Among organ transplant recipients there is a world wide increase in the number of de novo tumors ... more Among organ transplant recipients there is a world wide increase in the number of de novo tumors as well as a decrease in the time of the first appearance after the transplantation. Between 1973 and the 31th of August 1999 1709 cadaver renal allograft transplantations were perfomed in our Department. Four thyroid cancers were detected among the renal transplanted patients. Two of them proved to be papillary microcarcinomas. Although the elevated risk of thyroid cancers is well established in the literature pap-illary microcarcinomas have never been reported before in an immunosuppressed patient. Authors highlight that the thyroid gland should always be carefully checked in organ transplant recipients, since better survival might be achieve even in the immunosuppressed population. Metastatic tumor is relatively benign which is in correlation with the literature, but there has been little experience in organ transplanted patients so far.
Journal of the American Society of Nephrology, 2001
This study correlated the dynamic effects of sirolimus (rapamycin; RAPA) and cyclosporine (CsA) a... more This study correlated the dynamic effects of sirolimus (rapamycin; RAPA) and cyclosporine (CsA) alone versus in combination to produce renal dysfunction, myelosuppression, or hyperlipidemia, with their corresponding blood and tissue concentrations. After salt-depleted rats were treated with RAPA (0.4 to 6.4 mg/kg per d) and/or CsA (2.5 to 20.0 mg/kg per d) for 14 d, the GFR, lipid levels, bone marrow cellularity, and CsA/RAPA concentrations in whole blood versus liver or renal tissues were measured, and the median effect model was used to discern the type of drug interactions. Compared with vehicle controls (1.98 Ϯ 0.34 ml/min), GFR values were reduced only by large doses of drug monotherapy, namely RAPA (3.2 mg/kg per d ϭ 1.2 Ϯ 0.02 ml/min or 6.4 mg/kg per d ϭ 1.3 Ϯ 0.2 ml/min; both P Ͻ 0.01) or CsA (10.0 mg/kg per d ϭ 1.2 Ϯ 0.1 ml/min or 20.0 mg/kg per d ϭ 0.8 Ϯ 0.4 ml/min; both P Ͻ 0.01). In contrast, hosts that were treated with smaller
Introduction: Cholangiocarcinoma (CCA) is an aggressive malignancy that only recently has been su... more Introduction: Cholangiocarcinoma (CCA) is an aggressive malignancy that only recently has been successfully treated by liver transplant with the development of pre-transplant chemoradiation protocols. The purpose of this study was to investigate the factors associated with recurrence and survival of patients with incidentally discovered cholangiocarcinoma (CCA) after liver transplant. Methods: 1078 patients underwent liver transplant at our institution from 2003 to 2013. 13 were found to have the unexpected diagnosis of CCA on liver explant based on their pre-operative history and imaging. We investigated the relevance of clinical, pathologic and laboratory parameters on the recurrence of the tumor. Results: The most common diagnoses were HCV (46.2%), and PSC (30.8%). 9(69.2%) patients had a tumor demonstrated on pre-transplant imaging, size ranged from a 0.7 to 3.3 cm diameter. 8 of these lesions were initially diagnosed as hepatocellular carcinoma (HCC) based on their radiologic characteristics, 5 underwent locoregional treatment prior to transplant. None of the patients had pretransplant biopsies of their lesions. 4 (30.8%) patients had a mixed histology (HCC/ CCA). The overall recurrence rate was 46.2% and median time to recurrence was 8.1 months in patients treated with locoregional vs. 9.4 months in patients who did not receive locoregional therapy pre-transplant (p=NS). 83.3% of these recurrences were extrahepatic, with lung being the most frequent site of recurrence (50%). 66.6% of patients with moderate to poorly differentiated tumors recurred compared to 0% recurrence in the well-differentiated group (p=0.026). The median recurrence free survival with well-differentiated histology was 51.8 months vs. 10.1 months (p<0.05) for patients with poor or moderately differentiated CCA. Conclusion: Incidentally discovered CCA carries a poor prognosis with a high a rate of recurrence and poor survival. Locoregional treatment does not decrease incidence of, or time to recurrence. Not surprisingly moderate to poorly differentiated tumors are associated with high rates of recurrence and high mortality. However, welldifferentiated tumors had no incidence of recurrence in this group with excellent long-term survival. This could have important implications for patients diagnosed prior to transplant. These fi ndings reinforce the need for multicenter studies that could incorporate a greater number of patients.
