Low-dose Rabbit Antithymocyte Globulin Research Articles

Low dose rabbit antithymocyte globulin is non-inferior to higher dose in low-risk pediatric kidney transplant recipients.

Currently, there is no consensus among pediatric kidney transplant centers regarding the use and regimen for immunosuppressive induction therapy. In this single center, retrospective cohort study, pediatric kidney transplant recipients transplanted between 1 May 2013 and 1 May 2018 with rabbit antithymocyte globulin (rATG) induction were included. We stratified patients based on immunological risk, with high risk defined as those with repeat transplant, preformed donor specific antibody, current panel-reactive antibodies > 20%, 0 antigen match and/or African-American heritage. Outcome of interest was the incidence of biopsy proven acute rejection by 1year. A total of 166 patients met inclusion criteria. Age of patients was 12years (11 mo-21 y), (median, range), 21.5% received a living donor transplant and 50.6% were female. Low-immunologic-risk patients were divided into 2 groups, those who received the lower cumulative rATG dose of ≤ 3.5mg/kg (n = 52) versus the higher cumulative dose of > 3.5mg/kg (n = 47). The median total dose in the lower dose group was 3.1 (IQR 0.3) and 4.4 (IQR 0.8) in the higher dose group, P < 0.001. Rejection rate did not differ significantly between the 2 treatment groups (7/52 vs. 6/47). None in the lower dose group developed BK nephropathy versus 3 in the higher dose group. Graft loss due to BK nephropathy occurred in 1 patient in the higher dose group. Graft loss in the whole cohort at 12months was a rare event (n = 1) with 99.5% graft survival and 100% patient survival. Reduced rATG dosing (≤ 3.5mg/kg) when compared to higher dosing (> 3.5mg/kg) is safe and effective in low-risk pediatric kidney transplant recipients without increasing risk of rejection. A higher resolution version of the Graphical abstract is available as Supplementary information.

Lower Absolute Lymphocyte Count Before Conditioning Predicts High Relapse Risk in Patients After Haploidentical Peripheral Blood Stem Cell Transplantation With Low Dose Anti-Thymocyte Globulin/Post-Transplant Cyclophosphamide for GvHD Prophylaxis

Standard anti-thymocyte globulin (ATG) weight-based dosing often resulted in highly variable ATG exposure, which had profound effects on relapse and survival, especially in recipients with relatively low absolute lymphocyte count (ALC) before conditioning. Data regarding rabbit ATG pharmacokinetics and pharmacodynamics in the setting of HLA-haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) is lacking. We conducted a retrospective study on 90 consecutive patients who underwent haplo-PBSCT with low dose rabbit ATG (5 mg/kg) plus low dose post-transplant cyclophosphamide (50 mg/kg) based regimen for graft-versus-host disease (GvHD) prophylaxis. We compared serum concentration of ATG and post-transplant results between patients with ALC<500/μl and ALC≥500/μl before conditioning. Patients with ALC<500/μl had higher ATG concentrations, delayed immune reconstitution, lower incidence of grade II-IV acute GvHD (0 vs. 19.42%, P = 0.043), higher risk of Epstein-Barr virus infection within 100 days post-transplant (47.78% vs. 22.22%, P = 0.020) and 1-year relapse rate (33.33% vs.11.59%, P = 0.041), and lower 1-year overall survival (OS) (52.38% vs.79.71%, P = 0.004), 1-year relapse free survival (RFS) (47.62% vs. 75.36% for RFS, P = 0.014), and 1-year GvHD free relapse-free survival (GRFS) (42.89% vs. 65.22%, P = 0.043). ALC<500/μl before conditioning was a significant poor risk factor for relapse, OS, RFS, and GRFS.

Radiation-sparing reduced-intensity unrelated umbilical cord blood transplantation for rare hematological disorders in children.

