Cumulative Incidence Of Graft Failure Research Articles

Arthroscopic repair of proximal anterior cruciate ligament tears in children and adolescents: A systematic review

Purpose: Anterior cruciate ligament repair techniques are of growing interest because they allow for minimally invasive surgery that avoids harvesting of the transplant, without risking growth deficiencies in young patients. The aim of this study is to summarize the published evidence about arthroscopic repair of anterior cruciate ligament proximal tears in skeletally immature patients. Methods: In total, four studies were included and processed for data extraction after screening for eligibility for this systematic review: one retrospective cohort study and three retrospective case series. Altogether, the four studies included in this review included 61 skeletally immature patients with a mean age of 12.1 years diagnosed with proximal anterior cruciate ligament tear who underwent arthroscopic repair with preservation of the native ligament. The mean follow-up period was 2.8 years. Results: The most relevant and objective outcome that we considered was re-rupture rate. One study reports a cumulative incidence of graft failure in the first 3 years after surgery of 48.8% while the others report a 0%, 0% and 21.5% re-rupture rate. No growth disturbances were reported in the included studies. Conclusion: Despite growing interest surrounding anterior cruciate ligament repair techniques, the presence of limited quality studies in the literature means repair cannot be strongly supported at present. Some encouraging data regarding the absence of growth disturbance and functional outcomes does exist, but studies with larger samples are required. Level of evidence: level IV.

Prospective Study of a Modified Post-Transplantation Cyclophosphamide Regimen for Severe Aplastic Anemia Patients with HLA-Haploidentical Transplantation

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative modality for severe aplastic anemia (SAA). The availability of haploidentical donors has expanded valid options for SAA; however, previous post-transplantation cyclophosphamide (PTCy)-based protocols for HLA-haploidentical HSCT in SAA patients are associated with relatively delayed neutrophil and platelet engraftment. We prospectively studied HLA-haploidentical HSCT using bone marrow (BM) combined with peripheral blood stem cells (PBSC) as grafts and a modified PTCy regimen for treating SAA. We evaluated the efficacy and safety of this regimen, which had an increased dose (from 4.5 mg/kg to 6.0 mg/kg) and backward-adjusted timing (from day -9 to -7 to days -5 to -3) of antithymocyte globulin (ATG) compared with previous PTCy protocols. Seventy-one eligible patients were included in this prospective study between July 2019 and June 2022. The median time to neutrophil and platelet engraftment was 13 days (range, 11 to 19 days) and 12 days (range, 7 to 62 days), respectively, and the cumulative incidence (CuI) of neutrophil and platelet engraftment was 97.2 ± 2.2% and 94.4 ± 2.9%, respectively. Five patients experienced graft failure (GF), including 2 with primary GF and 3 with secondary GF. The CuI of GF was 7.0 ± 3.1%. A ≥1-year interval between diagnosis and transplantation was a risk factor for the development of GF (HR, 8.40; 95% confidence interval [CI], 1.40 to 50.47; P=.02). No patients developed grade IV acute graft-versus-host disease (aGVHD) or severe chronic graft-versus-host disease (cGVHD). The 100-day CuI of grade II-IV aGVHD was 13.4 ± 4.2%, and the 2-year CuI of cGVHD was 5.9 ± 2.9%. With a median follow-up of 580 days (range, 108 to 1014 days) for 63 survivors, the estimated 2-year overall survival (OS) and 2-year GVHD-free and failure-free survival (GFFS) were 87.3% (95% CI, 79.4% to 96.0%) and 83.8% (95% CI, 74.9% to 93.7%), respectively. In conclusion, the PTCy regimen with an increased dose and backward-adjusted timing of ATG is an effective and feasible choice for treatment with HLA-haploidentical HSCT using BM combined with PBSC as grafts, with a high rate of and faster engraftment, low rate and intensity of aGVHD and cGVHD, and prolonged OS and GFFS.

Second allogeneic hematopoietic stem cell transplantation in patients with inborn errors of immunity

Graft failure (GF) remains a serious issue of hematopoietic stem cell transplantation (HSCT) in inborn errors of immunity (IEI). Second HSCT is the only salvage therapy for GF. There are no uniform strategies for the second HSCTs and limited data are available on the second HSCT outcomes. 48 patients with various IEI received second allogeneic HSCT from 2013 to 2020. Different conditioning regimens were used, divided into two main groups: containing myeloablative doses of busulfan/treosulfan (n = 19) and lymphoid irradiation 2–6 Gy (n = 22). Irradiation-containing conditioning was predominantly used in suspected immune-mediated rejection of the first graft. Matched unrelated donor was used in 28 patients, mismatched related in 18, and matched related in 1. 35 patients received TCRαβ/CD19 graft depletion. The median follow-up time was 2.4 years post-HSCT. One patient died at conditioning. The OS was 0.63 (95% CI: 0.41–0.85) after busulfan/treosulfan and 0.68 (95% CI: 0.48–0.88) after irradiation-based conditioning, p = 0.66. Active infection at HSCT significantly influenced OS: 0.43 (95% CI: 0.17–0.69) versus 0.73 (95% CI: 0.58–0.88) without infection, p = 0.004. The cumulative incidence of GF was 0.15 (95% CI: 0.08–0.29). To conclude, an individualized approach is required for the second HSCT in IEI. Low-dose lymphoid irradiation in suspected immune-mediated GF may be a feasible option.

Graft failure rate and complications after Descemet membrane endothelial keratoplasty in eyes with pre-existing glaucoma

