Use Of Antithymocyte Globulin Research Articles

Unsupervised Clustering Analysis of Regimen and HLA Characteristics in Pediatric Umbilical Cord Blood Transplantation

BackgroundHuman leukocyte antigen (HLA) matching is a critical factor in allogeneic unrelated hematopoietic cell transplantation (HCT) due to its impact on post-transplant survival and quality of life. Umbilical cord blood transplantation (UCBT) offers unique advantages but the optimal approach to graft selection and immunosuppression remains challenging. Unsupervised clustering, a machine learning technique has potential in analyzing transplant outcomes but its application in investigating leukemia outcomes has been limited. ObjectiveTo identify optimal combinations of HLA/KIR donor-patient pairing, conditioning, and immunosuppressive regimens in pediatric patients with acute lymphoblastic (ALL) or acute myeloblastic (AML) leukemia undergoing umbilical cord blood transplantation (UCBT). Study designOutcome data for single, unmanipulated UCBT in pediatric AML (n=708) and ALL (n=1034) patients from the Eurocord/EBMT registry were analyzed using unsupervised clustering. Resulting clusters were used to inform post-hoc competing risks and Kaplan-Meier analyses. ResultsIn AML, single HLA-C mismatches with other loci fully matched (7/8) associated with poorer relapse-free survival (RFS) (p=0.039), but a second mismatch at any other locus counteracted this effect. In ALL, total body irradiation (TBI) effectively prevented relapse mortality (p=0.007). KIR/HLA-C match status affected RFS in AML (p=0.039) but not ALL (p=0.8). Anti-thymocyte globulin (ATG) administration substantially increased relapse, with no relapses occurring in the 85 patients not receiving ATG. ConclusionsOur unsupervised clustering analyses generate several key statistical and mechanistic hypotheses regarding the relationships between HLA matching, conditioning regimens, immunosuppressive therapies, and transplantation outcomes in pediatric AML and ALL patients. HLA-C and killer immunoglobulin receptor (KIR) combinations significantly impact RFS in pediatric AML, but not ALL. ATG use in fully matched pediatric patients is associated with late-stage relapse. TBI regimens appear beneficial in ALL, with efficacy largely independent of histocompatibility variables. These findings reflect the distinct genetic and biological profiles of AML and ALL.

Secondary solid malignancies and precancerous lesions after allogeneic hematopoietic stem cell transplantation using non-total body irradiation-based conditioning in acute myeloid leukemia

IntroductionLong-term survivors have an increased risk of developing secondary solid malignancies (SSMs) after allogeneic-hematopoietic stem cell transplantation (allo-HSCT) with graft-versus-host disease (GVHD) potentially modulating these risks.MethodsThis retrospective study analyzed the cumulative incidences of SSMs after chemotherapy-based conditioning for allo-HSCT patients with acute myeloid leukemia (n = 266) transplanted at the University Hospital Regensburg between 1999 and 2016.ResultsThe median follow-up was 11.4 years (Interquartile range, 9.0–14.9). The 100-day cumulative incidence of grade II-IV acute GVHD (aGVHD) was 44.4% [95% CI (38.3, 50.2)], while the 5-year cumulative incidence of chronic GVHD (cGVHD, requiring systemic immunosuppression) was 36.9% [95% CI (31.1, 42.6)]. The cumulative incidences of secondary squamous cell carcinomas (SCCs) at 10 and 15 years were 4.2% [95% CI (2.2, 7.2)] and 8.1% [95% CI (4.6, 12.8)], while the cumulative incidences of non-SCCs at 10 and 15 years were 5.4% [95% CI (3.1, 8.7)] and 6.9% [95% CI (4.0, 10.8)]. Antithymocyte globulin (ATG) was associated with reduced incidences of SCCs but not of non-SCCs. Patients with grade II-IV aGVHD had increased rates of SCCs after adjusting with patient age and ATG, while patients with cGVHD showed only a trend for increased rates of SCCs.ConclusionThe data indicate that aGVHD and cGVHD affect the rates of secondary SCCs. While the use of ATG is associated with lower incidences of SCCs via reduction of GVHD, there was no association of ATG with non-SCCs.

Aplastic Anaemia Associated with Bendamustine Therapy - A Rare Side Effect.

During treatment for malignant lymphoma, cytopenia can develop for several reasons. This can range from mild cytopenias leading to infection and bleeding to full-blown drug-induced aplastic anaemia. While aplastic anaemia affects individuals of all genders and ages, here, we describe aplastic anaemia after chemotherapy exposure to bendamustine in a 65-year-old female with non-Hodgkin's lymphoma. A 65-year-old woman with recurrent indolent marginal zone lymphoma and post-chemotherapy with bendamustine and rituximab, presented with a neutropenic fever and was admitted with a leading diagnosis of sepsis. In the previous two weeks, the patient required regular transfusions of packed red blood cells and platelets and maintained a daily ZARXIO® regimen. Laboratory results revealed pancytopenia, and broad-spectrum antibiotics (cefepime/vancomycin) were given. The patient was subsequently admitted to the hospital under the care of the haematology/oncology team and was ultimately diagnosed with aplastic anaemia, likely as a consequence of bendamustine chemoimmunotherapy. She elicited a positive response to the triple immunosuppressive therapy (IST) regimen (two immunotherapeutic agents plus one anti-thymocyte globulin (ATG), after which her cell counts returned to normal. This case underscores the importance of recognising haematologic complications linked to bendamustine and advocates for further research to increase the understanding among healthcare professionals of drug-induced aplastic anaemia. Bendamustine can cause severe autoimmune haemolytic anaemia and aplastic anaemia and may require multiple transfusions and a multidrug regimen for treatment. The use of ATG as a therapeutic intervention is appropriate because it has been effective in treating aplastic anaemia. Bendamustine can cause severe autoimmune haemolytic anaemia and aplastic anaemia, a side effect which has rarely been reported but is of significant clinical importance.Drug-induced aplastic anaemia is a complex, potentially devastating consequence of treating blood cancers and is a relatively unexplored area that requires further understanding.Anti-thymocyte globulin is effective in treating bendamustine-induced aplastic anaemia as it degrades lymphocytes that destroy the bone marrow.

Recent advancements in hematopoietic stem cell transplantation in Taiwan.