Graft failure is a major pitfall of unrelated umbilical cord blood transplantation (CBT) in children with rare hematological disorders other than acute leukemia, such as acquired and inherited bone marrow failure, myelodysplastic syndrome, juvenile myelomonocytic leukemia, and chronic myeloid leukemia. We developed a less-toxic conditioning regimen for CBT that achieves a higher rate of complete donor chimerism, and retrospectively compared it against two other conditioning regimens for CBT performed at our single institution. The engraftment rate with complete donor chimerism was 100% and 5-year event-free survival (5y-EFS) was 90.9% in patients using our latest regimen (n = 11) of reduced-intensity conditioning (RIC) containing fludarabine (Flu) 180mg/m2, melphalan (MEL) 210mg/m2, and low-dose rabbit anti-thymocyte globulin (LD-rATG) 2.5mg/kg without irradiation (regimen C). Outcomes were better than in patients (n = 10) treated with previous regimens involving irradiation (5y-EFS 30.0%, p = 0.004): regimen A, consisting of myeloablative conditioning containing cyclophosphamide (CY) and total body irradiation (TBI) with 8-12Gy, or regimen B, consisting of RIC with Flu, CY, horse ATG, and thoracoabdominal irradiation (TAI) with 6Gy. In conclusion, Flu/MEL/LD-rATG (regimen C) without TBI/TAI may be preferable as RIC for unrelated CBT in children with rare hematological disorders.

T-cell replete haploidentical stem cell transplantation with low dose anti-thymocyte globulin for relapsed/refractory Ewing sarcoma family tumors.

BackgroundDespite intensive multimodal therapies, the prognosis of relapsed/ refractory Ewing sarcoma family tumors (RR‐ESFTs) is dismal. Some case reports using allogeneic stem cell transplantation (allo SCT) for RR‐ESFTs have been reported, however, the efficacy of allo SCT is yet to be established.AimThe purpose of this study was to evaluate the response and toxicity of T‐cell replete haploidentical SCT (TCR‐haplo‐SCT) in RR‐ESFTs.Methods and resultsIn this study, we retrospectively analyzed six patients with RR‐ESFTs who received TCR‐haplo‐SCT. Four patients had relapsed and two patients had refractory Ewing sarcoma. Before the TCR‐haplo‐SCT, all patients received a reduced intensity‐conditioning regimen containing fludarabine, melphalan, and low‐dose rabbit anti‐thymocyte globulin (2.5 mg/kg), as well as graft‐versus‐host disease (GVHD) prophylaxis, which consisted of tacrolimus, methotrexate, and prednisolone. Primary neutrophil engraftment was achieved in all the patients. Four patients developed acute GVHD (aGVHD) (grade I, 1; grade II, 1; grade III, 2), and two patients developed chronic GVHD (cGVHD). Among the four that developed aGVHD, three survived for 14, 116, and 129 months without relapse, while one died due to a transplant‐related complication. In contrast, the two patients who did not develop aGVHD experienced relapse early after TCR‐haplo‐SCT.ConclusionsIn this study, three of the six patients with RR‐ESFTs survived for more than one year without relapse, and the treatment toxicity was considered acceptable even for patients who underwent high‐intensity pretreatment. TCR‐haplo‐SCT could be a potential therapeutic option for patients with RR‐ESFTs.

Impact of Low-Dose rATG Prior to Matched Sibling Donor Hematopoietic Stem Cell Transplantation for Hematologic Malignancies: Reduced Risk of Chronic Graft-versus-Host Disease and Improved Survival Outcomes.

PurposeTo explore the efficacy of low-dose rabbit antithymocyte globulin (rATG) in matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) for patients with acute leukemia or myelodysplastic syndrome.Patients and MethodsWe performed a retrospective study of 79 patients with hematologic malignancies who received MSD-HSCT. All patients received standard graft-versus-host disease (GVHD) prophylaxis comprising cyclosporine, mycophenolate mofetil and short-term methotrexate. Among them, 38 were administered 5 mg/kg rATG as part of GVHD prophylaxis. Clinical outcomes including overall survival (OS), GVHD and relapse were analyzed.ResultsNo graft failure occurred in the antithymocyte globulin (ATG) or non-ATG group. The cumulative incidences of grade 2–4 and 3–4 acute GVHD at day +100 were 13.3% versus 19.5% (p=0.507) and 5.7% versus 15.2% (p=0.196), respectively. The 2-year cumulative incidences of chronic GVHD (cGVHD) were 35.4% and 60.4% (p=0.039), and those of extensive cGVHD were 12.9% and 40.0% (p=0.015), respectively. In a multivariate analysis, the use of low-dose rATG was an independent protective factor for extensive cGVHD (hazard ratio [HR] 0.256; 95% confidence interval [CI], 0.080 to 0.822, p=0.022). The 2-year OS was 88.1% and 68.4% (p=0.038), respectively, and the use of low-dose rATG was the only protective factor in the multivariate analysis (HR 0.216; 95% CI, 0.059 to 0.792, p=0.021). There was no significant difference between the two groups in terms of the 2-year cumulative incidence of relapse, leukemia-free survival or GVHD-free and relapse-free survival.ConclusionLow-dose rATG used in MSD-HSCT as part of the conditioning regimen results in a reduced incidence of cGVHD and improves survival outcomes.

