Proportion Of Transplants Research Articles

Combining Low-Dose Post-Transplant Cyclophosphamide(PTCY) with Anti-Thymocyte Globulin(ATG) for Prophylaxis of Graft-Versus-Host Disease in Alternative-Donor Hematopoietic Stem Cell Transplantation for β-Thalassemia Major

Background ： The 5-year overall survival rate (OS) for children with thalassemia major who undergo allogeneic stem cell transplantation is 90% and the event-free survival (EFS) rate is 86%. Due to the limited availability of matched sibling donors, the proportion of transplantations from alternative donors is increasing, particularly from haplo-identical donors. Post-transplant infections and graft-versus-host disease (GVHD) remain the major causes of mortality, especially in those who receive transplantation from alternative donors. Post-transplant cyclophosphamide (PTCY) has shown outstanding results of GVHD prophylaxis in haploidentical matched related donors transplantation with hematological malignancies. However, there is insufficient clinical evidence for its application in pediatric patients who received transplantation from haplo-identical donors with non-malignant hematological disease. Here, we retrospectively analyzed the results of 40 cases that underwent allogeneic stem cell transplantation from haploidentical matched related donors (Haplo-RD) and unrelated donors (UD) to evaluate the safety and efficacy of the novel regimen in GVHD prophylaxis. Method A total of 40 patients with β-thalassemia major received stem cell transplantation, 10 haploid donors (Group Haplo-RD), and 30 unrelated donors (Group UD). Among Group UD, 15 donors were 1 or 2 HLA locus mismatched, remaining 15 were identically matched. The median age of the patients was 5.5 years, ranging from 2 to 12. The Conditioning regimen mainly consisted of fludarabine, busulfan, cyclophosphamide, and thiotepa. GVHD prophylaxis included ATG 1.5mg/kg×3d, cyclophosphamide (CTX) 25mg/kg×2d, cyclosporin A (CsA), and mycophenolate mofetil (MMF). We analyzed the engraftment rate, GVHD incidence, survival rate, and virus reactivation rate for each group. Results Engraftment rate was 100%, with a median time of 11 (10-15) days for neutrophil implantation and 12 (6-31) days for platelet implantation. All patients achieved complete chimerism on day 30 after transplantation. Three cases (7.5%) suffered from Ⅲ-Ⅳ aGVHD, with one being in the Group Haplo-RD group and two in the Group UD. Four cases (10.0%) of cGVHD were recorded. The overall survival (OS) rate and thalassemia-free survival rate were both 92.5%. In Group Haplo-RD, both the OS and thalassemia-free survival rates were 100%. Eight cases reported cytomegaloviremia but no one developed to CMV disease. The total activation rate for CMV was 20%. Nine cases suffered from BK virus urinary tract infection, resulting in a total activation rate of 22.5%. Detailed results are shown in Table 1 and Figure 1. Discussion Due to the high risk of GVHD and infection, stem cell transplantation from haploidentical and unrelated donors cannot be routine therapy for children with thalassemia major. Standard-dose PTCY regimen significantly increases the risk of CMV and BK infection after transplantation and is not suitable for non-malignant disease. The results have been reported that low-dose PTCY/ ATG can reduce the risk of GVHD as compared with standard-dose ATG in haploidentical donor stem cell transplantation. In our study, the novel GVHD prophylaxis regimen, semi-dose PTCY (25mg/kg×2d) combined with low-dose ATG (1.5mg/kg×3d), was used for stem cell transplantation from haploidentical and unrelated mismatched donors. The incidence of III-IV aGVHD was 7.5% and cGVHD was 10.0%, and there was no rejection of the transplant. The activation rate of CMV and BKV was significantly lower than reported in the literature, and the non-relapse mortality (NRM) after transplantation was significantly reduced. There was no statistical difference in the rate of OS, EFS, aGVHD, and cGVHD between Group Haplo-RD and Group UD. The results provide an effective approach for preventing GVHD and infectious diseases in thalassemia patients who underwent allo-HSCT with high-risk GVHD.

