Dose Of Globulin Research Articles

Cumulative rabbit anti-human thymocyte globulin dose to recipient weight during the peri-operative period is an independent risk factor for early postoperative urinary tract infection after kidney transplantation

Anti-human thymocyte globulin-Fresenius (ATG-F) is frequently utilized to achieve successful induction for kidney transplantation recipients. This study aimed to examine the association between the ATG-F dose-to-recipient-weight ratio (ADR) and the risk of developing urinary tract infections (UTIs) following kidney transplantation. Data of kidney transplant recipients who underwent ATG-F-induction peri-operatively in a medical center were retrospectively collected, and the incidence of UTIs during the first postoperative year was also recorded. The risk of UTI associated with ADR was analyzed, and receiver operating characteristic curves were drawn to determine the optimal ADR, followed by Cox regression models. In total, 131 recipients were included, with an UTI incidence of 19.08% and a mean interval of 3.08 months. The optimal ADR was 6.34, involving 41 and 90 patients in the low ADR and high ADR groups, respectively. The UTI-free rate in the low ADR group was significantly higher than that in the high ADR group (p = 0.007). Cox regression analysis indicated that a high ADR independently increased the risk of UTI following kidney transplantation (hazard ratio: 5.306, 95% confidence interval: 1.243–22.660, p = 0.024). There was no significant difference in rejection rate between the high ADR and low ADR groups. In conclusion, a high ADR increased the incidence of early postoperative UTI among kidney transplant recipients.

A Head-to-head Comparison of De Novo Sirolimus or Everolimus Plus Reduced-dose Tacrolimus in Kidney Transplant Recipients: A Prospective and Randomized Trial.

Mammalian target of rapamycin inhibitors (mTORi), sirolimus (SRL) and everolimus (EVR), have distinct pharmacokinetic/pharmacodynamics properties. There are no studies comparing the efficacy and safety of de novo use of SRL versus EVR in combination with reduced-dose calcineurin inhibitor. This single-center prospective, randomized study included first kidney transplant recipients receiving a single 3 mg/kg antithymocyte globulin dose, tacrolimus, and prednisone, without cytomegalovirus (CMV) pharmacological prophylaxis. Patients were randomized into 3 groups: SRL, EVR, or mycophenolate sodium (MPS). Doses of SRL and EVR were adjusted to maintain whole blood concentrations between 4 and 8 ng/mL. The primary endpoint was the 12-mo incidence of the first CMV infection/disease. There were 266 patients (SRL, n = 86; EVR, n = 90; MPS, n = 90). The incidence of the first CMV event was lower in the mTORi versus MPS groups (10.5% versus 7.8% versus 43.3%, P < 0.0001). There were no differences in the incidence of BK polyomavirus viremia (8.2% versus 10.1% versus 15.1%, P = 0.360). There were no differences in survival-free from treatment failure (87.8% versus 88.8% versus 93.3%, P = 0.421) and incidence of donor-specific antibodies. At 12 mo, there were no differences in kidney function (75 ± 23 versus 78 ± 24 versus 77 ± 24 mL/min/1.73 m2, P = 0.736), proteinuria, and histology in protocol biopsies. Treatment discontinuation was higher among patients receiving SRL or EVR (18.6% versus 15.6% versus 6.7%, P = 0.054). De novo use of SRL or EVR, targeting similar therapeutic blood concentrations, shows comparable efficacy and safety. The reduced incidence of CMV infection/disease and distinct safety profile of mTORi versus mycophenolate were confirmed in this study.

(1153) Characterization of CD3-Guided Anti-Thymocyte Globulin Dose Minimization for Renal Sparing Induction after Heart Transplant

(1153) Characterization of CD3-Guided Anti-Thymocyte Globulin Dose Minimization for Renal Sparing Induction after Heart Transplant

336.3: Clinical Utility of Donor-Derived Cell-Free DNA During the Period of Recovery of Renal Function After Kidney Transplantation

