Standard Donor Research Articles

Long-term outcomes of kidney transplantation from standard criteria donors with acute kidney injury

Long-term outcomes of kidney transplantation from standard criteria donors with acute kidney injury

Expanding the pool of kidney donors: use of kidneys with acute renal dysfunction.

ABSTRACTGiven the shortage of organs transplantation, some strategies have been adopted by the transplant community to increase the supply of organs. One strategy is the use of expanded criteria for donors, that is, donors aged >60 years or 50 and 59 years, and meeting two or more of the following criteria: history of hypertension, terminal serum creatinine >1.5mg/dL, and stroke as the donor´s cause of death. In this review, emphasis was placed on the use of donors with acute renal failure, a condition considered by many as a contraindication for organ acceptance and therefore one of the main causes for kidney discard. Since these are well-selected donors and with no chronic diseases, such as hypertension, renal disease, or diabetes, many studies showed that the use of donors with acute renal failure should be encouraged, because, in general, acute renal dysfunction is reversible. Although most studies demonstrated these grafts have more delayed function, the results of graft and patient survival after transplant are very similar to those with the use of standard donors. Clinical and morphological findings of donors, the use of machine perfusion, and analysis of its parameters, especially intrarenal resistance, are important tools to support decision-making when considering the supply of organs with renal dysfunction.

Urologic Disorders in Living Renal Donors and Outcomes of Their Recipients

BackgroundThere is an expanding gap between the number of patients listed for kidney transplantation and the number of kidney transplantations performed annually. The use of sensitive imaging methods results in increased discovery of many urologic asymptomatic problems, such as urolithiases, renal cysts, and solid renal masses. This result has brought the question of whether all donors with these urologic disorders should be rejected for donation. MethodsWe retrospectively analyzed donor and recipient records of all living kidney transplantations performed from 2004 to 2014. ResultsAmong 251 living-related donor kidney transplantations, 51 donors (20.3%) had urologic disorders. Mean donor age was significantly higher in donors with urologic disorders than in the standard donor group (50 y vs 41 y). The identified disorders were 32 renal cysts, 8 urolithiases, 3 renal tumors, 6 adrenal adenomas, and 2 microscopic hematurias. After nephrectomy, the graft kidneys with cysts were inspected carefully and all of the cortical-peripheral cysts were decorticated. Renal tumors were excised in 3 renal units. Transplantations had proceeded after the confirmation of low malignancy potentials of the lesions with safe surgical margins. Two out of 8 patients had undergone stone removal with ex vivo ureteroscopy and 1 by means of pyelotomy incision because of calix neck stenosis. None of those donors and recipients developed clinically significant renal stone disease with a mean follow-up of 28 months. Neither donors nor recipients of asymptomatic microscopic hematuria patients developed any problem with a mean 28 months' follow-up period. ConclusionsAsymptomatic urologic problems are very common. The significance of these asymptomatic pathologies is unclear. Our results suggest that in a selected group, at least some of these candidates can be accepted for donation.

Manganese and the Evolution of Photosynthesis.

Oxygenic photosynthesis is the most important bioenergetic event in the history of our planet-it evolved once within the Cyanobacteria, and remained largely unchanged as it was transferred to algae and plants via endosymbiosis. Manganese plays a fundamental role in this history because it lends the critical redox behavior of the water-oxidizing complex of photosystem II. Constraints from the photoassembly of the Mn-bearing water-oxidizing complex fuel the hypothesis that Mn(II) once played a key role as an electron donor for anoxygenic photosynthesis prior to the evolution of oxygenic photosynthesis. Here we review the growing body of geological and geochemical evidence from the Archean and Paleoproterozoic sedimentary records that supports this idea and demonstrates that the oxidative branch of the Mn cycle switched on prior to the rise of oxygen. This Mn-oxidizing phototrophy hypothesis also receives support from the biological record of extant phototrophs, and can be made more explicit by leveraging constraints from structural biology and biochemistry of photosystem II in Cyanobacteria. These observations highlight that water-splitting in photosystem II evolved independently from a homodimeric ancestral type II reaction center capable of high potential photosynthesis and Mn(II) oxidation, which is required by the presence of homologous redox-active tyrosines in the modern heterodimer. The ancestral homodimer reaction center also evolved a C-terminal extension that sterically precluded standard phototrophic electron donors like cytochrome c, cupredoxins, or high-potential iron-sulfur proteins, and could only complete direct oxidation of small molecules like Mn(2+), and ultimately water.