OPTN/SRTR 2021 Annual Data Report: Pancreas

The number of pancreas transplants in the United States was largely unchanged in 2021 at 963 transplants compared with 962 in 2020, showing that recovery from the COVID-19 pandemic was not as pronounced in pancreas transplantation as in other organs. The number of simultaneous pancreas-kidney transplants (SPKs) decreased from 827 to 820, whereas the number of pancreas-after-kidney transplants and pancreas transplants alone increased marginally to compensate. The proportion of patients with type 2 diabetes on the waiting list increased to 22.9% in 2021, compared with 20.1% in 2020. Consequently, the proportion of transplants in patients with type 2 diabetes increased from 21.3% in 2020 to 25.9% in 2021. The proportion of transplants in older recipients (aged 55 years or older) also increased to 13.5% in 2021 from 11.7% in 2020. Outcomes after SPK continue to be the best of the three categories of pancreas transplants: 1-year graft failure for kidney at 5.7% and pancreas at 10.5% for transplants performed in 2020. The proportion of pancreas transplants performed by medium-volume centers (11-24 transplants per year) increased sharply to 48.3% in 2021 from 35.1% in 2020, with a corresponding decrease in transplants in large-volume centers (25 or more transplants per year) to 15.9% in 2021 from 25.7% in 2020.

Interaction between socioeconomic deprivation and ethnicity for likelihood of receiving living-donor kidney transplantation

BackgroundThe interplay between ethnicity and socioeconomic deprivation for living-donor kidney transplantation (LDKT) opportunities is unclear.MethodsData for 2040 consecutive kidney-alone transplant recipients receiving an allograft between 1st January 2007 and 30th June 2020 at a single center were retrospectively analyzed. The associations between the proportions of transplants that were LDKT (versus deceased donation) and both ethnicity and socioeconomic deprivation were assessed, with the latter quantified by the Index of Multiple Deprivation (IMD) quintile.ResultsThe cohort comprised recipients of White (64.7%), South Asian (21.7%), Black (7.0%) and other (6.6%) ethnic groups. Recipients tended to be from socioeconomically deprived areas, with the most deprived quintile being the most frequently observed (quintile 1: 38.6% of patients); non-White recipients were significantly more likely to live in socioeconomically deprived areas (p < 0.001). Overall, 36.5% of transplants were LDKT, with this proportion declining progressively with socioeconomic deprivation, from 50.4 to 27.6% in the least versus most deprived IMD quintile (p < 0.001). A significant difference across recipient ethnicities was also observed, with the proportion of LDKTs ranging from 43.2% in White recipients to 17.8% in Black recipients (p < 0.001). Both socioeconomic deprivation (p < 0.001) and ethnicity (p = 0.005) remained significant predictors of LDKT on multivariable analysis, with a significant interaction between these factors also being observed (p < 0.001). Further assessment of this interaction effect found that, whilst there was a marked difference in the proportions of transplants that were LDKT between White versus non-White recipients in the most socioeconomically deprived groups (39.5% versus 19.3%), no such difference was seen in the least deprived recipients (48.5% versus 51.9%).ConclusionsWhilst both socioeconomic deprivation and non-White ethnicity are independent predictors for lower proportions of LDKTs, the significant interaction between the two factors should be appreciated.

Prolonged Ischemia Times for Heart Transplantation: Impact of the 2018 Allocation Change

BackgroundIn 2018, the United Network for Organ Sharing implemented a change in heart allocation policy resulting in increased organ ischemia times in early analyses. This study evaluated the effect of ischemia time on 1-year mortality in the context of allocation policy changes implemented in 2006 and 2018. MethodsThe United Network for Organ Sharing registry was used to identify adults undergoing heart transplantation from 2000 to 2020. Patients were stratified by the allocation policy era in which they received a transplant (2000–June 2006, July 2006–October 2018, October 2018–2020) and by ischemia time, defined as normal (≤4 hours) and prolonged (>4 hours). One-year survival was estimated using Kaplan-Meier analysis. Cox regression was used to determine risk-adjusted hazards for ischemia time on 1-year mortality. ResultsThere were 40 052 patients included for analysis. Ischemia times were normal in 32 585 (81.36%) and prolonged in 7467 (18.64%) patients. The proportion of transplantations with prolonged ischemia times increased with each subsequent policy era. After the 2018 policy change, 1-year survival was 90.92% with normal ischemia times vs 87.52% with prolonged ischemia times (P < .001). Ischemia time independently predicted 1-year mortality in each era with a hazard ratio of 1.20 per hour (P = .004) in the current era. ConclusionsProlonged ischemia times occur in a minority of cases but are increasing in frequency. The independent risk of prolonged ischemia time on 1-year mortality persists despite advances in storage technology and should remain a consideration in donor-recipient matching.