Hematopoietic stem cell transplantation (HSCT) can cure malignant and nonmalignant hematological disorders. From 1983 to 2022, Taiwan performed more than 10,000 HSCT transplants. The Taiwan Blood and Marrow Transplantation Registry collects clinical information to gather everyone's experience and promote the advances of HSCT in Taiwan to gather everyone's experience and promote advances of HSCT in Taiwan. Compared with matched sibling donors, transplants from matched unrelated donors exhibited a trend of superior survival. In Taiwan, transplant donors showed remarkable growth from unrelated (24.8%) and haploidentical (10.5%) donors. The number of older patients (17.4%; aged ≥61 years) who underwent transplantation has increased markedly. This review summarizes several significant developments in HSCT treatment in Taiwan. First, the use of Anti-thymocyte globulin (ATG) and intravenous busulfan regimens were important risk factors for predicting hepatic sinusoidal obstruction syndrome. Second, a new, machine learning-based risk prediction scoring system for posttransplantation lymphoproliferative disorder has identified five risk factors: aplastic anemia, partially mismatched related donors, fludarabine use, ATG use, and acute skin graft-versus-host disease. Third, although the incidence of idiopathic pneumonia syndrome was low (1.1%), its mortality rate was high (58.1%). Fourth, difficult-to-treat mantle cell and T-cell lymphomas treated with autologous HSCT during earlier remission had higher survival rates. Fifth, treatment of incurable multiple myeloma with autologous HSCT showed a median progression-free survival and overall survival of 46.5 and 70.4 months, respectively. Sixth, different haploidentical transplantation strategies were compared. Seventh, caution should be taken in administering allogeneic HSCT treatment in older patients with myeloid leukemia with a Charlson Comorbidity Index ≥3 because of a higher risk of nonrelapse mortality.

TBI-Containing with T-Cell Replete Full Haplotype Mismatched Hematopoietic Stem Cell Transplantation in Adult Patients with De Novo Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is the 2nd most frequent developing hematologic malignancy with deep heterogeneity, but unfortunately the majority of patients relapse even after allogeneic hematopoietic stem cell transplantation (HSCT) in complete remission (CR). We have developed allogeneic HSCT from familial mismatched/haploidentical donors (FMT) in adult patients with a single disease entity of AML lacking of both HLA-identical siblings and well-matched unrelated donors (WMUD) from the mid 1990s. Previously, several pilot studies of FMT performed with various total body irradiation (TBI)-based conditioning regimens (2~12 gray) with or without post-transplant cyclophosphamide (PT-Cy) as a graft-versus-host disease (GvHD) prophylaxis were reported. Here, we demonstrate about the encouraging outcomes of FMT using unmanipulated peripheral blood donor stem cells (PBSCs) and de-escalated dose of TBI (4~8 gray) containing conditioning regimen without T-cell depletion manner. Although PT-Cy as a specific GvHD prophylaxis regimen is increasingly used for both adult and pediatric FMT, our group investigated the clinical outcomes in adult patients with de novo AML who received full haplotype mismatched HSCT after TBI containing preparation regimen consisted of fractionated TBI (total 4 gray for elderly and 8 gray for <60 years old), fludarabine (150 mg/m 2/day), busulfex (6.4mg/kg/day), and anti-thymocyte globulin (ATG). For GvHD prophylaxis, rabbit ATG (thymoglobulin, Genzyme, 1.25mg/kg/day for 4 days at D-4 to D-1) and a combination of tacrolimus and short-term methotrexate was used. G-CSF mobilized unmanipulated PBSCs were used with a median CD34+ dose of 6.5 x 10 6/kg (1~25.6). From 2008 to the end of 2022, total 429 adult patients were enrolled, and data demonstrated that our trial of intermediate-dose of ATG and reduced toxicity of TBI-containing conditioning regimen to reduce graft-failure even for high levels of donor-specific antibody titer, early transplant-related mortality, critical cytomegalovirus (CMV) disease, and emerging post-transplant lymphoproliferative disease with rapid immune recovery has shown very successful outcomes. Briefly, the median absolute neutrophil count recovery was 12 days (10~26) and the platelet of 14 days (5~38). There was no either primary or secondary graft-failures at all. With a median follow-up of 36.5 months (2~242) for survivors, overall survival rate (OS) and relapse-free survival (RFS) for patients in any CR (n=338) and relapse/refractory status (n=91) were 62.9% vs. 34.3% and 59.5% vs. 32.2%, respectively. Although there was no significant difference in the subgroup analysis, de novo and young aged patients in any CR showed the best OS 73% (Figure 1). Cumulative incidences of acute GvHD and chronic GvHD were 66% (59-73), 70% (63-76), respectively. The incidences of moderate to severe acute GvHD and chronic GvHD were 16.1%, 30.5%, respectively. By univariate and multivariate analyses, patient's age <54 (p=0.043), pre-HSCT CR1 (p <0.001), absence of mod to severe chronic GvHD (p <0.001), and use of post-transplant iron-chelating agent (p=0.001) were the statistically significant in the study. The GvHD-free and relapse-free survival rate in CR1 was 62.4% for younger patients (age <54) and 47.9% for older patients (p=ns). The non-relapse mortality rate was 27.2% for all enrolled patients and 16% for CR patients. The rapidity of immune recovery was also compared with our old control cohort when we performed T-cell depletion using the CliniMACS system, and it showed a significant reconstitution of CD4+ cells (>300/ul) at 3 months post-FMT compared to the much delayed T-cell depleted FMT. Of note, CMV DNAemia was relatively higher (76.9%) than reported in other studies, likely due to the use of ATG and the endemic region of our country. Therefore, we suggest that the strategic reduction of fractionated TBI 4~8 gray-based conditioning with unmanipulated PBSCs graft without PT-Cy seems feasible with favorable outcomes for adult patients with de novo AML undergoing FMT in CR, especially even in a certain subgroup of elderly patients with AML.

A Co-Reactivation Model of Cytomegalovirus and Epstein-Barr Virus after Allogeneic Hematopoietic Stem Cell Transplantation Was Constructed to Predict Mortality after Transplantation

Abstract Objective: The aim of this study was to create a predictive model for the occurrence of co-reactivation of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: The study included 373 patients who underwent allo-HSCT. The patient population was randomly divided into two groups: a training cohort comprising 70% of patients (n=261) and a validation cohort comprising 30% of patients (n=112). The predictive model was developed using several variables, including the time of reactivation of CMV and EBV, patient age and gender, presence of hepatitis B core antibody (HbcAb), type of transplant, use of anti-thymocyte globulin (ATG), and the occurrence of acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively). Results: The developed predictive model was expressed as y = -6.21338339 + 0.01923832 × (CMV reactivation time) + 0.00362628 × (EBV reactivation time) - 0.57604523 × (patient gender) + 0.01974136 × (patient age) + 0.85514424 × (presence of HbcAb) + 1.13782872 × (transplant type) + 0.95376138 × (use of ATG) - 0.62393602 × (aGVHD) - 1.09485262 × (cGVHD). The model demonstrated a g-mean value of 0.685 and a probability threshold of 0.297, allowing for the classification of patients into high-risk and low-risk groups. The incidence of co-reactivation of CMV and EBV over 100 days was significantly higher in the high-risk group compared to the low-risk group. In the high-risk group, the incidence was 49.3%, while in the low-risk group, it was 16.9% (P<0.0001, HR 95%CI 3.693(2.493,5.47)). For patients with aGVHD, the incidence was 41.7% in the high-risk group and 17.9% in the low-risk group (P=0.00026, HR 95%CI 2.7473(1.560,4.839)). In patients without aGVHD, the incidence was 53% in the high-risk group and 14.0% in the low-risk group (P<0.0001, HR 95%CI 4.9439(2.347,10.4)). Additionally, the model was able to predict post-transplant mortality and survival. Conclusion: Overall, the findings of this study suggest that the developed model is a valuable tool for predicting the risk of CMV and EBV co-reactivation following allo-HSCT. By identifying high-risk patients, clinicians can take proactive measures to prevent or manage viral infections, ultimately improving patient outcomes. Therefore, this model can potentially enhance clinical decision-making and optimize post-transplant care.