The projected adult population growth in the US from 2014-2023 will be 8.1%. However, we project ... more The projected adult population growth in the US from 2014-2023 will be 8.1%. However, we project there will be a 4.6% increase in the number of available donors and a 5.4% increase in the number of utilized liver grafts. The overall US adult population growth will outpace the growth of available donor organs, thus likely exacerbating the existing liver graft shortage. Strategies to increase organ availability are warranted in order to alleviate this shortage and prevent waitlist dropout.
Introduction. Kidney transplant patients with acute rejection episodes refractory to antilymphocy... more Introduction. Kidney transplant patients with acute rejection episodes refractory to antilymphocyte preparations require aggressive treatment to salvage renal function and reduce the progression of chronic allograft nephropathy. Patients and methods. During a 6-month period, we administered Campath-1H as salvage therapy to five patients who had been previously treated with thymoglobulin and/or OKT3. In addition to measurements of the serum creatinine and BUN levels, we estimated creatinine clearance and glomerular filtration rates (GFR) using the Cockcroft-Gault and the MDRD equations at the time of initiation of therapy as well as at 2 weeks and 2 months thereafter. Result. Four of the five patients responded to Campath-1H therapy; kidney function improved to nearly the level before the rejection episode. The estimated creatinine clearance increased approximately threefold and the GFR approximately fourfold higher than the values before Campath-1H administration. The adverse events were mild and self-limited. Conclusion. Salvage of refractory acute rejection episodes may be possible in selected patients using Campath-1H.
Aim. To evaluate the outcome of single pediatric kidneys transplanted into adult recipients. Meth... more Aim. To evaluate the outcome of single pediatric kidneys transplanted into adult recipients. Methods. A retrospective single-center review was performed of transplants from donors less than 5 years of age. Outcomes were compared with recipients of grafts from donors 18 to 45 years transplanted during the same time period. Results. Thirty single renal transplants from pediatric donors and 117 transplants from adult donors between 18 and 45 years of age were performed during the study period. The mean age of the pediatric donors was 2.9 Ϯ 0.8 years versus 31.5 Ϯ 8.9 years for adult donors (P Ͻ .001). The mean age of the recipients of pediatric donors was 41.9 Ϯ 13 years versus 48 Ϯ 12.6 years for recipients of adult grafts (P ϭ .020). The mean recipient weight of pediatric donors was 55.9 Ϯ 7.8 kg versus 78.0 Ϯ 17.7 kg for recipients of adult donors (P Ͻ .001). Sixty-six percent of pediatric donor recipients were of female gender compared to only 36% of adult donor recipients (P ϭ .005). Death-censored actuarial graft survivals at 1 and 4 years for recipients of pediatric donor grafts were 90% and 85% compared to 93% and 85% for recipients of adult donor grafts (P ϭ NS). The mean calculated creatinine clearances of adult donor graft recipients at 1 and 4 years posttransplantation were 70.8 Ϯ 26.5 and 73.7 Ϯ 27.2 mL/min, respectively, compared to 50.3 Ϯ 20.1 and 56.3 Ϯ 21.4 mL/min for pediatric donor grafts (P Ͻ .01 at 1 and 4 years). Conclusion. The use of single pediatric donor kidneys provides an excellent opportunity to safely expand the donor pool.
Background. We sought to determine whether pancreas transplantation reduced the incidence of peri... more Background. We sought to determine whether pancreas transplantation reduced the incidence of peripheral vascular complications in diabetics with renal insufficiency. Methods. A retrospective single-center review was done of 36 kidney-pancreas (KP) and 88 kidney-alone (KA) recipients with a diagnosis of diabetes and end-stage renal disease (ESRD) transplanted between May 1997 and July 2002. Risk factors studied included type of transplant, age, gender, history of smoking, coronary artery disease, hypertension, and peripheral vascular disease (PVD). The endpoint was first peripheral vascular event occurring after transplantation, defined as either an amputation or revascularization procedure. Results. The mean age of the cohort was 51 Ϯ 9 years, 64% of patients were of male gender, 20% with a history of smoking, 98% with hypertension, 15% with coronary artery disease (CAD), and 12% with a history of PVD. With a median follow-up of 45 months (12 to 79 months), 3/36 (8%) of KP recipients suffered a PVD complication, compared to 10/88 (11%) of KA recipients (P ϭ NS). Similarly, age, gender, a past history of smoking, CAD, and hypertension were not predictive of PVD complications. Five of 15 patients (33%) with a pretransplant history of PVD suffered a postoperative PVD event compared to only 8 of 109 patients (7%) with no prior history of PVD (P ϭ .008). Conclusions. Restoration of normoglycemia by pancreas transplantation did not reduce the risk of PVD complications in diabetics with renal failure. A pretransplant history of PVD was the only risk factor associated with posttransplant PVD events.