Outcome Comparison between Low-Dose Rabbit Anti-Thymocyte Globulin and Basiliximab in Low-Risk Living Donor Kidney Transplantation.

The objective of this study was to compare outcomes between basiliximab and low-dose r-ATG in living donor kidney transplantation recipients with low immunological risk. Patients in the low-dose r-ATG group received 1.5 mg/kg of r-ATG for 3 days (total 4.5 mg/kg). Graft survival, patient survival, acute rejection, de novo donor specific antibody (DSA), estimated glomerular filtration rate (e-GFR) changes, and infection status were compared. Among 268 patients, 37 received r-ATG, and 231 received basiliximab. There was no noticeable difference in the graft failure rate (r-ATG vs. basiliximab: 2.7% vs. 4.8%) or rejection (51.4% vs. 45.9%). de novo DSA was more frequent in the r-ATG group (11.4% vs. 2.4%, p = 0.017). e-GFR changes did not differ noticeably between groups. Although most infections showed no noticeable differences between groups, more patients in the r-ATG group had cytomegalovirus (CMV) antigenemia and serum polyomavirus (BK virus) (73.0% vs. 51.9%, p = 0.032 in CMV; 37.8% vs. 15.6%, p = 0.002 in BK), which did not aggravate graft failure. Living donor kidney transplantation patients who received low-dose r-ATG and patients who received basiliximab showed comparable outcomes in terms of graft survival, function, and overall infections. Although CMV antigenemia, BK viremia were more frequent in the r-ATG group, those factors didn’t change the graft outcomes.

Comparison of clinical outcomes of deceased donor kidney transplantations, with a focus on three induction therapies.

BackgroundGraft survival rate of kidney transplantation recipients improves after induction therapy. However, there is no conclusive evidence on which regimen is superior for deceased donor kidney transplantation (DDKT). This study aims at discussing effective induction therapy in DDKT.MethodsBetween 2003 and 2016, 395 DDKT recipients were divided into three groups following induction therapy. Recipients of the basiliximab group (n=184) received basiliximab (20 mg/kg) on days 0 and 4. Recipients of the low-dose rabbit anti-thymocyte globulin (rATG) group (n=113) received rATG (1.5 mg/kg) on days 0, 1, and 2, while those of the high-dose rATG group (n=98) received it for more than 4 days. We retrospectively reviewed and analyzed the clinical outcomes and adverse effects of induction therapy.ResultsCompared to other groups, the low-dose rATG group donors were older (P<0.001); rATG group donors had higher serum creatinine levels (P<0.001), and the basiliximab group showed a lower delayed graft function rate (P=0.004). In graft failure, the low-dose rATG group did not differ significantly from the basiliximab group (P=0.080), but was significantly different from the high-dose rATG group (P=0.004).ConclusionsThe low-dose rATG group had the best graft survival rate, although it had older donors and higher serum creatinine levels. Therefore, low-dose rATG may be considered an effective induction therapy in DDKT.

Long-Term Clinical and Immunological Profile of Kidney Transplant Patients Given Mesenchymal Stromal Cell Immunotherapy.