Antithymocyte Globulin in Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia: Evaluating Outcomes According to Cytogenetic Risk

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an essential therapeutic approach for the management of acute myeloid leukemia (AML). Nevertheless, graft-versus-host disease (GVHD) remains a significant complication, significantly affecting the recipients' quality of life and overall survival. Antithymocyte globulin (ATG) has demonstrated promise in preventing GVHD during allo-HSCT. However, concerns persist regarding its potential impact on disease relapse. This retrospective single-center study aims to evaluate the prognostic implications of ATG based on cytogenetic risk stratification in AML patients undergoing transplantation from an HLA-matched sibling. A total of 124 AML patients who underwent allo-HSCT from an HLA-matched sibling in their first complete remission state between 2003 and 2022 were eligible for the study. Among them, fifty patients received rabbit ATG at a dose of 2.5mg/kg/day for days -2 to -1, while 74 patients did not receive ATG. All patients received cyclosporine and methotrexate in addition to their respective conditioning regimens (ATG or no ATG). The ATG group consisted of 38 patients classified as having a non-high cytogenetic risk, and 12 patients classified as having a high cytogenetic risk. Conversely, the non-ATG group included 68 patients with a non-high cytogenetic risk and 6 patients with a high cytogenetic risk. After a median follow-up of 48 months, there were no significant differences in median overall survival between the ATG and Non-ATG groups, regardless of cytogenetic risk status (non-high cytogenetic risk; 12.4 months vs. NA, p = 0.578; high cytogenetic risk; 13.2 months vs. 14.2 months, p = 0.729, Figure A-1,B-1). The ATG group in the non-high cytogenetic risk group demonstrated a significant decrease in the 1-year cumulative incidence (CI) of chronic GVHD compared to the non-ATG group (21.7% vs. 54.4%, p = 0.001, Figure A-2; and in those with moderate to severe cGVHD, it was 21.6% vs. 51.5%, p = 0.003, respectively). Additionally, the 1-year Chronic GVHD-free and relapse-free survival (cGRFS) was higher in the ATG group of the non-high cytogenetic risk group (45.8vs. 26.5%; p = 0.048, Figure A-3). Moreover, there were no significant differences in 1-year CI of relapse and 1-year non-relapse mortality (NRM) within the non-high cytogenetic risk group (ATG vs. non-ATG; 29.7% vs. 20.6%, p = 0.225; 8.4% vs. 4.4%, p = 0.635, Figure A-4,5). In the subgroup analysis of patients with high cytogenetic risk, although there was no statistical significance, the ATG group showed a trend towards decreased 1-year CI of chronic GVHD and higher cGRFS compared to the non-ATG group (10.4% vs. 40.0%, p = 0.342; 31.2% vs. 16.7%, p = 0.929, Figure B-2,3). However, the ATG group exhibited a significantly higher 1-year CI of relapse compared to the non-ATG group (60.0% vs. 16.7%, p = 0.019, Figure B-4). In conclusion, our study findings indicate that ATG was effective in preventing chronic GVHD and demonstrated higher cGRFS in AML patients undergoing matched sibling donor HSCT. However, AML patients with high cytogenetic risk should carefully consider the use of ATG due to the associated higher risk of relapse. Further investigations are warranted to validate these findings and determine the appropriate dosage of ATG for high cytogenetic risk AML patients.

Impact of Letermovir Prophylaxis for Cytomegalovirus Reactivation on Post-Transplant Outcomes 100 Days before and after Allogeneic Hematopoietic Cell Transplantation

Background: Cytomegalovirus (CMV) infection is a major infectious complication following allogeneic hematopoietic cell transplantation (allo-HCT). Although letermovir (LMV) prophylaxis dramatically reduces the incidence of early clinically significant CMV (csCMV) infection, it remains unclear whether it has a beneficial effect on nonrelapse mortality (NRM) and overall survival (OS). Additionally, because the incidence of csCMV infection increases after completing LMV prophylaxis, the impact of late csCMV infection beyond 100 days after transplantation on posttransplant outcomes should also be verified. Study Design: We included adult patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), or myelodysplastic syndrome (MDS) aged ≥16 years who underwent allo-HCT between 2017 and 2019. These patients' data were obtained from the registry database of the Japanese Society for Transplantation and Cellular Therapy (JSTCT). Results: Donor CMV seronegativity (D-CMV −)/recipient CMV seronegativity (R-CMV −) was recorded in 558 cases (9.3%), and R-CMV +/D-CMV + or - was recorded in 4,562 cases (78.0%). The median age was 51 (range, 16-80) years. The median follow-up length was 389 (range, 0-1,334) days. LMV prophylaxis was administered to 1,640 patients (LMV group), and the median duration of LMV prophylaxis was 85 (range, 2-152) days. LMV prophylaxis significantly reduced the incidence of early csCMV infection compared with those not administered LMV prophylaxis (15.4% vs. 54.1%; p<0.01, hazard ratio [HR], 0.30; p<0.01)). However, LMV prophylaxis did not have any beneficial effect on the 1-year NRM (HR, 0.93; p=0.40) and OS (HR, 0.96; p=0.49) in multivariate analysis. The possible causes were breakthrough csCMV infection within 100 days after transplantation during LMV prophylaxis and late csCMV infection after 100 days after transplantation after completion of LMV prophylaxis. Breakthrough csCMV infection during LMV prophylaxis developed in 74 (4.5%) of the 1,640 patients who had received LMV prophylaxis. Breakthrough csCMV infection occurred at a median of 33 (range, 6-139) days after transplantation. R-CMV +, prior transplantation, cord blood (CB) transplants, anti-thymocyte globulin (ATG) or posttransplant cyclophosphamide (PTCY) use for GVHD prophylaxis, and grade II-IV acute GVHD were associated with an increased risk of breakthrough csCMV infection. The breakthrough csCMV infection group showed inferior NRM (HR, 3.44; p<0.01) and OS (HR, 1.93; p=0.02) compared with those without infection among LMV prophylaxis group. After completing LMV prophylaxis, 252 patients had late csCMV infection at a median of 134 (range, 101-405) days after transplantation. In multivariate analysis, R-CMV +, older age, CB transplantation, ATG and/or PTCY use for GVHD prophylaxis, grade II-IV acute GVHD, and LMV prophylaxis before day 100 after transplantation were associated with an increased risk of late csCMV infection. Late csCMV infection showed inferior NRM (HR, 1.83; p<0.01) and OS (HR, 1.58; p<0.01) in multivariate analysis. Conclusion: LMV prophylaxis efficiently suppressed the development of early csCMV infection; however, this effect did not translate into improved posttransplant outcomes. Breakthrough csCMV infection during LMV prophylaxis and the development of late csCMV infection after completing LMV prophylaxis worsened transplant outcomes in the LMV prophylaxis group. Further improvements in posttransplant CMV management will be required to address these issues.