Right nephrectomy vs left nephrectomy in living donor transplantation, analysis of evolution and prognosis. Report from a tertiary care hospital

Abstract Kidney transplantation is the best renal replacement therapy for end-stage renal disease. Living donation constitutes the highest proportion of transplants in our country; donation nephrectomy requires assessment of renal function, which will influence the surgical planning of the kidney to donate. Methods We made a comparison between the evolutions of patients who underwent right nephrectomy versus left nephrectomy, for donation purposes in our center. Results Out of a total of 395 cases, 86 (21.7%) were right nephrectomies. With significant differences in the proportion of intraoperative complications, 2% for left nephrectomy and none for right nephrectomy; and more patients with postoperative complications (Clavien-Dindo II) for the left nephrectomy group, with a statistically significant difference (p = 0.02) Discussion and Conclusions Adequate surgical planning of the kidney to donate is required to ensure renal function after the donation event, as well as verification of the safety of the surgical act in the donor and the recipient, this must be collegiate and individualized for each transplant binomial.

IMPACT OF DONOR OVERDOSE DEATH ON HEART TRANSPLANTATION OUTCOMES IN BRITISH COLUMBIA

BACKGROUND In Canada, 3,799 opioid-related deaths were recorded in 2019, and this number remains elevated since the overdose emergency was declared in June 2016. British Columbia (BC) has the highest overdose death rate in Canada. Individuals who died after an overdose are eligible to donate organs for transplantation. This study aims to 1) examine the number of overdosed deceased heart donors (ODDs) over time and 2) examine the safety of ODD heart transplantation in BC. METHODS AND RESULTS We studied heart transplant recipients in the Patient Records and Outcome Management Information System from 2013 to 2019. Chart review was conducted to ascertain the cause of death. We examined longitudinal trends in the number of transplants after ODD heart donation. Kaplan-Meier and inverse probability of treatment weighted Cox-proportional hazard regression analysis (accounting for differences in donor and recipient factors) were conducted in the first 3 years post-transplant to examine the association of cause of donor death (ODD vs non-ODD) and recipient survival. During the study period, the proportion of transplants from ODDs increased from 0% to 30%. Of the 113 recipients, 73 (65%) received non-ODD hearts and 40 (35%) received ODD hearts. ODDs were less likely to have comorbidities such as diabetes (0.0% vs 2.7%) and hypertension (5.0% vs 12.3%), and the incidence of HCV positivity was low among ODD donors (n=2, 5%). Recipients of ODDs were older than non-ODDs (48% vs 37% were ≥60 years respectively), and more likely male (75% vs 64%). Crude 3-year survival was high in both groups (87.9% and 90.2% for ODD and non-ODD hearts respectively, p=0.65) Weighted cox models accounting for differences between groups, showed no significant difference in risk of death (HR: 1.66; 95% CI 0.76, 3.62, p = 0.203). CONCLUSION Heart transplantation from donors who died as a result of overdose death has increased significantly in the last decade. Survival after ODD heart transplantation is high and similar to survival after transplantation from non-ODD donors. As the number of individuals dying after overdose remains increased, organs from these donors should continue to be used to reduce the time on the wait-list. In Canada, 3,799 opioid-related deaths were recorded in 2019, and this number remains elevated since the overdose emergency was declared in June 2016. British Columbia (BC) has the highest overdose death rate in Canada. Individuals who died after an overdose are eligible to donate organs for transplantation. This study aims to 1) examine the number of overdosed deceased heart donors (ODDs) over time and 2) examine the safety of ODD heart transplantation in BC. We studied heart transplant recipients in the Patient Records and Outcome Management Information System from 2013 to 2019. Chart review was conducted to ascertain the cause of death. We examined longitudinal trends in the number of transplants after ODD heart donation. Kaplan-Meier and inverse probability of treatment weighted Cox-proportional hazard regression analysis (accounting for differences in donor and recipient factors) were conducted in the first 3 years post-transplant to examine the association of cause of donor death (ODD vs non-ODD) and recipient survival. During the study period, the proportion of transplants from ODDs increased from 0% to 30%. Of the 113 recipients, 73 (65%) received non-ODD hearts and 40 (35%) received ODD hearts. ODDs were less likely to have comorbidities such as diabetes (0.0% vs 2.7%) and hypertension (5.0% vs 12.3%), and the incidence of HCV positivity was low among ODD donors (n=2, 5%). Recipients of ODDs were older than non-ODDs (48% vs 37% were ≥60 years respectively), and more likely male (75% vs 64%). Crude 3-year survival was high in both groups (87.9% and 90.2% for ODD and non-ODD hearts respectively, p=0.65) Weighted cox models accounting for differences between groups, showed no significant difference in risk of death (HR: 1.66; 95% CI 0.76, 3.62, p = 0.203). Heart transplantation from donors who died as a result of overdose death has increased significantly in the last decade. Survival after ODD heart transplantation is high and similar to survival after transplantation from non-ODD donors. As the number of individuals dying after overdose remains increased, organs from these donors should continue to be used to reduce the time on the wait-list.