We report here the long-term clinical and immunological results of four living-donor kidney transplant patients given autologous bone marrow-derived mesenchymal stromal cells (MSCs) as part of a phase 1 study focused on the safety and feasibility of this cell therapy. According to study protocols implemented over time, based on initial early safety findings, the patients were given MSC at day 7 posttransplant (n = 2) or at day −1 pretransplant (n = 2) and received induction therapy with basiliximab and low-dose rabbit anti-thymocyte globulin (RATG) or RATG alone, and were maintained on low-dose ciclosporin (CsA)/mycophenolate mofetil (MMF). All MSC-treated patients had stable graft function during the 5- to 7-year follow-up, without increased susceptibility to infections or neoplasm. In three MSC recipients, but not historical control patients, circulating memory CD8+ T cell percentages remained lower than basal, coupled with persistent reduction of ex vivo donor-specific cytotoxicity. Two patients showed a long-lasting increase in the regulatory T cell/memory CD8+ T cell ratio, paralleled by high circulating levels of naïve and transitional B cells. In one of these two patients, CsA was successfully discontinued, and currently the low-dose MMF monotherapy is on the tapering phase. The study shows that MSC therapy is safe in the long term and could promote a pro-tolerogenic environment in selected patients. Extensive immunomonitoring of MSC-treated kidney transplant recipients could help selection of patients for safe withdrawal of maintenance immunosuppressive drugs (NCT00752479 and NCT02012153).

Low Dose Rabbit Anti-Thymocyte Globulin as an Induction immunosuppression in High-Risk Renal Transplant Recipients

Low Dose Rabbit Anti-Thymocyte Globulin as an Induction immunosuppression in High-Risk Renal Transplant Recipients

Impact of low-dose rabbit anti-thymocyte globulin in unrelated hematopoietic stem cell transplantation.

We retrospectively evaluated the outcome of administering low-dose rabbit anti-thymocyte globulin (thymoglobulin: ATG-T) to 219 patients (ATG-T group, n = 30; no-ATG-T group, n = 189) who received an initial unrelated hematopoietic stem cell transplantation (uHSCT). The median total dose of ATG-T was 1.5 mg/kg. There was no significant difference in the cumulative incidences of grade II-IV (42 vs. 38 %, P = 0.87) and grade III-IV (5 vs. 7 %, P = 0.52) acute GVHD. In patients who received uHSCT from a donor with at least one HLA allele mismatch, the cumulative incidence of extensive chronic GVHD was significantly lower in the ATG-T group than that in the no-ATG-T group (13 vs. 44 %, P = 0.02). No patient in the ATG-T group developed chronic lung dysfunction. The probabilities of 1-year, GVHD-free/relapse-free survival (GRFS) were 61 % in the ATG-T group and 35 % in the no-ATG-T group (P = 0.02). Patients in the ATG-T group discontinued immunosuppressive drugs significantly earlier than those in the no-ATG-T group (P < 0.01). The use of low-dose ATG-T did not increase the incidence of severe infectious disease. The use of low-dose ATG-T in patients who received uHSCT was associated with a superior GRFS, reflecting the reduced incidence of severe/persistent GVHD without compromising overall survival.

A case report of refractory cytopenia of childhood effectively treated with low-dose rabbit anti-thymocyte globulin in immunosuppressive therapy

A case report of refractory cytopenia of childhood effectively treated with low-dose rabbit anti-thymocyte globulin in immunosuppressive therapy

Risk Factors of Cytomegalovirus Disease in Kidney Transplant Recipients: A Single-Center Study in Thailand