PurposeTo evaluate the outcome of Descemet Membrane Endothelial Keratoplasty (DMEK) in eyes with pre-existing glaucoma.DesignIn this retrospective, observational case series we included data of 150 consecutive DMEKs in eyes with pre-existing glaucoma of 150 patients after excluding data of the second treated eye of each patient and of re-DMEKs during follow-up. Cumulative incidences of IOP elevation (IOP > 21 mmHg or ≥ 10 mmHg increase in IOP from preoperative value), post-DMEK glaucoma (need of an additional intervention due to worsening of the IOP), graft rejection, and graft failure rate were analyzed using Kaplan–Meier survival analysis. COX regression analysis was used to evaluate independent risk factors.ResultsThe 36-month cumulative incidence of IOP elevation was 53.5% [95 CI 43.5–63.5%] and of post-DMEK glaucoma 36.3% [95 CI 26.3–46.3%]. Graft rejection occurred with a 36-month cumulative incidence of 9.2% [CI 95% 2.3–16.1]. None of the analyzed risk factors increased the risk for the development of graft rejection. The 36-month cumulative incidence of graft failure was 16.6% [CI 95% 8.4–24.8]. Independent risk factors for graft failure were the indication for DMEK “status after graft failure” (n = 16) compared to Fuchs’ dystrophy (n = 74) (p = 0.045, HR 8.511 [CI 95% 1.054–68.756]) and pre-existing filtrating surgery via glaucoma drainage device (GDD) (n = 10) compared to no surgery/iridectomy (n = 109) (p = 0.014, HR 6.273 [CI 95% 1.456–27.031]).ConclusionThe risks of postoperative complications (IOP elevation, post-DMEK glaucoma, graft rejection, and graft failure) in patients with pre-existing glaucoma are high. In particular, pre-existing filtrating surgery via GDD implantation—but not trabeculectomy—and DMEK after graft failure increase the risk of graft failure.

Lung Transplant Outcomes in Adults in the United States: Retrospective Cohort Study Using Real-world Evidence from the SRTR.

Background.The Scientific Registry of Transplant Recipients was retrospectively analyzed to provide real-world evidence of the efficacy and safety of tacrolimus-based immunosuppressive regimens in adult lung transplant recipients in the United States.Methods.Adult recipients (N = 25 355; ≥18 y) of a primary deceased-donor lung transplant between January 1, 1999, and December 31, 2017, were followed for 3 y posttransplant based on immunosuppressive regimen at discharge: immediate-release tacrolimus (TAC) + mycophenolate mofetil (MMF), TAC + azathioprine (AZA), cyclosporine (CsA) + MMF, or CsA + AZA. The primary outcome was the composite endpoint of graft failure or death (all-cause) at 1 y posttransplant (calculated via a modified Kaplan–Meier method).Results.Discharge immunosuppressive regimens in lung transplant recipients changed over time, with a substantial increase in the use of TAC + MMF. TAC + MMF was the most common immunosuppressive regimen (received by 61.0% of individuals at discharge). The cumulative incidence of graft failure or death at 1 y posttransplant in adult lung transplant patients receiving TAC + MMF was 8.6% (95% confidence interval 8.1-9.1). Risk of graft failure or death was significantly higher in adults receiving CsA + MMF or CsA + AZA compared with TAC + MMF, with no significant difference seen between TAC + MMF and TAC + AZA. TAC + MMF had the highest continued use at 1 y posttransplant (72.0% versus 35.4%–51.5% for the other regimens). There was no increase in the rate of infection or malignancy in the TAC + MMF group.Conclusions.Real-world evidence from the most comprehensive database of transplant recipients in the United States supports the use of TAC in combination with MMF or AZA as maintenance immunosuppression in adult lung transplant recipients.

Peri-Transplant Alemtuzumab Levels Predict Risk of Secondary Graft Failure and Inversely Impact CXCL9 Levels after RIC HCT (A Correlative Biology Study to BMT-CTN 1204 RICHI)

IntroductionThe BMT-CTN 1204 study for Hemophagocytic Syndromes or Selected Primary Immune Deficiencies (NCT01998633) (RICHI) was a single arm study testing safety and efficacy of reduced intensity conditioning (RIC) with alemtuzumab (1mg/kg), fludarabine (150 mg/m2) and melphalan (140 mg/m2). Survival was favorable compared to historical studies, but patients experienced high rates of mixed chimerism (MC) and ultimate secondary graft failure (GF). Mechanisms for GF are not known. Expansion of recipient T cells and interferon-gamma pathway activation have been proposed as drivers for GF. However, high peri-transplant alemtuzumab levels have been associated with higher risk of MC and eventual secondary GF, suggesting an inverse relationship between GF and immune activation in the context of RIC. In order to elucidate mechanisms of GF for patients on the RICHI study, we systematically evaluated cytokine patterns and alemtuzumab levels and their association with durable engraftment.MethodsSerial blood samples were collected, processed, and stored for consenting patients at day -14 (window: day -28 to -14), day -7 (+/- 1 day), day -1 (+/- 1), day +1 (+1 to +3), day +14 (+/- 2), day +28 (+/- 2), day +42 (+/- 3), day +70 (+/- 10), and day +100 (+/- 10). Alemtuzumab levels were measured using a flow cytometric assay as previously described. Comprehensive cytokine analysis was performed for over 100 analytes using the MagPix platform. Primary GF was defined as donor chimerism <5% prior to day +42. Secondary GF was defined as donor chimerism <5% after initial engraftment and/or requirement of donor lymphocyte infusion (DLI) or second HCT (with or without conditioning) to manage MC or graft loss. Mixed chimerism (MC) was defined as donor chimerism <95% on at least one occasion.ResultsThirty-three patients were included in this study with HLH (n=25), CAEBV (n=3), CGD (n=2), HIGM (n=2), and IPEX (n=1). All patients received bone marrow grafts and 27 (82%) patients had unrelated donors. Twenty-one grafts were 8/8 or 6/6 HLA-matched (64%) and 12 grafts were 7/8 HLA-matched (36%). Among all patients, 1 patient (3%) developed primary GF, 22 (67%) developed mixed chimerism (MC), and 11 patients (33%) developed secondary GF. Survival with sustained engraftment without DLI or second HCT was 40.0%.We first evaluated peripheral blood levels of 100+ cytokines. Analysis revealed significant differences between patients with and without GF as shown in Figure 1A. Notably, on day +14 and +28, patients with secondary GF had significantly lower CXCL9 levels than those without GF.We then estimated the cumulative incidence (CI) of secondary GF among patients with CXCL9 levels above and below the day +14 median level of 2394pg/mL. The CI of secondary GF in patients with a day +14 CXCL9 level ≤2394pg/mL was 73.6% vs 0% in patients with a level >2394pg/mL (p=0.002). The CI of secondary GF in patients with a day +28 CXCL9 level ≤2867pg/mL (day +28 median) was 64.3%, vs 0% in patients with levels >2867pg/mL (p=0.004).We then sought to correlate CXCL9 levels with alemtuzumab exposure, as high alemtuzumab levels would result in more efficient T cell depletion of donor grafts that could lead to lower CXCL9 levels. Indeed, CXCL9 levels inversely correlated with day 0 alemtuzumab levels. Patients with day 0 alemtuzumab levels >0.32µg/mL had lower CXCL9 levels compared to patients with levels ≤0.32µg/mL (Figure 1B).Finally, we examined the impact of alemtuzumab levels on MC and secondary GF. Patients with day 0 alemtuzumab levels ≤0.32µg/mL had a lower CI of MC compared to patients with levels >0.32µg/mL, 14.3% vs 90.9%, respectively (p=0.03). The CI of secondary GF was 0% in patients with day 0 alemtuzumab levels ≤0.32µg/mL compared to 54.3% in patients with levels >0.32µg/mL (p=0.08).ConclusionsThis study demonstrates a strong relationship between alemtuzumab levels and durable engraftment. Further, interferon gamma activity, as reflected by CXCL9, inversely correlates with peri-transplant alemtuzumab levels in this prospective cohort treated with RIC. Our findings support the paradigm that higher alemtuzumab levels drive efficient T cell depletion of the stem cell product which increases the risk of MC and secondary GF, suggesting that donor T cells promote engraftment via a graft versus hematopoiesis function. Precision alemtuzumab dosing strategies may offer an opportunity to improve outcomes for patients who undergo RIC HCT. [Display omitted] DisclosuresPulsipher: Adaptive: Research Funding; Equillium: Membership on an entity's Board of Directors or advisory committees; Jasper Therapeutics: Honoraria. Bollard: Neximmune: Current equity holder in publicly-traded company; Catamaran Bio: Membership on an entity's Board of Directors or advisory committees; Cabaletta Bio: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Mana Therapeutics: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Cellectis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Repertoire Immune Medicines: Current equity holder in publicly-traded company; ROCHE: Consultancy, Honoraria; SOBI: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kean: Regeneron: Research Funding; Bristol Myers Squibb: Patents & Royalties: From clinical trial data, Research Funding; Bluebird Bio: Research Funding; Gilead: Research Funding; Vertex: Consultancy; Novartis: Consultancy; EMD Serono: Consultancy. Jordan: Sobi: Consultancy. Allen: Sobi: Consultancy. OffLabel Disclosure:Alemtuzumab, humanized monoclonal antibody against CD52, used as part of allogeneic HCT conditioning