Aims. To determine outcomes utilizing thymoglobulin and sirolimus immunosuppression, with early s... more Aims. To determine outcomes utilizing thymoglobulin and sirolimus immunosuppression, with early steroid withdrawal in low-immune responder pancreas-kidney (SPK) recipients, and conversion from cyclosporine (CsA) to mycophenolic acid (MPA) in all recipients at 6 months posttransplantation. Methods. SPK recipients received thymoglobulin, sirolimus, and reduced-dose CsA immunosuppression. Low immune responders (non-African-Americans with a pretransplant PRA Ͻ 30%) were withdrawn from prednisone on posttransplant day 5 and high immune responders were continued on prednisone. All recipients were converted from CsA to MPA at 6 months posttransplantation. During conversion, recipient immune response was monitored by flow PRA and a T-cell stimulation assay (Cylex). Results. With a mean follow-up of 9 Ϯ 4 months, one pancreas was lost to pancreatitis, with no patient or kidney losses and no acute rejection episodes. All eight low immune responder patients were steroid-free at 9 Ϯ 5 months posttransplantation. Seven patients (five low and two high immune responders) with at least 6-month follow-up were converted from CsA to MPA. One high immune responder with a pretransplant PRA of 43% remained with a PRA of 53% Ϯ 2% postconversion. The second high immune responder had a pretransplant PRA of 34% and a postconversion PRA of 0%. The five low immune responders had a mean pretransplant PRA of 16% Ϯ 15% and a postconversion PRA of 0% (P Ͻ .01). The Cylex assay resulted in 67% low responsiveness for both high and low immune responders. Conclusion. Thymoglobulin induction with sirolimus maintenance therapy permitted immunosuppression minimization in selected pancreas transplant recipients. Posttransplant evaluation revealed a diminished (regulated) immune response in six of seven patients.
Introduction. African-American renal transplant recipients are prone to acute rejection episodes ... more Introduction. African-American renal transplant recipients are prone to acute rejection episodes and graft loss owing to genetic, pharmacokinetic, cultural, and socioeconomic factors. While more intense exposures to antirejection agents can mitigate this propensity, heightened immunosuppressive regimens are accompanied by an array of toxicities. Our study sought to examine the impact of a combination of sirolimus (SRL) and cyclosporine (CsA) on the outcomes of African-Americans vs Caucasians. Materials and Methods. The outcomes of African-Americans treated with either CsA-prednisone (Pred, n ϭ 90) or SRL-CsA-Pred (n ϭ 86) were compared with 148 SRL-CsA-Pred-treated Caucasians. Results. The addition of SRL to a CsA-Pred regimen reduced the rate of acute rejection episodes within 2 years in African-Americans from 43.3% to 17% (P ϭ .004), a value similar to that observed in Caucasian patients (18%). At 2 years, the graft survival rate of 79% among African-American patients treated with SRL-CsA-Pred was similar to that in the Caucasian cohort (80%). The respective patient survival rates also were similar: 93% and 90%, respectively. Multivariate analysis of 5-year outcomes among patients treated with SRL-CsA-Pred revealed the hazard ratios of African-Americans vs Caucasians to actually be reduced for acute rejection (.22; P ϭ .01) and for death (.15; P ϭ .01), but similar for chronic rejection (.77; P ϭ NS) and graft loss (1.03; P ϭ NS). Conclusion. The use of SRL-based regimens mitigated the otherwise enhanced risk for acute rejection episodes or graft loss otherwise experienced by CsA-treated African-American renal transplant recipients.