Endourological management of live donors with urolithiasis at the time of donor nephrectomy: a single center experience.

Live related renal donors with urolithiasis are made suitable for renal transplantation in two-stage procedure in most of the centers: first making the donor kidney stone free surgically or by ESWL and then proceeding to renal transplantation. To reduce the cost and morbidity of two surgical procedures in donors, we did a pilot study of removing subcentimeter renal calculi in live donors, after explanting the kidney, during bench surgery. We included all prospective renal donors with subcentimeter (4-10 mm) calculi in one kidney in our study (n = 14). All these patients underwent standard donor evaluation and metabolic work up. After the donor nephrectomy, bench retrograde intra-renal surgery (RIRS) with or without pyelotomy was done for stone clearance followed by renal transplantation. Stone clearance was achieved in 13 out of 14 donors. Donors and recipients were followed for 6-24 months. No stone recurrence or graft dysfunction was seen in the follow-up period. We concluded that bench RIRS is an excellent modality in the management of small renal calculi in prospective renal donors who are not having metabolically active disease. This reduced the cost and morbidity to the donor and minimized waiting time for transplant.

Outcomes Using Grafts from Donors after Cardiac Death

Previous reports suggest that donation after cardiac death (DCD) liver grafts have increased primary nonfunction (PNF) and cholangiopathy thought to be due to the graft warm ischemia before cold flushing. In this single-center, retrospective study, 866 adult liver transplantations were performed at our institution from January 2005 to August 2014. Forty-nine (5.7%) patients received DCD donor grafts. The 49 DCD graft recipients were compared with all recipients of donation after brain death donor (DBD) grafts and to a donor and recipient age- and size-matched cohort. The DCD donors were younger (age 28, range 8 to 60 years) than non-DCD (age 44.3, range 9 to 80 years) (p < 0.0001), with similar recipient age. The mean laboratory Model for End-Stage Liver Disease (MELD) was lower in DCD recipients (18.7 vs 22.2, p = 0.03). Mean cold and warm ischemia times were similar. Median ICU and hospital stay were 2 days and 7.5 days in both groups (p = 0.37). Median follow-ups were 4.0 and 3.4 years, respectively. Long-term outcomes were similar between groups, with similar 1-, 3- and 5-year patient and graft survivals (p = 0.59). Four (8.5%) recipients developed ischemic cholangiopathy (IC) at 2, 3, 6, and 8 months. Primary nonfunction and hepatic artery thrombosis did not occur in any patient in the DCD group. Acute kidney injury was more common with DCD grafts (16.3% of DCD recipients required dialysis vs 4.1% of DBD recipients, p = 0.01). An increased donor age (>40 years) was shown to increase the risk of IC (p = 0.006). Careful selection of DCD donors can provide suitable donors, with results of liver transplantation comparable to those with standard brain dead donors.

(246) - A Prospective Randomized Trial of Ex Vivo Lung Perfusion in Standard Donor: Lungs: Can It Improve the Results?

(246) - A Prospective Randomized Trial of Ex Vivo Lung Perfusion in Standard Donor: Lungs: Can It Improve the Results?

(20) - Heart Transplantation From Donors Outside Standard Acceptability Criteria Using Ex-Vivo Normothermic Perfusion: The End of Donor Shortage?

