whether long-term peritoneal dialysis before transplantation entails a higher risk than hemodialysis for intra-abdominal infection after bladder-drained simultaneous pancreas-kidney transplantations. DESIGN: Large single-center case-control study. SETTING: A large university hospital (referral center). PATIENTS: In all, 189 bladder-drained simultaneous pancreas-kidney transplantations were done from January 1, 1986, to December 31, 1994: before transplantations were performed, 32 recipients (17%) were undergoing peritoneal dialysis, 71 recipients (38%) were undergoing hemodialysis, and 86 recipients (46) were not undergoing dialysis. MAIN OUTCOME MEASURES: The intra-abdominal infection rate after transplantation and the rate of graft loss due to infection. RESULTS: Intra-abdominal infections developed in 33 recipients (18%) after transplantation. Graft and patient survival rates were significantly lower for recipients with vs without an infection (P < .001 for both). Both the dialysis mode and dialysis dependence did not affect the infection rate: of the 33 recipients with an infection, 7 (21%) were undergoing peritoneal dialysis, 15 (46%) were undergoing hemodialysis, and 11 (33%) were not undergoing dialysis before transplantation (P = .3). The rate of graft loss due to infection was not significantly different for recipients who were undergoing peritoneal dialysis vs hemodialysis (P = .1). However, it was higher for recipients who were undergoing dialysis (peritoneal dialysis and hemodialysis) vs those patients who were not undergoing dialysis (P = .04). CONCLUSIONS: Candidates for simultaneous pancreas-kidney transplantation should undergo the transplantation preemptively (ie, before they become dependent on dialysis) because the rate of graft loss due to infection was higher for recipients who were undergoing dialysis (irrespective of the dialysis mode). If dialysis cannot be avoided, the choice of peritoneal dialysis vs hemodialysis can be individualized, since these dialysis modes do not have significantly different rates of infection or of graft loss due to infection.

Adult↗

A comparison of the patterns of migration and the destinations of homotopically transplanted neonatal subventricular zone cells and heterotopically transplanted telencephalic ventricular zone cells.

The cells arising in the anterior part of the subventricular zone (SVZa) migrate along a well-demarcated pathway which lacks radial glial fibers to the olfactory bulb where they differentiate into interneurons of the granule cell layer or glomerular layer (Luskin, 1993, Neuron 11, 173). To analyze the mechanisms underlying this highly directed migration, we have compared the migratory behavior of unmanipulated SVZa-derived cells to that of homotopically transplanted SVZa cells and of heterotopically transplanted telencephalic ventricular zone (VZ) cells that ordinarily migrate in association with radial glial fibers. To identify the phenotype of the SVZa progenitor cells prior to their transplantation, we characterized them in vitro using cell type-specific markers. After 1 day in culture nearly all the SVZa cells were stained with TuJ1, a neuron-specific marker; only an occasional cell exhibited a glial phenotype as judged by the presence of GFAP-immunoreactivity. This indicates that SVZa cells express a neuronal phenotype. To reveal the spatiotemporal distribution of homotopically transplanted neonatal SVZa cells in a host brain, dissociated SVZa cells from Postnatal Day 0 (P0)-P2 animals were labeled with the lipophilic dye PKH26 or the cell proliferation marker BrdU and implanted into the SVZa of host animals of the same age. Within the first week after transplantation there were vast numbers of labeled cells throughout the pathway. Over the next 2 weeks the labeled cells migrated into the overlying cellular layer of the olfactory bulb and began to differentiate, and within 4 weeks the transplanted cells had reached their final positions in the granule cell and glomerular layers of the olfactory bulb in the same proportions as for unmanipulated SVZa-derived cells. While en route to the olfactory bulb the homotopically transplanted cells never strayed from the migratory pathway. In contrast, heterotopically transplanted VZ cells from the embryonic telencephalon did not undergo migration although they did differentiate. These results demonstrate that the homotopically transplanted SVZa-derived cells adopt a mode of migration indistinguishable from that ordinarily utilized by SVZa-derived neurons and that the VZ cells are unable to decipher the same set of guidance cues.

Animals↗

Attitudes of donors towards organ transplantation in living related kidney transplantations.