Abstract 15953: Impact of Citizenship on Heart Transplantation Outcomes in the United States

Background: Non-citizens of the United States face complex social and economic issues, which may impact their post-transplant outcomes compared to US citizens. To this end, we utilized the United Network for Organ Sharing (UNOS) database to examine post-heart transplant (OHT) outcomes, stratified by citizenship status. Methods: UNOS was queried to identify OHT recipients from 03/01/12 (start of new schema for citizenship categorization) through 10/18/18 (start of new heart allocation algorithm). Groups for analysis, were as follows: US Citizen, Non-US Citizen/Resident (NC-R) and Non-US Citizen/Non-US Resident (NC-NR). Post-transplant survival and rate of post-transplant rejection were assessed via Kaplan-Meier analysis and tests of proportions. Results: Of the 16,211 OHT recipients identified, 15,677 (96.7%) were US citizens and 534 (3.3%) were Non-Citizens. Among Non-Citizens, 430 were NC-R and 104 were NC-NR, representing 2.7% and 0.6% of the total transplants. Notably, NC-NR were younger than either Citizens or NC-R, and had the shortest median time from listing to transplant (NC-R 80 days vs. Citizens 107 days vs. NC-NR 76 days, p=0.001). The proportion of transplants received by non-citizens varied widely by region, ranging from 0.59% in region 8 (6/1018) to 8.31% (84/1011) in region 9. There was no significant difference in post-transplant survival estimates in citizens vs. non-citizens (logrank p = 0.542), nor in the proportion of patients treated for rejection by one year (15.0% vs. 16.1%, p= 0.504) Conclusion: Non-US Citizens receive three percent of heart transplants performed in the US each year. Post-heart transplant survival and rate of rejection are similar in US citizens and non-citizens. These data may be relevant in the context of evolving UNOS policies. Additional studies are needed are to further inform organ allocation policy.

Recipient Age, Not Donor Age, Impacts on Long Term Outcomes Following Heart Transplantation: A 23-year National Analysis from the United Kingdom

The impact of donor and recipient age on outcomes following heart transplantation remains controversial. The aim of this study was to evaluate the impact of donor and recipient age on survival following heart transplantation in the United Kingdom. All heart transplants in recipients over 18, performed at the six transplant centres in the UK between 01/01/1995 and 31/12/2018 were included. Data were obtained from the National Health Service: Blood and Transplant database. Recipients were divided into the following groups for analysis: 18-30, 31-40, 41-50, 51-60, 61+ years, and donors: 18-30, 31-40, 41-50, 51-55, 56+ years. 3161 patients were included in this study. The overall median recipient age was 50, which has remained constant over the study period, but the proportions of transplants in the 61+ and <41 groups have increased over time. The median donor age was 38, with a trend towards more donors >50 years being used over time, although the proportion of donors <40 has increased recently with utilisation of donors after circulatory death. Kaplan Meier survival analysis demonstrated a significant decrease in long-term survival with increasing recipient age post-transplantation that was retained with 90-day conditional survival (Table 1). Whilst donor age was also correlated with reduced recipient survival, with 90-day conditional survival, there was no such association (Table 1). The impact of donor age on unconditional survival was particularly significant for recipients <40 years (p=0.002). However, with 90-day conditional survival there was no such association between outcome and donor age even in this young cohort. In this national dataset, we demonstrate that with 90-day conditional survival, donor age has no impact on long-term outcomes following heart transplantation. However, longer term survival appears more dependent on recipient age. These data support the utilisation of hearts from older donors.

KAS Turns Four: The State of Deceased Donor Kidney Allocation in the U.S.