Purpose: Utilization of the organs from high-risk donors may increase the number of orthotopic heart transplants (OHTx), however, with possible detrimental effect on outcomes. The Organ Care System (OCS) (TransMedics, MA, USA) allows organ evaluation during normothermic perfusion and reduces the cold ischemic time below 100 minutes with potential benefit for post-transplant results when transplanting extended criteria allografts. In this study we analyze the results of OHTx from donors outside standard criteria following ex vivo perfusion. Methods: Between February 2013 and September 2014 (n= 40) patients underwent heart transplantation at our institution using the OCS as a method of graft preservation and assessment. Fifteen patients received organs from standard criteria donors (group I) and 25 from extended criteria donors (group II) with at least one of the following risk factors; LVEF ≤ 50%, LV hypertrophy (LVH); interventricular septum in diastole > 14 mm, donor cardiac arrest, coronary artery disease or donor death due to cocaine. Results: Donor age: 41±11 (17-59 yo) gender F/M: 22.5/77.5%. Transport time was ≥ 2.5 hours in 19 donors. Seven donors had reduced LVEF ≤ 50%, seven had LVH, two donors died due to cocaine overdoses, ten had a previous cardiac arrest; 30±9 min and six palpable coronary artery disease. Both groups (standard vs. extended criteria) were statistically comparable regarding recipient characteristics. Ex vivo perfusion parameters; lactate trend, haemodynamic data and ischemic times were also unaffected. No significant differences were observed on postoperative outcome. There was a trend towards less duration of mechanical ventilation in hours in the extended criteria group 56 (21; 125) vs. 100 (41; 336) (p= 0.074). At follow up of 268 ± 84 days, biventricular graft function was comparable. 30-days, 90 days and 1-year survival (group I vs. II) was also similar: 92.9 vs.91.8; 84.4 vs. 87.5 and 84.4 vs. 81.6% (log rank p= 0.832) Conclusion: Transplantation of hearts from extended criteria donors with moderate left ventricular dysfunction, donor cardiac arrest, left ventricular hypertrophy or coronary artery disease is safe and feasible with normothermic ex vivo preservation as a method of graft assessment pre-implantation and therefore should be considered in times of donor shortage.

(244) - Metabolic Assessment of Marginal Donor Lungs During Ex-Vivo Perfusion (EVLP): New Parameters for Decision Making

EVLP has become a widespread method to evaluate marginal donor lungs. Nevertheless, strong evidence on accurate judgment of graft quality by individual functional parameters is still missing. Anaerobic glucose metabolism might be dependent on graft quality and serve as a parameter for decision making during EVLP. This is an analysis of our prospective EVLP database. Since 2010, 43 EVLP were performed with initially rejected marginal donor lungs. 28 (65%) of these lungs were accepted after EVLP and transplanted with results comparable to standard donor lungs. Absolute glucose consumption and lactate production were calculated and corrected for hourly changes of perfusate and additional glucose administration. These values were compared between accepted (group A) and rejected lungs (group B). Linear regression was performed and the slope values were indexed for donor pTLC to correct for graft size. Mean EVLP Duration was 275±87 min. (group A, n=28) vs. 297 min. (group B, n=15: 238 min; p=0.039). Subsequently accepted lungs showed a significantly lower total glucose consumption (T1h:-899 vs.-1258 mg; p=0.29/ T2h:-1625 vs.-2293 mg; p=0.058/ T3h: 2432 vs.-3380 mg; p=0.015/ T4h:-2812 vs.-4771 mg; p<0.001) and lower lactate production (T1h:7.5 vs.9.5mmol; p=0.44/ T2h: 15 vs. 19.6 mmol; p=0.09/ T3h: 22.3 vs. 29 mmol; p=0.02/ T4h:27 vs. 42.7mmol; p<0.001). In linear regression analysis glucose consumption and lactate production slopes were significantly different between the groups (glucose:-2.03 ±1.03 vs.-3.06 ±1.41 mg/min/LTLCp;p=0.021/ lactate: 0.019 ±0.008 vs. 0.028 ±0.013 mmol/min/LTLCp; p=0.038. Lactate and glucose slopes were significantly correlated(r=-0.798; p<0.001) During EVLP, lactate and glucose changes are linear and highly correlated over time. Glucose consumption and lactate production are significantly higher in unacceptable donor lungs and should be considered as important parameters for decision making during EVLP.