International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome

Background:Activated phosphoinositide 3-kinase delta syndrome (APDS) is a combined immunodeficiency with a heterogeneous phenotype considered reversible by allogeneic hematopoietic cell transplantation (HCT).Objectives:This study sought to characterize HCT outcomes in APDS.Methods:Retrospective data were collected on 57 patients with APDS1/2 (median age, 13 years; range, 2–66 years) who underwent HCT.Results:Pre-HCT comorbidities such as lung, gastrointestinal, and liver pathology were common, with hematologic malignancy in 26%. With median follow-up of 2.3 years, 2-year overall and graft failure–free survival probabilities were 86% and 68%, respectively, and did not differ significantly by APDS1 versus APDS2, donor type, or conditioning intensity. The 2-year cumulative incidence of graft failure following first HCT was 17% overall but 42% if mammalian target of rapamycin inhibitor(s) (mTORi) were used in the first year post-HCT, compared with 9% without mTORi. Similarly, 2-year cumulative incidence of unplanned donor cell infusion was overall 28%, but 65% in the context of mTORi receipt and 23% without. Phenotype reversal occurred in 96% of evaluable patients, of whom 17% had mixed chimerism. Vulnerability to renal complications continued post-HCT, adding new insights into potential nonimmunologic roles of phosphoinositide 3-kinase not correctable through HCT.Conclusions:Graft failure, graft instability, and poor graft function requiring unplanned donor cell infusion were major barriers to successful HCT. Post-HCT mTORi use may confer an advantage to residual host cells, promoting graft instability. Longer-term post-HCT follow-up of more patients is needed to elucidate the kinetics of immune reconstitution and donor chimerism, establish approaches that reduce graft instability, and assess the completeness of phenotype reversal over time.

Hematopoietic Cell Transplantation Outcomes among Medicaid and Privately Insured Patients with Sickle Cell Disease

Compared with privately insured patients, recipients of Medicaid have been reported to have worse outcomes in several clinical conditions and following various surgical and medical procedures. However, the relationship between health insurance status and allogeneic hematopoietic cell transplantation (alloHCT) outcomes among patients with sickle cell disease (SCD) is not well described. We sought to compare alloHCT outcomes between patients with SCD who underwent alloHCT while enrolled on Medicaid versus those who underwent alloHCT while covered by private health insurance. We conducted a retrospective multicenter study using data reported to the Center for International Blood and Marrow Transplant Research. US patients enrolled on Medicaid or private insurance who underwent a first alloHCT for SCD between 2008 and 2018 were eligible for this study. The primary outcome was event-free survival (EFS), defined as time to death or graft failure. Secondary outcomes included overall survival (OS), graft failure, acute graft-versus-host disease (GVHD), and chronic GVHD. Univariate analysis was performed using the Kaplan-Meier method for EFS and OS. The proportion of patients with graft failure, acute GVHD, and/or chronic GVHD was calculated using the cumulative incidence estimator to accommodate competing risks (ie, death). Cox regression was used to identify factors associated with EFS, OS, graft failure, and acute and chronic GVHD. A total of 399 patients (Medicaid, n=225; private insurance, n=174) were included in this study. The median duration of follow-up was 34 months (range, 1.0 to 134.7 months) for the Medicaid group and 38.7 months (range, 0.3 to 139.3 months) for the private insurance group. Compared with the patients with private insurance, those on Medicaid had a significantly lower 3-year EFS (75.4% [95% confidence interval (CI), 69.4% to 81%] versus 82.2% [95% CI, 76.9% to 87.8%]; P=.0279) and a significantly higher 3-year cumulative incidence of graft failure (17.2% [95% CI, 12.5% to 22.5%] versus 10.5% [95% CI, 6.4% to 15.4%]; P=.0372). There were no significant between-group differences in 3-year OS (P=.6337) or in the cumulative incidence of acute GVHD (P=.4556) or chronic GVHD (P=.6878). Cox regression analysis after adjusting for other significant variables showed that the patients enrolled on Medicaid had a lower EFS (hazard ratio [HR], 2.36; 95% CI, 1.44 to 3.85; P=.0006) and a higher cumulative incidence of graft failure (HR, 2.57; 95% CI, 1.43 to 4.60; P=.0015), with no significant between-group differences in OS (HR, 0.99; 95% CI, 0.47 to 2.07; P=.9765), acute GVHD (HR, 0.94; 95% CI, 0.59 to 1.49; P=.7905), or cGVHD (HR, 0.98; 95% CI, 0.65 to 1.48; P=.9331). That EFS is worse in patients on Medicaid compared with privately insured individuals following alloHCT for SCD provides the rationale for research to better understand the mechanisms by which insurance status impacts alloHCT outcomes among patients with SCD.