Background: The transplant of kidneys with high KDPI, and the incidence and duration of delayed graft function (DGF) are risk factors associated with incomplete recovery of kidney function (IRF). In both situations, kidney biopsies are essential to exclude the diagnosis of acute rejection (AR). Purpose: This study evaluates the clinical utility of monitoring donor-derived cell-free DNA (dd-cfDNA), a biomarker of kidney injury, in recipients of high Kidney Donor Profile Index (KDPI) transplants during the period of kidney function recovery. Methods: This is a single center, prospective, cohort study in recipients of high KDPI kidneys who developed delayed graft function (DGF), defined as the need for dialysis within the first week after transplantation. All patients received a single 3 mg/kg anti-thymocyte globulin dose, tacrolimus, mycophenolate, and prednisone. Blood samples were obtained at 14 (D14) and 30 (D30) days to measure the percentage (%) of dd-cfDNA. The dd-cfDNA > 1% is associated with increased probability for acute rejection (AR). Results: This preliminary analysis includes data from 69 patients. The median KDPI was 73% [IQR 47-87] and the mean cold ischemia time was 27± 7 hours. The incidence of DGF was 89.8% with a median duration of 6 (IQR 2 – 9) days. At D14 the median GFR was 12 ml/min/1.73 m2 (IQR 6-21) and the median dd-cfDNA levels were 0.43% (IQR 0.02-0.78), with 19 patients (28%) showing dd-cfDNA >1%. Surveillance biopsies during DGF were performed in 42 (61%) patients showing one T-cell mediated rejection IA (dd-cfDNA of 0.41%) and 4 borderline changes (dd-cfDNA 0.82%, 0.85%, 0.98%, 1.90%). Using dd-cfDNA >1% to guide the indication of the surveillance biopsy, we would have avoided 22 (52%) biopsies but missed 1 (2%) patient with AR. At D30, the median GFR was 36 ml/min/1.73 m2 (IQR 28-48) and the median dd-cfDNA levels were 0.40% (IQR 0.01-0.66), with 12 patients (19%) showing dd-cfDNA >1%. Surveillance biopsies performed in 21 (30.43%) patients with incomplete recovery of kidney function showed 4 borderline changes (dd-cfDNA 0.17%, 0.66%, 0.67%, and 2.80%). Using dd-cfDNA >1% to guide the indication of the surveillance biopsy, we would have avoided 12 (57%) biopsies without missing any AR episodes. Overall, 5 (7%) patients showed dd-cfDNA >1% at D14 and D30, but none of them showed biopsy confirmed AR. Conclusions: This preliminary analysis suggests that monitoring dd-cfDNA may assist clinical decision during the period of DGF and in kidney transplant recipients with incomplete recovery of graft function.

Impact of Anti-T-lymphocyte globulin dosing on GVHD and Immune reconstitution in matched unrelated myeloablative peripheral blood stem cell transplantation

Data on the influence of different Anti-lymphocyte globulin (ATLG) doses on graft versus host disease (GVHD) incidence and immune reconstitution in matched unrelated (MUD) allogeneic Stem cell transplantation (allo-SCT) is limited. This retrospective study conducted at the University Medical-Center Hamburg compares GVHD and Immune reconstitution after myeloablative MUD (HLA 10/10) PBSC allogeneic stem cell transplant between 30 mg/Kg (n = 73) and 60 mg/Kg (n = 216) ATLG. Detailed phenotypes of T, B natural killer (NK), natural killer T (NKT) cells were analyzed by multicolor flow at day 30, 100, and 180 posttransplant. Neutrophil and platelet engraftments were significantly delayed in the 60 mg/kg group with a higher Cumulative incidence of Infections (67% vs 75% p = 0.049) and EBV (21% vs 41% p = 0.049) reactivation at day 100 in this group. In the 30 mg/kg group, we observed a faster reconstitution of naïve-B cells (p < 0.0001) and γδ T cells (p = 0.045) at day+30 and a faster naïve helper T-cell (p = 0.046), NK-cells (p = 0.035), and naïve B-cell reconstitution (p = 0.009) at day+180. There were no significant differences in aGVHD, cGVHD, NRM, RI, PFS, and OS between the groups. The choice of ATLG dose has significant impact on IR but not on GVHD after MUD-allo-SCT. Higher doses are associated with delayed engraftment and increased infections.