MP79-07 USEFULNESS OF KIDNEY PREIMPLANTATION BIOPSIES FROM DECEASED DONORS FOR KIDNEY TRANSPLANT ALLOCATION

INTRODUCTION AND OBJECTIVES: The number of discarded kidneys for transplantation approaches 25% in the Spanish transplant registry. The main cause(w50%) is the presence of advanced histological lesions in kidney pre-implantation biopsies. Transplants results with expanded criteria donors are poorer than results with standard donors and kidneys with advanced histological lesions are not used in many transplant centers. AIM: To analyze transplant results from deceased donors using pre-implantation biopsies to evaluate expanded donors in our renal transplant unit. METHODS: Since 2009 all kidneys offered to our transplant unit were accepted for clinical examination. A pre-implantation kidney biopsy is obtained in patients with expanded criteria. Pre-implantation biopsies are processed in paraffin and pathologists cathegorizes the biopsies according to the Banff criteria (from 0 to 3). Individual scores are added and a pre-implantation score ranging from 0 to 15 is obtained. In general, kidneys with a pre-implantation donor score > 7 are discarded. An old-for-old policy is applied for kidney allocation with a donor/recipient age difference lower than 15 years. Kidneys with a donor biopsy score >5 were only transplanted in recipients older than 60 years RESULTS: Between 2009 and 2013 we evaluated 404 kidneys and 41 (10%) were discarded. Only 20 kidneys (5%) were discarded due to a pre-implantation biopsy score >7. Thus, 362 transplants were performed and according to our protocol in 254 cases (70%) a pre-implantation biopsy was obtained. Donors with a pre-implantation biopsy were older (61 10 vs. 39 10 years, p 5, n1⁄479) have a similar renal function at 1 year (45 14 vs. 46 15 mL/min) and a similar 5-year graft survival (81.4% vs. 83.5%) than transplants from kidneys with lower scores (1 to 5). CONCLUSIONS: Careful evaluation and selection of deceased donors and renal transplant recipients allows to reduce the number of discarded kidneys (10% in our unit) and to maintain standard transplant results.

85 Usefulness of kidney preimplantation biopsies from deceased donors for kidney transplant allocation

INTRODUCTION AND OBJECTIVES: The number of discarded kidneys for transplantation approaches 25% in the Spanish transplant registry. The main cause(w50%) is the presence of advanced histological lesions in kidney pre-implantation biopsies. Transplants results with expanded criteria donors are poorer than results with standard donors and kidneys with advanced histological lesions are not used in many transplant centers. AIM: To analyze transplant results from deceased donors using pre-implantation biopsies to evaluate expanded donors in our renal transplant unit. METHODS: Since 2009 all kidneys offered to our transplant unit were accepted for clinical examination. A pre-implantation kidney biopsy is obtained in patients with expanded criteria. Pre-implantation biopsies are processed in paraffin and pathologists cathegorizes the biopsies according to the Banff criteria (from 0 to 3). Individual scores are added and a pre-implantation score ranging from 0 to 15 is obtained. In general, kidneys with a pre-implantation donor score > 7 are discarded. An old-for-old policy is applied for kidney allocation with a donor/recipient age difference lower than 15 years. Kidneys with a donor biopsy score >5 were only transplanted in recipients older than 60 years RESULTS: Between 2009 and 2013 we evaluated 404 kidneys and 41 (10%) were discarded. Only 20 kidneys (5%) were discarded due to a pre-implantation biopsy score >7. Thus, 362 transplants were performed and according to our protocol in 254 cases (70%) a pre-implantation biopsy was obtained. Donors with a pre-implantation biopsy were older (61 10 vs. 39 10 years, p 5, n1⁄479) have a similar renal function at 1 year (45 14 vs. 46 15 mL/min) and a similar 5-year graft survival (81.4% vs. 83.5%) than transplants from kidneys with lower scores (1 to 5). CONCLUSIONS: Careful evaluation and selection of deceased donors and renal transplant recipients allows to reduce the number of discarded kidneys (10% in our unit) and to maintain standard transplant results.

Compensatory hypertrophy of the remaining kidney in medically complex living kidney donors over the long term.

The criteria for living kidney donation are changing, resulting in increased numbers of individuals with risk factors being accepted as donors. The long-term function and volume changes in the remaining kidney of these medically complex donors remain largely unknown. Living kidney donors with three separate risk factors (older age, obesity, or hypertension) were reevaluated 5 years after donation. The function and volume of the remaining kidney were assessed and compared to those of standard donors. The body size correlated significantly with the kidney size and glomerular filtration rate (GFR) at the time of donation. Five years after donation, the remaining kidney size increased by a mean of 29.3%, and the GFR by 35.6%. The increase in GFR was uniform. In univariate analysis, neither the changes in the size nor the changes in the 1GFR were found to be associated with the risk factors. Medically complex living donors demonstrate similar compensatory increase in function and volume of the remaining kidney compared to standard donors, 5 years after donation.

Hypothermic machine perfusion of kidneys retrieved from standard and high-risk donors.

Hypothermic machine perfusion (HMP) of kidneys is a long-established alternative to static cold storage and has been suggested to be a better preservation method. Today, as our deceased donor profile continues to change towards higher-risk kidneys of lower quality, we are confronted with the limits of cold storage. Interest in HMP as a preservation technique is on the rise. Furthermore, HMP also creates a window of opportunity during which to assess the viability and quality of the graft before transplantation. The technology might also provide a platform during which the graft could be actively repaired, making it particularly attractive for higher-risk kidneys. We review the current evidence on HMP in kidney transplantation and provide an outlook for the use of the technology in the years to come.