BackgroundCytomegalovirus (CMV) infection significantly causes morbidity in kidney transplant (KT) recipients. This study aims to investigate the incidence, timing, and risk factors of CMV infection in KT recipients. MethodsThis is a single-center retrospective study at a tertiary referral hospital. Patients who underwent KT from January 2012 to September 2014 were included. CMV infection was defined as the presence of CMV measured by polymerase chain reaction. Logistic regression analysis was performed to assess independent risk factors of CMV infection after KT. ResultsOf 121 KT patients enrolled, 120 patients had CMV D+/R+ serostatus, and 1 had D-/R+. CMV infection occurred in 33 (27.2%) of patients with a median follow-up time of 16 (IQR 4–25) months. Of those, 25 had CMV viremia and 8 had CMV disease mainly involving the gastrointestinal system. In total, 86% of CMV cases occurred within 3 months. All recipients received anti–IL-2 receptor antibody (IL-2 RA), low-dose rabbit antithymocyte globulin (rATG; total of 1.5 mg/kg), or standard-dose rATG (1.5 mg/kg/day for 3–5 days) for induction. Of those, the incidences of CMV infection were 19.6%, 50%, and 67%, respectively. Preemptive strategy was used in all but 1 patient in the IL-2 RA and low-dose rATG group, whereas universal prophylaxis was given in 67% of patients in the standard-dose rATG group. Independent risk factors of CMV infection were older recipient age (per 10-year increase, OR 1.5; 95% CI 1.04–2.23), and induction with standard (OR 8.19; 95% CI 2.29–34) and low-dose rATG (OR 3.87; 95% CI 1.06–12.23). ConclusionsMore than 25% of KT recipients developed CMV infection within 6 months after KT. The risk is increased in older recipients and induction with rATG. The level of CMV risk in low-dose rATG is 52% lower than in standard-dose rATG. In a limited-resource setting such as Thailand, deferred or preemptive strategy may be acceptable in patients who received IL-2 RA and low-dose rATG, while prophylactic therapy should be given to patients who received standard-dose rATG.

Low-Dose RATG with or without Basiliximab in Renal Transplantation: A Matched-Cohort Observational Study

Background/Aims: In renal transplantation, peri-operative low-dose rabbit-antithymocyte-globulin (RATG) plus basiliximab induction prevented acute allograft rejection more effectively than post-operative RATG plus basiliximab induction. We investigated the specific antirejection contribution of basiliximab in this context. Methods: This single-center, observational, matched-cohort study evaluated allograft rejections (primary outcome), steroid exposure and side effects, GFR (iohexol plasma clearance) and treatment costs in 16 deceased-donor renal transplant recipients induced with RATG (0.5 mg/kg/day) and 32 age-, gender- and treatment-matched reference-patients given RATG plus basiliximab (20 mg on days 0 and 4). Results: Induction was well tolerated. At 18 months, 8 patients (50%) vs. 3 reference-patients (9.4%) rejected the graft [HR (95% CI): 6.53 (1.73-24.70), p = 0.006]. Difference was significant (p < 0.01) even after adjusting for recipient/donor age and gender, cold ischemia time and HLA mismatches. There were 1 antibody-mediated rejection and 2 moderate cellular rejections in patients vs. none in reference-patients (p = 0.032). The median (interquartile range) prednisone cumulative dose was remarkably higher in patients than reference-patients [4.78 (1.12-6.10) vs. 0.19 (0.18-3.81) grams, p = 0.002]. Three patients vs. 24 reference-patients were off-steroid at study end (p < 0.001). Three patients vs. no reference-patient developed new-onset diabetes (p = 0.003). Both inductions similarly depleted B-cells. Outcomes of AZA- vs. MMF-treated participants were similar. GFR was similar in all groups. Compared to MMF, AZA therapy saved ≈ EUR 2,500/year and by month 14.3 post-transplant compensated basiliximab costs. Conclusion: In renal transplantation, basiliximab plus peri-operative low-dose RATG more efficiently prevented allograft rejection than RATG monotherapy, and minimized steroid exposure and toxicity. AZA- vs MMF-based maintenance immunosuppression largely compensated the extra costs of basiliximab.

Similar outcomes of peripheral blood stem cells vs. bone marrow for human leukocyte antigen‐matched unrelated donor transplantation in adult patients with acute myeloid leukemia using risk‐adapted graft‐versus‐host disease prophylaxis