Comparison of Two Reduced Intensity Conditioning Regimens (Baltimore with Clofarabine vs Thiotepa-Busulfan-Fludarabine) in Adults Receiving Peripheral Blood Stem Cell Haploidentical Transplantation for Myeloid Malignancies: A Retrospective Study of the SFGM-TC

Background: Haploidentical transplantation (haploT) has become a routine practice in many centers but the optimal conditioning regimen has yet to be determined. Indeed, the historic Baltimore reduced intensity conditioning (RIC) regimen has been associated with poor outcomes in myeloid malignancies. Two alternative RIC regimens have recently demonstrated promising results in this setting. One of them replaces fludarabine with second-generation nucleoside analogue clofarabine (Clo-Baltimore regimen [CloB], Chevallier et al., Oncotarget 2018) and the other combines thiotepa-busulfan-fludarabine (TBF, Duléry et al., BBMT 2019). Here we compared outcomes in order to determine if one of these two regimens was superior for the treatment of myeloid malignancies. Methods: This was a multicenter retrospective study conducted by the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). All consecutive adults having received a haploT after a CloB or a TBF RIC regimen for a myeloid malignancy between September 2013 and May 2023 were eligible. Patients data were extracted from the PROMISE database. CloB consisted of clofarabine 30 mg/m²/day (d) 5 d, cyclophosphamide (Cy) 14.5mg/kg/d 2 d, and 2-Gy TBI on d-2. TBF consisted of thiotepa 5mg/kg 1 d, busulfan 3.2 mg/kg 2 d, a fludarabine total dose of 120 to 150 mg/m². Graft-versus-host disease (GVHD) prophylaxis consisted of post-transplant Cy (2 doses of 50mg/kg), followed by cyclosporine A and mycophenolate mofetil starting on d+5. Some patients received antithymocyte globulin (ATG) 2.5mg/kg/d on d-2. Graft source was exclusively peripheral blood stem cells (PBSC). To minimize bias between the CloB and the TBF groups, a propensity score matching (PSM) was constructed using a logistic regression model that included age, donor and recipient sex, hematopoietic cell transplantation-specific comorbidity index (HCT-CI), disease, cytogenetic risk (European LeukemiaNet [ELN] 2022), previous transplant, use of ATG, and cytomegalovirus (CMV) status, with the nearest-neighbor algorithm, and strict matching of key factors. Matched groups were then compared for time to engraftment (absolute neutrophil count > 0.5 x 10 9/L) and platelet (PLT) recuperation (>50 x 10 9/L), overall survival (OS), progression-free survival (PFS), GVHD-free, progression-free survival (GRFS), non-relapse mortality (NRM), and incidences of relapse as well as acute and chronic GVHD. Results: A total of 329 patients from 25 centers were included, 267 (81%) receiving TBF and 62 (19%) CloB. After PSM, 51 patients remained in each group, with comparable baseline characteristics except for the proportion of previous allotransplants ( Table). Median age was 60 years, and median HCT-CI score was 2. Main diagnoses comprised acute myeloblastic leukemia (AML, n=72 [71%]), including 42% with adverse genetic risk, and myelodysplastic syndrome (MDS, n=22 [22%]), including 25% with high or very high Revised International Prognostic Scoring System (R-IPSS). Thirty-eight (37%) patients received ATG. Time to engraftment was equivalent after both TBF and CloB (19 d vs 19.5 d, respectively, p=0.70), but TBF patients achieved PLT recuperation faster (27 d vs 31 d, p=0.03). Median follow-up was 24 months. Two-year OS, PFS and GRFS were 55% vs 60% (p=0.19), 52% vs 60% (p=0.25), and 37% vs 50% (p=0.15) for TBF and CloB patients, respectively. No differences were observed in terms of grade 3-4 acute GVHD at 3 months (18 vs 20%, p=0.86) nor two-year extensive chronic GVHD (16% vs 8.3%, p=0.25). However, two-year NRM was significantly higher after TBF (41% vs 16%, p=0.003), while relapse incidence was lower (7.1% vs 24%, p=0.02, Figure). In multivariate analysis, CloB was associated with a lower risk of NRM (hazard ratio [HR] 0.31, 95%CI: 0.1-0.7, p=0.008) and a higher risk of relapse (HR 4.03, 95%CI: 1.2-13.9, p=0.03). Finally, in patients aged >60y, two-year OS was significantly lower for those receiving TBF conditioning (39% vs 61%, p=0.02, Figure) due to higher NRM (56% vs 23%, p=0.005). Conclusions: In this retrospective study, a TBF RIC regimen used for PBSC haploT in adults with myeloid malignancies appeared substantially more toxic than a CloB RIC regimen. However, its enhanced anti-leukemic effect suggests that it should be offered to younger patients with no comorbidities or to those with high-risk disease. Conversely, CloB should be proposed for older or frail patients.