Alternative donor transplantation--"mixing and matching": the role of combined cord blood and haplo-identical donor transplantation (haplo-cord SCT) as a treatment strategy for patients lacking standard donors?

In the past decade, haplo-cord stem cell transplantation (SCT) using myeloablative or reduced intensive conditioning regimens has been shown to result in reliable and fast engraftment of neutrophils and platelets comparable to HLA-matched donors and much faster than after cord stem cell transplant. Haplo-cord SCT also has a low incidence of early non-relapse mortality, low incidences of acute and chronic graft-vs-host disease (GVHD), and excellent graft-vs-leukemia (GVL) effects. Favorable long-term outcomes for high-risk patients with hematologic malignancies have been reported, including older patients. Haplo-cord SCT will likely overcome the limitations of cell dose during cord stem cell selection and might significantly expand the use of cord stem cell transplant in the adult population. The comparable survival outcomes of matched related donor (MRD), matched unrelated donor (MUD), and haplo-cord stem cell transplant strongly argue that haplo-cord SCT should be considered as effective alternative stem cell transplant for high-risk patients lacking standard donors. Further improvement in supportive care and incorporation of a better understanding of the human fetal immune development into the haplo-cord SCT are required to further improve this strategy.

Outcomes in kidney transplant recipients from older living donors.

Previous studies demonstrate that graft survival from older living kidney donors (LD; age>60 years) is worse than younger LD but similar to deceased standard criteria donors (SCD). Limited sample size has precluded more detailed analyses of transplants from older LD. Using the United Network for Organ Sharing database from 1994 to 2012, recipients were categorized by donor status: SCD, expanded criteria donor (ECD), or LD (by donor age: <60, 60-64, 65-69, ≥70 years). Adjusted models, controlling for donor and recipient risk factors, evaluated graft and recipient survivals. Of 250,827 kidney transplants during the study period, 92,646 were LD kidneys, with 4.5% of these recipients (n=4,186) transplanted with older LD kidneys. The use of LD donors 60 years or older increased significantly from 3.6% in 1994 to 7.4% in 2011. Transplant recipients with older LD kidneys had significantly lower graft and overall survival compared to younger LD recipients. Compared to SCD recipients, graft survival was decreased in recipients with LD 70 years or older, but overall survival was similar. Older LD kidney recipients had better graft and overall survival than ECD recipients. As use of older kidney donors increases, overall survival among kidney transplant recipients from older living donors was similar to or better than SCD recipients, better than ECD recipients, but worse than younger LD recipients. With increasing kidney donation from older adults to alleviate profound organ shortages, the use of older kidney donors appears to be an equivalent or beneficial alternative to awaiting deceased donor kidneys.

Hypothermic Machine Perfusion in Kidney Transplantation: Back to the Future?

Static cold storage is currently the most used method of organ preservation worldwide. However, cutting edge technology and dramatic changes in the donor pattern have lately renewed the interest toward hypothermic machine perfusion. Marginal and cardiac death donors show higher rates of primary non function and delayed graft function compared to standard criteria donors. In this setting, machine perfusion may offer several theoretical advantages such as improved organ preservation, continuous graft evaluation, and ex-vivo conditioning of the graft before implantation. These topics have been recently reassessed by several studies. In particular, perfusion characteristics (renal resistance) and perfusate biomarker concentrations (lactate dehydrogenase, aspartate aminotransferase, heart-type fatty acid binding protein, and IL-18) during machine preservation, proved to be reliable tools to rule out graft viability and predict outcomes after transplantation. Treatment strategies acting on tissue repair, cell metabolism, and allorecognition pathway are also under investigation with promising results. Machine perfusion has finally shown its real potential however, stronger evidences and updated cost-effectiveness analysis are needed to fully support its role for the next future.

The risk of cancer in recipients of living-donor, standard and expanded criteria deceased donor kidney transplants: a registry analysis.

