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See detailImpact of co-transplantation of mesenchymal stem cells on lung function after unrelated allogeneic hematopoietic stem cell transplantation following non-myeloablative conditioning
MOERMANS, Catherine ULg; LECHANTEUR, Chantal ULg; BAUDOUX, Etienne ULg et al

in Transplantation (2014), 98(3), 348-353

Background: In the context of hematopoietic stem cell transplantation (HSCT), mesenchymal stem cells (MSC) have been used to promote engraftment and prevent graft- versus-host-disease. However, in animal ... [more ▼]

Background: In the context of hematopoietic stem cell transplantation (HSCT), mesenchymal stem cells (MSC) have been used to promote engraftment and prevent graft- versus-host-disease. However, in animal models, MSC were shown to cause pulmonary alterations after systemic administration. The impact of MSC infusion on lung function has not been studied in humans. The objective of the study was to investigate the impact of MSC co-infusion on lung function and airway inflammation as well as on the incidence of pulmonary infections and cytomegalovirus (CMV) reactivation after HSCT. Methods: We have prospectively followed 30 patients who underwent unrelated HSCT with MSC co-infusion after non-myeloablative conditioning (NMA). Each patient underwent detailed lung function testing (FEV1, FVC, FEV1/FVC, RV, TLC, DLCO and KCO) and measurement of exhaled nitric oxide before HSCT and 3, 6 and 12 months posttransplant. The incidence of pulmonary infections and CMV reactivation were also monitored. This group was compared with another group of 28 patients who underwent the same type of transplantation but without MSC co-infusion. Results: Lung function tests did not show important modifications over time and did not differ between the MSC and control groups. There was a higher 1-year incidence of infection, particularly of fungal infections, in patients having received a MSC co-infusion. There was no difference between groups regarding the 1-year incidence of CMV reactivation. Conclusions: MSC co-infusion does not induce pulmonary deterioration 1 year after HSCT with NMA conditioning. MSC appear to be safe for the lung but close monitoring of pulmonary infections remains essential. [less ▲]

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See detailMesenchymal Stem Cells in Solid Organ Transplantation (MiSOT) Fourth Meeting: Lessons Learned from First Clinical Trials.
Franquesa, Marcella; Hoogduijn, Martin J.; Reinders, Marlies E. et al

in Transplantation (2013), 96(3), 234-238

The Fourth Expert Meeting of the Mesenchymal Stem Cells in Solid Organ Transplantation (MiSOT) Consortium took place in Barcelona on October 19 and 20, 2012. This meeting focused on the translation of ... [more ▼]

The Fourth Expert Meeting of the Mesenchymal Stem Cells in Solid Organ Transplantation (MiSOT) Consortium took place in Barcelona on October 19 and 20, 2012. This meeting focused on the translation of preclinical data into early clinical settings. This position paper highlights the main topics explored on the safety and efficacy of mesenchymal stem cells as a therapeutic agent in solid organ transplantation and emphasizes the issues (proper timing, concomitant immunossupression, source and immunogenicity of mesenchymal stem cells, and oncogenicity) that have been addressed and will be followed up by the MiSOT Consortium in future studies. [less ▲]

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See detailMDRD Versus CKD_EPI equation to estimate glomerular filtration rate in kidney transplant recipients
masson, Ingrid; Flamant, Martin; Maillard, Nicolas et al

in Transplantation (2013), 95(10),

Background. The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based equation was developed to address the systematic underestimation of the glomerular filtration rate (GFR) by ... [more ▼]

