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Biomedical subjects

M Roy First

Publications and source records attributed to M Roy First.

31 records · Page 2Linked to original sources
PubMed2003

Donors with central nervous system malignancies: are they truly safe?

BACKGROUND: In an era of organ shortage, the use of expanded or marginal donors has been attempted to increase transplantation rates and diminish waiting list mortality. One strategy is the use of organs from patients with a history of or active central nervous system (CNS) tumor. METHODS: Sixty-two recipients were identified as the recipients of organs from donors with a history of or active CNS malignancy. Patient demographics, donor tumor management, incidence of tumor transmission, and patient survival were examined. RESULTS: Of the organs recovered and transplanted from donors with astrocytoma, 14 were associated with at least one risk factor including high-grade tumor (n=4), prior surgery (n=5), radiation therapy (n=4), and systemic chemotherapy (n=4). One tumor transmission was identified at 20 months posttransplant with the patient expiring from metastatic disease. Twenty-six organs were transplanted from glioblastoma patients with 15 demonstrating risk factors including high-grade tumor (n=9) and prior surgery (n=10). Eight transmissions were identified with a range of 2 to 15 months posttransplant, with seven patients dying as the result of metastatic disease. Seven organs were used from donors with a medulloblastoma. Three transmissions were identified at a range of 5 to 7 months, all associated with ventriculoperitoneal shunts. Two medulloblastoma recipients died as the result of metastatic disease, whereas the third is alive with diffuse disease. The rate of donor tumor transmission, in the absence of risk factors, was 7%, whereas in the presence of one or more risk factor this rate dramatically rose to 53% (P<0.01). CONCLUSIONS: Organs from donors with CNS tumors can be used with a low risk of donor tumor transmission in the absence of the following risk factors: high-grade tumors, ventriculoperitoneal or ventriculoatrial shunts, prior craniotomy, and systemic chemotherapy.

Astrocytoma↗
PubMed2003

MALToma: a Helicobacter pylori-associated malignancy in transplant patients: a report from the Israel Penn International Transplant Tumor Registry with a review of published literature.

BACKGROUND: Mucosa-associated lymphoid tissue lymphoma (MALToma) is a Helicobacter pylori-related tumor of B-cell origin, the malignant potential for which remains to be defined in immunosuppressed patients. METHODS: Review of the Israel Penn International Transplant Tumor Registry identified six cases of gastric MALToma. Patient demographics, management, and outcomes were compared and published literature was reviewed. RESULTS: MALToma developed in six transplant recipients (three kidney, two heart, one kidney-pancreas). All were treated with immunosuppression minimization and therapy for H. pylori, resulting in disease regression in five patients. One patient developed progression to high-grade MALToma despite documented H. pylori eradication, required surgery and chemotherapy, and died, with significant disease at autopsy. CONCLUSIONS: Treatment of MALToma with immunosuppression minimization and anti-H. pylori therapy results in a majority of patients becoming disease free. Observation of malignant degeneration into an aggressive, high-grade lymphoma in one patient indicates the malignant potential. Diligent follow-up of these patients with endoscopy and biopsy is therefore indicated.

Adult↗
PubMed2003

Renal function as a predictor of long-term graft survival in renal transplant patients.

Acute rejection is a major risk factor for kidney graft failure. However, as acute rejection has been progressively reduced by recent immunosuppressive regimens, other risk factors are becoming increasingly important. Evidence is accumulating that early renal function predicts long-term outcome. A recent registry survey of more than 100 000 kidney transplants found that 6- and 12-month serum creatinine levels, as well as the change between 6 and 12 months, are strongly associated with long-term graft survival. A survey of paediatric renal transplant recipients showed that poor creatinine clearance (<50 ml/min) as early as 30 days post-transplant predicted an annual rate of graft loss of 13% compared with <3% in patients with 30-day clearance >50 ml/min. This association between early renal function and long-term outcome was confirmed in multicentre studies. Renal transplant recipients (n=572) with 6-month serum creatinine levels >1.5 mg/dl suffered 3-year graft loss of 19.3% compared with only 8.5% in patients with levels <1.6 mg/dl (P<0.001). Significantly fewer patients receiving tacrolimus had 12-month serum creatinine levels >1.5 mg/dl compared with cyclosporin (42 versus 54%, P<0.05). Interestingly, a single-centre study (n=436) found that while glomerular filtration rate (GFR) at 6 months post-transplant had remained stable over the last decade, the rate of loss of renal function had decreased. A lower rate of GFR loss was associated with absence of rejection, use of mycophenolate mofetil rather than azathioprine and use of tacrolimus rather than cyclosporin (P<0.01). In conclusion, early measures of renal function allow identification of those patients at highest risk of graft failure and provide an invaluable tool for improving outcomes by tailored immunosuppression. The choice of such immunosuppression should be guided not only by its ability to prevent rejection, but also by its impact on renal function.