In unrelated donor allogeneic stem cell transplantation (URD-SCT), most studies reported that peripheral blood stem cells (PBSC) resulted in higher incidence of acute and/or chronic graft-versus-host disease (GVHD) without survival benefits compared with bone marrow (BM). To overcome these shortcomings of PBSC, we have used a risk-adapted GVHD prophylaxis for patients that received HLA-matched URD-SCT, which was adding low-dose rabbit antithymocyte globulin (Thymoglobulin(®) , 1.25 mg/kg for 2 d) to conditioning in the transplants with PBSC and not BM. To determine whether this strategy is effective, we analyzed 115 adult patients with acute myeloid leukemia who received HLA-matched URD-SCT with PBSC (n = 70) or BM (n = 45) using our risk-adapted GVHD prophylaxis strategy. The PBSC group showed faster neutrophil (11 d vs. 13 d; P < 0.01) and platelet (12 d vs. 18 d; P < 0.01) engraftment compared with the BM group. No difference was observed in the incidence of acute GVHD grade II-IV at 100 d (54.3% vs. 64.4%; P = 0.38) and chronic GVHD at 4 yr (65.1% vs. 60.0%; P = 0.83). Other outcomes including the incidence of relapse (30.8% vs. 31.2%; P = 0.53), non-relapse mortality (13.5% vs. 6.9%; P = 0.24), disease-free survival (55.7% vs. 61.9%; P = 0.68), and overall survival (62.2% vs. 63.2%; P = 0.96) at 4 yr were not significantly different. Our risk-adapted GVHD prophylaxis strategy resulted in similar transplant outcomes including comparable incidence of GVHD between the PBSC and BM groups in HLA-matched URD-SCT.

Favorable T Cell Reconstitution In Reduced Intensity Conditioned Allogeneic Stem Cell Transplantation with Low-Dose Rabbit Anti-Thymocyte Globulin and Total Body Irradiation

Severe graft versus host disease (GVHD) continues to compromise transplant outcomes following reduced intensity (RI) allogeneic stem cell transplantation (SCT). ATG reduces the risk of GVHD in unrelated donor (URD) stem cell transplant (SCT) recipients. Here we report the results of a randomized phase II clinical trial evaluating two doses of rabbit ATG (Thymoglobulin, Sanofi Aventis) 5.1 (ATG5) and 7.5 mg/kg (ATG7.5) administered along with 450 cGy total body irradiation (TBI). This study followed an earlier trial which examined the optimal schedule of ATG administration in this regimen (Toor et al, BMT 2008). ATG was administered from day -9 to day -7, and fractionated TBI on day -1 and 0. Tacrolimus and mycophenolate mofetil were administered for GVHD prophylaxis. Forty-one patients with advanced hematologic malignancies were randomized and conditioned with ATG-TBI, stratified according to donor type, HLA-matched related (MRD) or unrelated (URD) donor. ATG5 had 10/19 URD recipients compared to 12/22 ATG7.5. Median age of the patients was 57; 9 patients had MM, 15 NHL, 12 CLL/PLL and 6 MDS/AML. Twenty-six were in CR at SCT (11 ATG5, 15 ATG7.5), 13 were in PR/SD (7 and 6 in the two arms) and 2 (1 in each arm) were in untreated relapse. Median number of prior therapies was 4 in each arm; 6 (ATG5) and 9 (ATG7.5) patients had a prior autologous SCT. Myeloid engraftment occurred at a median of 12 days after stem cell infusion in both arms; median neutrophil chimerism at 4, 8, 12 and 24 weeks was 0% recipient in both arms. Persistent mixed T cell chimerism was observed more frequently in the ATG7.5 arm with a trend toward full donor chimerism over time in the ATG5 patients (Figure 1); mean T cell chimerism was 14% in ATG5 and 25% in ATG7.5 at 4 weeks; 8 and 26 (repeated measures ANOVA p=0.058) at 8 weeks; 9 and 31 (RMANOVA p=0.016) at 12 weeks; and 6 and 27 (p=0.029) at 24 weeks respectively. Mean donor derived T cell counts (ddCD3; product of absolute CD3+ cell count and donor T cell chimerism) were 182/microliter, 1080, 872, 876 in ATG5 and 182, 290, 296, 445 in ATG7.5 patients at the corresponding time points, being significantly larger in the ATG5 arm compared to ATG7.5 at 8 (p = 0.008) and 12 weeks (p = 0.052). The changes in ddCD3 between successive months were significantly larger in the ATG5 cohort between 1 and 2 months (p = 0.004). Further, 2 patients in the ATG7.5 arm developed secondary graft loss indicating more robust engraftment in the ATG5 cohort, likely due to superior immune reconstitution. There was no significant difference in the survival between arms (Log-Rank P = 0.8). The 2-year survival rates were 64% (95%CI: 61%, 67%) ATG5 and 54% (95%CI: 50%, 58%) ATG7.5. Day 100 TRM was 0% in both arms; classical onset grade III-IV acute GVHD was not observed in either arm, 2 patients in the ATG7.5 arm developed grade II acute GVHD. Delayed onset acute GVHD occurred in 5 patients in the ATG5 cohort, (3 Grade III-IV) and 4 ATG7.5 (2 Grade III-IV) following early tapering of immunosuppression. Chronic GVHD occurred in 2 patients in ATG5 (1 mild, 1 severe) compared to 7 in ATG7.5 cohort (2 mild, 1 moderate, 4 severe). Overlap syndrome occurred in 2 in ATG5 patients and none in ATG7.5 cohort. GVHD was observed more frequently in patients with higher ddCD3 counts at 8 weeks. Relapse occurred in 26% vs 27%, ATG5 and ATG7.5 (Grey's test P=0.9). Two patients in the ATG5 cohort needed donor lymphocyte infusions (DLI) compared to 8 in ATG7.5 (Grey's test P = 0.07); 6 of these patients received prophylactic DLI for declining donor chimerism (5 in the ATG 7.5 cohort). A composite index (relapse, DLI, non-relapse mortality) was not significantly different between the cohorts (Log Rank P = 0.9). High-dose valacyclovir was used for CMV prophylaxis; CMV reactivation (&gt;1000 copies/microl) developed in 2 ATG5 patients and 3 in ATG7.5 arm; EBV reactivation (&gt;10 copies/microl) developed in 1 and 2 patients respectively in the two cohorts. In summary our clinical trial demonstrates that ATG5 in combination with low dose TBI yields optimal T cell engraftment, with an excellent safety profile and good clinical outcomes, and may serve as a platform for adoptive immunotherapy. Phase III clinical trial comparing this regimen with more established regimens for RI-SCT is being planned. Disclosures: Toor: Sanofi Avnetis: Research Funding.