Background: This study examines very recent trends in deceased donor kidney transplantation to assess the performance of the kidney allocation system (KAS), implemented December 4, 2014, and whether bolus effects associated with KAS have stabilized nearly four years after implementation. Methods: The overall number of deceased donor kidney transplants, as well as the proportion of transplants by recipient and transplant characteristics, were calculated monthly from December 2013 through September 2018 and examined graphically. Kidney discard rates – the percentage of kidneys recovered for transplant not transplanted – were analyzed overall and stratified by donor Kidney Donor Profile Index (KDPI). Delayed graft function (DGF) was defined as the recipient requiring dialysis within one week of transplant; monthly rates were examined graphically. We also surveyed other published research to round out our assessment of KAS’s impact. Results: Marked bolus effects, particularly a sharp increase in transplants to highly sensitized and high dialysis time recipients, were associated with KAS implementation but have since stabilized. Transplant access has improved for African American candidates, who now receive a proportion of transplants comparable to their representation on the waiting list. Subtype-compatible (“A2/A2B to B”) transplants have increased sharply but are still numerically small (~20/month) and may have plateaued. Though the overall kidney discard rate has not changed appreciably over the past five years, the rate for KDPI 35-85% kidneys has trended slightly downward since 2017. After initially rising with KAS, DGF rates have tapered but still remain slightly above pre-KAS levels. One-year graft and patient survival remain excellent. Conclusions: The number of deceased donor kidney transplants has reached an all-time high and continues to rise, a boon for the nearly 100,000 patients with kidney failure on the waiting list. Several key bolus effects that were anticipated with KAS did indeed materialize, drastically changing the characteristics of the initial wave of post-KAS recipients. These bolus effects have since tapered, suggesting KAS has, by and large, reached a steady state. KAS has improved equity across ethnicities and levels of sensitization but did not attempt to resolve geographic inequities. Published research has confirmed that substantial geographic disparities remain. The goal of increasing utilization of kidneys at high risk of discard has not been met. Numerous policy changes and system improvement initiatives have been proposed, many of which are currently underway or pending implementation, to improve organ utilization.

The effect of inter-unit HLA matching in double umbilical cord blood transplantation for acute leukemia.

The effects of inter-unit HLA-match on early outcomes with regards to double cord blood transplantation have not been established. Therefore, we studied the effect of inter-unit HLA-mismatching on the outcomes of 449 patients with acute leukemia after double cord blood transplantation. Patients were divided into two groups: one group that included transplantations with inter-unit mismatch at 2 or less HLA-loci (n=381) and the other group with inter-unit mismatch at 3 or 4 HLA-loci (n=68). HLA-match considered low resolution matching at HLA-A and -B loci and allele-level at HLA-DRB1, the accepted standard for selecting units for double cord blood transplants. Patients’, disease, and transplant characteristics were similar in the two groups. We observed no effect of the degree of inter-unit HLA-mismatch on neutrophil (Hazard Ratio 1.27, P=0.11) or platelet (Hazard Ratio 0.1.13, P=0.42) recovery, acute graft-versus-host disease (Hazard Ratio 1.17, P=0.36), treatment-related mortality (Hazard Ratio 0.92, P=0.75), relapse (Hazard Ratio 1.18, P=0.49), treatment failure (Hazard Ratio 0.99, P=0.98), or overall survival (Hazard Ratio 0.98, P=0.91). There were no differences in the proportion of transplants with engraftment of both units by three months (5% after transplantation of units with inter-unit mismatch at ≤2 HLA-loci and 4% after transplantation of units with inter-unit mismatch at 3 or 4 HLA-loci). Our observations support the elimination of inter-unit HLA-mismatch criterion when selecting cord blood units in favor of optimizing selection based on individual unit characteristics.

OPTN/SRTR 2015 Annual Data Report: Early effects of the new kidney allocation system

In December 2014, a new kidney allocation system (KAS) was implemented in the United States in an attempt to improve access to transplant for historically underrepresented groups, and to incorporate longevity matching such that donor kidneys with the longest projected graft survival are given to recipients with the longest projected patient survival. The development of organ allocation policies is often guided by simulated allocation models, computer programs that simulate the arrival of donated organs and new candidates on the waiting list over a 1-year period to project outcomes under a new allocation method. We examined the early outcomes under the new KAS using quarterly data beginning in 2013, revealing whether trends were already underway before implementation. Quarterly data also serve to reveal any bolus effect, or a rapid rise or fall in the proportion of transplants in a given group due to reordering of the list, followed by tapering toward a new steady state. Post-KAS changes were notable for an increase in the proportion of transplants among younger candidates, black and Hispanic candidates, highly sensitized candidates, and those on dialysis for at least 5 years. Transplants among blood type B candidates increased slightly but these candidates remain underrepresented relative to their prevalence on the waiting list. Regional and national sharing increased under the new KAS, but transplants of kidneys with a kidney donor profile index above 85% decreased. Early graft survival appears unchanged, but given the increases in regional sharing, cold ischemia time, and transplants among highly sensitized candidates and candidates with long pretransplant dialysis time, long-term graft survival will need to monitored.