Lung Transplant Outcomes Based on Immunosuppressive Regimen at Discharge: Data from the US Scientific Registry of Transplant Recipients (SRTR)

<h3>Purpose</h3> There is currently no FDA approved immunosuppressive regimen for lung transplant (Tx) recipients; however, patients routinely receive a CNI-based regimen. The SRTR database was analyzed to provide real-world evidence of the efficacy and safety of tacrolimus-based immunosuppressive regimens post lung Tx. <h3>Methods</h3> Adult and pediatric recipients of a primary deceased donor lung Tx between January 1, 1999 and December 31, 2017 were followed for 3 years post-transplant based on immunosuppressive regimen at discharge: immediate-release tacrolimus (TAC IR)+mycophenolate mofetil (MMF), TAC IR+azathioprine (AZA), cyclosporine (CYA)+MMF, or CYA+AZA. The primary outcome was the composite endpoint of graft failure or death (all cause) at 1 year post-transplant. Cox proportional hazard models were used to test for baseline characteristics associated with a greater risk of graft failure or death in adults. <h3>Results</h3> Data were available for 26,080 lung Tx recipients (25,355 adults and 725 pediatric patients). The most common discharge immunosuppressive regimen was TAC IR+MMF in both groups. Post-transplant outcomes are shown in Tables 1 (adults) and 2 (pediatrics). Factors associated with a greater risk of graft failure or death in adults on TAC IR+MMF included: recipient age ≥65 years, single lung transplant, hospital stay >24 days, BMI <18.5 kg/m², serum creatinine ≥1.0 mg/dL, donor age ≥55 years, and donor race (Black). The risk of graft failure or death was significantly greater in adults receiving CYA+MMF or CYA+AZA compared to TAC IR+MMF. <h3>Conclusion</h3> Discharge immunosuppressive regimens in lung Tx recipients changed over the period from 1999-2017, with a substantial increase in the use of TAC IR+MMF. Adult and pediatric lung Tx recipients receiving TAC IR+MMF had a cumulative incidence of graft failure or death at 1 year post transplant less than 9% (graft survival >91%) and had the lowest rejection rates without increased risks of infection or malignancy.

363 - Hematopoietic Cell Transplant Outcomes Among Medicaid and Privately Insured Patients with Sickle Cell Disease

Abstract Background Compared to privately insured patients, recipients of Medicaid have been reported to have worse outcomes in several clinical conditions and following various surgical and medical procedures. However, the relationship between health insurance status and allogeneic hematopoietic cell transplant (alloHCT) outcomes among patients with sickle cell disease (SCD) is not well described. Objective We sought to compare alloHCT outcomes among patients with SCD who received an alloHCT while enrolled on Medicaid versus private health insurance. Study design We conducted a retrospective multicenter study utilizing data reported to the Center for International Blood and Marrow Transplant Research. US patients enrolled on Medicaid or private insurance, who received a first alloHCT for SCD between 2008 and 2018 were eligible for this study. The primary outcome was event-free survival (EFS), defined as time to death or graft failure. Secondary outcomes included overall survival (OS), graft failure, acute and chronic graft-versus-host disease (GVHD). Univariate analysis was performed using Kaplan-Meier Method for EFS and OS. The proportion of patients with graft failure, acute and/or chronic GVHD was calculated using the cumulative incidence estimator to accommodate competing risks (ie, death). Cox regression was used to identify factors associated with EFS, OS, graft failure, acute and chronic GVHD. Results A total of 399 patients (Medicaid: 225; private insurance: 174) were included in this study. The median follow-up was 34 months (range 1.0-134.7) and 38.7 months (range 0.3-139.3) for patients enrolled on Medicaid and private insurance, respectively. Patients on Medicaid compared to private insurance had significantly lower 3-year EFS 75.4 (95%CI: 69.4-81)% vs. 82.2 (95%CI: 76.9-87.8)%, p=0.0279 and significantly higher 3-year cumulative incidence of graft failure 17.2 (95%CI: 12.5-22.5)% vs. 10.5 (95%CI: 6.4-15.4)%, p=0.0372. There were no significant differences in 3-year OS p=0.6337, the cumulative incidence of aGVHD p=0.4556 or cGVHD p=0.6878 between the two groups. Cox-regression analysis, adjusting for other significant variables showed that patients enrolled on Medicaid compared to private insurance had lower EFS (hazard ratio (HR): 2.36, 95% CI: 1.44-3.85; p=0.0006) and higher cumulative incidence of graft failure (HR: 2.57, 95% CI: 1.43-4.60; p=0.0015 with no significant difference in OS (HR: 0.99, 95% CI: 0.47-2.07; p=0.9765); aGVHD (HR: 0.94, 95% CI: 0.59-1.49; p=0. 7905), or cGVHD (HR: 0.98, 95 CI: 0.65-1.48; p=0.9331). Conclusion That EFS is worse in patients with Medicaid as compared to privately insured individuals following alloHCT for SCD provides the rationale for research to better understand the mechanisms by which insurance status impacts alloHCT outcomes among patients with SCD.

