Pre-transplant Status Research Articles

Is Obesity Associated With Better Liver Transplant Outcomes? A Retrospective Study of Hospital Length of Stay and Mortality Following Liver Transplantation.

The rise in obesity in the United States, along with improvements in antiviral therapies, has led to an increase in the number of obese patients receiving liver transplants. Currently, obesity is a relative contraindication for liver transplant, although exact body mass index (BMI) limits continue to be debated. Studies conflict regarding outcomes in obese patients, while some argue that BMI should not be used as an exclusion criterion at all. Therefore, this retrospective study-utilizing a large national database-seeks to elucidate the association between recipient BMI and hospital length of stay and mortality following liver transplant. A retrospective study was conducted using the United Network for Organ Sharing Standard Transplant Analysis and Research database. Fine-Gray competing risk regressions were used to explore the association between BMI and rate of discharge, which varies inversely with length of stay. In our model, subdistribution hazard ratio (SHR) represented the relative change in discharge rate compared to normal BMI, with in-hospital death was considered as a competing event for live discharge. Cox proportional hazard models were built to assess the association of BMI category on all-cause mortality after liver transplantation. Cluster-robust standard errors were used in all analyses to construct confidence intervals. Within the final sample (n = 47,038), overweight (≥25 and <30 kg/m2) patients comprised the largest BMI group (34.7%). The competing risk regression model showed an association for increased length of stay among underweight (SHR = 0.82, 95% confidence interval [CI], 0.77-0.89; P < .001) and class 3 obesity patients (SHR = 0.88, 95% CI, 0.83-0.94; P < .001), while overweight (SHR = 1.05, 95% CI, 1.03-1.08; P < .001) and class 1 obesity (SHR = 1.04, 95% CI, 1.01-1.07; P = .01) were associated with decreased length of stay. When the sample excluded patients with low pretransplant functional status, however, length of stay was not significantly shorter for overweight and obesity class 1 patients. Cox proportional hazard models demonstrated increased survival among overweight, class 1 and class 2 obesity patients and decreased survival among underweight patients. Our results provide evidence that overweight and obesity class 1 are associated with decreased length of stay and mortality following liver transplant, while underweight and obesity class 3 are associated with prolonged length of stay. Pretransplant functional status may contribute to outcomes for overweight and class 1 obese patients, which necessitates continued investigation of the isolated impact of BMI in those who have had a liver transplant.

The Assessment and Outcomes of Crossmatching in Lung Transplantation in Korean Patients.

BackgroundIn lung transplantation, human leukocyte antigen (HLA) compatibility is not included in the lung allocation score system or considered when placing donor allografts. However, HLA matching may affect the outcomes of lung transplantation. This study evaluated the current assessment status, prevalence, and effects of HLA crossmatching in lung transplantation in Korean patients using nationwide multicenter registry data.MethodsTwo hundred and twenty patients who received lung transplantation at six tertiary hospitals in South Korea between March 2015 and December 2019 were retrospectively reviewed. Clinical data, including general demographic characteristics, primary diagnosis, and pretransplant status of the recipients and donors registered by the Korean Organ Transplant Registry, were retrospectively analyzed. Survival analysis was performed using the Kaplan-Meier method with log-rank tests.ResultsComplement-dependent cytotoxic crossmatch (CDC-XM) was performed in 208 patients (94.5%) and flow cytometric crossmatch (flow-XM) was performed in 125 patients (56.8%). Among them, nine patients (4.1%) showed T cell- and/or B cell-positive crossmatches. The incidences of postoperative complications, including primary graft dysfunction, acute rejection, and chronic allograft dysfunction in positively crossmatched patients, were not significant compared with those in patients without mismatches. Moreover, Kaplan-Meier analyses showed poorer 1-year survival in patients with positive crossmatch according to CDC-XM (P < 0.001) and T lymphocyte XM (P = 0.002) than in patients without mismatches.ConclusionPositive CDC and T lymphocyte crossmatching results should be considered in the allocation of donor lungs. If unavailable, the result should be considered for postoperative management in lung transplantation.