Establishment of Subspecialized Care in Hematologic Malignancies and a Hematopoietic Cell Transplantation Program

Establishment of Subspecialized Care in Hematologic Malignancies and a Hematopoietic Cell Transplantation Program

P015 Impact of the new kidney allocation system on highly sensitized recipient transplant rates: The utah experience

Aim A new deceased donor kidney allocation system (KAS) was implemented by UNOS on December 4, 2014. One key goal was to change the algorithm to better assist the previously disadvantaged highly sensitized population in receiving organ offers, regardless of the originating center’s geographical region. Candidate recipients with an allosensitization of 99% or 100% cPRA have been awarded an additional 50, and 202 points, respectively, to the waitlist score, thus giving them the highest priority for each kidney offer nationwide. One-year OPTN data indicate that overall in the US, the proportion of transplants occurring in the most highly sensitized patients has increased dramatically compared to the previous year. The goal of this study was to evaluate, and compare data from Utah to the national average. Method We reviewed and analyzed the annual rate of transplants in Utah based on recipient cPRA scores from 2011 through April 2016 and compared it to the OPTN data. Results One year prior to the implementation of the new KAS, in 2014 only two 99–100% cPRA patients were transplanted. In 2015, the first full year following implementation of the new KAS, a total of seven 99–100% cPRA patients were transplanted. Although comparison of the 1-year before versus after implementation of the new KAS suggests a 3.5 fold increase in the number of transplanted highly sensitized patients (cPRA 99–100%), this increase is more modest, only 2.3 fold if we compare it to the average number (3 per year) of highly sensitized recipients transplanted between 2011 and 2014. Conclusions The increase in transplant rates for 99–100% cPRA patients was more modest in Utah, compared to the national average. Possible reasons include that under the old KAS, local candidates were favored more heavily, and due to shorter overall wait times in Utah, highly sensitized patients may have had more offers compared to the national average. Other factors that may affect current transplant rates include a lower percentage of highly sensitized recipients locally, the EPTS of the local recipient pool, and the KDPI of donors. Although 2016 promises a greater rate of highly sensitized recipient transplants (4 performed through April), more data are needed to determine if the new KAS has a significant impact on the highly sensitized recipient transplant rate in Utah.

The weekend effect alters the procurement and discard rates of deceased donor kidneys in the United States

Factors contributing to the high rate of discard among deceased donor kidneys remain poorly understood and the influence of resource limitations of weekends on kidney transplantation is unknown. To quantify this we used data from the Scientific Registry of Transplant Recipients and assembled a retrospective cohort of 181,799 deceased donor kidneys recovered for transplantation from 2000-2013. We identified the impact of the day of the week on the procurement and subsequent utilization or discard of deceased donor kidneys in the United States, as well as report the geographic variation of the impact of weekends on transplantation. Compared with weekday kidneys, organs procured on weekends were significantly more likely to be discarded than transplanted (odds ratio: 1.16; 95% confidence interval: 1.13-1.19), even after adjusting for organ quality (adjusted odds ratio: 1.13; 95% confidence interval: 1.10-1.17). Weekend discards were of a significantly higher quality than weekday discards (Kidney Donor Profile Index: 76.5% vs. 77.3%). Considerable geographic variation was noted in the proportion of transplants that occurred over the weekend. Kidneys available for transplant over the weekend were significantly more likely to be used at larger transplant centers, be shared without payback, and experienced shorter cold ischemia times. Thus, factors other than kidney quality are contributing to the discard of deceased donor kidneys, particularly during weekends. Policy prescriptions, administrative or organizational solutions within transplant programs may potentially mitigate against the recent increase in kidney discards.

Changing the paradigm of organ utilization from PHS increased-risk donors: an opportunity whose time has come?

Approximately 8-11% of all organ donors are classified by Public Health Service (PHS) as increased-risk. The proportion of PHS increased-risk donors is on the rise. At the University of Washington Medical Center, in 2014, the proportion of transplants from PHS increased-risk donors was 28% of liver transplants and 23% of kidney transplants. Nationally, transplant providers have been reluctant to use organs from PHS increased-risk donors because of concern for transmission of HIV, HCV, or HBV. There is also patient apprehension when these organs are being offered, and thus the discard rate of these otherwise good quality organs is high. Because of the organ shortage, preventing underutilization of such organs is essential. We provide data and considerations that should be used to guide the use of organs from PHS increased-risk donors.