Background. The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based equation was developed to address the systematic underestimation of the glomerular filtration rate (GFR) by the Modification of Diet in Renal Disease (MDRD) Study equation in patients with a relatively well-preserved kidney function. The performance of the new equation for kidney transplant recipients is discussed. Methods. We analyzed the performances of the CKD-EPI equation in comparison with the MDRD Study equation in 825 stable kidney transplant recipients. Bias, precision, and accuracy within 30% of true GFR were determined. GFR was measured by urinary clearance of inulin (n=488) and plasma clearance of 51Cr-EDTA (n=337). Results. Mean measured GFR (mGFR) was 50T19 mL/min/1.73 m2. On the whole cohort, bias was significantly lower for MDRD Study equation compared with CKD-EPI creatinine. This superiority translates into a better accuracy (80% and 74% for the MDRD and CKD-EPI creatinine, respectively). The best performance of the MDRD Study equation is confirmed both in the subgroups of patients with mGFR G60 mL/min/1.73 m2 and between 60 and 90 mL/min/1.73 m2. For mGFR 990 mL/min/1.73 m2, there were no significant differences between the two equations in terms of performance. Conclusions. The CKD-EPI creatinine equation does not offer a better GFR prediction in renal transplant patients compared with the MDRD Study equation, even in the earlier CKD stages. [less ▲]

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See detailMDRD versus CKD-EPI equation to estimate glomerular filtration rate in kidney transplant recipients
Masson, Ingrid; Flamant, Martin; Maillard, Nicolas et al

in Transplantation (2013), 95(10), 1211-1217

Background. The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based equation was developed to address the systematic underestimation of the glomerular filtration rate (GFR) by ... [more ▼]

Background. The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based equation was developed to address the systematic underestimation of the glomerular filtration rate (GFR) by the Modification of Diet in Renal Disease (MDRD) Study equation in patients with a relatively well-preserved kidney function. The performance of the new equation for kidney transplant recipients is discussed. Methods. We analyzed the performances of the CKD-EPI equation in comparison with the MDRD Study equation in 825 stable kidney transplant recipients. Bias, precision, and accuracy within 30% of true GFR were determined. GFR was measured by urinary clearance of inulin (n=488) and plasma clearance of 51Cr-EDTA (n=337). Results. Mean measured GFR (mGFR) was 50T19 mL/min/1.73 m2. On the whole cohort, bias was significantly lower for MDRD Study equation compared with CKD-EPI creatinine. This superiority translates into a better accuracy (80% and 74% for the MDRD and CKD-EPI creatinine, respectively). The best performance of the MDRD Study equation is confirmed both in the subgroups of patients with mGFR G60 mL/min/1.73 m2 and between 60 and 90 mL/min/1.73 m2. For mGFR 990 mL/min/1.73 m2, there were no significant differences between the two equations in terms of performance. Conclusions. The CKD-EPI creatinine equation does not offer a better GFR prediction in renal transplant patients compared with the MDRD Study equation, even in the earlier CKD stages. [less ▲]

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See detailIsoform 111 of vascular endothelial growth factor (VEGF111) improves angiogenesis of ovarian tissue xenotransplantation
Labied, Soraya ULg; Delforge, Yves ULg; Munaut, Carine ULg et al

in Transplantation (2013), 95(3), 426-433

Background: Cryopreservation of cortex ovarian tissue before anti-cancer therapy is a promising technique for fertility preservation mainly in children and young women. Ischemia in the early stage after ... [more ▼]

Background: Cryopreservation of cortex ovarian tissue before anti-cancer therapy is a promising technique for fertility preservation mainly in children and young women. Ischemia in the early stage after ovarian graft causes massive follicle loss by apoptosis. VEGF111 is a recently described VEGF isoform that does not bind to the extracellular matrix, diffuse extensively and is resistant to proteolysis. These properties confer a significantly higher angiogenic potential to VEGF111 in comparison to the other VEGF isoforms. Methods: We evaluated the morphology of cryopreserved sheep ovarian cortex, grafted in the presence or absence of VEGF111. Ovarian cortex biopsies were embedded in type I collagen with or without VEGF111 addition before transplantation to SCID mice ovaries. Transplants were retrieved 3 days or 3 weeks later. Follicular density, vasculature network, haemoglobin content and cell proliferation were analysed. Results: Addition of VEGF111 increased density of functional capillaries (p=0.01) 3 days after grafting. By double immunostaining of Ki-67 and von Willebrand Factor (vWF) we demonstrated that proliferating endothelial cells were found in 83% of the VEGF111 group when compared to 33% in the control group (p=0.001). This angio-stimulation was associated with a significant enhancement of haemoglobin content (p=0.03). Three weeks after transplantation, the number of primary follicles was significantly higher in VEGF111 grafts (p=0.02). Conclusion: VEGF111 accelerates blood vessels recruitment, functional angiogenesis and improves the viability of ovarian cortex by limiting ischemia and ovarian cortex damage. [less ▲]