Clinical Trials as Topic↗
PubMed2003

The Israel Penn International Transplant Tumor Registry.

The Israel Penn International Transplant Tumor Registry is literally the world's premier repository of information on patients who have developed malignancies after organ transplants. The administrators of the Registry not only collect information but also provide consulting services based on the accumulated knowledge that the Registry contains. By creating a secure Web-based front end, we have made it possible for the Registry to keep pace with its burgeoning international caseload.

Humans↗
PubMed2002

Safety, efficacy, and cost analysis of thymoglobulin induction therapy with intermittent dosing based on CD3+ lymphocyte counts in kidney and kidney-pancreas transplant recipients.

BACKGROUND: In view of the superior T-cell depletion and prolonged half-life of thymoglobulin, we initiated a protocol to administer thymoglobulin intermittently based on peripheral blood CD3+ lymphocyte counts. METHODS: In this prospective study, 41 consecutive high-risk cadaver transplant recipients (panel reactive antibody level >30%, repeat transplant recipients, simultaneous pancreas and kidney or pancreas after kidney recipients, prolonged cold-ischemia time, prolonged donor hypotension, non-heart-beating donors) who received thymoglobulin induction therapy were included. The first dose (1.5 mg/kg) of thymoglobulin was administered intraoperatively. CD3+ lymphocyte count in the peripheral blood was determined daily and repeat doses were administered when the CD3+ count was >20 cells/mm3. Calcineurin inhibitors (CI) in low doses were introduced when the allograft function recovered and the serum creatinine level dropped by at least 25% from the pretransplant level. Thymoglobulin treatment was discontinued once therapeutic CI drug levels were achieved. Concomitant immunosuppression consisted of mycophenolate mofetil and prednisone. RESULTS: The mean individual thymoglobulin dose was 104 mg (1.4 mg/kg), and the total cumulative dose per patient was 318 mg (4.2 mg/kg). Patients received an average of three doses and a mean of six CD3 counts were obtained per patient. Introduction of CI was delayed for an average of 6 days posttransplantation. At a mean follow-up of 340 days, two (4.9%) patients died; three (7.3%) renal allografts and two (18.2%) pancreas allografts were lost. Five (12.2%) patients developed a total of six acute rejection episodes. The mean serum creatinine in the 38 patients with a functioning kidney was 1.47 mg/dl, and the mean blood glucose in the 9 pancreas allograft recipients was 89 mg/dl. Cytomegalovirus (CMV) infection occurred in one (2.4%) patient. No posttransplant lymphoproliferative disorders were seen in this patient cohort. The hospital pharmacy charge for a 100-mg dose of thymoglobulin at this center was $2,165, and the laboratory charge for a single CD3 determination was $70. In this study, the average charges per patient for the total dose of thymoglobulin and six CD3 determinations were $7305. In comparison, the charge for daily administration of 104 mg of thymoglobulin (which was the mean dose) for 6 days (mean time to CI therapy initiation) would be $13,510 and for 10 days (mean time to therapeutic CI levels) would be $22,516. This represents a savings of 46% and 68%, respectively. CONCLUSIONS: Intermittent thymoglobulin therapy, based on peripheral blood CD3+ lymphocyte counts, is safe and associated with low acute rejection rate in high-risk kidney and kidney-pancreas transplant recipients. A mean of three doses resulted in adequate suppression of CD3+ lymphocytes permitting delayed introduction of CI in low doses until recovery of renal function occurred. When compared to traditional daily administration, intermittent therapy results in significant cost savings and reduces the total cumulative dose of this potent immunosuppressive agent.

Antilymphocyte Serum↗
PubMed2002

Posttransplant diabetes mellitus in kidney allograft recipients: incidence, risk factors, and management.

BACKGROUND: Posttransplant diabetes mellitus (PTDM), associated with the use of immunosuppressants, occurs at varying rates in kidney transplant recipients. METHODS: Five transplant centers conducted a retrospective review of 435 kidney recipients completing at least 6 months of follow-up to determine risk factors, incidence, and management strategies for posttransplant glucose intolerance. A distinction was made between hyperglycemia and diabetes. RESULTS: The incidence of PTDM was found to be 4.9%. Among tacrolimus-treated patients it was 5.7%, compared with 3.3% among cyclosporine-treated patients (P=0.453). Mean daily maintenance doses of prednisone and mycophenolate mofetil (MMF) were significantly lower in tacrolimus-treated patients. Significantly more tacrolimus-treated patients were prednisone-free (9.0%/0%; P<0.001). Logistic regression analysis revealed that the absence of an antiproliferative agent correlated with the development of PTDM (odds ratio=3.56; P=0.01). CONCLUSIONS: Based on this study, we propose management guidelines specifically for glucose intolerance developing after renal transplantation. Maintenance of blood glucose levels within strict limits is recommended, and the contribution of immunosuppressive agents to the development of PTDM is accounted for. Gradual tapering of prednisone and tacrolimus is proposed for patients who develop PTDM but also bear minimal risk of rejection. Tapering and eventual withdrawal of insulin should be attempted once blood glucose levels normalize. Switching to the alternative calcineurin inhibitor should only be considered as a late intervention. Tacrolimus therapy should be considered even in patients at high risk for diabetes, because the benefit of reduced acute rejection incidence and severity, as demonstrated in other studies, outweighs the risk of PTDM.