Kidneys from expanded criteria deceased donors may elicit a strong inflammatory response, predisposing recipients to an increased risk of cancer after transplantation. We aimed to determine the association between donor types and cancer risk after kidney transplantation. Using the Australian and New Zealand Dialysis and Transplant Registry, we assessed the association between different donor types (living donor, standard, and expanded criteria deceased donors) and the risk of cancer after kidney transplantation using adjusted Cox proportional hazard and competing risk models. Over a median follow-up period of 4.4 years in 7,040 patients (34,684 patient-years), 468 patients (6.6%) developed cancer. The overall risks for cancer were 1,080, 1,444, and 2,018 per 100,000 patient-years for recipients of living donor, standard, and expanded criteria deceased donor kidneys, respectively. Compared to recipients of living-donor kidneys, recipients of expanded criteria deceased donor kidneys were at an increased risk of cancer (adjusted hazard ratio [HR], 1.52; 95% confidence interval [95% CI], 1.15-2.02; P = 0.004), particularly for genitourinary cancer (adjusted HR, 1.79; 95% CI, 1.03-3.10; P = 0.038) and post-transplant lymphoproliferative disease (adjusted HR, 2.72; 95% CI, 1.38-5.37; P = 0.004). Recipients of expanded criteria deceased donor kidneys are at substantially increased risk of cancer, especially cancers with a viral etiology. Allocation of expanded criteria deceased donor kidneys to potential recipients should balance the harms, such as the excess risk of cancer against the survival gains and quality-of-life benefits associated with transplantation.

Microtransplantation: HLA-Mismatched Allogeneic Cellular Therapy of Acute Myeloid Leukemia (HMMACT)

Background: This clinical trial addressed feasibility and safety of microtransplantation by HLA-mismatched allogeneic cellular therapy (HMMACT) in poor risk acute myeloid leukemia patients. A secondary objective was to estimate complete response rate, infections, GVHD incidence, and induction mortality.Methods: Patients with high risk AML were enrolled: 4 were > 75 yo, 3 with MLL+ ((t(6;11), 11+ and t(10;11)), 3 complex/del7, one FLT3+. Patients received induction chemotherapy with mitoxantrone (10 mg/m2 IV for 3 days) and cytarabine (150 mg/m2 IV for 7 days) and received HLA-mismatched GCSF mobilized PBSCs on day 9 or 10. Family donors were concurrently HLA typed and best available donor underwent GCSF mobilization (5 mg/kg SQ BID x 4 days) and leukapheresis after medical evaluation and safety testing. HLA partial mismatch patients (4- 5/10 antigen) were chosen. Apheresis cells were counted and analyzed by flow cytometry for CD34+ cells; CD3+, CD4+CD25+ and CD8 + cells; and CD3-CD56+ NK cells. Target CD3 cell dose was 1 x 108/kg per cycle; cells cryopreserved as for standard stem cell donors. Family donor HLA-mismatched GCSF mobilized peripheral blood cells were infused fresh on day 9 or 10 (up to day 16), 36-50 hours after end of cytarabine. Bone marrow biopsy was evaluated on day 14 and 28 for AML remission status, and T/NK cell number. Patients achieving a complete response proceeded to consolidation with cytarabine 0.5 -1.0 gram/m2 x 6 doses with fresh or cryopreserved HMMACT cells from their donor for 2 courses a month apart. Patients: 10 patients age 31 – 80 yo consented: 8 received allo cells; 1 screen failure (no haplo family member identified); 1 patient too ill after initiating chemo to collect donor. Eight patients received at least one course of HMMACT; 1 withdrew early due to AML progression, a second for poor performance status. Three patients had de novo AML; 5 patients had secondary AML. Six Patients had2 or more cycles of HMMACT: four achieved CR: Pt 1 and 4 received 3 cycles, Pt 2 and 6 received 2 cycles of cell infusions and all achieved CR. Pt 9 received 2 inductions with cells, and sustained a partial clinical remission for 6 months. Two Patients had 1 cycle of HMMACT:Pt 3: received 1 cycle cells, but response not assessed; Pt 8: received 1 cycle cells, and achieved CR 3+mos but declined further therapy. Safety: Acute reactions to cell infusions were minimal. Delayed reactions attributed to cell infusions included fever grade 1-2, rash grade 1-2, diarrhea grade 1-2 resolving in 7-10 days. Patients with prior MDS or refractory leukemia requiring 2 inductions had a longer time to ANC and platelet recovery. Feasibility: Two patients had no donor; 2 donors only collected enough for 2 cell infusions. Response: 5/8 pts receiving cells had CR/CRi (62.5%) lasting 3 to 10+ months.Conclusions: Although there were the usual significant complications of treating leukemia and infections, the cellular therapy itself was well-tolerated. Patients often had fevers in first week after cell infusions, or experienced transient rash and diarrhea in the same time period, which were self resolving in all cases and may reflect elimination of allogeneic cells by the patient’s immune system. No patient developed GVHD. Feasibility of obtaining family donors was as expected for this diverse US population. Infectious complications were low by AML treatment standards. Complete remission rates are encouraging, but not as durable as hoped, likely reflecting the fact that all of our patients had high risk cytogenetics in contrast to the prior published studies by Chinese investigators. The majority were elderly who would not otherwise be offered intensive therapy. Family donors achieved expected cell targets and tolerated mobilization/collection procedures well. All but one patient receiving 2 to 3 cycles achieved complete remission. Two elderly patients who received one or two cell infusions during induction sustained prolonged survival of 6 months in spite of no further therapy, one achieving a CR and the other a sustained PR. Neutrophil and platelet recoveries tended to follow the pattern of the patient’s prior secondary leukemia or myelodysplastic disorder. Once patients achieved complete remission however, recovery of blood counts was relatively rapid on further cycles of consolidation. We are now assessing Treg, T and NK cell phenotype of patient and donor cells by flow cyAtometry as biological correlates. DisclosuresChaudhary:University of Southern California: Inventor on a patent application relevant to this work filed to US patent office (No. 62/031,053). Patents & Royalties.