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See detailWhat is the potential increase of the heart graft pool by cardiac donation after circulatory death?
NOTERDAEME, Timothée; NELLESSEN, Eric ULg; HANS, Marie-France ULg et al

in Transplantation (2012, November), 94

Background: Heart transplantation remains to date the only definite treatment option for end-stage heart diseases. Currently only heart procured from brain death (DBD) donors are used. Combined with an ... [more ▼]

Background: Heart transplantation remains to date the only definite treatment option for end-stage heart diseases. Currently only heart procured from brain death (DBD) donors are used. Combined with an increasing demand, the constant heart graft shortage leads to an increase of deaths on cardiac transplantation waiting lists. The use of hearts procured after donation after circulatory death (DCD) could help to partly decrease the heart graft shortage. The aim of this study was to evaluate the potential increase of heart graft pool by development of DCD heart transplantation. Methods: The authors retrospectively reviewed their local donor database for the period 2006-2011, and screened the complete controlled DCD donor population for potential heart donors, using the same criteria as for DBD heart transplantation. The acceptable warm ischemic time (WIT) was limited to 30min from life support withdrawal to aortic cannulation. Results: During the analyzed timespan, 177 DBD and 70 DCD were effectively performed. From the 177 DBD, a total of 70 (39.5%) hearts were procured and transplanted locally or in another center. Out of the 70 DCD, 8 (11%) donors fulfilled the criteria for heart graft procurement and had a WIT of less than 30 minutes. During the same period, 82 patients were newly listed for heart transplantation, of which 53 were transplanted, 20 died or were unlisted, and 9 were still awaiting transplantation. Conclusions: Based on our database and a WIT of less than 30min, it could be estimated that 11% of the DCD might be heart graft donors, representing a 11% increase in heart graft procurement, as well as potential reduction of the deaths on the waiting list by 40%. [less ▲]

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See detailTacrolimus-Based, Steroid-Free Regimens in Renal Transplantation: 3-year Follow-up of the ATLAS Trial
Krämer, Bernhard k; Klinger, Marian; Vitko, Stefan et al

in Transplantation (2012), 94(5), 492-498

Background. Long-term use of corticosteroids is associated with considerable morbidity, including cardiovascular and metabolic adverse effects. Methods. This study evaluated the long-term efficacy and ... [more ▼]

Background. Long-term use of corticosteroids is associated with considerable morbidity, including cardiovascular and metabolic adverse effects. Methods. This study evaluated the long-term efficacy and safety of two steroid-free regimens compared with a triple immunosuppressive therapy in renal transplant recipients. This was a 3-year follow-up to a 6-month, open-label, randomized, multicenter study. Results. Data from 3 years were available for 421 (93.3%) of 451 patients in the original intent-to-treat population (143 tacrolimus/basiliximab [Tac/Bas], 139 tacrolimus/mycophenolate mofetil [Tac/MMF], and 139 tacrolimus/MMF/ [less ▲]

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See detailThe value of machine perfusion perfusate biomakers for predicting kidney transplant outcome
Moers, Cyril; Varnay, Oana C; Van Heurn, Ernest et al

in Transplantation (2010), 90

Background. Retrospective evidence suggests that lactate dehydrogenase, aspartate aminotransferase, total glutathione-S-transferase (GST), alanine-aminopeptidase, N-acetyl- -D-glucosaminidase (NAG), and ... [more ▼]