Background. Our objective was to determine the impact of thymoglobulin-sirolimuscyclosporine immu... more Background. Our objective was to determine the impact of thymoglobulin-sirolimuscyclosporine immunosuppression on the alloimune response of pancreas-kidney transplant recipients. Methods. Thirty-six pancreas transplant recipients received an induction protocol of thymoglobulin, sirolimus, reduced-dose cyclosporine, and corticosteroids. A subset of 10 recipients were also enrolled in a study to measure immune responsiveness. Flow PRA-determined HLA antibody, donor-specific flow cytometry crossmatching (FCXM), T-cell subset, and suppressor cell assays were performed at various timepoints during the first posttransplant year. Results. One-year patient, kidney, and pancreas survivals were 97%, 94%, and 92%, respectively. There was 1 death due to sepsis, and 1 kidney and 2 pancreas graft losses. There were no acute rejection episodes. Recipients in the immune-monitoring study displayed depression of CD3, CD4, and CD8 counts (Ͻ80%) until 3 months posttransplant. At transplantation, 9 of 10 patients displayed Ͻ10% class I HLA antibody. By 3 months, 7 of 10 showed a transient elevation in class I HLA antibodies, with 2 patients expressing Ͼ80% flow PRA. At transplant 1 patient was FCXM-positive, whereas, by 3 months posttransplant, 2 of 10 patients demonstrated a positive FCXM. There were no clinical consequences to either the presence of HLA antibody or the positive FCXMs. By 6 months, 7 of 9 patients expressed immunoregulatory suppressor cell activity. Conclusions. The absence of acute rejection events was likely due to inhibition of donor-specific immunity. Seventy percent of patients demonstrated an early non-donordirected HLA antibody response that had no adverse effect on graft function and 78% of the patients displayed immunoregulatory suppressor cell function, probably contributing to the successful clinical outcome. MATERIALS AND METHODS Study Design This prospective study included 31 simultaneous pancreas-kidney (SPK), 3 pancreas after kidney (PAK), and 2 pancreas-alone (PA) transplant recipients receiving induction immunosuppression con-From the
Among organ transplant recipients there is a world wide increase in the number of de novo tumors ... more Among organ transplant recipients there is a world wide increase in the number of de novo tumors as well as a decrease in the time of the first appearance after the transplantation. Between 1973 and the 31th of August 1999 1709 cadaver renal allograft transplantations were perfomed in our Department. Four thyroid cancers were detected among the renal transplanted patients. Two of them proved to be papillary microcarcinomas. Although the elevated risk of thyroid cancers is well established in the literature pap-illary microcarcinomas have never been reported before in an immunosuppressed patient. Authors highlight that the thyroid gland should always be carefully checked in organ transplant recipients, since better survival might be achieve even in the immunosuppressed population. Metastatic tumor is relatively benign which is in correlation with the literature, but there has been little experience in organ transplanted patients so far.
Journal of the American Society of Nephrology, 2001
This study correlated the dynamic effects of sirolimus (rapamycin; RAPA) and cyclosporine (CsA) a... more This study correlated the dynamic effects of sirolimus (rapamycin; RAPA) and cyclosporine (CsA) alone versus in combination to produce renal dysfunction, myelosuppression, or hyperlipidemia, with their corresponding blood and tissue concentrations. After salt-depleted rats were treated with RAPA (0.4 to 6.4 mg/kg per d) and/or CsA (2.5 to 20.0 mg/kg per d) for 14 d, the GFR, lipid levels, bone marrow cellularity, and CsA/RAPA concentrations in whole blood versus liver or renal tissues were measured, and the median effect model was used to discern the type of drug interactions. Compared with vehicle controls (1.98 Ϯ 0.34 ml/min), GFR values were reduced only by large doses of drug monotherapy, namely RAPA (3.2 mg/kg per d ϭ 1.2 Ϯ 0.02 ml/min or 6.4 mg/kg per d ϭ 1.3 Ϯ 0.2 ml/min; both P Ͻ 0.01) or CsA (10.0 mg/kg per d ϭ 1.2 Ϯ 0.1 ml/min or 20.0 mg/kg per d ϭ 0.8 Ϯ 0.4 ml/min; both P Ͻ 0.01). In contrast, hosts that were treated with smaller