In Kidney Transplant Patients, Alemtuzumab but Not Basiliximab/Low-Dose Rabbit Anti-Thymocyte Globulin Induces B Cell Depletion and Regeneration, Which Associates with a High Incidence of De Novo Donor-Specific Anti-HLA Antibody Development

In this single-center matched-cohort study, we evaluated the phenotype of repopulating B cells and its correlation with donor-specific anti-HLA Ab development and long-term graft function in 16 renal transplant recipients and 32 age- and gender-matched controls induced with alemtuzumab or basiliximab (Bas)/low-dose rabbit anti-thymocyte globulin (rATG), respectively. Alemtuzumab, but not Bas/rATG, profoundly depleted peripheral B cells in the first 2 mo posttransplantation. Early posttransplant, naive B cells were significantly depleted, whereas Ag-experienced and memory B cells were partially spared. Transitional B cells transiently increased 2 mo posttransplant. At month 6 posttransplant, pregerminal center B cells emerged, a process promoted by increased BAFF serum levels. Thereafter, B cell counts increased progressively, mainly due to expansion of naive B cells. Conversely, Bas/rATG did not modify the B cell phenotype throughout the follow-up period. Alemtuzumab was associated with a higher incidence of de novo DSA compared with Bas/rATG. DSA development was predicted by changes in the B cell compartment and correlated with worse long-term graft function. Thus, alemtuzumab-induced B cell depletion/reconstitution may promote chronic humoral responses against the graft.

Graft-versus-Host Disease: State of the Science

Despite concerted research efforts, prevention and treatment of graft-versus-host disease (GVHD) have not changed significantly over the past 3 decades. The goal of this session is to provide an outline of the current state of the science with respect to the prevention, treatment, and evaluation of acute and chronic GVHD. In addition, we detail those strategies most likely to be at the forefront of clinical research in the upcoming years.