Adolescent↗
PubMed2002

The role of immunosuppression in lymphoma.

Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized yet serious complication in solid organ transplant recipients and currently represents the second most common de novo malignancy following solid organ transplantation. PTLD has been noted in all transplant immunosuppressive eras including the pre-cyclosporine, cyclosporine, and post-cyclosporine eras. The time from organ transplantation to PTLD presentation varies widely from less than 1 month to several years. PTLD presents with a broad spectrum of clinical manifestations depending on the transplanted organ, immunosuppressive therapy and patient age. Intense immunosuppressive therapy is a major risk factor for development of PTLD. Whenever a new agent is introduced, there is a learning curve that leads to dosing modifications, which in turn result in optimization of its immunosuppressive efficacy and reduction of toxicities, including PTLD. We review the major historical and recent immunosuppression trials to assess the impact of individual immunosuppressive agents and regimens on PTLD risk.

Humans↗
PubMed2002

Incidental diagnosis of gastric cancer in transplant recipients improves patient survival.

BACKGROUND: Gastric cancer in the United States is often diagnosed at advanced stages, resulting in dismal outcomes. In the immunosuppressed transplant recipient population, little is known about the clinical staging and outcome of these compromised patients. METHODS: All US cases reported to the Israel Penn International Transplant Tumor Registry were retrospectively examined for patient demographics, immunosuppressive therapy, tumor characteristics, therapeutic modalities, and mortality. Statistical analysis was performed with Students t test, chi-square analysis, and log-rank analysis by the method of Kaplan-Meier. RESULTS: Gastric cancer was identified in 34 recipients: 28 (82%) were male; 24 (71%) were white. Mean age at diagnosis was 58 +/- 11 years. Twenty-four (71%) patients received kidney transplants, 7 (21%) received heart transplants, and 3 (9%) received liver transplants. Fifty percent received induction therapy, whereas 94% were maintained on calcineurin inhibitors and corticosteroids. Thirty-five percent of patients were diagnosed during evaluation for gastrointestinal symptoms, with the remaining cases discovered incidentally during endoscopy (53%) or during computed tomography (12%) performed for other reasons. Stage varied at presentation as follows: stage I (n = 6), stage II (n = 11), stage III (n = 13), and stage IV (n = 4). Incidental diagnoses resulted in a lower stage malignancy (P <.001) and greater 1-year and 5-year survivals (P <.05) compared with those patients whose were diagnosed after being evaluated of gastrointestinal symptoms. CONCLUSION: In the United States, because gastric cancer in the transplant recipient is frequently identified at an earlier stage (50% were stages I and II) than in the general population, survivals are equivalent despite continued administration of immunosuppression. This early identification may be attributed to more frequent presymptom diagnosis and staging, resulting from incidental detection of these malignancies during posttransplant upper endoscopy or computed tomography. Early detection has resulted in a 29% 5-year survival for the entire transplant recipient group compared with a 5% to 15% 5-year survival in the general population.

Comorbidity↗
PubMedDate not supplied

Tacrolimus based immunosuppression.

The safety and efficacy of tacrolimus (Prograf) in renal transplantation is well established. Achieving longterm patient and graft survival are the ultimate goals following transplantation. Many factors negatively impact long-term transplant outcomes, including graft rejection, renal dysfunction and cardiovascular risk factors (hypertension, hyperlipidaemia, and post-transplant diabetes mellitus (PTDM)). Accordingly, careful consideration of the immunosuppressive strategy and its impact on these factors is critical to optimising outcomes. Clinical trials and registry studies conducted over the past decade have demonstrated tacrolimus to be a cornerstone immunosuppressant in renal transplantation. Compared with cyclosporine treatment, tacrolimus has been shown to be associated with decreased acute and chronic rejection, improved renal function over the long-term post-transplant, and a lower incidence of hyperlipidaemia and hypertension. In early studies, the incidence of PTDM was significantly higher in patients receiving tacrolimus; however, recent large clinical trials have revealed no significant between-group differences in the incidence of PTDM with tacrolimus treatment and cyclosporine microemulsion treatment. Together, these findings may translate into improved long-term transplant outcomes with tacrolimus-based immunosuppression. Although approved only for kidney and liver transplantation in the US, Prograf was the calcineurin inhibitor used in the majority of patients transplanted in 2003: kidney (67%), liver (89%), kidney/pancreas (81%), pancreas (77%), lung (65%), heart/lung (48%), and heart (42%).

Graft Rejection↗