Introduction: Cholangiocarcinoma (CCA) is an aggressive malignancy that only recently has been su... more Introduction: Cholangiocarcinoma (CCA) is an aggressive malignancy that only recently has been successfully treated by liver transplant with the development of pre-transplant chemoradiation protocols. The purpose of this study was to investigate the factors associated with recurrence and survival of patients with incidentally discovered cholangiocarcinoma (CCA) after liver transplant. Methods: 1078 patients underwent liver transplant at our institution from 2003 to 2013. 13 were found to have the unexpected diagnosis of CCA on liver explant based on their pre-operative history and imaging. We investigated the relevance of clinical, pathologic and laboratory parameters on the recurrence of the tumor. Results: The most common diagnoses were HCV (46.2%), and PSC (30.8%). 9(69.2%) patients had a tumor demonstrated on pre-transplant imaging, size ranged from a 0.7 to 3.3 cm diameter. 8 of these lesions were initially diagnosed as hepatocellular carcinoma (HCC) based on their radiologic characteristics, 5 underwent locoregional treatment prior to transplant. None of the patients had pretransplant biopsies of their lesions. 4 (30.8%) patients had a mixed histology (HCC/ CCA). The overall recurrence rate was 46.2% and median time to recurrence was 8.1 months in patients treated with locoregional vs. 9.4 months in patients who did not receive locoregional therapy pre-transplant (p=NS). 83.3% of these recurrences were extrahepatic, with lung being the most frequent site of recurrence (50%). 66.6% of patients with moderate to poorly differentiated tumors recurred compared to 0% recurrence in the well-differentiated group (p=0.026). The median recurrence free survival with well-differentiated histology was 51.8 months vs. 10.1 months (p<0.05) for patients with poor or moderately differentiated CCA. Conclusion: Incidentally discovered CCA carries a poor prognosis with a high a rate of recurrence and poor survival. Locoregional treatment does not decrease incidence of, or time to recurrence. Not surprisingly moderate to poorly differentiated tumors are associated with high rates of recurrence and high mortality. However, welldifferentiated tumors had no incidence of recurrence in this group with excellent long-term survival. This could have important implications for patients diagnosed prior to transplant. These fi ndings reinforce the need for multicenter studies that could incorporate a greater number of patients.
The projected adult population growth in the US from 2014-2023 will be 8.1%. However, we project ... more The projected adult population growth in the US from 2014-2023 will be 8.1%. However, we project there will be a 4.6% increase in the number of available donors and a 5.4% increase in the number of utilized liver grafts. The overall US adult population growth will outpace the growth of available donor organs, thus likely exacerbating the existing liver graft shortage. Strategies to increase organ availability are warranted in order to alleviate this shortage and prevent waitlist dropout.
Introduction. Kidney transplant patients with acute rejection episodes refractory to antilymphocy... more Introduction. Kidney transplant patients with acute rejection episodes refractory to antilymphocyte preparations require aggressive treatment to salvage renal function and reduce the progression of chronic allograft nephropathy. Patients and methods. During a 6-month period, we administered Campath-1H as salvage therapy to five patients who had been previously treated with thymoglobulin and/or OKT3. In addition to measurements of the serum creatinine and BUN levels, we estimated creatinine clearance and glomerular filtration rates (GFR) using the Cockcroft-Gault and the MDRD equations at the time of initiation of therapy as well as at 2 weeks and 2 months thereafter. Result. Four of the five patients responded to Campath-1H therapy; kidney function improved to nearly the level before the rejection episode. The estimated creatinine clearance increased approximately threefold and the GFR approximately fourfold higher than the values before Campath-1H administration. The adverse events were mild and self-limited. Conclusion. Salvage of refractory acute rejection episodes may be possible in selected patients using Campath-1H.