Universal perioperative antimicrobial prophylaxis is not necessary in kidney transplantation

Despite significant improvements in renal transplantation, certain basic issues remain unresolved such as the routine use of perioperative antimicrobial prophylaxis (AMP). To address the need for AMP, we retrospectively evaluated the clinical course of 442 consecutive renal transplant recipients (RTRs) who did not receive any AMP except for trimethoprim/sulfamethoxazole. Three hundred and forty RTRs received induction therapy with low-dose rabbit anti-thymocyte globulin, while the other 102 patients were treated with basiliximab. All RTRs received tacrolimus, mycophenolic acid, and prednisone. Nine patients (2%) developed surgical site infection (SSI). SSIs were more common in obese and older patients. All SSIs were superficial and responded well to wound drainage and outpatient antibiotic therapy. No patient or graft was lost owing to SSI. Our study shows that despite many predisposing factors, SSIs are rare following renal transplantation even in the absence of AMP. Therefore, to avoid the emergence of antibiotic-resistant pathogens, excessive costs, and antibiotic-related adverse events, we suggest that AMP should be used only in selected circumstances such as in recipients older than 65 yr or when the body mass index (BMI) is > 35.

Low-Dose Rabbit Antithymocyte Globulin Versus Basiliximab Induction Therapy in Low-Risk Renal Transplant Recipients: 8-Year Follow-Up

Antibody induction is effective in preventing acute rejection, but its effects on long-term renal allograft function and survival remain controversial. Moreover, given the risks of antibody induction, full-dose lymphocyte-depleting therapy for low-risk patients is usually avoided. However, the benefit and risks associated with low-dose (Lo) rabbit antithymocyte globulin (rATG; 3–5 mg/kg total) induction in a low-risk population have not been explored. We now report the long-term outcomes in this patient population. We defined low risk as white, panel-reactive antibody < 30%, and non-Donor with Cardiac Death (DCD) recipients. We compared the risk of acute rejection and graft survival for both living donor (LD) and deceased donor (DD) recipients. The average dose of rATG was 3.1 ± 1.2 mg/kg. Forty DD recipients received basiliximab (BSX) and 145 patients were induced with Lo rATG. Twenty LD recipients received BSX and 64 received Lo rATG. The groups did not differ in demographics, donor characteristics, and maintenance immunosuppression. At 8 years, patient survival was higher for LD patients compared to DD recipients (91% vs 45%, P = .004). In recipients of LD kidneys, 8-year patient survivals were not different comparing Lo rATG and BSX groups (92% vs 91%, respectively, P = .55). In LD, 8-year graft survival was excellent irrespective of induction (Lo rATG 100% vs BSX 98%); however, Lo rATG was associated with a lower rate of acute rejection (7.8% vs 35% BSX, P < .01) and better mean serum creatinine at 3 and 5 years (1.2 vs 1.5, P = .02 and 1.18 vs 1.54, P = .04, respectively). For DD, Lo rATG was associated with a better long-term graft survival (86% vs 76% BSX, P = .02). Viral infections and cancer rates were similar for Lo rATG and BSX. Thus, we conclude that Lo rATG induction may add long-term benefit in low-risk patients compared to anti-interleukin-2 receptor therapy without incurring additional risks of infectious or malignant diseases.

The Role of Antibiotic Prophylaxis in the New Era of Immunosuppression

Despite significant improvements in renal transplantation (RTX), certain basic issues remain unresolved such as the routine use of perioperative antibiotic prophylaxis (PAP). To address the need for PAP, we retrospectively evaluated the clinical course of 349 consecutive RTX patients who did not receive any PAP except for Bactrim. Of the 349 transplant recipients, 77% received induction therapy with low-dose rabbit antithymocyte globulin (rATG) and the others were treated with basiliximab. All patients received triple immunosuppression with tacrolimus, mycophenolic acid, and prednisone. Seven patients (2%) developed wound infections. Wound infections were more common in obese and older patients. All wound infections were superficial and responded well to wound drainage and outpatient antibiotic therapy. Six patients (1.7%) experienced a urinary tract infection (UTI) within the first postoperative month. UTIs were more common in the patient with ureteral stent compared to nonstented patients (11.4% vs 0.3%, P < .001). No patient or graft was lost due to perioperative bacterial infections (PBI). Our study shows that despite many predisposing factors, PBI are rare following RTX even in the absence of PAP. Therefore, in order to avoid emergence of multiantibiotic-resistant pathogens, excessive costs, and antibiotic-related adverse events, we suggest that PAP should be used only in selected circumstances such as in recipients older than 60 or when the body mass index is greater than 35.