The Area Under Tacrolimus Concentrations on Day 14-28 Is the Independent Predictor of the Development of Chronic Gvhd in Patients without Severe Acute Gvhd after Unrelated Allogeneic HSCT

Introduction: In unrelated allogeneic hematopoietic stem cell transplantation (UR-SCT), chronic graft-versus-host disease (GVHD) is a critical complication that affects not only patients' quality of life but also post-transplant outcome. Acute GVHD is a major risk factor for the subsequent development of chronic GVHD. The combination of tacrolimus and short-term methotrexate (TAC+sMTX) has been widely used as a GVHD prophylaxis for UR-SCT in Japan. Previous reports have shown that tacrolimus blood concentrations early after transplantation are associated with the development of acute GVHD, but not with that of chronic GVHD. On the other hand, among UR-SCT recipients who did not develop severe acute GVHD, the relationship between tacrolimus blood concentrations and the development of chronic GVHD remains unclear. Methods: To examine the association between tacrolimus blood concentrations and post-transplant outcomes, the area under the tacrolimus concentration on day 0-14 (AUTC 0-14) and day 14-28 (AUTC 14-28) was calculated simply as the sum of the area of the trapezoid for the corresponding period ( Figure). Tacrolimus was initiated by continuous intravenous administration from day -1 in all patients, and no patients were switched to oral administration prior to day 28. Short-term methotrexate was administered at 10 mg/m 2 on day 1 and 7 mg/m 2 on day 3, day 6, and day 11. Among all 151 adult patients with hematopoietic malignancies who underwent first UR-SCT with GVHD prophylaxis of TAC+sMTX between 2010 and 2022 at the Jikei University Hospital, the following were excluded from the analysis: developing grade III-to-IV acute GVHD, using prednisolone or methyl-prednisolone ≥0.5 mg/kg within day 100, engraftment failure, death before day 100, and relapse before day 100. Results: A total of 68 patients were included in the analysis. Median age was 50.5 (range, 16-68) years. Twenty-seven (40%) patients had acute myeloid leukemia, and 18 (27%) had acute lymphoblastic leukemia. Fifty-five (81%) were in complete remission/chronic phase/early stage. The donor source consisted of 42 (62%) bone marrow transplantation (BMT), 20 (29%) cord blood transplantation (CBT), and 6 (9%) peripheral blood stem cell transplantation (PBSCT). BMT recipients transplanted from 22 (52%) HLA 8/8 matched donor, 19 (45%) HLA 7/8 matched donor, and one (3%) HLA 6/8 matched donor. CBT recipients transplanted from 15 (75%) HLA 4/6 matched donor and 5 (25%) HLA 5/6 matched donor. PBSCT recipients transplanted from 5 (83%) HLA 8/8 matched donor and one (17%) HLA 7/8 matched donor. Fifteen (22%) patients were administered additional low-dose anti-thymocyte globulin (ATG) as GVHD prophylaxis. Fifteen male patients transplanted from female donors (22%). Thirty-nine (57%) patients received myeloablative conditioning regimen. The median time from UR-SCT to neutrophil engraftment was 19 days (range, 11-34). Regarding acute GVHD, 46 patients (68%) developed none, 13 patients (19%) developed grade I, and 9 patients (13%) developed grade II. The median observation period for all 68 patients was 48.2 months (4.0 years). The 4-year cumulative incidence (CI) of chronic GVHD was 51%, of which 24% were moderate-to-severe. The CI of moderate-to-severe chronic GVHD was not associated with age, disease status, donor source, HLA incompatibility, ATG use, female to male, intensity of conditioning regimen, and grade I-to-II acute GVHD development. AUTC 14-28 <200 was the only risk factor (AUTC 14-28<200: 32% vs AUTC 14-28≥200: 11%; p=0.047). Multivariate analysis also showed that AUTC 14-28 <200 was the independent factor for development of moderate-to-severe chronic GVHD ( p=0.04). In all 68 patients, 4-year CI of relapse was 20%, 4-year CI of non-relapse mortality was 10%, 4-year GVHD-free, relapse-free, survival (GRFS) was 50%, and 4-year Overall survival was 80%, all of which did not differ between AUTC 14-28 <200 and AUTC 14-28 ≥200 groups. Conclusion: In UR-SCT, our data showed that AUTC 14-28 <200 may be an independent risk factor for developing moderate-to-severe chronic GVHD, even in patients who did not develop severe acute GVHD.

Different effects of thymoglobulin on acute leukemia with pre-transplant residual blasts in HLA mismatch transplantation.

Anti-thymocyte globulin (ATG) is widely used to reduce acute and chronic graft-versus-host disease (a/cGVHD), one of the leading causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). As the removal of alloreactive T cells by ATG may also reduce the graft-versus-leukemia effect, the question of whether ATG use affects relapse incidence and survival outcomes in acute leukemia patients with pre-transplant bone marrow residual blasts (PRB) remains controversial. Here, we evaluated the impact of ATG on transplant outcomes in acute leukemia patients with PRB (n = 994) who underwent HSCT from HLA 1-allele mismatched unrelated donors (MMUD) or HLA 1-antigen mismatched related donors (MMRD). In MMUD with PRB (n = 560), multivariate analysis demonstrated that ATG use significantly decreased grade II-IV aGVHD (hazard ratio [HR], 0.474; P = 0.007) and non-relapse mortality (HR, 0.414; P = 0.029) and marginally improved extensive cGVHD (HR, 0.321; P = 0.054) and GVHD-free/relapse-free survival (HR, 0.750; P = 0.069). We concluded that ATG had different effects on transplant outcomes using MMRD and MMUD, and its use would be beneficial to decrease a/cGVHD without increasing non-relapse mortality and relapse incidence in acute leukemia patients with PRB following HSCT from MMUD.

P3.01: Similar Graft-Versus-Host Disease (GVHD) Incidence Among Unrelated and Identical Sibling Donor Transplantation With the Use of Anti-thymocyte Globulin (ATG)

Introduction: GVHD is the main cause of morbidity and mortality associated with allogeneic hematopoietic stem cell transplantation (HSCT) with an incidence rate of 40-60%. Addition of ATG has shown to reduce its incidence. We report the GVHD outcomes with the use of ATG as part of the prophylaxis regimen in a group of patients (pts) undergoing HSCT. Methods: From March 2018 to June 2021 we conducted a prospective multicenter study including 95 consecutive pts.: 33 transplanted with an identical sibling donor (ISD), 33 with an HLA-matched unrelated donor(MUD) and 18 with an HLA 1 miss-matched donor (MMUD). Conditioning regimen was according to institutional protocol. GVHD prophylaxis included tacrolimus and methotrexate plus ATG (Timoglobulina®Sanofi) 2.25 mg/kg days -3 and -2. GVHD incidence, relapse and death were recorded. Acute GVHD (aGvHD) and chronicGVHD (cGVHD) were defined using Glucksberg criteria and NIH clinical grading respectively. Median and interquartile range (IQR) were used to describe non-parametric data, group comparison with X2, Kaplan Meyer curve and multi-sample log Rank test for survival analysis, considering a statistically significant p value of less than 0.05. Results: 42 pts were male and donors were female in 56% (n:54). Conditioning regimen was myeloablative in 81% (n:77). Median time to neutrophil and platelet engraftment were 17 days (range 15-21) and 17 days (range 12-20) respectively. 6/95 pts presented graft failure. aGVHD incidence was 36% (n:34), grades I-II 19% (n:19) and III-IV 16% (n:15). Incidence of grades III-IV did not varied according to donor: 15% (n:7) for ISD, 9% (n:3) for MUD and 27% (n:5) for (X2 3.06, p0.21) Overall incidence of cGVHD was 23% MMUD (n:21): Grades mild 6% (n:6), moderate 11% (n:11) and severe 4% (n:4). According to donor type, severe cGVHD was 2% (n:1), 3% (n:1) and 11% (n:2) using ISD, MUD and MMUD respectively (X2 2.65, p0.26). At one year, 15/79 pts (19%) were under immunosuppressive treatment. Transplant related mortality at day 100 was 9% (n:9). Most frequent cause was sepsis (n:4). In 31 pts CMV reactivation was detected (more than one reactivation in 6 pts of which 5 had GVHD) and 7 reactivated EBV infection. None evolved to PTLD. Median follow-up time was 524 days (IQR 168-833). cGVHD–free and relapse-free survival (combined endpoint) at 1 year was 57% (n:54) of 79 evaluables patients. cGVHD and relapse free survival at 1 year was 48% for IDS (33-63%CI), 66% for MUD (47-81%CI) and 38% for MMUD (21-60%CI). No significant difference was found according to donor type (X2 4.98; p0.083). Conclusion: With the use of ATG no difference was observed in the incidence of aGVHD grades III-IV and severe cGvHD between the different types of donor. This results should be confirmed with a higher level of evidence study.