The demand for transplantation exceeds the availability of cadaveric organs, which is why the importance of living, related kidney transplantation is increasing. In our study we wanted to evaluate the experiences of living related donors (LRD). Between 1973 and 1996, 1325 kidney transplantations were performed at our Department. Of these 1247 were from cadaver donors while 78 were from LRD. We contacted each living donor by post. We carried out a physical examination, laboratory tests, ultrasound and isotope investigations and they were interviewed and completed a questionnaire. Thirty previous kidney donors came to our Department who were all blood relatives of the recipients. In the recipient group, 16 still have a functioning kidney, the average time since transplantation being 8.92 years. The longest kidney survival time is 18 years. All the donors willingly donated their kidney, none was worried about their own health and their only concern was whether the kidney would function or not. Regarding general attitudes towards living related organ transplantation, all were in favour of blood relative donor transplantation and also husband/wife transplantation. Opinions regarding non-related transplantation were more mixed; 63.3% would have given their kidneys to a friend, only 46.6% to a stranger. Almost two-thirds (63.3%) of donors were not in favour of selling and buying organs but, controversially, they would have bought an organ had one been available. All agreed that the donation did not change their general health. In conclusion, the donors of living, related kidney transplantation all agreed that it was a good thing to donate; All confirmed they would go through the same procedure again in order to help. Apart from one person, who emphasised that he is agnostic, all belonged to a Christian religion.

Adolescent↗

Subcutaneous, isogeneic transplantation of duct-ligated pancreas in streptozotocin diabetic mice: relationships between recovery and hormone contents in transplants or host pancreas.

Recovery from diabetes was observed in streptozotocin-treated mice that received subcutaneous, isogeneic transplants of duct-ligated pancreas. Transplants excised from recovered hosts contained both immunoreactive insulin (IRI) and glucagon (IRG), indicating that both A and B cells capable of hormone storage were present. The IRI content in transplants, although only one sixth of that transplanted 6 wk earlier, was still 21/2 times greater than that in the host pancreas and was inversely related to the plasma glucose of the recipient during and after recovery. The IRI content in the transplant added to that in the host pancreas totaled 13% of the IRI found in the normal mouse pancreas, which sufficed for over-all recovery from diabetes but was insufficient to provide normal glucose tolerance and insulin response to a major glucose challenge. The abnormally high content of glucagon noted in the pancreas of hyperglycemic, sham transplanted mice was reduced by one-half in the pancreas of those transplanted mice returning to normal plasma glucose and insulin. Thus, the insulin content of the transplant was important to the recovery of isografted mice, but in addition, and perhaps as a consequence of recovery, there was a slight increase in the insulin storage capacity of the host pancreas and a marked reduction of glucagon compared to the content of these hormones in the pancreas of hyperglycemic, sham transplanted mice.

Animals↗

Survival after liver transplantation in patients with hepatic iron overload: the national hemochromatosis transplant registry.

BACKGROUND & AIMS: Previous uncontrolled studies have suggested that patients with hepatic iron overload have a poor outcome after liver transplantation. We examined the effect of HFE mutations on posttransplantation survival in patients with hepatic iron overload. METHODS: Two hundred sixty patients with end-stage liver disease and hepatic iron overload were enrolled from 12 liver transplantation centers. Hepatic iron concentration (HIC), hepatic iron index (HII), HFE mutation status, and survival after liver transplantation were recorded. RESULTS: HFE-associated hemochromatosis (HH) defined as homozygosity for the C282Y (n = 14, 7.2%) mutation or compound heterozygosity for the C282Y/H63D (n = 11, 5.6%) mutation was identified in 12.8% of patients. Survival postliver transplantation was significantly lower among patients with HH (1-, 3-, and 5-year survival rates of 64%, 48%, 34%, respectively) compared with simple heterozygotes (C282Y/wt or H63D/wt) or wild-type patients. Patients with HH had a hazard ratio for death of 2.6 (P = .002) after adjustment for age, United Network for Organ Sharing status, year of transplantation, and either elevated HII or HIC. Non-HH patients with hepatic iron overload also had significantly decreased survival when compared with the overall population undergoing liver transplantation (OR = 1.4, 95% CI: 1.15-1.61, P < .001). CONCLUSIONS: One- and 5-year survivals after liver transplantation are significantly lower among patients with HFE-associated HH. Our data also suggest that hepatic iron overload may be associated with decreased survival after liver transplantation, even in patients without HH. Early diagnosis of hepatic iron overload using HFE gene testing and iron depletion prior to liver transplantation may improve posttransplantation survival, particularly among patients with HH.

Adult↗

Should we consider excessive weights in pediatric kidney transplant recepient candidates?: A systematic review and meta-analysis of kidney transplantation outcomes.