Prognostic value of minimal residual disease before allogeneic hematopoietic stem cell transplantation in patients with acute leukemia

Introduction. One of the main causes of treatment failure after allogeneic hematopoietic stem cells transplantation (alloHSCT) for acute leukemia (AL) is disease relapse. In recent years, multiparameter fl ow cytometry (MPC) has been widely used to detect minimal residual disease (MRD) because of its capacity to identify patients with a high risk of relapse due to availability and the ability to obtain results in a timely manner.Aim — to evaluate the prognostic value of MRD status before allo-HSCT and the effect of donor type and conditioning intensity on long-term results of allo-HSCT of MOB-positive patients.Patients and methods. The analysis included 107 patients with acute myeloid leukemia (AML) and 63 patients with acute lymphoblastic leukemia (ALL) who underwent allo-HSCT between September 2015 and June 2020. All patients were in complete morphological remission before allo-HSCT. At the time of allo-HSCT 91 patients with AML and 37 patients with ALL were in the first complete remission (CR), in their second and more than two CRs were 16 and 26 patients, respectively. The median follow-up was 18 (1.5–48) months for AML and 14 (1.8–60.1) months for ALL. Immunophenotypic study was performed before allo-HSCT. MRD was detected using a combination of the “different from normal” method and the search for cells with a leukemia-associated immunophenotype.Results. The disease status at the time of transplantation and the presence of MRD before allo-HSCT were independent factors infl uencing the probability of relapse (disease status: HR = 2.911, 95% CI: 1.328–6.379; MRD before allo-HSCT: HR = 7.667, 95% CI: 3.606–16.304) and post-transplant mortality (disease status: HR = 2.911, 95% CI: 1.328–6.379; MRD before allo-HSCT: HR = 7.667, 95% CI: 3.606–16.304). In univariate analysis, the relapse-free survival of MRD+ patients with AL in the first CR was significantly worse than in MRD– (AML: 23 % versus 57 %, p &lt; 0.0001, ALL: 34 % versus 61.7 %, p = 0.0484), and the probability of relapse in MRD+ patients was significantly higher (AML: 75 % versus 12 %, p &lt; 0.0001, ALL: 57 % versus 7 %, p = 0.0072). Pre-transplant MRD status was not prognostically significant for AL-patients in the second and third remission. The development of chronic GVHD reduces post-transplant mortality if it does not require systemic therapy with glucocorticosteroids (HR = 0.006, 95% CI: 0.008–0.446).Conclusion. Testing for MRD of patients with AL in the first CR before allo-HSCT is necessary for risk stratification and identification of patients who will need preventive post-transplant therapy in order to prevent disease relapse.

Post-Transplant Cyclophosphamide after HLA Identical Compared to Haploidentical Donor Transplant in Acute Myeloid Leukemia: A Study on Behalf of Geth-TC