Assessment of rabies immune globulin dose rounding at a university health system

PurposeDescribe a dose rounding strategy for rabies immune globulin (RIG) administration. MethodsMulticenter, retrospective, observational review of patients that received RIG following an exposure from an animal with potential to transmit rabies infection in one health-system from March 2011 through December 2021. The primary outcome was to describe the RIG dose rounding strategy and population of patients that received RIG rounded to the nearest vial size compared to those that did not. Secondary outcomes evaluated additional costs and RIG international units (IU) wasted that could have occurred (rounded group) or did occur (not rounded group), re-presentation to the ED or primary care provider (PCP) within 7 days due to RIG related complaint, and occurrence of rabies infection. Data collection included patient demographics, exposure information, and RIG dose administered. Descriptive data and univariate analyses are reported. Cost and RIG IU wasted were calculated for the dosing strategies. Results426 patients were included; 373 (88%) had RIG rounded to the nearest vial size and 53 (12%) did not (mean age 36.1 years ±20.5, 51.6% male, most common exposures were bats [50%], type was bite [58%], and category III exposures [92%]). Those that had RIG rounded were younger and had lower total RIG doses, but similar IU/kg doses to those not rounded. A cost savings of $144,815 and prevention of 40,572 RIG IU wasted was calculated from those patients that had RIG rounded. There was no difference in the rate of re-presentation within 7 days and no cases of human rabies infection in the region during the study period. ConclusionsRIG dose rounding to the nearest vial size is associated with cost savings and prevention of wasting RIG IU. There was no association with re-presentation to the ED or PCP with RIG related issues within 7 days from administration.

Fetomaternal hemorrhage assessment in Rh-negative patients undergoing dilation and evacuation between 20 and 24 weeks’ gestational age: A retrospective cohort study

ObjectiveTo estimate the rate of requiring more than one 300-mcg Rh D immune globulin dose for fetomaternal hemorrhage (FMH) at the time of second-trimester dilation and evacuation (D + E). Study designWe performed a retrospective cohort analysis of patients at greater than 20 weeks’ gestation who underwent D + E, had Rh D-negative blood type, and received FMH quantification testing. ResultsOf 25 eligible patients, 24 had negative quantification of FMH; one had positive quantification that did not meet the clinical threshold for additional dosing. ConclusionsThe absolute risk of requiring additional Rh D immune globulin after D+E for pregnancies greater than 20 weeks’ gestation was 0%.

Individualised dosing of anti-thymocyte globulin in paediatric unrelated allogeneic haematopoietic stem-cell transplantation (PARACHUTE): a single-arm, phase 2 clinical trial

Anti-thymocyte globulin, which is used in the conditioning of haematopoietic stem-cell transplantation (HSCT) to prevent graft-versus-host disease (GVHD) and graft failure, has highly variable pharmacokinetics. Overexposure to anti-thymocyte globulin leads to poor CD4+ T-cell immune reconstitution, which is associated with inferior overall survival. We hypothesised that individualised anti-thymocyte globulin dosing would promote CD4+ immune reconstitution, while still preventing GVHD and graft failure. We report the results of a prospective, single-arm, phase 2 clinical trial done at the University Medical Center Utrecht and the Princess Máxima Center for Pediatric Oncology (Utrecht, Netherlands) to investigate individualised dosing of anti-thymocyte globulin for unrelated allogeneic HSCT in paediatric patients. Anti-thymocyte globulin dosing was based on bodyweight, absolute lymphocyte counts before the first dose, and the stem-cell source, with cumulative doses ranging from 2-10 mg/kg. Patients younger than 18 years receiving a first HSCT with a T-cell repleted graft for any indication and a Lansky/Karnofsky performance status of at least 70% were eligible for inclusion. The primary endpoint was CD4+ immune reconstitution (>0·05 × 109 CD4+ T-cells per L twice within 100 days [±3] after transplantation). The primary endpoint needed to be met in 38 of 53 evaluable patients (no death, relapse, or graft failure before day 100). Toxicity was registered according to Common Terminology Criteria for Adverse Events criteria version 4.0. The study is registered with the Dutch Trial Register, NL4836. Between July 1, 2015, and Aug 22, 2018, 58 patients were included in the study, of whom 51 were evaluable for the primary endpoint. Median follow-up was 25·6 months (IQR 15·0-37·0) and median age was 7·4 years (IQR 2·8-13·2). 29 (50%) of 58 patients were female. CD4+ immune reconstitution was reached in 41 (80%, 95% CI 67-90, in survival analysis) of 51 evaluable patients, hence the study met its primary endpoint. There was no difference in CD4+ immune reconstitution between patients who received different stem-cell sources (87% [95% CI 61-96] in cord blood, 77% [54-89] in bone marrow [p=0·62]). The most common grade 3-5 adverse events were infections (32 [50%] patients had grade 3, two [3%] patients had grade 4, and seven [11%] patients had fatal events) and immunological disorders (seven [11%] patients had grade 3, three [5%] patients had grade 4, and five [8%] patients had fatal events). Two (3%) of 64 patients died of GVHD, which might be indirectly related to the intervention. Individualised dosing of anti-thymocyte globulin led to a significant improvement in early CD4+ immune reconstitution without increasing GVHD and graft failure incidence. Promotion of early CD4+ immune reconstitution by individualising anti-thymocyte globulin dose might improve outcomes of allogeneic HSCT. Sanofi.