INTRODUCTION: In adult populations, excess body weight has been associated with an increased risk of adverse clinical outcomes and mortality following kidney transplantation. In contrast, the influence of obesity on transplantation outcomes among pediatric populations is not yet fully understood. This study aimed to evaluate the association between pre-transplant excess weight and post-transplant outcomes in pediatric kidney transplant recipients. MATERIAL & METHODS: A systematic literature search was performed across PubMed, ScienceDirect, and the Cochrane Library, covering publications up to December 31, 2025. The quality of the included studies was evaluated using the ROBINS-E tool. Statistical analysis was conducted using Review Manager version 5.4. RESULTS: From a total of 1465 records screened, six studies that included 65,483 participants were selected in the meta-analysis. The results indicated that pre-transplant excess weight was significantly associated with an increased risk of acute rejection (OR = 1.09; P = 0.009), delayed graft function (OR = 1.17; P < 0.00001), 1-year graft failure (OR = 1.16; P = 0.0002), and 5-year graft failure (OR = 1.13; P = 0.009). Although 5-year mortality was also higher among recipients with excess weight, this association was not statistically significant (OR = 1.08; P = 0.11). CONCLUSION: Pediatric patients with pre-transplant excess weight had higher post-transplant odds of acute rejection, delayed graft function, and both 1-year and 5-year graft failure compared to those without excess weight. These findings highlight the importance of assessing and managing excess weight prior to kidney transplantation to help prevent adverse outcomes in the future.

Humans↗

Renal transplantation in diabetic patients is confirmed therapy while pancreas transplantation should be performed only in an investigational setting.

Kidney transplantation is now firmly established as the standard treatment for all diabetic patients with end-stage renal failure. In an analysis of all renal transplants at the University of Minnesota between June 1, 1980 and May 31, 1987, there were no differences in renal allograft functional survival rates for diabetic and nondiabetic recipients. At one year the survival rates were 84% (n = 151) and 86% (n = 260) for those treated with azathioprine, prednisone and ALG; 86% (n = 101) and 87% (n = 104) for those treated with cyclosporine-prednisone, and 92% (n = 165) and 89% (n = 191) for those treated with triple therapy (cyclosporine, azathioprine, and prednisone). Pancreas transplantation remains an investigational procedure for nonuremic diabetic patients but may be considered therapeutic in diabetic renal allograft recipients because such patients are obligated to immunosuppression and only the surgical risks of pancreas transplantation need to be considered, which are now acceptably low. Recipients of pancreas transplants performed simultaneous with the kidney have patient and pancreas graft survival rates of greater than 90% and +/- 60% at several institutions, including our own. The potential for benefit of pancreas transplantation, however, is greater in the nonuremic nonkidney transplant patient, and pancreas transplantations are being performed in such patients at a few institutions. An early beneficial effect of pancreas transplantation preexisting proliferative retinopathy has not been discerned, although long-term retinopathy has been stable in patients with functioning grafts. Preliminary studies have shown a beneficial effect on neuropathy and on microscopic lesions of diabetic nephropathy, but at the expense of cyclosporine toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 1↗

Increasing transplant mass results in long-term allograft survival and recovery from transplant vasculopathy.

Late allograft rejection due to transplant vasculopathy continues to be a major clinical problem. Increasing the ratio of donor transplant size to recipient weight has been shown to reduce the incidence of late allograft failure. Using a murine pancreas transplant model we have tested the hypothesis that increasing the donor transplant size in a recipient can promote long-term allograft survival by promoting recovery from transplant vasculopathy. Recipients of an allograft that showed extensive vasculopathy were transplanted with a second donor transplant. The effect of the second allograft on the vasculopathy present in the first graft was measured. Transplanting a second allograft reversed all signs of ongoing rejection, including transplant vasculopathy, resulting in long-term survival of the first graft. Vasculopathy was only reversed if the first and second grafts were from the same mouse strain, suggesting an antigen-specific mechanism. However, the recovery of the first graft was not associated with antigen-specific peripheral tolerance.

Animals↗

Short-term effects of calcium antagonists on hemodynamics and cyclosporine pharmacokinetics in heart-transplant and kidney-transplant patients.

Effects of two calcium antagonists on hemodynamics and on cyclosporine pharmacokinetics were studied in eight transplant patients (four heart-transplant and four kidney-transplant patients) by use of a single-blind, randomized, crossover, and placebo-controlled design. Patients received, at least 1 week apart, either 90 mg diltiazem, 20 mg nifedipine (in tablet form), or placebo, given 1 hour before cyclosporine. Cyclosporine and its main metabolite (metabolite 17) were measured in plasma (separated at 25 degrees C) by use of HPLC. Both calcium antagonists tended to increase absorption rate and elimination rate, but none of the pharmacokinetic parameters of cyclosporine were significantly altered. Moreover, the area under the curve of plasma concentrations of metabolite 17 did not change. On the other hand, both nifedipine and diltiazem significantly altered the hemodynamics, but to a different extent in the two groups of patients. The heart-transplant patients showed larger decreases in systolic and diastolic blood pressure than the kidney-transplant patients after administration of both nifedipine and diltiazem, but they showed smaller increases in cardiac index and heart rate with nifedipine. In contrast, diltiazem caused small decreases in heart rate and cardiac index in heart-transplant patients and small increases in heart rate and cardiac index in kidney-transplant patients. We conclude that a single dose of either nifedipine or diltiazem does not affect, to a clinically significant extent, the pharmacokinetics of cyclosporine. In addition, heart-transplant patients show different hemodynamic responses to these two calcium antagonists than the responses shown by kidney-transplant patients, probably because of cardiac denervation.