348.5: Life Threatening, Cytokine Release Storm (CRS) With Antithymocyte Globulin (ATG) And Its Management

Introduction: Cytokine Release Storm (CRS) leading to fatal or near fatal hypotension has been reported in association with anti thymocyte globulin (ATG) administration. This is a very rare and unusual manifestation of ATG and early recognition and management of this unexpected manifestation will help save lives. We report a near fatal case of CRS, during renal transplantation, associated with ATG administration, its diagnosis and management. Materials and Methods: A 27-year-old, otherwise healthy male with Alport’s syndrome was undergoing live related preemptive renal transplant. Patient received morning dose of Solu-Medrol and CellCept and was getting Anti Thymocyte Globulin (ATG) slowly after the test does, as the recipient vascular bed was being prepared. Patient started to become hypotensive which was treated with IV fluids and pressors including norepinephrine, epinephrine and dopamine.There was no bleeding from recipient vascular bed.A stat chest x-ray, EKG and echocardiogram on the OR table were normal with good LV function. Despite maximum dose pressor support and IV fluids, the mean blood pressure was around 45 - 50 mm Hg and a systolic blood pressure was around 65-70 mm Hg, leading to severe metabolic acidosis and lactate buildup. The transplant was canceled and the donor was closed unharmed and the patient was moved to ICU, intubated. His response to colloids was slightly better, but transient, so he was transfused 4 units of blood as volume expander that does not leak into 3rd space.This brought his blood pressure to about 90 mm Hg. A presumptive diagnosis of ATG induced CRS was made. His inflammatory markers including IL-6, ferritin, D-dimers and CRP were very high. 400 mg of Tocilizumab (Actemra) an IL-6 inhibitor along with broad-spectrum antibiotics were given. Patient also started to developed disseminated intravascular coagulation (DIC) with deranged coagulation screen and some oozing from the wound which was treated with FFPs. In next 12 hours, the patient started to stabilize and in next 48 hours he was extubated. Discussion: Cytokine Release Storm (CRS) is a potentially fatal condition unless recognized and treated early and aggressively. In COVID pandemic, much better understanding of CRS along with its symptomatology, easy availability of its lab tests and IL- 6 inhibitors became possible. High index of suspicion is extremely important in making an early diagnosis and for early treatment. In transplant patients, use of ATG is now standard of care and very few cases of ATG induced CRS are reported. In our case, early diagnosis of CRS from ATG, use of blood as volume expander, early administration of IL-6 inhibitor and aggressive management of DIC turned out to be the life Saver. Conclusion: In patients receiving ATG, with unexplained hypotension, nonresponsive to IV fluids and pressors, high index of suspicion of ATG induced CRS with early diagnosis and aggressive management can save lives.

Characteristics of Graft-Versus-Host Disease (GvHD) After Post-Transplantation Cyclophosphamide Versus Conventional GvHD Prophylaxis

Post-transplantation cyclophosphamide (PTCy) has been shown to effectively control graft-versus-host disease (GvHD) in haploidentical (Haplo) transplantations. In this retrospective registry study, we compared GvHD organ distribution, severity, and outcomes in patients with GvHD occurring after Haplo transplantation with PTCy GvHD prophylaxis (Haplo/PTCy) versus HLA-matched unrelated donor transplantation with conventional prophylaxis (MUD/conventional). We evaluated 2 cohorts: patients with grade 2 to 4 acute GvHD (aGvHD) including 264 and 1163 recipients of Haplo and MUD transplants; and patients with any chronic GvHD (cGvHD) including 206 and 1018 recipients of Haplo and MUD transplants, respectively. In comparison with MUD/conventional transplantation ± antithymocyte globulin (ATG), grade 3-4 aGvHD (28% versus 39%, P=.001), stage 3-4 lower gastrointestinal (GI) tract aGvHD (14% versus 21%, P=.01), and chronic GI GvHD (21% versus 31%, P=.006) were less common after Haplo/PTCy transplantation. In patients with grade 2-4 aGvHD, cGvHD rate after Haplo/PTCY was also lower (hazard ratio [HR]=.4, P < .001) in comparison with MUD/conventional transplantation without ATG in the nonmyeloablative conditioning setting. Irrespective of the use of ATG, non-relapse mortality rate was lower (HR=.6, P=.01) after Haplo/PTCy transplantation, except for transplants that were from a female donor into a male recipient. In patients with cGvHD, irrespective of ATG use, Haplo/PTCy transplantation had lower non-relapse mortality rates (HR=.6, P=.04). Mortality rate was higher (HR=1.6, P=.03) during, but not after (HR=.9, P=.6) the first 6 months after cGvHD diagnosis. Our results suggest that PTCy-based GvHD prophylaxis mitigates the development of GI GvHD and may translate into lower GvHD-related non-relapse mortality rate.