Background. Retrospective evidence suggests that lactate dehydrogenase, aspartate aminotransferase, total glutathione-S-transferase (GST), alanine-aminopeptidase, N-acetyl- -D-glucosaminidase (NAG), and hearttype fatty acid binding protein (H-FABP) measured during kidney machine perfusion (MP) could have predictive value for posttransplant outcome. However, these data may be biased due to organ discard based on biomarker measurements, and previous analyses were not adjusted for likely confounding factors.Noreliable prospective evidence has been available so far. Nevertheless, some centers already use these biomarkers to aid decisions on accepting or discarding a donor kidney. Methods. From 306 deceased-donor kidneys donated after brain death or controlled cardiac death and included in an international randomized controlled trial, these six biomarkers were measured in the MP perfusate. In this unselected prospective data set, we tested whether concentrations were associated with delayed graft function, primary nonfunction, and graft survival. Multivariate regression models investigated whether the biomarkers remained independent predictors when adjusted for relevant confounding factors. Results. GST, NAG, and H-FABP were independent predictors of delayed graft function but not of primary nonfunction and graft survival. Lactate dehydrogenase, aspartate aminotransferase, and alanine-aminopeptidase had no independent prognostic potential for any of the endpoints. Perfusate biomarker concentrations had no relevant correlation with cold ischemic time or renal vascular resistance on the pump. Conclusions. Increased GST, NAG, or H-FABP concentrations during MP are an indication to adjust posttransplant recipient management. However, this study shows for the first time that perfusate biomarker measurements should not lead to kidney discard. Keywords: Machine perfusion, Kidney transplantation, Perfusate biomarkers, Delayed graft function, Graft survival [less ▲]

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See detailPolyomavirus in Renal Transplantation: A Hot Problem
Bonvoisin, Catherine ULg; Weekers, Laurent ULg; Xhignesse, Patricia ULg et al

in Transplantation (2008), 85(7S), 42-48

Polyomavirus BK has emerged as an important complication after kidney transplantation. Although, BK nephropathy develops in only1%to5%of renal transplant recipients, its prognosis when present is very ... [more ▼]

Polyomavirus BK has emerged as an important complication after kidney transplantation. Although, BK nephropathy develops in only1%to5%of renal transplant recipients, its prognosis when present is very poor. The most accepted risk factor is the level of immunosuppressive treatment, but the serostatus of donor and recipient and the absence of human leukocyte antigen C7 in donor and/or recipient influence the BK virus (BKV) reactivation. The gold standard in diagnosing BKV nephropathy (BKVN) continues to be biopsy with use of immunohistochemistry for large T antigens. Urinary decoy cells and blood BKV DNA polymerase chain reaction are used in the screening, but their positive predictive values are poor. However, their use as predictors of the evolution of BKVN is more valuable. The reduction of immunosuppressive therapy currently represents the first-line treatment for BKVN. Cidofovir and leflunomide can be used when BKVN continues to progress. In the event of graft loss, retransplantation is possible with a low risk of recurrence when the infection is no longer active. [less ▲]

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See detailIntensified postgrafting immunosuppression failed to assure long-term engraftment of dog leukocyte antigen-identical canine marrow grafts after 1 gray total body irradiation.
Sorror, Mohamed L; Leisenring, Wendy; Mielcarek, Marco et al

in Transplantation (2008), 85(7), 1023-9

BACKGROUND: Late graft rejection after conditioning with 1 Gy of total body irradiation (TBI) was consistently seen in historical dogs given two postgrafting immunosuppressive drugs. METHODS: Here, 16 ... [more ▼]