Absorption↗

Delayed or delayed sequential bone marrow transplantation: relevance for acute graft-versus-host disease prevention after major H2 incompatible transplantation.

During this study, BalB/C mice were used as recipients and C57 bl/6 mice as donors. Recipients were given 800 cGys of total body irradiation (TBI) on day 0. Transplantation was carried out as follows: group (1): TBI on day 0; group (2): TBI on day 0 and transplantation on day +1; group (3): TBI on day 0 and transplantation on day 4; group (4): TBI on day 0 and transplantation started from day 4 through day 8. Mice that received TBI only died by day 11. All group 2 mice developed aGVHD and died by day +15. In total, 70% of group 3 were still surviving by day 60 (P<0.001, compared to day +1 transplantation). Survival rates were 90% at day 60 for group 4 (P<0.001 compared to day 1 transplantation). No survival advantage was found between animals transplanted on day 4 and animals with delayed sequential transplantation (P=0.1). Significant engraftment was found in both groups 3 and 4, with no significant differences in the percentages of donor-derived cells between the two groups (P>0.05). These data demonstrate that either delayed or delayed sequential transplantation after TBI can be an effective approach for aGVHD prevention.

Animals↗

Second early allogeneic stem cell transplantations for graft failure in acute leukaemia, chronic myeloid leukaemia and aplastic anaemia. French Society of Bone Marrow Transplantation.

In this retrospective multicentre study, we analysed the results of 82 consecutive second early allogeneic transplants for primary (n = 28) or secondary ([n = 54) graft failures performed between 1985 and 1997 in patients with acute leukaemia (n = 33), aplastic anaemia (n = 29) or chronic myeloid leukaemia (n = 20). HLA-matched siblings were used in 64 cases. The same donors were used for both transplants in 56 cases and the first transplant was T-cell depleted in 30 cases. The median age at transplant was 25 years and the median intertransplant time interval was 2 months. Estimates of the 3-year overall survival and day 100 transplant-related mortality were 30% and 53% respectively. A recipient age < 34 years at transplant, an intertransplant time interval > or = 80 d and a positive recipient cytomegalovirus serology were predictors of a better outcome. The use of cyclosporin A (CsA) after second transplant had a dramatic impact on outcome, the best results being observed with CsA alone. The day 40 probability of neutrophil recovery was 73%. The use of peripheral blood progenitor cells (PBPCs) was associated with a higher and faster neutrophil recovery. Other factors associated with neutrophil recovery were an intertransplant time interval > or = 80 d and a positive recipient cytomegalovirus serology. Therefore, second early allogeneic transplantation for graft failure is an effective treatment, especially if patients can receive CsA for graft-versus-host disease prevention and are retransplanted more than 80 d from first transplant.

Adolescent↗

Variability in standard care for cytomegalovirus prevention and detection in pediatric lung transplantation: survey of eight pediatric lung transplant programs.

Cytomegalovirus (CMV) infection after pediatric lung transplantation is a significant risk factor for morbidity and mortality in the first year after transplantation. Multiple strategies have been reported for CMV prevention among adult lung transplant programs. In contrast, little information has been reported regarding protocols for prevention and detection of CMV from pediatric programs. We conducted a survey to better understand the range of practice patterns for CMV prevention and detection at pediatric lung transplant centers. A self-administered questionnaire was distributed to 11 pediatric lung transplant centers identified through the International Pediatric Lung Transplant Collaborative in September 2002. A member of the lung transplant team from each institution was asked to provide the methods of CMV prevention and surveillance. Eight of 11 centers surveyed responded to the questionnaire accounting for 45.6% (26 of 57) and 100% (three of three) of the pediatric lung transplants performed in the US and UK in 2001, respectively. All centers used prophylactic therapy against CMV with either ganciclovir or valganciclovir with duration ranging from 3.5 wk to indefinitely. Most centers (six of eight) prescribed a prophylactic regimen based on donor and recipient CMV serostatus. Half (four of eight) of the centers report using CMV hyperimmune globulin in addition to an antiviral agent. Method for CMV detection varied widely, including use of conventional viral culture (n = 1), antigenemia (n = 7), and polymerase chain reaction (n = 2). A wide range of strategies is used to prevent and detect CMV in pediatric lung transplant recipients with little empiric evidence demonstrating the optimal approach. A retrospective analysis among these centers is being conducted to evaluate the efficacy of these approaches.

Antiviral Agents↗