Outcome After Cord Blood Transplantation Using Busulfan Pharmacokinetics-Targeted Myeloablative Conditioning for Hurler Syndrome

We report the outcomes of cord blood transplantation (CBT) with a busulfan (Bu) pharmacokinetics-targeted myeloablative conditioning regimen in 97 children with Hurler syndrome (HS) performed between 2004 and 2016. The median age at CBT was 10.8 months (range, 0.23 to 63.2 months). The median duration of follow-up for surviving patients was 4.2 years (range, 1.0 to 12.8 years). Five-year overall survival (OS) and engrafted survival (ES) were 88% and 79%, respectively. OS was 95% in patients who received Bu/fludarabine (Flu)/antithymocyte globulin (ATG) conditioning, 90% in those who received Bu/cyclophosphamide (Cy)/ATG, and 74% in those who received Bu/Cy/alemtuzumab (P = .02). ES was 84% for recipients of Bu/Flu/ATG conditioning, 83% for recipients of Bu/Cy/ATG conditioning, and 65% for recipients of Bu/Cy/alemtuzumab conditioning (P = .34). Receipt of washed CB units (P = .03) and HLA matching ≤6/10 (P = .02) were associated with significantly lower ES. The 1-year cumulative incidence of graft failure was 11% (95% confidence interval, 6% to 21%). Five patients (5%) had grade III-IV acute GVHD, 5 patients had limited chronic GVHD, and 1 patient had extensive GVHD. The incidence of veno-occlusive disease was higher in patients conditioned with Bu/Cy compared with those conditioned with Bu/Flu (19% [n = 10] versus 5% [n = 2]: P = .03). Of the 11 patients with graft failure, 8 (73%) were aplastic, and 3 (27%) had autologous reconstitution. Of 11 patients with graft failure, 9 underwent a second CBT, and 8 (89%) survived. Full donor chimerism was observed in 89% patients after first CBT and in all patients after second CBT. Survival after CBT for HS has improved, but better strategies are still needed to improve graft outcomes.

Haploidentical transplantation in pediatric non-malignant diseases: A retrospective analysis on behalf of the Spanish Group for Hematopoietic Transplantation (GETH).

Describe the GETH haploidentical stem cell transplantation (haplo-HSCT) activity in non-malignant disease (NMDs). We retrospectively analyzed data from children with NMDs who underwent haplo-HSCT. From January 2001 to December 2016, 26 pediatric patients underwent 31 haplo-HSCT through ex vivo T cell-depleted (TCD) graft platforms or post-transplantation cyclophosphamide (PT-Cy) at 7 Spanish centers. Five cases employed unmanipulated PT-Cy haplo-HSCT, 16 employed highly purified CD34+ cells, and 10 employed ex vivo TCD grafts manipulated either with CD3+ CD19+ depletion, TCRαβ+ CD19+ selection or naive CD45RA+ T-cell depletion. Peripheral blood stem cells were the sole source for patients following TCD haplo-HSCT, and bone marrow was the source for one PT-Cy haplo-HSCT. The most common indications for transplantation were primary immunodeficiency disorders (PIDs), severe aplastic anemia, osteopetrosis, and thalassemia. The 1-year cumulative incidence of graft failure was 27.4%. The 1-year III-IV acute graft-versus-host disease (GvHD) and 1-year chronic GvHD rates were 34.6% and 16.7%, respectively. The 2-year overall survival was 44.9% for PIDs, and the 2-year graft-versus-host disease-free and relapse-free survival rate was 37.6% for the other NMDs. The transplantation-related mortality at day 100 was 30.8%. Although these results are discouraging, improvements will come if procedures are centralized in centers of expertise.

Improvement in Non-Relapse Mortality Following Allogeneic Transplantation for Chronic Lymphocytic Leukaemia in Australia and New Zealand: An Australasian Bone Marrow Transplant Recipient Registry Study

Background The treatment landscape for chronic lymphocytic leukaemia (CLL) has significantly changed over the past decade with the advent of targeted therapies. Subsequent improvement in remission rates has been seen in all patient groups, however patients with high-risk genetic features (del17p, TP53 mutation) continue to have poorer outcomes. In such patients, and in multiply relapsed/refractory standard risk patients, allogeneic stem cell transplantation remains a viable management option despite the associated morbidity and mortality. The aim of this study was to examine trends in allogeneic stem cell transplantation for CLL in Australia and New Zealand over the past decade, and to identify predictive factors for overall survival (OS) and progression free survival (PFS). Methods Data was collected through the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) for patients receiving a first allogeneic stem cell transplantation for CLL, in the absence of Richter's transformation, between January 2009 and December 2018. Transplant outcomes were compared between 2 time periods, 2009-2013 and 2014-2018 using log rank test for survival and Gray's test for cumulative incidence curves. Cox regression analysis was performed to identify factors predictive of survival. Medians are reported with ranges, hazard ratios (HR) and cumulative incidence with 95% confidence intervals (CI). Results A total of 153 patients (75% males) were included. Median age at transplantation was 55 years (range 23-69) with a median time from diagnosis to transplantation of 5.7 years (range 100days - 24.7years). Most patients received reduced intensity or non-myeloablative conditioning (84.3%, n=129) and did not receive T cell depleting therapy (73%, n=94). The median follow up was 5.9 years (range 0.8-11years). Median time to neutrophil engraftment was 16 days (range 6-49) and median time to platelet engraftment was 18 days (range 1-69). At 100 days following transplantation the cumulative incidence of graft failure was 3.9%, CMV reactivation 41% (95% CI 31-50%) and CMV disease 3.2% (95% CI 1-8%). Acute graft versus host disease (aGVHD) grade II-IV occurred in 39% (95% CI 29-49%) of patients and grade III-IV in 17% (95% CI 9-25%). The cumulative incidence of chronic GVHD (cGVHD) was 65% (95% CI 53-76%) at 5 years; extensive cGVHD occurred in 77% of patients with cGVHD. Median OS was 4.3 years (95% CI 3.6-not reached) and PFS was 2.6 years (95% CI 1.7-3.9). The most common contributors to mortality were infection (43%), GVHD (40%) and persistent disease or relapse (24%). In a multivariate analysis active disease at time of transplantation was associated with a worse OS (HR 2.16, 1.01-4.63), however, age, matched sibling donor, myeloablative conditioning and the use of T cell depleting therapies did not have a significant impact. The use of myeloablative conditioning was associated with improved PFS (HR 1.85, 1.1-3.1) in a univariate analysis but lost significance in multivariate analysis. Ninety-seven patients underwent transplantation between 2009-2013 and 56 patients between 2014-2018. There was no statistical difference in patient age, performance status, donor or disease status at transplantation between the groups. Myeloablative conditioning was used in 18.6% and 8.9% (p=0.197), and T cell depleting therapy in 25% and 31% (p=0.58), for the 2009-2013 and 2014-2018 periods respectively. There was a significant improvement in 5-year non-relapse mortality (NRM) from 41.5% (31-52%) to 23.4% (13-29%; p=0.04). Five year OS (46% vs 56%), PFS (36% vs 46%) and relapse rates (21% vs 31%) were not statistically different. Cumulative incidence of both acute and chronic GVHD was reduced in the later cohort; aGVHD 51% (95% CI 34-65%) vs 29% (95% CI 16-43%; p=0.03), cGVHD 76% (95% CI 57-88%) vs 53% (36-66%; p=0.02). Kaplan-meier and cumulative incidence curves for these outcomes are presented in figure 1. Conclusion The number of allogeneic stem cell transplantations performed for CLL has reduced over the past decade in Australasia. There has been an improvement in NRM and incidence of GVHD, however OS and PFS have not significantly changed. This may reflect improved GVHD prophylaxis and management, or advances in supportive care. Further analysis of impact of high-risk genetic factors at transplantation is pending at the time of abstract submission. Figure Disclosures Spencer: Celgene, Janssen and Takeda: Speakers Bureau; AbbVie, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Consultancy; Amgen, Celgene, Haemalogix, Janssen, Servier and Takeda: Research Funding; AbbVie, Amgen, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Honoraria. Greenwood:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Tam:AbbVie: Honoraria, Research Funding; BeiGene: Honoraria; Janssen: Honoraria, Research Funding. Di Ciaccio:Jansen: Honoraria, Other: travel and accomodation grant. Hamad:Novartis: Honoraria; Abbvie: Honoraria.