Advantages of peripheral blood stem cells from unrelated donors versus bone marrow transplants in outcomes of adult acute myeloid leukemia patients

Background aimsIn allogeneic stem cell transplantation, unrelated donors are chosen in cases where appropriate related donors are not available. Peripheral blood stem cells (PBSCs) are more often selected as a graft source than bone marrow (BM). However, the prognostic benefits of PBSCs versus BM transplants from unrelated donors have not been carefully examined in patients with acute myeloid leukemia (AML). This study compared outcomes of adult AML patients who underwent unrelated PBSC and BM transplantation, evaluating post-transplant complications, including engraftment, graft-versus-host disease (GVHD) and infections, and determined subgroups of patients who are most likely to benefit from unrelated PBSCs compared with BM transplants. MethodsThe authors analyzed 2962 adult AML patients who underwent unrelated PBSC or BM transplants between 2011 and 2018 (221 PBSC and 2741 BM) using the Japanese nationwide registry database, in which graft source selection is not skewed toward PBSCs. ResultsIn 49.7% of patients, disease status at transplantation was first complete remission (CR1). In 57.1% of cases, HLA-matched donors were selected. Myeloablative conditioning was performed in 75.1% of cases, and anti-thymocyte globulin (ATG) was added to conditioning in 10.5%. Multivariate analyses showed a trend toward favorable non-relapse mortality (NRM) in PBSC recipients compared with BM recipients (hazard ratio [HR], 0.731, P = 0.096), whereas overall survival (OS) (HR, 0.959, P = 0.230) and disease-free survival (DFS) (HR, 0.868, P = 0.221) were comparable between PBSC and BM recipients. Although the rate of chronic GVHD (cGVHD) was significantly higher in PBSC patients (HR, 1.367, P = 0.016), NRM was not increased, mainly as a result of significantly reduced risk of bacterial infections (HR, 0.618, P = 0.010), reflecting more prompt engraftments in PBSC recipients. Subgroup analyses revealed that PBSC transplantation was advantageous in patients transplanted at CR1 and in those without ATG use. PBSC recipients experienced significantly better OS and/or DFS compared with BM recipients in this patient group. ConclusionsThe authors' results confirmed the overall safety of unrelated PBSC transplantation for adult AML patients and suggested an advantage of PBSCs, especially for those in CR1. Further optimization of the prophylactic strategy for cGVHD is required to improve the overall outcome in transplantation from unrelated PBSC donors.

Early Estimated Glomerular Filtration Rate Trajectories After Kidney Transplant Biopsy as a Surrogate Endpoint for Graft Survival in Late Antibody-Mediated Rejection.

BackgroundLate antibody-mediated rejection (ABMR) after kidney transplantation is a major cause of long-term allograft loss with currently no proven treatment strategy. Design for trials testing treatment for late ABMR poses a major challenge as hard clinical endpoints require large sample sizes. We performed a retrospective cohort study applying commonly used selection criteria to evaluate the slope of the estimated glomerular filtration rate (eGFR) within an early and short timeframe after biopsy as a surrogate of future allograft loss for clinical trials addressing late ABMR.MethodsStudy subjects were identified upon screening of the Vienna transplant biopsy database. Main inclusion criteria were (i) a solitary kidney transplant between 2000 and 2013, (ii) diagnosis of ABMR according to the Banff 2015 scheme at >12 months post-transplantation, (iii) age 15–75 years at ABMR diagnosis, (iv) an eGFR > 25 mL/min/1.73 m2 at ABMR diagnosis, and (v) a follow-up for at least 36 months after ABMR diagnosis. The primary outcome variable was death-censored graft survival. A mixed effects model with linear splines was used for eGFR slope modeling and association of graft failure and eGFR slope was assessed applying a multivariate competing risk analysis with landmarks set at 12 and 24 months after index biopsy.ResultsA total of 70 allografts from 68 patients were included. An eGFR loss of 1 ml/min/1.73 m2 per year significantly increased the risk for allograft failure, when eGFR slopes were modeled over 12 months [HR 1.1 (95% CI: 1.01–1.3), p = 0.020] or over 24 months [HR 1.3 (95% CI: 1.1–1.4), p = 0.001] after diagnosis of ABMR with landmarks set at both time points. Covariables influencing graft loss in all models were histologic evidence of glomerulonephritis concurring with ABMR as well as the administration of anti-thymocyte globulin (ATG) at the time of transplantation.ConclusionOur study supports the use of the eGFR slope modeled for at least 12 months after biopsy-proven diagnosis of late ABMR, as a surrogate parameter for future allograft loss. The simultaneous occurrence of glomerulonephritis together with ABMR at index biopsy and the use of ATG at the time of transplantation–likely representing a confounder in pre-sensitized recipients–were strongly associated with worse transplant outcomes.

Characterization of Cytomegalovirus Viremia in Renal Transplant Recipients.

Kidney transplantation, while improving outcomes for patients with end-stage renal disease, comes with a risk of potentially life-threatening infections such as infection with cytomegalovirus (CMV), a virus associated with allograft rejection, organ dysfunction, and increased mortality. To characterize whether the choice and dose of immunosuppressant therapy and the duration of antiviral prophylaxis after transplant are associated with the incidence of CMV viremia. This study was a retrospective review of all kidney-only transplant recipients at the authors' centre from 2012 to 2016, with a minimum 1 year of follow-up. Patients with CMV viremia (defined as serum CMV viral load greater than 1000 IU/mL) were compared with patients who did not have viremia to investigate potential demographic and treatment-related risk factors. A total of 653 patients were included in the study, of whom 161 (25%) met the criteria for CMV viremia. In univariate analysis, patients with CMV viremia had older age (55 versus 53 years, p = 0.038) and lower mean body weight (75 versus 79 kg, p = 0.015); in addition, the CMV viremia group included larger proportions of patients with Asian descent (40% [64/161] versus 21% [104/492]) and donor-positive/recipient-negative CMV serostatus (29% [47/161] versus 14% [70/492]). With respect to immunosuppressant therapy, patients with CMV viremia more frequently received antithymocyte globulin (ATG) induction (50% [80/161] versus 28% [138/492], p < 0.001) and received a higher weight-based cumulative ATG dose (mean 4.5 versus 4.1 mg/kg, p = 0.038). The multivariate analysis retained use of ATG, cumulative dose of ATG, Asian descent, and CMV serostatus as risk factors for CMV viremia. No statistically significant differences were found for the maintenance immunosuppressant dosing or duration of antiviral prophylaxis. Use of ATG for induction and higher weight-based dose of ATG were associated with an increased risk of CMV viremia. In addition, a component of race may also be involved, with patients of Asian descent being at higher risk. No differences were found in the maintenance dose of immunosuppression or the duration of antiviral prophylaxis.