Rabbit antithymocyte globulin dose and early subclinical and clinical rejections in kidney transplantation.

Antithymocyte globulin (ATG) is a commonly used induction agent in kidney transplant recipients. However, the optimal dosing has not been well defined. Our protocol aims for a 5-6mg/kg cumulative dose. It is unclear if a dose lower than 5mg/kg is associated with more rejection. We performed a retrospective cohort study of patients who received a kidney transplant at our center between January 1, 2013 and December 31, 2016. Primary outcome was biopsy proven acute rejection (clinical and subclinical) in the first 6months after kidney transplant. CMV viremia in high risk (D+/R-) recipients and BK viremia was compared as a secondary endpoint. Of the 543 patients, the Low Dose (LD) group (n = 56) received <5mg/kg ATG and Regular Dose (RD) group (n = 487) received ≧5mg/kg. Patients in RD were more sensitized (higher PRA and CPRA). LD received a dose of 4 ± 1.1mg/kg ATG whereas RD received 5.6 ± .3mg/kg ATG (P < .001). TCMR (Banff 1A or greater) was present in 34% of patients in LD versus 22% in RD (P = .04) (OR 2.1; 95%CI 1.12-3.81; P = .019). There was no difference in the incidence of CMV or BK viremia. ATG doses lower than 5mg/kg may be associated with a heightened risk of rejection despite a low degree of sensitization.

Optimized antithymocyte globulin dose in high risk kidney transplantation

Optimized antithymocyte globulin dose in high risk kidney transplantation

Malignancy among adult heart transplant recipients following patient-tailored dosing of anti-thymocyte globulin: a retrospective, nested case-control study of individualized dosing.

Post-transplant malignancy is diagnosed in approximately 18% of heart transplant patients and is a leading cause of death post-transplant. One modifiable risk factor is the type and amount of immunosuppression received. Contemporary rabbit anti-thymocyte globulin (rATG) dosing strategy using T-cell-guided dosing, and its effect on malignancy in heart transplant patients is unclear. This was a single-center, retrospective chart review of heart transplant recipients receiving rATG for induction. Patients diagnosed with malignancy post-transplant were matched 1:2 to controls using a nested case-control design. The primary endpoint was to determine the relative risk of rATG exposure with the actual incidence of malignancy post-transplant. The secondary endpoint was the impact of maintenance immunosuppression on malignancy risk. Of the 126 patients included in the study, 25 developed malignancy and were matched to 50 control patients. The median cumulative rATG dose in milligrams (mg) between groups was 365 mg in malignancy cases and 480 mg in controls (OR 0.90, 95% CI 0.75-1.08, P = 0.28). In both the univariate and multivariable analysis, there was no statistically significant difference in malignancy risk found with any maintenance immunosuppressant. The results of this study showed that patient-tailored rATG dosing strategies may not be associated with malignancy development as previously thought.