BACKGROUND: Late graft rejection after conditioning with 1 Gy of total body irradiation (TBI) was consistently seen in historical dogs given two postgrafting immunosuppressive drugs. METHODS: Here, 16 dogs were given four different three-drug combinations of cyclosporine, mycophenolate mofetil, sirolimus, or methotrexate after 1 Gy TBI and dog leukocyte antigen-identical marrow grafts. In addition, we assessed the effects of TBI doses of 0.5, 1.0, 2.0, or 3.0 Gy, respectively, on immune functions in six dogs not given marrow grafts. RESULTS: All dogs showed initial engraftment, 13 rejected, and three had sustained grafts beyond 26 weeks. The dogs with durable grafts had received greater median numbers of nucleated marrow cells compared with the 13 dogs that rejected their grafts (6.14 vs. 3.6 x 10(8) per kg; P=0.03). In a Cox proportional hazard model, which included data from 16 historical dogs, each increase in transplanted marrow cell numbers by 1 x 10(8) per kg decreased the hazard ratio of rejection by 0.5. Decreasing percents of remaining CD3, CD4, and CD8 cells in peripheral blood and lymph nodes were observed with increasing TBI doses. Further, greater suppressions of B-cell- and T-cell-dependent production of IgM and IgG antibodies in response to sheep red blood cell injections were observed after 2 Gy compared with 1 Gy TBI. CONCLUSION: Overall, triple postgrafting immunosuppression after 1 Gy TBI was well tolerated but failed to prevent graft rejection in this model. In vivo radiation studies have shown higher numbers of remaining host lymphocytes and better T-cell-dependent antibody production after 1 Gy compared with 2 Gy TBI. [less ▲]

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See detailPancreas graft drainage in recipient duodenum: Preliminary experience
De Roover, Arnaud ULg; Coimbra Marques, Carla ULg; Detry, Olivier ULg et al

in Transplantation (2007), 84(6), 795-797

Pancreas graft survival has continuously improved over the years to become a main treatment option of uncontrolled complicated diabetes. Rejection remains the major challenge as it often goes unnoticed ... [more ▼]

Pancreas graft survival has continuously improved over the years to become a main treatment option of uncontrolled complicated diabetes. Rejection remains the major challenge as it often goes unnoticed until severe damage of the graft manifests itself by elevated blood sugar. Pancreas enzymes monitoring in the blood and in the urine is a sensitive marker of rejection but lack of specificity. Biopsy remains the gold standard. Cystoscopy-guided biopsy of bladder-drained pancreas has a good success rate for obtaining tissue but the vesical drainage exposes to metabolic and urologic morbidity. Percutaneous pancreas biopsy can be performed with a low morbidity rate but severe complications can occur. We discuss a technique of pancreas transplantation with the drainage of exocrine secretions of the pancreatic graft in the recipient duodenum, which permits easy monitoring of the graft by upper endoscopy of the duodenum. [less ▲]

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See detailIs cystatin C useful for the detection and the estimation of low glomerular filtration rate in heart transplant patients?
Delanaye, Pierre ULg; Nellessen, Eric ULg; Cavalier, Etienne ULg et al

in Transplantation (2007), 83(5), 641-644

Although previously studied in patients with chronic kidney disease, there is less data for the use of cystatin C and cystatin C-based formulas in heart transplant recipients. The ability of creatinine ... [more ▼]

Although previously studied in patients with chronic kidney disease, there is less data for the use of cystatin C and cystatin C-based formulas in heart transplant recipients. The ability of creatinine and cystatin C to detect renal failure (glomerular filtration rate [GFR] below 60 mL/min/1.73 m(2)) in heart transplant patients has been compared. The accuracy and precision of a creatinine-based formula (Modification of Diet in Renal Disease [MDRD]) versus a cystatin C-based formula (Rule's formula) to estimate GFR have also been studied. GFR was measured using the (51)Crethylenediamine tetraacetic acid tracer in 27 patients. There was no significant difference between GFR and the reciprocal of creatinine or cystatin C. Receiver operating characteristic curves for cystatin C and creatinine were similar. Both formulas were well correlated with the GFR. The bias of the cystatin C-based was significantly better than one of the MDRD formula, but the standard deviation appeared better for the MDRD formula (bias of +3.9 mL/min/1.73 m(2) versus +12 mL/min/1.73 m(2) and SD of 8.5 versus 11.6, respectively). Plasma cystatin C has no clear advantage over serum creatinine to detect renal failure in heart transplanted patients. [less ▲]