Cytomegalovirus and Epstein Barr Virus Reactivation after Allogeneic Stem Cell Transplantation in Pre- and Post-Letermovir Era

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation are two of the most frequent infections affecting patients receiving allogeneic stem cell transplantation (HSCT). Up to 80% of seropositive patients might experience CMV reactivation in absence of prophylaxis, expecially when a seropositive patient receive stem cell graft from seronegative donor. The introduction of Letermovir notably reduced the risk of CMV infection also in high risk patients. EBV is a herpesvirus widely spread in common population with a prevalence of approximatively 80%. As a consequence, many recipient and donor have EBV seropositive status. We would evaluate if a difference occurred in the CMV and EBV incidence after Letermovir introduction, which casually coincided in our center with the transition to a single graft-versus host disease (GvHD) prophylaxis schedule including cyclophosphamide post (Cy-post).We enrolled patient submitted to allogeneic stem cell transplant in our centre from January 2015 to december 2020. Patients were divided into two groups. The pre-letermovir group (group A, n=230) included patients who had received prophylaxis with ciclosporine A (CSA) plus micophenolic acid (MFA) (N=17) or CSA plus short course methotrexate (MTX) (N=96) or CSA plus MFA plus Cy-post (n=117). In the post-letermovir group (group B, n=135) all patients received the same GvHD prophylaxis with CSA plus MFA plus Cy-post. Sixty-eight of them received letermovir in addition to acyclovir as CMV prophylaxis.In the group A, CMV infection rate was affected by HLA mismatch (HR 1.70, p=0.003), Cy-post use (HR1.49, p=0.02), anti-thymocyte globulin (ATG) use (HR 0.62, p=0.01), bone marrow or cord blood source (HR 1.46, p=0.03), CMV seropositive recipient (HR 10, p=0.0001) and CMV seronegative donor for a seropositive recipient (HR 2.2, p<0.0001). Multivariate analysis confirmed CMV seropositive recipient (HR 9, p=0.002), CMV seronegative donor for seropositive recipient (HR 1.67, p=0.008) and HLA mismatch (HR 3.58, p=0.006) as independent variables for CMV infection. EBV infection appeared to be affected by underlying disease remission status at transplant (HR 1.64, p=0.01), HLA mismatch (HR 0.42, p<0.0001), GvHD prophylaxis other than Cy-post (HR 2.60, p<0.0001), ATG use (HR 2.60, p<0.0001), unrelated donor (MUD) (HR 2.01, p=0.0005) and aGvHD occurrence (HR 1.62, p=0.01). Multivariate analysis confirmed aGvHD occurrence (HR 1.74, p=0.007) and underlying disease remission at transplant (HR 1.90, p=0.002) as independent variables for EBV infection.In the group B, reduced intensity conditioning (HR 5.94, p=0.007), letermovir use (HR 0.23, p=0.0009), and aGvHD occurrence (HR 3.13, p=0.007) were independent risk factors for CMV infection in multivariate analysis. The 100-day CI of CMV infection was of 3% (95% CI 1-12) in patients receiving letermovir vs. 26% (95% CI 17-39) in the others (p=0.02, figure 1A). In the same cohort of patients EBV infection appeared to be more frequent for patients receiving ATG (57% vs. 24%, p=0.05), MUD donor (32% vs. 17%, p=0.04) and who experienced CMV concomitant infection (42% vs. 28%, p=0.03). However, these data were not confirmed in multivariate analysis.According to GvHD prophylaxis, CMV infection appeared to be more frequent in patients receiving Cy-post as GvHD prophylaxis (1-yr CI 68% vs. 54.6%, p=0.02, figure 1B), contrarily to EBV infection which appeared to be less frequent in the same patients (1-yr CI 41% vs. 62%, p<0.0001, figure 1C). However, CMV infection rate was notably reduced by letermovir introduction, while EBV infection rate not appeared to be affected by that.Figure 1: A) Day 100 cumulative incidence of CMV according to letermovir prophylaxis administration; B) One year cumulative incidence of CMV according to cyclophosphamide post transplant administration; C) One year cumulative incidence of EBV according to cyclophosphamide post transplant administration. [Display omitted] DisclosuresMetafuni: Jazz: Other: Invited Clinical case presentation at meeting. Laurenti: Roche: Honoraria; Gilead: Honoraria; Abbvie: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; AstraZeneca: Honoraria, Speakers Bureau. Sica: Alexion: Consultancy; Jazz Pharma: Consultancy.

Safety of Antithymocyte Globulin Use in Kidney Graft Recipients During the COVID-19 Pandemic.

BackgroundThere are many safety concerns regarding the use of antithymocyte globulin (ATG) in kidney transplant recipients (KTRs) during the ongoing COVID-19 pandemic. Hereby, we present our recent experience with ATG administration both as induction therapy and as an anti-rejection treatment.Material/MethodsWe retrospectively analyzed all patients transplanted during the first 12 months of the COVID-19 pandemic who were treated with thymoglobulin. The ATG dosing, lymphocyte number and percentage in blood smear, adverse effects (thrombocytopenia and infectious complications), and kidney graft function up to 12 months and patients’ outcomes were analyzed and compared to KTRs who received basiliximab induction.ResultsDuring pandemic, a total of 31 patients were treated with ATG and 59 received basiliximab. The median cumulative ATG doses were 275 (175–325) mg in the induction subgroup and 263 (200–275) mg in the anti-rejection treatment subgroup. Mild thrombocytopenia was noted in 7 (22.6%) and 13 (29.5%) patients, respectively. There were more infectious complications among patients treated with ATG as compared with the basiliximab subgroup (32.3 vs 10.2%, P<0.01), but there were similar incidence rates of thrombocytopenia. Kidney graft function up to 12 months after transplant was comparable (1.1 [1.0–1.9] vs 1.1 [1.0–1.4] mg/dl, respectively).Conclusions1. ATG use in the induction protocol or as the anti-rejection treatment during the COVID-19 pandemic appears to be safe and the risk of adverse events is acceptable. 2. During the COVID-19 pandemic the necessary use of ATG should not be postponed, especially in KTRs with increased immunologic risk.

Clinical Correlates and Outcomes of Dual Basiliximab and Antithymocyte Globulin Induction in Kidney Transplant Recipients: A National Study.

We used national transplant registry data to study clinical correlates and outcomes of single versus dual induction therapy in adult kidney-only transplant recipients in the United States (2005-2018). The risk of death and graft loss at 1 and 5 y, according to induction therapy type, was assessed using multivariate Cox regression analysis (adjusted hazard ratio with 95% upper and lower confidence limits [LCLaHRUCL]). Of the 157 351 recipients included in the study, 67% were treated with ATG alone, 29% were treated with IL2rAb alone, and 5% were treated with both. Compared with IL2rAb alone, the strongest correlates of dual induction included Black race, calculated panel reactive antibody ≥80%, prednisone-sparing maintenance immunosuppression, more recent transplant eras, longer cold ischemia time, and delayed graft function. Compared with ATG alone, dual induction was associated with an increased 5-y risk of death (aHR 1.071.151.23; P < 0.0001), death-censored graft failure (aHR 1.051.131.22; P < 0.05), and all-cause graft failure (aHR 1.061.121.18; P < 0.0001). Further research is needed to develop risk-prediction tools to further inform optimal, individualized induction protocols for kidney transplant recipients.