Optimizing antithymocyte globulin dosing in haploidentical hematopoietic cell transplantation: long-term follow-up of a multicenter, randomized controlled trial

Given that randomized studies testing the long-term impact of antithymocyte globulin (ATG) dosing are scarce, we report the results of an extended follow-up from the original trial. In our prospective, multicenter, randomized trial, 408 leukemia patients 14–65 years of age who underwent haploidentical hematopoietic cell transplantation (haplo-HCT) under our original “Beijing Protocol” were randomly assigned one-to-one to ATG doses of 7.5 mg/kg (n = 203, ATG-7.5) or 10 mg/kg (n = 205, ATG-10.0) at four sites. Extended follow-up (median 1968 d (range: 1300–2710 d) indicated comparable 5-year probabilities of moderate-to-severe chronic graft-versus-host disease (GVHD) (hazard ratio (HR): 1.384, 95% confidence interval (CI): 0.876–2.189, P = 0.164), nonrelapse mortality (HR: 0.814, 95% CI: 0.526–1.261, P = 0.357), relapse (HR: 1.521, 95% CI: 0.919–2.518, P = 0.103), disease-free survival (HR: 1.074, 95% CI: 0.783–1.473, P = 0.658), and GVHD-free/relapse-free survival (HR: 1.186, 95% CI: 0.904–1.555, P = 0.219) between groups (ATG-7.5 vs. ATG-10.0). The 5-year rate of late effects did not differ significantly. However, the cytomegalovirus/Epstein-Barr virus-related death rate was much higher in the ATG-10.0 cohort than in the ATG-7.5 cohort (9.8% vs. 1.5%; P = 0.003). In summary, patients undergoing haplo-HCT benefit from 7.5 mg/kg ATG compared to 10.0 mg/kg ATG based on a balance between GVHD and infection control. ATG (7.5 mg/kg) is potentially regarded as the standard regimen in the platform. These results support the optimization of ATG use in the “Beijing Protocol”, especially considering the potential economic advantage in developing countries.

The influence of the antithymocyte globulin dose on clinical outcomes of patients undergoing kidney retransplantation

Optimizing antithymocyte globulin (rATG) dosage is critical for high immunological risk patients undergoing a repeat kidney transplant. This natural retrospective cohort study compared clinical outcomes of two successive cohorts of consecutive recipients of retransplants receiving 5 x 1 mg/kg (rATG-5, n = 100) or a single 3 mg/kg (rATG-3, n = 110) dose of rATG induction therapy. All patients had negative complement-dependent cytotoxicity crossmatch and no anti-HLA A, B, DR donor-specific antibodies (DSA). The primary endpoint was efficacy failure (first biopsy-proven acute rejection, graft loss, or death) at 12 months. There was no difference in the cumulative incidence of efficacy failure (18.0% vs. 21.8%, HR = 1.22, 95% CI 0.66-2.25), respectively. There were no differences in 3-years freedom from biopsy proven acute rejection, and patient, graft, and death-censored graft survivals. There were no differences in the incidence of surgical complications (25.0% vs. 18.2%; p 0.151), early hospital readmission (27.8% vs. 29.5%; p = 0.877) and CMV infections (49% vs. 40%; p = 0.190). There were also no differences in the incidence (59.6% vs. 58.7%, p = 0.897) and duration of delayed graft function but a stable difference in estimate glomerular filtration rate was observed from month 1 (54.7±28.8 vs. 44.1±25.3 ml/min/1.73 m2, p = 0.005) to month 36 (51.1±27.7 vs. 42.5±24.5, p = 0.019). Mean urinary protein concentration (month 36: 0.38±0.81 vs. 0.70±2.40 g/ml, p = 0.008) and mean chronic glomerular Banff score in for cause biopsies (months 4-36: 0.0±0.0 vs. 0.04±0.26, p = 0.044) were higher in the rATG-3 group. This cohort analysis did not detect differences in the incidence of efficacy failure and in safety outcomes at 12 months among recipients of kidney retransplants without A, B, and DR DSA, receiving induction therapy with a single 3 mg/kg rATG dose or the traditional 5 mg/kg rATG.