Mid-Term Results of Endovascular Aneurysm Sealing in the Treatment of Abdominal Aortic Aneurysm With Unfavorable Morphology.

To report mid-term results of endovascular aneurysm sealing (EVAS) of abdominal aortic aneurysms (AAA) deemed unsuitable for a standard endovascular aneurysm repair (EVAR). A prospectively maintained database of 42 patients with EVAR-unfavorable anatomy treated by EVAS combined with chimney grafts in case of the proximal AAA neck shorter than 5 mm was analyzed. Early outcomes included final angiographic result, intra- and early post-operative deaths, and complications. Mid-term outcomes included all-cause mortality (ACM), aneurysm-related mortality (ARM), patency of the stents, occurrence of endoleaks, serious complications and graft failures defined as the AAA growth of more than 5 mm, type I endoleak, occlusion of the stent-graft or chimney graft, aorto-duodenal fistula, or aneurysm rupture. The procedure was completed in all patients. Twenty-eight chimney grafts were implanted in 19 patients. Patients were followed for a median of 24 months (range 12-34 months). There were 2 intraoperative ruptures and 1 patient died in an early postoperative period. The cumulative ACM was 15, 21, and 36% at 12, 24, and 36 months, respectively, and the cumulative ARM was 8, 11, and 27% at 12, 24, and 36 months, respectively. Three out of 5 aneurysm-related deaths were due to a secondary aorto-duodenal fistula. The cumulative incidence of graft failure was 20, 27, and 42% at 12, 24, and 36 months, respectively. The cumulative incidence of an endoleak was 5, 9, and 23% at 12, 24, and 36 months, respectively. The graft failure increased significantly both ACM (p = .012) and ARM (p = .00003). The implantation of chimney grafts at the initial procedure increased ARM significantly (p = .008). The presence of an endoleak did not have any significant influence on ACM and ARM. Patients treated with EVAS for AAAs with EVAR-unfavorable anatomy, especially those with chimney grafts, exhibit a high risk of graft failure and subsequent death.

International Retrospective Study of Allogeneic Hematopoietic Cell Transplantation (HCT) for Activated Phosphoinositide 3-Kinase Delta (PI3K) Syndrome

Mutations resulting in increased PI3K signaling confer increased risk of B cell lymphoma, recurrent infections, poor viral control, and autoimmunity. Allogeneic HCT is curative, but the optimal approach to HCT for these patients is still evolving as experience grows. Herein, we present the clinical outcomes of 27 patients transplanted for activating PI3K mutations. Required approvals were obtained by contributing centers. Nineteen <i>PIK3CD</i> patients and 8 <i>PIK3R1</i> patients received 22 and 10 HCTs respectively, at median age 12 years (range 2-66) at time of first HCT. Significant pre-HCT comorbidities were common, Fig 1. Conditioning platforms varied in intensity; most included serotherapy (84%). With median survivor follow up of 26.3 months from first HCT (range 2.4-71.8), overall survival was 85% (3 infectious deaths and 1 due to organ toxicity); graft failure (GF)-free survival (GFFS) was estimated at 80% at 1 year but declined to 68% by 2 years, Fig 2. Neutrophil engraftment occurred at median 15.5 days (range 11-33) with autologous recovery in 1 patient at day +14 and another deceased prior to engraftment. Four engrafted patients are alive and well despite mixed donor chimerism (<95%). Nine (33%) patients required 24 total subsequent unplanned donor cell infusions (DCI) for mixed chimerism (n=15), poor graft function (n=2), infection (n=1), GF (n=3), malignancy relapse (n=1), or to improve immune reconstitution (n=2). Grade 2-4 acute graft versus host disease (GVHD) occurred in 27% patients, with Grade 3-4 acute GVHD and limited self-resolved chronic GVHD in 1 (4%). Organ toxicities and infectious complications are summarized in Fig 3; CMV infection requiring treatment occurred in 11 (41%) patients with disease in 3 (11%). Serotherapy use, conditioning intensity, and degree of donor human leukocyte antigen (HLA) match were not significantly associated with cumulative incidence of GF or subsequent unplanned DCI (with death as a competing risk), while mTOR inhibitor use post-HCT was associated with subsequent unplanned DCI for graft augmentation or GF (p=0.006). An mTOR inhibitor was used within the year following 12 HCTs, for primary GVHD prophylaxis (n=7) or to treat disease manifestations or GVHD; loss of chimerism and/or need for subsequent DCI occurred in 9 of these. Patients with activating PI3K mutations are at overall significant risk of GF or need for subsequent DCI. While we found no association with GF or DCI for discrete elements such as serotherapy use, donor source, or conditioning intensity, small numbers preclude conclusions regarding the optimal HCT approach, and more HCTs with longer follow up are needed to refine these preliminary findings. Post-HCT mTOR inhibitor exposure was associated with need for subsequent unplanned DCI, perhaps by providing a survival advantage to host lymphocytes, and may thus be detrimental in these patients during the early post-HCT timeframe.