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See detailExtending postgrafting cyclosporine decreases the risk of severe graft-versus-host disease after nonmyeloablative hematopoietic cell transplantation
Burroughs, Lauri; Mielcarek, Marco; Leisenring, Wendy et al

in Transplantation (2006), 81(6), 818-25

BACKGROUND: It is unknown whether the duration of systemic immunosuppressive treatment after allogeneic nonmyeloablative hematopoietic cell transplantation (HCT) might influence the incidence, severity ... [more ▼]

BACKGROUND: It is unknown whether the duration of systemic immunosuppressive treatment after allogeneic nonmyeloablative hematopoietic cell transplantation (HCT) might influence the incidence, severity, timing, and/or corticosteroid-responsiveness of graft-versus-host disease (GVHD). METHODS: We retrospectively analyzed outcomes among 185 patients with hematologic malignancies who were given grafts from HLA-matched related donors following conditioning with 2 Gy total body irradiation alone or in combination with fludarabine between December 1998 and March 2003. Postgrafting immunosuppression consisted of mycophenolate mofetil (days 0-27) in combination with 3 different cyclosporine (CSP) regimens: taper from (A) days 35 to 56 (n=107), (B) days 56 to 77 (n=35), and (C) days 56 to 180 (n=43). RESULTS: The overall incidences of grades II-IV and III-IV acute GVHD, and extensive chronic GVHD were 52%, 13%, and 56%, respectively. The duration of CSP prophylaxis did not significantly influence the overall rate of acute GVHD (grade II-IV), extensive chronic GVHD, or non-relapse mortality. However, prolonged administration of CSP (group C) was associated with a significantly decreased hazard of grades III-IV acute GVHD (HR 0.2, 95% CI [0.04, 0.9]) and with an increased likelihood of discontinuing all systemic immunosuppression (HR 2.4, 95% CI [1.1, 5.2]) when compared to the shortest course of CSP (group A). CONCLUSION: Longer CSP duration decreased the risk of severe GVHD and increased the likelihood of discontinuing all systemic immunosuppression after nonmyeloablative HCT with HLA-matched related grafts. [less ▲]

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See detailT-cell reconstitution after unmanipulated, CD8-depleted or CD34-selected nonmyeloablative peripheral blood stem-cell transplantation.
Baron, Frédéric ULg; Schaaf-Lafontaine, Nicole ULg; Humblet-Baron, Stéphanie ULg et al

in Transplantation (2003), 76(12), 1705-13

BACKGROUND: We have previously shown that CD8 depletion or CD34 selection of peripheral blood stem cells (PBSC) reduced the incidence of acute graft-versus-host disease (GvHD) after nonmyeloablative stem ... [more ▼]