Impact of anti-thymocyte globulin dose for graft-versus-host disease prophylaxis in allogeneic hematopoietic cell transplantation from matched unrelated donors: a multicenter experience

Despite the widespread use of rabbit anti-thymocyte globulin (ATG) to prevent acute and chronic graft-versus-host disease (aGVHD, cGVHD) after allogeneic hematopoietic cell transplantation (allo-HCT), convincing evidence about an optimal dose is lacking. We retrospectively evaluated the clinical impact of two different ATG doses (5 vs 6–7.5 mg/kg) in 395 adult patients undergoing HSCT from matched unrelated donors (MUD) at 3 Italian centers. Cumulative incidence of aGVHD and moderate-severe cGVHD did not differ in the 2 groups. We observed a trend toward prolonged overall survival (OS) and disease-free survival (DFS) with lower ATG dose (5-year OS and DFS 56.6% vs. 46.3%, p=0.052, and 46.8% vs. 38.6%, p=0.051, respectively) and no differences in relapse incidence and non-relapse mortality. However, a significantly increased infection-related mortality (IRM) was observed in patients who received a higher ATG dose (16.7% vs. 8.8% in the lower ATG group, p=0.019). Besides, graft and relapse-free survival (GRFS) was superior in the lower ATG group (5-year GRFS 43.1% vs. 32.4%, p=0.014). The negative impact of higher ATG dose on IRM and GRFS was confirmed by multivariate analysis. Our results suggest that ATG doses higher than 5 mg/kg are not required for MUD allo-HCT and seem associated with worse outcomes.

West Nile Viral Meningitis in a Heart Transplant Recipient

Introduction West Nile virus (WNV) infection is uncommon and can cause encephalitis or meningitis. The CDC reported 958 cases diagnosed in 47 continental states and Washington DC in 2019. Only one other case has been reported in San Diego County so far in 2020. WNV infection in solid organ transplant recipients is rare and typically presents as encephalitis, with few reported cases in orthotopic heart transplant (OHT) recipients. Here we describe a case of WNV meningitis in a patient 1-year post-OHT. Case Report A 53-year-old female with history of non-ischemic cardiomyopathy due to myocarditis underwent OHT at UC San Diego 1 year ago. Her postoperative course was complicated by 3R rejection and was treated with anti-thymocyte globulin and pulse dose steroids. She recovered well, however 11 months post-OHT she experienced insidious onset of nausea and vomiting. One month later she started to experience malaise, tremors and headaches so she presented to our emergency room. Her immunosuppression regimen at that time included tacrolimus 2 mg twice daily and mycophenolate mofetil 750 mg twice daily. She was febrile to 103°F so blood and sputum cultures were obtained, lumbar puncture (LP) was performed and broad-spectrum antibiotics were started. The LP demonstrated elevated opening pressures of 31 mmHg, pleocytosis and elevated glucose, however cerebrospinal fluid (CSF) cultures and PCR array were unremarkable. Antibiotics were discontinued after 48 hours of negative cultures. CSF and blood returned positive for anti-WNV IgM and IgG. Later in her admission she developed reactive polyarthralgia which was treated with a 5-day burst of oral prednisone. She was discharged after 9 days, but continued to experience nausea, vomiting and polyarthralgia. She was readmitted 2 weeks later (13 months after transplant) with worsening joint pain, nausea, vomiting and blurry vision. Ophthalmologic exam was notable for papilledema, and brain magnetic resonance imaging revealed ventriculomegaly. Repeat LP was notable for interval decrease in opening pressures (now 22 mmHg), and CSF serology remained positive for anti-WNV IgM and IgG. Serum WNV PCR was negative. Given the improvement in her opening pressures, she was managed supportively and discharged after 4 days on a longer prednisone taper for reactive arthritis. Summary Here we report a rare case of WNV meningitis in a recent OHT recipient whose condition improved with supportive care.

Long-term Efficacy and Safety of Everolimus Versus Mycophenolate in Kidney Transplant Recipients Receiving Tacrolimus.