Long-term Results of Endovascular Aneurysm Sealing in Treatment of Infrarenal Abdominal Aortic Aneurysm With Unfavourable Morphology

Introduction: Endovascular aneurysm repair (EVAR) is a less invasive alternative of treatment of patients with abdominal aortic aneurysm (AAA). Its applicability however is limited by the AAA anatomy. Endovascular aneurysm sealing originally emerged as an endovascular solution for AAA repair with very promising early results. The purpose of this study was to report long-term results of EVAS of AAAs with unfavourable anatomy for EVAR. Methods: A prospectively maintained database of 42 patients with EVAR-unfavourable anatomy treated by EVAS was analysed. The median age of the patients was 74 (IQR 67-80) years. The median diameter of AAA was 61 (IQR 56-71) mm. The EVAS consisted of implantation of two balloon expandable aorto-iliac stent-grafts surrounded by polymer filled endobags. In case of proximal AAA neck shorter than 5 mm chimney grafts were implanted. The final angiographic result, intra- and early post-operative complications were noted. A follow-up included a clinical assessment angio-CT 4-6 weeks and 12 months after the procedure and duplex Doppler at 12 months intervals thereafter. In case of any abnormalities detected in either clinical or duplex Doppler examination an angio-CT was performed. Patency of the aorto-iliac stents and chimney grafts, occurrence of graft failure and all additional interventions and/or events were noted in the database. The graft failure was defined as AAA growth of more than 5mm, type I endoleak, occlusion of the stent-graft or chimney graft or aneurysm rupture. All-cause mortality (ACM) and aneurysm related mortality (ARM) were analysed with Kaplan-Meier estimates. Results: The procedure was completed in all patients. Twenty-eight chimney grafts were implanted in 19 patients. There were two intraoperative ruptures, one of an aortic neck that required conversion to an open repair and one of an external iliac artery that was successfully treated with implantation of a self-expandible covered stent. One patient died in an early postoperative period. The median follow-up period was 24 (IQR 12-34) months. The cumulative ACM was 15, 21 and 35% at 12, 24 and 36 months respectively and the cumulative ARM was 8, 11 and 27% at 12, 24 and 36 months respectively. Three out of five aneurysm related deaths were due to a secondary aorto-duodenal fistula. The cumulative incidence of graft failure was 20, 27 and 42% at 12, 24 and 36 months, respectively. Cumulative incidence of endoleak was 5, 9 and 23% at 12, 24 and 36 months, respectively.The graft failure increased significantly both ACM (p = 0,012) and ARM (p = 0,00003). The implantation of chimney grafts at the initial procedure increased significantly ARM (p=0,008). The presence of endoleak did not have any significant influence on ACM and ARM. Conclusion: Patients treated with EVAS for AAA with EVAR-unfavourable anatomy, especially those with chimney grafts, have a high risk of graft failure and subsequent death. These patients require more rigorous monitoring than patient after standard EVAR. Disclosure: Nothing to disclose

Outcomes of Quadriceps Tendon With Patellar Bone Block Anterior Cruciate Ligament Reconstruction in Adolescent Patients With a Minimum 2-Year Follow-up

Background: The incidence of anterior cruciate ligament (ACL) injury in the adolescent population is increasing. The quadriceps tendon–patellar bone autograft (QPA) has been established as a reliable graft choice for ACL reconstruction in the adult population. Purpose: To investigate graft failure, ability to return to sport, patient-reported functional outcomes, joint laxity, and subsequent injury among adolescent patients >2 years after primary ACL reconstruction with the QPA. Study Design: Case series; Level of evidence, 4. Methods: Consecutive patients who underwent QPA ACL reconstruction performed by a single surgeon were identified from an existing database. Information available in the database included demographics, concomitant/subsequent injuries, surgical procedures, graft failure, return to sport, and Lachman examination collected by medical record review. Pediatric International Knee Documentation Committee (Pedi-IKDC) and Lysholm scores were collected by telephone or during a clinic visit >2 years postoperatively. Results: The final cohort included 81 of 104 consecutive adolescent patients aged 10 to 18 years (mean ± SD, 15.9 ± 1.7 years at the time of surgery) for whom follow-up information was collected at >2 years after surgery. The cumulative incidence of graft failure within the 36-month follow-up period was 1.2% (95% CI, 0.1%-11.4%). The rate of ipsilateral non-ACL injuries was similar (1.2%; 95% CI, 0.2%-7.6%). Contralateral ACL and non-ACL injuries requiring surgical intervention were documented in 9.8% (95% CI, 4.9%-19.5%). The median Pedi-IKDC score was 94 (interquartile range, 89-98). The median Lysholm score was 99.5 (interquartile range, 89.0-100.0). At 36 months after surgery, 87.9% (95% CI, 81.4%-94.9%) of individuals had returned to play. Conclusion: The quadriceps tendon–patellar autograft is a novel graft that demonstrates excellent stability and favorable patient-reported outcomes. Based on these results, the QPA is a reliable choice for primary ACL reconstruction in adolescent patients.

Reduced-Toxicity (BuFlu) Conditioning Is Better Tolerated but Has a Higher Second Transplantation Rate Compared to Myeloablative Conditioning (BuCy) in Children with Inherited Metabolic Disorders.