BACKGROUND: We have previously shown that CD8 depletion or CD34 selection of peripheral blood stem cells (PBSC) reduced the incidence of acute graft-versus-host disease (GvHD) after nonmyeloablative stem-cell transplantation (NMSCT). In this study, we analyze the effect of CD8 depletion or CD34 selection of the graft on early T-cell reconstitution. METHODS: Nonmyeloablative conditioning regimen consisted in 2 Gy total-body irradiation (TBI) alone, 2 Gy TBI and fludarabine, or cyclophosphamide and fludarabine. Patients 1 to 18 received unmanipulated PBSC, patients 19 to 29 CD8-depleted PBSC, and patients 30 to 35 CD34-selected PBSC. RESULTS: T-cell counts, and particularly CD4+ and CD4CD45RA+ counts, remained low the first 6 months after nonmyeloablative stem-cell transplantation (NMSCT) in all patients. CD34 selection (P<0.0001) but not CD8 depletion of PBSC significantly decreased T-cell chimerism. Donor T-cell count was similar in unmanipulated compared with CD8-depleted PBSC recipients but was significantly lower in CD34-selected PBSC recipients (P=0.0012). T cells of recipient origin remained stable over time in unmanipulated and CD8-depleted PBSC patients but expanded in some CD34-selected PBSC recipients between day 28 and 100 after transplant. Moreover, whereas CD8 depletion only decreased CD8+ counts (P<0.047), CD34 selection reduced CD3+(P<0.001), CD8+(P<0.016), CD4+ (P<0.001), and CD4+CD45RA+ (P<0.001) cell counts. T-cell repertoire was restricted in all patients on day 100 after hematopoietic stem-cell transplantation but was even more limited after CD34 selection (P=0.002). CONCLUSIONS: Despite of the persistence of a significant number of T cells of recipient origin, T-cell counts were low the first 6 months after NMSCT. Moreover, contrary with CD8 depletion of the graft that only affects CD8+ lymphocyte counts, CD34 selection dramatically decreased both CD8 and CD4 counts. [less ▲]

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See detailErythropoiesis after nonmyeloablative stem-cell transplantation is not impaired by inadequate erythropoietin production as observed after conventional allogeneic transplantation.
Baron, Frédéric ULg; Fillet, Georges ULg; Beguin, Yves ULg

in Transplantation (2002), 74(12), 1692-6

BACKGROUND: It is now well established that after conventional allogeneic hematopoietic stem-cell transplantation (HSCT), erythropoietic recovery is impaired because erythropoietin (Epo) production ... [more ▼]

BACKGROUND: It is now well established that after conventional allogeneic hematopoietic stem-cell transplantation (HSCT), erythropoietic recovery is impaired because erythropoietin (Epo) production remains inadequate for prolonged periods of time. However, erythropoietic reconstitution after nonmyeloablative SCT (NMSCT) has never been characterized. METHODS: Twelve patients received a nonmyeloablative conditioning regimen consisting of 2 Gy total body irradiation (TBI) alone (n=6), 2 Gy TBI and fludarabine (n=3), or cyclophosphamide and fludarabine (n=3), followed by transplantation of allogeneic peripheral blood stem cells. Graft-versus-host-disease (GvHD) prophylaxis was carried out with mycophenolate mofetil (from day -1 to day 28) plus cyclosporine (from day -1 to day 120 or longer in case of chronic GvHD). Erythropoiesis was quantitated by soluble transferrin receptor (sTfR) levels, and the adequacy of Epo production was evaluated by the observed-to-predicted Epo ratio (O/P Epo). RESULTS: Mean sTfR levels decreased following the conditioning regimen but remained well within the normal range throughout the posttransplant period. The O/P Epo ratio presented an initial surge quite similar to that observed after conventional conditioning. Thereafter, the O/P Epo ratio normalized rapidly, and Epo levels remained adequate during the whole observation period. CONCLUSION: Contrarily to what is observed after myeloablative transplant, Epo levels remained adequate after NMSCT, resulting in normal erythropoiesis. These results suggest that the administration of erythropoietin therapy (rHuEpo) could be less effective after NMSCT than after conventional allogeneic transplant. [less ▲]

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See detailOrgan donors with primary central nervous system tumor
Detry, Olivier ULg; Honore, Pierre ULg; Hans, Marie-France ULg et al

in Transplantation (2000), 70(1), 244-8251-2

Patients with primary central nervous system (CNS) tumor have been accepted for organ donation because these tumors very rarely spread outside the CNS. However several case reports of CNS tumor ... [more ▼]