Improving Geographic Equity in Kidney Transplantation Using Alternative Kidney Sharing and Optimization Modeling.

The national demand for kidney transplantation far outweighs the supply of kidney organs. Currently, a patient's ability to receive a kidney transplant varies depending on where he or she seeks transplantation. This reality is in direct conflict with a federal mandate from the Department of Health and Human Services. We analyze current kidney allocation and develop an alternative kidney sharing strategy using a multiperiod linear optimization model, KSHARE. KSHARE aims to improve geographic equity in kidney transplantation while also respecting transplant system constraints and priorities. KSHARE is tested against actual 2000-2009 kidney allocation using Organ Procurement and Transplant Network data. Geographic equity is represented by minimizing the range in kidney transplant rates around local areas of the country. In 2009, less than 25% of standard criteria donor kidneys were allocated beyond the local area of procurement, and Donor Service Area kidney transplantation rates varied from 3.0% to 30.0%, for an overall range of 27.0%. Given optimal sharing of kidneys within 600 miles of procurement for 2000-2009, kidney transplant rates vary from 5.0% to 12.5% around the country for an overall kidney transplant range of 7.5%. Nationally sharing kidneys optimally between local areas only further decreases the transplant rate range by 1.7%. Enhancing the practice of sharing kidneys by the KSHARE model may increase geographic equity in kidney transplantation.

Proposal of Categorization of Expanded Criteria Donors in Renal Transplantation

IntroductionTransplantation of renal allografts that have been procured from expanded criteria donors (ECD) have prevailed in an attempt to expand the donor pool. Even though ECD is an acceptable source of donors, the wide range of age along with the presence or not of risk factors necessitates further categorization. The aim of this study was to analyze the allograft and recipient survival of the ECD renal grafts and to propose an ECD categorization model. Patients and MethodsWe reviewed the medical records of renal transplant recipients from January 2002 to July 2012, who received renal allografts from expanded and standard criteria donors (SCD) without risk factors such as hypertension, cerebrovascular disease or impaired renal function. ResultsDuring the study period, 310 renal transplantations were performed in our Transplant Unit, of which 86 and 114 renal grafts were procured from ECD and SCD respectively. ECD renal graft survival the first, third and fifth year was 92%, 82% and 70% while respective recipient survival was 95%, 87% and 82%. Comparison with the control group of SCD showed that ECD renal graft survival after the third post-transplant year was significantly inferior (P < .0001). Donor age was a considerable prognostic factor of long-term renal graft function. Serum creatinine of ECD grafts was the first and third year 1.86 ± 0.6 mg/dL and 1.91 ± 0.8 mg/dL, respectively, showing significant difference to that of SCD grafts (P < .0001). Further categorization of ECD showed that renal allografts procured from donors above 60 years old without risk factors had better renal graft survival and function compared to grafts procured from donors aged 50–59 with 2 or 3 risk factors. ConclusionsRenal transplantation from ECD offers acceptable graft survival rates, however they are inferior compared to renal grafts from optimal kidney donors. ECD kidney grafts have to be categorized, taking into consideration the independent risk factors.