Aim. To evaluate the outcome of single pediatric kidneys transplanted into adult recipients. Meth... more Aim. To evaluate the outcome of single pediatric kidneys transplanted into adult recipients. Methods. A retrospective single-center review was performed of transplants from donors less than 5 years of age. Outcomes were compared with recipients of grafts from donors 18 to 45 years transplanted during the same time period. Results. Thirty single renal transplants from pediatric donors and 117 transplants from adult donors between 18 and 45 years of age were performed during the study period. The mean age of the pediatric donors was 2.9 Ϯ 0.8 years versus 31.5 Ϯ 8.9 years for adult donors (P Ͻ .001). The mean age of the recipients of pediatric donors was 41.9 Ϯ 13 years versus 48 Ϯ 12.6 years for recipients of adult grafts (P ϭ .020). The mean recipient weight of pediatric donors was 55.9 Ϯ 7.8 kg versus 78.0 Ϯ 17.7 kg for recipients of adult donors (P Ͻ .001). Sixty-six percent of pediatric donor recipients were of female gender compared to only 36% of adult donor recipients (P ϭ .005). Death-censored actuarial graft survivals at 1 and 4 years for recipients of pediatric donor grafts were 90% and 85% compared to 93% and 85% for recipients of adult donor grafts (P ϭ NS). The mean calculated creatinine clearances of adult donor graft recipients at 1 and 4 years posttransplantation were 70.8 Ϯ 26.5 and 73.7 Ϯ 27.2 mL/min, respectively, compared to 50.3 Ϯ 20.1 and 56.3 Ϯ 21.4 mL/min for pediatric donor grafts (P Ͻ .01 at 1 and 4 years). Conclusion. The use of single pediatric donor kidneys provides an excellent opportunity to safely expand the donor pool.
Background. We sought to determine whether pancreas transplantation reduced the incidence of peri... more Background. We sought to determine whether pancreas transplantation reduced the incidence of peripheral vascular complications in diabetics with renal insufficiency. Methods. A retrospective single-center review was done of 36 kidney-pancreas (KP) and 88 kidney-alone (KA) recipients with a diagnosis of diabetes and end-stage renal disease (ESRD) transplanted between May 1997 and July 2002. Risk factors studied included type of transplant, age, gender, history of smoking, coronary artery disease, hypertension, and peripheral vascular disease (PVD). The endpoint was first peripheral vascular event occurring after transplantation, defined as either an amputation or revascularization procedure. Results. The mean age of the cohort was 51 Ϯ 9 years, 64% of patients were of male gender, 20% with a history of smoking, 98% with hypertension, 15% with coronary artery disease (CAD), and 12% with a history of PVD. With a median follow-up of 45 months (12 to 79 months), 3/36 (8%) of KP recipients suffered a PVD complication, compared to 10/88 (11%) of KA recipients (P ϭ NS). Similarly, age, gender, a past history of smoking, CAD, and hypertension were not predictive of PVD complications. Five of 15 patients (33%) with a pretransplant history of PVD suffered a postoperative PVD event compared to only 8 of 109 patients (7%) with no prior history of PVD (P ϭ .008). Conclusions. Restoration of normoglycemia by pancreas transplantation did not reduce the risk of PVD complications in diabetics with renal failure. A pretransplant history of PVD was the only risk factor associated with posttransplant PVD events.
Aims. To determine outcomes utilizing thymoglobulin and sirolimus immunosuppression, with early s... more Aims. To determine outcomes utilizing thymoglobulin and sirolimus immunosuppression, with early steroid withdrawal in low-immune responder pancreas-kidney (SPK) recipients, and conversion from cyclosporine (CsA) to mycophenolic acid (MPA) in all recipients at 6 months posttransplantation. Methods. SPK recipients received thymoglobulin, sirolimus, and reduced-dose CsA immunosuppression. Low immune responders (non-African-Americans with a pretransplant PRA Ͻ 30%) were withdrawn from prednisone on posttransplant day 5 and high immune responders were continued on prednisone. All recipients were converted from CsA to MPA at 6 months posttransplantation. During conversion, recipient immune response was monitored by flow PRA and a T-cell stimulation assay (Cylex). Results. With a mean follow-up of 9 Ϯ 4 months, one pancreas was lost to pancreatitis, with no patient or kidney losses and no acute rejection episodes. All eight low immune responder patients were steroid-free at 9 Ϯ 5 months posttransplantation. Seven patients (five low and two high immune responders) with at least 6-month follow-up were converted from CsA to MPA. One high immune responder with a pretransplant PRA of 43% remained with a PRA of 53% Ϯ 2% postconversion. The second high immune responder had a pretransplant PRA of 34% and a postconversion PRA of 0%. The five low immune responders had a mean pretransplant PRA of 16% Ϯ 15% and a postconversion PRA of 0% (P Ͻ .01). The Cylex assay resulted in 67% low responsiveness for both high and low immune responders. Conclusion. Thymoglobulin induction with sirolimus maintenance therapy permitted immunosuppression minimization in selected pancreas transplant recipients. Posttransplant evaluation revealed a diminished (regulated) immune response in six of seven patients.