Patients with primary central nervous system (CNS) tumor have been accepted for organ donation because these tumors very rarely spread outside the CNS. However several case reports of CNS tumor transferral with organ transplantation recently challenged this attitude. Some risk factors for extraneural spread of CNS tumors have been determined, but the absence of risk factors does not exclude the possibility of metastases. To our knowledge, 13 cases of CNS tumor transferral with organ transplantation (one heart, three livers, eight kidneys, one kidney/pancreas) have been reported in the literature. Even if no prospective evaluation of the CNS tumor transmission risk with transplantation has been undergone, this risk may be estimated between a little more than 0% and 3% from retrospective series. The authors consider that patients with CNS tumor should be accepted as donors as long as the risk of dying on the waiting lists is significantly higher than the tumor transferral risk. Therefore the authors would have no restriction for transplanting organs from donors with benign or low-grade CNS tumor. For high-grade tumors, the authors would consider these donors as "marginal donors," and balance the risk of tumor transmission with the medical condition of the recipient. [less ▲]

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See detailEffects of cold and warm ischemia on the mitochondrial oxidative phosphorylation of swine lung.
Willet, Katty; Detry, Olivier ULg; Lambermont, Bernard ULg et al

in Transplantation (2000), 69(4), 582-588

BACKGROUND: The aim of the study was to investigate the consequence of warm and cold ischemia on lung mitochondria in order to define bioenergetic limits within lung could be suitable for pulmonary ... [more ▼]

BACKGROUND: The aim of the study was to investigate the consequence of warm and cold ischemia on lung mitochondria in order to define bioenergetic limits within lung could be suitable for pulmonary transplantation. METHODS: Twenty-two pigs underwent lung harvesting after lung flush with Euro-Collins solution. Mitochondria were isolated from fresh lungs, from lungs submitted to 24 or 48 hr of cold ischemia, to 30 or 45 min of warm ischemia, and to 30 min of warm ischemia followed by 24 or 48 hr of cold ischemia. Mitochondrial oxidative phosphorylation parameters were determined in isolated mitochondria by in vitro measurement of oxygen consumption. RESULTS: Relative to controls, mitochondria submitted to cold ischemia showed an alteration in the oxidoreductase activities of the respiratory chain but no membrane permeability alteration. After 48 hr of cold ischemia, there was a decrease in the yield of the oxidative phosphorylation. Thirty minutes of warm ischemia did not alter the mitochondrial respiratory parameters. However, lung submitted to 45 min of warm ischemia showed mitochondrial damage as a decrease in the oxidative phosphorylation efficiency and ADP availability but no change in the oxidoreductase activities. Relative to cold ischemia alone, 30 min of warm ischemia preceding cold ischemia promoted no significant change in the respiratory parameters. CONCLUSIONS: On bioenergetic basis, lung submitted to warm ischemia could be suitable for transplantation if the warm ischemia duration does not exceed 30 min. This could be a major concern in lung procurement from non-heart beating donors. [less ▲]

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See detailIntracranial pressure during liver transplantation for fulminant hepatic failure.
Detry, Olivier ULg; Arkadopoulos, N.; Ting, P. et al

in Transplantation (1999), 67(5), 767-70

During orthotopic liver transplantation (OLT) for fulminant hepatic failure (FHF), some patients develop cerebral injury secondary to intracranial hypertension. We monitored intracranial pressure (ICP ... [more ▼]

During orthotopic liver transplantation (OLT) for fulminant hepatic failure (FHF), some patients develop cerebral injury secondary to intracranial hypertension. We monitored intracranial pressure (ICP) and cerebral perfusion pressure (CPP) before and during OLT in 12 FHF patients undergoing transplantation. All four patients who had normal ICP preoperatively maintained normal ICP/CPP throughout OLT. During OLT, four of the eight patients with pretransplant intracranial hypertension had six episodes of ICP increase. These episodes of intracranial hypertension occurred during failing liver dissection (n=3) and graft reperfusion (n=3). At the end of the anhepatic phase, the ICP was lower than the preoperative ICP in all patients, and was below 15 mmHg in all but one patient. These data suggest that in FHF patients who develop intracranial hypertension before OLT, dissection of the native liver and graft reperfusion are associated with a risk of brain injury resulting from intracranial hypertension and cerebral hypoperfusion. [less ▲]

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