BFR (bendamustine, fludarabine, and rituximab) allogeneic conditioning for chronic lymphocytic leukemia/lymphoma: reduced myelosuppression and GVHD

AbstractMyelosuppression, graft-versus-host disease (GVHD), and relapse remain major causes of morbidity after stem cell transplantation for relapsed lymphoma. In this phase 1/2 study, we tested the safety and efficacy of escalating doses of bendamustine (70, 90, 110, and 130 mg/m2 per day for 3 days), coupled with our historical fixed doses of fludarabine and rituximab (BFR), as a nonmyeloablative allogeneic conditioning regimen for patients with relapsed lymphoma (n = 41) and chronic lymphocytic leukemia (CLL) (n = 15). Ten patients entered the phase 1 study; none experienced a dose-limiting toxicity. Forty-six additional patients were then treated in the phase 2 study at the maximum dose of 130 mg/m2 per day for 3 days. The proportions of transplants from matched siblings or unrelated donors were 54% and 46%. Remarkably, 55% of patients did not experience severe neutropenia. Forty-nine patients (88%) did not require platelet transfusion. The incidence of acute grade II-IV GVHD was 11%. The 2-year rate of extensive chronic GVHD was 26%. After a median follow-up duration of 26 months (range, 6-50 months), the 2-year overall and progression-free survival rates were 90% and 75%. In conclusion, our new BFR regimen is safe and effective for relapsed CLL and lymphoma patients. This trial was registered at www.clinicaltrials.gov as #NCT00880815.

Impact of Different Levels of Preformed Anti-HLA Donor Specific Antibodies Detected by Single Antigen Luminex Assay on Kidney Transplants Performed with Negative Complement Dependent Cytotoxicity T and B Crossmatches

This study aimed to evaluate the clinical relevance of different levels of preformed anti-HLA donor specific antibodies (DSA), revealed by Luminex single antigen beads assay (SAB) in kidney transplants performed with negative complement dependent cytotoxicity (CDC) crossmatches against donor T (CDC-anti-human globulin) and B lymphocytes. The study comprised 298 recipients of first (N=256) or second (N=42) kidney grafts, transplanted in a single center, between 2001 and 2006. At the time of transplantation no information regarding Luminex-detected antibodies was available. In this study, stored pre-transplant sera were screened for anti-HLA antibodies (Labscreen® Mixed, One Lambda) and the positive ones were further analyzed with the SAB assay (Labscreen® Single Antigen, One Lambda). In the SAB assay, all reactions with normalized mean fluorescence intensity (nMFI) >300 were classified as positive and DSA were defined as antibodies against HLA-A, B or DR mismatches. Based on these results, the recipients were divided into three groups: PRA+,DSA+, PRA+,DSA-, and PRA-. Females, non-white patients, retransplants, and ATG induction therapy were significantly (p< 0.001) more frequent among PRA+ recipients. The proportion of transplants with deceased donors was the same in the three groups (42, 43 and 36%, in PRA+,DSA+, PRA+,DSA-, and PRA- recipients, respectively). The mean time of post-transplant follow-up was 57.8, 59.0 and 54.4 months for PRA+,DSA+, PRA+,DSA-, and PRA- recipients, respectively. Graft survival curves were constructed with Kaplan-Meier method and compared with the log-rank test; Cox regression analysis was used to calculate risk of graft loss. Graft survival did not differ between the three above mentioned groups of recipients. We then sub-divided the PRA+,DSA+ recipients into the following DSA nMFI ranges: 300-1,500, >1,500-3,000, >3,000-6,000 and >6,000. No difference in graft survival was observed among PRA+,DSA+ with nMFIs 300-1,500, PRA+,DSA-, and PRA- recipients. On the other hand, no graft survival difference was observed among recipients with DSA with nMFIs >1,500-3,000, >3,000-6,000 or >6,000. Therefore, further analyses were conducted considering only two groups of recipients: one comprising all recipients without DSA or with DSA < 1500 nMFI (N=228), and the other comprising recipients with DSA >1,500 MFI (N=70). Graft survival was significantly lower (p< 0.001) in recipients with DSA >1,500 MFI (one-year graft survival: 78.6% vs 92.1%; 5-year graft survival: 64.3% vs 78.9%). DSA >1500 MFI conferred a relative risk of 4.4 (95% CI 1.7-11.1) for graft loss at one year and of 3.0 (95% CI 1.4-6.4) for late graft loss in recipients with functional kidneys at one year. Recipients transplanted with DSA >1500 nMFI also presented lower estimated glomerular filtration rates (Cockroft-Gault formula), at the first month (43.0±19.9 vs. 56.0±20.3 ml/min, p< 0.001) and first year (56.6±17.2 vs. 65.0±21.2 ml/min, p< 0.01). In conclusion, the results of this study showed that DSAs directed to HLA-A, B and DR mismatches with nMFIs from 300 to 1,500 did not have any influence on the transplant outcome, whereas DSAs with nMFIs >1,500, although not associated with immediate graft losses, conferred a risk for graft dysfunction already at the end of the first month, and a risk for long-term graft loss.