Introduction. African-American renal transplant recipients are prone to acute rejection episodes ... more Introduction. African-American renal transplant recipients are prone to acute rejection episodes and graft loss owing to genetic, pharmacokinetic, cultural, and socioeconomic factors. While more intense exposures to antirejection agents can mitigate this propensity, heightened immunosuppressive regimens are accompanied by an array of toxicities. Our study sought to examine the impact of a combination of sirolimus (SRL) and cyclosporine (CsA) on the outcomes of African-Americans vs Caucasians. Materials and Methods. The outcomes of African-Americans treated with either CsA-prednisone (Pred, n ϭ 90) or SRL-CsA-Pred (n ϭ 86) were compared with 148 SRL-CsA-Pred-treated Caucasians. Results. The addition of SRL to a CsA-Pred regimen reduced the rate of acute rejection episodes within 2 years in African-Americans from 43.3% to 17% (P ϭ .004), a value similar to that observed in Caucasian patients (18%). At 2 years, the graft survival rate of 79% among African-American patients treated with SRL-CsA-Pred was similar to that in the Caucasian cohort (80%). The respective patient survival rates also were similar: 93% and 90%, respectively. Multivariate analysis of 5-year outcomes among patients treated with SRL-CsA-Pred revealed the hazard ratios of African-Americans vs Caucasians to actually be reduced for acute rejection (.22; P ϭ .01) and for death (.15; P ϭ .01), but similar for chronic rejection (.77; P ϭ NS) and graft loss (1.03; P ϭ NS). Conclusion. The use of SRL-based regimens mitigated the otherwise enhanced risk for acute rejection episodes or graft loss otherwise experienced by CsA-treated African-American renal transplant recipients.
Background. Our objective was to determine the impact of thymoglobulin-sirolimuscyclosporine immu... more Background. Our objective was to determine the impact of thymoglobulin-sirolimuscyclosporine immunosuppression on the alloimune response of pancreas-kidney transplant recipients. Methods. Thirty-six pancreas transplant recipients received an induction protocol of thymoglobulin, sirolimus, reduced-dose cyclosporine, and corticosteroids. A subset of 10 recipients were also enrolled in a study to measure immune responsiveness. Flow PRA-determined HLA antibody, donor-specific flow cytometry crossmatching (FCXM), T-cell subset, and suppressor cell assays were performed at various timepoints during the first posttransplant year. Results. One-year patient, kidney, and pancreas survivals were 97%, 94%, and 92%, respectively. There was 1 death due to sepsis, and 1 kidney and 2 pancreas graft losses. There were no acute rejection episodes. Recipients in the immune-monitoring study displayed depression of CD3, CD4, and CD8 counts (Ͻ80%) until 3 months posttransplant. At transplantation, 9 of 10 patients displayed Ͻ10% class I HLA antibody. By 3 months, 7 of 10 showed a transient elevation in class I HLA antibodies, with 2 patients expressing Ͼ80% flow PRA. At transplant 1 patient was FCXM-positive, whereas, by 3 months posttransplant, 2 of 10 patients demonstrated a positive FCXM. There were no clinical consequences to either the presence of HLA antibody or the positive FCXMs. By 6 months, 7 of 9 patients expressed immunoregulatory suppressor cell activity. Conclusions. The absence of acute rejection events was likely due to inhibition of donor-specific immunity. Seventy percent of patients demonstrated an early non-donordirected HLA antibody response that had no adverse effect on graft function and 78% of the patients displayed immunoregulatory suppressor cell function, probably contributing to the successful clinical outcome. MATERIALS AND METHODS Study Design This prospective study included 31 simultaneous pancreas-kidney (SPK), 3 pancreas after kidney (PAK), and 2 pancreas-alone (PA) transplant recipients receiving induction immunosuppression con-From the
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