The short-term efficacy and safety of everolimus in combination with tacrolimus have been described in several clinical trials. Yet, detailed long-term data comparing the use of everolimus or mycophenolate in kidney transplant recipients receiving tacrolimus are lacking. This is a 5-y follow-up post hoc analysis of a prospective trial including 288 patients who were randomized to receive a single 3-mg/kg dose of rabbit antithymocyte globulin, tacrolimus, everolimus (EVR), and prednisone (rabbit antithymocyte globulin/EVR, n = 85); basiliximab, tacrolimus, everolimus, and prednisone (basiliximab/EVR, n = 102); or basiliximab, tacrolimus, mycophenolate, and prednisone (basiliximab/mycophenolate, n = 101). There were no differences in the incidence of treatment failure (31.8% versus 40.2% versus 34.7%, P = 0.468), de novo donor-specific HLA antibodies (6.5% versus 11.7% versus 4.0%, P = 0.185), patient (92.9% versus 94.1% versus 92.1%, P = 0.854), and death-censored graft (87.1% versus 90.2% versus 85.1%, P = 0.498) survivals. Using a sensitive analysis, the trajectories of estimated glomerular filtration rate were comparable in the intention-to-treat (P = 0.145) and per protocol (P = 0.354) populations. There were no differences in study drug discontinuation rate (22.4% versus 30.4% versus 17.8%, P = 0.103). In summary, this analysis in a cohort of de novo low/moderate immunologic risk kidney transplant recipients suggests that the use of a single 3 mg/kg rabbit antithymocyte globulin dose followed by EVR combined with reduced tacrolimus concentrations was associated with similar efficacy and renal function compared with the standard of care immunosuppressive regimen.

Low-Dose Antithymocyte Globulin Has No Disadvantages to Standard Higher Dose in Pediatric Kidney Transplant Recipients: Report From the Pediatric Nephrology Research Consortium

IntroductionRabbit antithymocyte globulin (rATG) dosing strategies for induction in pediatric kidney transplantation vary between centers. It is not known whether a lower rATG induction dose provides safe and effective immunosuppression compared with a “standard” higher dose.MethodsWe performed a retrospective multicenter study of all isolated first-time kidney transplant recipients <21 years old who received rATG induction between 1 January 2010 and 31 December 2014 at 9 pediatric centers. An a priori cutoff of a 4.5-mg/kg cumulative rATG dose was used to identify low (≤ 4.5 mg/kg) and standard (> 4.5 mg/kg) exposure groups. Outcomes examined included 12 months posttransplant graft function (estimated glomerular filtration rate [eGFR]); the occurrence of acute rejection, donor-specific antibody (DSA), neutropenia, and viral infection (cytomegalovirus [CMV], Epstein-Barr virus [EBV], and BK virus); and 24-month outcomes of posttransplant lymphoproliferative disorder (PTLD) occurrence and patient and graft survival.ResultsTwo hundred thirty-five patients were included. Baseline features of the low and standard rATG dose groups were similar. By 12 months, the rATG dose group had no significant impact on the occurrence of neutropenia, positive DSA, or viral polymerase chain reaction (PCR). Graft function was similar. Acute rejection rates were similar at 17% (low dose) versus 19% (standard dose) (P = 0.13). By 24 months, graft survival (96.4% vs. 94.6%) and patient survival (100% vs. 99.3%) were similar between the low- and standard-dose groups (P = 0.54 and 0.46), whereas the occurrence of PTLD trended higher in the standard-dose group (0% vs. 2.6%, P = 0.07).ConclusionA low rATG induction dose ≤ 4.5 mg/kg provided safe and effective outcomes in this multicenter low immunologic risk pediatric cohort. Prospective studies are warranted to define the optimal rATG induction dose in pediatric kidney transplantation.

Optimizing Antithymocyte Globulin Dosing in Haploidentical Hematopoietic Cell Transplantation: Long-Term Follow-Up of a Multicenter, Randomized Controlled Trial