Hematopoietic stem cell transplantation (HCT) is a primary treatment for various inherited metabolic disorders (IMDs). Achieving stable and sustained engraftment while minimizing transplantation-related morbidity and mortality is critical to optimizing outcomes for IMDs. Traditional regimens have used myeloablative approaches, primarily busulfan and cyclophosphamide (BuCy), which is associated with significant regimen-related toxicity. Alternatively, reduced-toxicity regimens, such as busulfan and fludarabine (BuFlu), have been proposed to offer similar efficacy with reduced toxicities. We compared transplantation-related outcomes with BuCy-based and BuFlu-based conditioning in patients with IMDs. We retrospectively analyzed the University of Minnesota's transplantation database for patients with IMDs who underwent HCT using a BuCy (with alemtuzumab) or BuFlu (with antithymocyte globulin) preparative regimen between March 2008 and September 2017. Overall survival (OS), event-free survival (EFS), and incidence of neutrophil and platelet recovery were determined using standard definitions. Complications such as graft failure, sinusoidal obstruction syndrome, hemorrhagic cystitis, and respiratory failure were compared. Graft failure includes primary and secondary aplastic graft failure with and without autologous recovery. The incidence of viral infections post-transplantation in the 2 regimens was also determined. A total of 99 patients underwent HCT for IMDs during the study period. Sixty-four patients received BuCy conditioning, and the other 35 received BuFlu. Hurler syndrome (46%) and adrenoleukodystrophy (43%) were the most common IMDs, and umbilical cord blood was the most common graft source (74%). One-year OS was similar in the 2 groups (81.2% in BuCy versus 85.5% in BuFlu; P=.8), with an EFS of 75% versus 63%, respectively. The 2 groups also had similar incidences of grade III-IV acute GVHD (9% versus 6%; P=.5) and chronic GVHD (9% versus 7%; P=.67). Neutrophil and platelet recovery were similar in the 2 groups, with a significantly shorter duration of hospital stay noted in the BuFlu cohort (median, 21 days versus 34 days; P=.002). The cumulative incidence of graft failure was significantly higher in the BuFlu group (29% versus 14%; P=.08), as was the rate of second HCT (27% versus 3%; P=.001). The incidences of adenoviral infection (14% versus 0%; P=.02) and hemorrhagic cystitis (23% versus 3%; P=.01) were higher in the BuCy group. T cell engraftment occurred significantly sooner with BuCy conditioning until 1-year post-transplantation, but donor myeloid engraftment was similar in the 2 groups. Our data indicate that reduced-toxicity conditioning is associated with lower rates of infection and other transplantation-related complications but is concerning for a higher rate of graft failure in patients with IMDs. Alternate immunosuppressive agents and novel techniques should be considered to minimize toxicities and reduce complications.

Risk Factors for Primary and Secondary Graft Failure in Allogenic Hematopoietic Cell Transplantation: A Single Center Study

Introduction: Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for high risk hematological diseases and sustained engraftment of the donor stem cells is essential for transplant success. Graft failure (GF) is a rare, but serious complication post allo-HCT. In the presented study we aimed to assess the incidence, risk factors in a single-center population and as well the impact on transplant outcome. Methods: Between 01 January 2015 and 31 December 2018, 557 patients underwent allo-HCT at our center. Data was collected retrospectively and updated in June 2019. Cases were included regardless of the underlying diagnosis, disease status prior to transplant, preparative regimen, or stem cell source. Primary graft failure was defined as failure to achieve an absolute neutrophil count (ANC) of &gt;500/ µL by 28 days after bone marrow (BM) or peripheral blood stem cell (PB) transplantation. In contrast, secondary graft failure was defined as cytopenias after initial engraftment (ANC &lt;500/µL), with (a) donor chimerism of less than 5% or (b) falling donor chimerism with intervention such as second transplant or donor lymphocyte infusion (DLI) or (c) patient death due to cytopenias, and fall in donor chimerism, even if chimerism was &gt;5%. Exclusion criteria for diagnosis of GF were (a) disease relapse (b) graft versus host disease or (c) other causes of cytopenias such as, viral infections, or drug induced. Outcomes examined included overall survival (OS), cumulative incidence of GF, non-relapse mortality (NRM) and cause of death. Results: Baseline characteristics are summarized in (Table 1). GF was seen in 43 (7.7%) patients. Of these 43 patients, 9 (21%) had primary GF, and 34 (79%) had secondary GF. The cumulative incidence of GF overall (primary and secondary) is 1.6% (0.8- 3.0%) at day 100 and 6.5% (4.5-8.8%) at day 800. The median survival of patients following primary GF was 41 days versus 144 days in secondary GF. At one hundred days OS in primary GF was 22% and in secondary GF was 64%. The 1y and 2y OS for secondary GF was 33% and 28% respectively (Figure 1-A). Multivariable analysis demonstrated that the (a) diagnosis/transplant indication (MDS, myelofibrosis, lymphoma or non-malignant diseases) and (b) donor type (HLA-mismatched unrelated or haploidentical) were the only factors significantly associated with increased GF (Table 2). We determined the effect of more than one of these risk factors on the occurrence of graft failure as seen in (Figure 1-B). In the absence of any of the risk factors, the incidence of GF was 3.6%. If one risk factor was present, the incidence of GF was 9.9%, and if 2 risk factors were present, the incidence of GF was 24.5%. In primary GF, 5 patients underwent second allo-HCT. In secondary GF, 15 patients (44%) underwent a second allo-HCT and another 8 patients received donor lymphocyte infusion. All the patients with primary GF died because of graft failure and its associated complications. In secondary GF, 22 patients (51%) died, 30% of causes related to infections. Conclusions: Our study showed an increased risk for graft failure following the use of mismatched unrelated or haploidentical donors for diseases such as lymphoma, myelofibrosis, myelodysplastic syndrome and non-malignant diseases. As well, we found that a presence of two risk factors puts patients at clinically significant increased risk of graft failure. More intense conditioning therapy should be considered for patients with one but in particular two risk factors. Disclosures Michelis: CSL Behring: Other: Financial Support.

The Effect of the Opioid Epidemic on Donation After Circulatory Death Transplantation Outcomes.

The opioid epidemic and the deaths of otherwise healthy individuals due to drug overdose in the United States has major implications for transplantation. The current extent and safety of utilization of liver and kidney grafts from donation after circulatory death (DCD) donors who died from opioid overdose is unknown. Using national data from 2006 to 2016, we estimated the cumulative incidence of graft failure for recipients of DCD grafts, comparing the risk among recipients of organs from donors who died of anoxic drug overdose and recipients of organs from donors who died of other causes. One hundred seventy-nine (6.2%) of 2908 liver graft recipients and 944 (6.1%) of 15520 kidney graft recipients received grafts from donors who died of anoxic drug overdose. Grafts from anoxic drug overdose donors were less frequently used compared with other DCD grafts (liver, 25.9% versus 29.6%; 95% confidence interval [CI] for difference, -6.7% to -0.7%; kidney, 81.0% versus 84.7%; 95% CI for difference, -7.3% to -0.1%). However, the risk of graft failure at 5 years was similar for recipients of anoxic drug overdose donor grafts and recipients of other grafts (liver risk difference, 1.8%; 95% CI, -7.8% to 11.8%; kidney risk difference, -1.5%; 95% CI, -5.4% to 3.1%). In the context of the current opioid epidemic, utilization of anoxic drug overdose DCD donor grafts does not increase the risk of graft failure and may help to address waitlist demands.