Changes in Pediatric Renal Transplantation After Implementation of the Revised Deceased Donor Kidney Allocation Policy

In October 2005, the United Network for Organ Sharing (UNOS) implemented a revised allocation policy requiring that renal allografts from young deceased donors (DDs) (<35 years old) be offered preferentially to pediatric patients (<18 years old). In this study, we compare the pre- and postpolicy quarterly pediatric transplant statistics from 2000 to 2008. The mean number of pediatric renal transplants with young DDs increased after policy implementation from 62.8 to 133 per quarter (p < 0.001), reflecting a change in the proportion of all transplants from young DDs during the study period from 0.33 to 0.63 (p < 0.001). The mean number of pediatric renal transplants from old DDs (> or =35 years old) decreased from 22.4 to 2.6 per quarter (p < 0.001). The proportion of all pediatric renal transplants from living donors decreased from 0.55 to 0.35 (p < 0.001). The proportion from young DDs with five or six mismatched human leukocyte antigen (HLA) loci increased from 0.16 to 0.36 (p < 0.001) while those with 0 to 4 HLA mismatches increased from 0.18 to 0.27 (p < 0.001). Revision of UNOS policy has increased the number of pediatric renal transplants with allografts from young DDs, while increasing HLA-mismatched allografts and decreasing the number from living donors.

Novel features of computer-simulated clonal life of Paramecium caudatum

The clone of the ciliated protozoan Paramecium caudatum has the immaturity period of about 60 fissions and the lifespan of about 600 fissions. These life cycle figures have been depicted through laboratory experiments that allow continuous cell divisions for hundreds, which never occur in nature. We here constructed the nature-mimicking model culture that alternated the log- and stationary phases to allow conjugation, and computer-simulated the age structure modifying parameters such as cell distributions to start the culture, fission rates, death rates, immaturity periods, probabilities of conjugation, proportions of transplantation and so on. The average and maximum ages in the culture after thousands of alternations were converged to 43±2 and 140±5 fissions, respectively, when parameters for the immaturity period and the maximum clonal lifespan were set at 60 and 600 fissions. This result explains why cells collected in nature are usually young and vigorous. The average and maximum ages proportionally prolonged as the immaturity period was prolonged, as reported true for species of the ciliate. These results indicate the validity of our simulation. The average and maximum ages remained unchanged when the initial condition for starting the culture was changed from two complementary mating-type cells to a population with a quadratic-function distribution, and when the fission rate at the log-phase and the death rate at the stationary phase were modified for older ages. The average and maximum ages changed slightly when either the conjugation rate or the proportion of transplantation was somewhat lowered. Although they changed considerably when such parameters as the immaturity period, conjugation rate and death rate were extremely modified, no clones with the age over 230 fissions appeared in any simulations. These results indicate the robustness of the model, which provides us with fresh insight into the structural system of the clonal lifespan of P. caudatum in nature.

The activity of hematopoietic stem cell transplantation in Korea

Since the first successful allogeneic hematopoietic SCT (HSCT) was performed in Korea in 1983, there has been a noticeable progress in both the quantity and quality of HSCT over 24 years. There are 38 HSCT centers in Korea and the number of both allogeneic and autologous HSCTs has been increasing every year. As of December 2006, a total of 9561 HSCTs have been carried out in Korea, including 5617 allogeneic (59%) and 3944 autologous HSCTs (41%). The main indications were acute leukemia (3979, 78% allogeneic); lymphoma (1244, 90% autologous); myeloma (939, 92% autologous) and aplastic anemia (938). Characteristically, severe aplastic anemia accounts for a considerable proportion of transplants (10%), compared with western countries. Recently, there has been a marked increase in the number of unrelated transplants and the usage of PBSCs. The pattern of infectious diseases associated with HSCT is quite different. The rapid expansion of unrelated donor pools worldwide has changed the outlook of an unrelated donor search in Korea.