Background: Since randomised studies testing the long-term impact of antithymocyte globulin (ATG) dosing are scarce, we report the results of an extended follow-up from the original trial. Methods: In our prospective, multi-center, randomized trial, 408 patients 14 to 65 years of age with acute leukemia who underwent myeloablative haploidentical hematopoietic cell transplantation (haplo-HCT) were randomly assigned one to one to ATG dosing of 7.5mg/kg (n =203, ATG-7.5) or 10 mg/kg (n = 205, ATG-10) at 4 sites. We analyzed the long-term clinical outcomes including late effects. The original trial was registered at clinicaltrials.gov as NCT01883180. Findings: Extended follow-up (median 1968 days (range, 1300-2710) indicated comparable 5-year probabilities of moderate-to-severe chronic graft-versus-host disease (GVHD) (hazard ratio (HR): 1.384, 95% confidence interval (CI): 0.876–2.189, P = .164), non-relapse mortality (HR: 0.814, 95% CI: 0.526–1.261, P = .357), disease-free survival (HR: 1.074, 95% CI: 0.783–1.473, P = .658), and GVHD-free/relapse-free survival (HR: 1.186, 95% CI: 0.904–1.555, P = . 219) between groups (ATG-7.5 vs ATG-10). 5-year rate of late effects did not differ significantly. However, the infection related deaths rate was much more in ATG-10 cohort compared with that of the ATG-7.5 cohort (18.0% vs 11.3%; P = .069). Interpretation: Patients undergoing haplo-HCT benefit from the use of 7.5 mg/kg ATG as opposed to 10 mg/kg ATG, with the balance between GVHD and infection control. 7.5mg/kg ATG should thus be regarded as the standard regimen in the platform. Trial Registration: The original trial was registered at clinicaltrials.gov as NCT01883180. Funding The National Key Research and Development Program of China. Declaration of Interest: None of the authors has any potential financial conflict of interest related to this manuscript. Ethical Approval: The study protocol was approved by the 8 ethics committee of each participating center.

Reassessing Rabbit Antithymocyte Globulin Induction in Kidney Transplantation (RETHINK): An Analysis of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) Registry.

There is no consensus on rabbit antithymocyte globulin (rATG) dose used for induction immunosuppression in pediatric kidney transplants. We aimed to identify whether a lower rATG dose provides safe and effective immunosuppression compared with a higher dose. We retrospectively analyzed all first-time kidney transplant recipients (aged <21 y) in the North American Pediatric Renal Trials and Collaborative Studies registry since 1998 on mycophenolate mofetil- and tacrolimus-based immunosuppression with rATG induction. An a priori cutoff of 7.5 mg/kg cumulative rATG dose was used to identify low (<7.5 mg/kg) and high (≥7.5 mg/kg) exposure groups. Primary outcome was time to first-acute rejection episode. Secondary outcomes included graft function, patient survival, hospitalizations due to infections, and time to first-posttransplant lymphoproliferative disorder episode. Four hundred fifty-five patients met inclusion criteria (59% male, 49% whites, 26% blacks, 38% living donor source). Median cumulative rATG dose was 6.8 mg/kg with a median of 5 doses and a median 1.5 mg/kg/dose introduced at a median of postoperative 0 days. Sixty-four percent received <7.5 mg/kg total rATG. There was no difference in age at transplant, gender, race, end-stage renal disease causes, or HLA mismatch among groups. Time to first-acute rejection was similar (P = 0.07). There was no significant difference in graft or patient survival or time to posttransplant lymphoproliferative disorder. Hospitalization for infection rates was similar. These data demonstrate a wide variation in cumulative rATG induction dose. A smaller rATG dose <7.5 mg/kg may provide effective and safe immunosuppression compared with a higher dose.

Cytomegalovirus Experience in Pediatric Kidney Transplantation in 26 Years’ Time

IntroductionIn this study,we investigated the presence of cytomegalovirus (CMV) infection in kidney transplanted children and its effect on kidney dysfunction. Material and MethodsOne hundred thirty-five pediatric renal transplant patients were included in this study. The presence of CMV infection, CMV risk status, and other clinical features of the patients were evaluated retrospectively. ResultsFifty-three percent of all patients and 68.8% of patients with CMV were male. The mean age was 12 years in all patients and CMV groups. According to the CMV risk classification, 40.9% of the patients with CMV infection/disease were in the high-risk group (CMV D+R-). In CMV risk groups, the presence of CMV infection/disease was similar. Cold ischemia time, male sex (patients and donors), deceased donor, higher HLA-mismatches, and cumulative antithymocyte globulin dose were found as risk factors for CMV infection/disease. Acute rejection/graft failure was observed in 27% of all patients. CMV infection has no effect on rejection/graft failure and survival. DiscussionThe frequency and risk factors of CMV in renal transplant children in our study were consistent with the literature. ConclusionsCMV infection was found in one-fifth of our patients and the majority (71.9%) of them developed infection in the first 6 months. In one-third of our patients acute rejection/graft failure was observed. There was no effect of CMV infection on rejection/graft failure and survival in pediatric patients with proper and effective treatment.