Introduction: High-dose post transplant cyclophosphamide (PTCY) effectively prevents graft-versus-host disease (GVHD) after unmanipulated HLA-haploidentical hematopoietic stem cell transplant (HSCT) and offer low rates of GVHD in the setting of HLA identical transplant. The objective of our study was to compare the outcomes of haplo vs HLA identical HSCT in patients undergoing HSCT for acute myeloid leukemia (AML) using PTCY.Patients and methods: We conducted a retrospective study of 229 patients undergoing a first HSCT for AML using PTCY, 130 from an haploidentical donor between 2013 and 2018 (median follow up 62.5 months) and 99 from a matched sibling (MSD) (n=38) or unrelated donor (MUD) (n=61) (median follow up 27 months) between 2013 and 2019, in 20 centers in Spain. Last update of the cohort was performed in March 2021.Results: Baseline characteristics are summarized in Table 1. There were more patients with active disease at transplant (5% MSD/MUD vs. 20% haplo, p=0.001), high/very high DRI (32% vs. 67%, p=0.000) and prior autologous HSCT (2% vs. 11%, p=0.010) in the haplo group. Mobilized peripheral blood stem cells was the most frequent stem cell source in both groups. Most patients received myeloablative conditioning (55% vs. 64%, p=0.170). All Patients in the haplo group received PTCY days +3+4 followed by a calcineurin inhibitor (CNI) and MMF from +5. In the MSD/MUD group, 37% received both CNI+MMF, 33% only CNI and 30% PTCY with sirolimus+MMF (this group included only MUD donors). None of the patients received ATG. Cumulative incidence of neutrophil recovery at day 28 was 97% in both groups, with a median of 16 and 17 days respectively (p=0.948). Both 2-year overall survival (OS) (72% vs. 62%, p=0.07) and event-free survival (EFS) (70% vs. 54%, p=0.055) were higher in the MSD/MUD group, but the difference was not statistically significant (Figure 1). Multivariate analysis only identified age and pre-transplant status as independent risk factors for OS, and pre-transplant status for EFS. No differences were found in the cumulative incidence of relapse at 2 years (19% vs. 25%, p=0.13) and non-relapse mortality (14% vs. 19%, p=0.145). Cumulative incidence of grade II-IV acute GVHD was lower in MSD/MUD (14% vs. 47%, p=0.000, Figure 2), while III-IV aGVHD was similar (4% vs. 9%, p=0.14). Cumulative incidence of chronic GVHD and moderate-severe cGVHD at 2 years was similar for both groups (42% vs. 33% (p=0.051); 22% vs. 19% (p=0.28)). No differences were found in GRFS (48% vs. 46% (p=0.506)). Most frequent cause of death in the early post-transplant period was non-GVHD related infection in both groups.Conclusions: in our experience, PTCY as GVHD prophylaxis in both MSD/MUD and Haplo transplant in AML using mostly PBSC effectively prevents GVHD and offers similar NRM, relapse and survival rates. Poor control of the disease before transplant was the only factor affecting OS and EFS in this setting. Prospective studies are needed to confirm our results. [Display omitted] DisclosuresBailen: Pfizer, Kite-Gilead, Gilead: Honoraria. Guerreiro: Novartis, Gilead: Consultancy, Honoraria. Oarbeascoa: Gilead: Honoraria, Speakers Bureau. Kwon: Novartis, Celgene, Gilead, Pfizer: Consultancy, Honoraria.

Nonmyeloablative Allogeneic Transplantation in First Remission for Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia with Post-Transplantation Cyclophosphamide: Outcomes By Receipt of Pre-Transplant Blinatumomab

Nonmyeloablative Allogeneic Transplantation in First Remission for Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia with Post-Transplantation Cyclophosphamide: Outcomes By Receipt of Pre-Transplant Blinatumomab

Safety of Autologous Hematopoietic Stem Cell Transplantation in Patients over 75 Years Old. Single Center Experience Serving a Minority Population

Background:Autologous hematopoietic stem cell transplant (auto-HSCT) is a commonly used treatment for multiple myeloma (MM) and for relapsed/refractory non-Hodgkin lymphomas (NHL) for patients who are <65 years old. However, the majority of new diagnoses of MM and NHL are in patients >65 years old, and nearly half of those are in patients >75 years old. While some studies have evaluated the use of auto-HSCT in older patients 65-75 years of age, there are few studies evaluating the relative safety of this treatment in patients above the age of 75 years. Such patients and their providers require outcome data of auto-HSCT in the elderly in order to help guide informed decision-making.Methods:We conducted a retrospective cohort study comparing short-term outcomes for auto-HSCT in patients >75 years old and 55-65 years old for the diagnosis of MM or NHL, who were conditioned with either melphalan or BEAM (carmustine, etoposide, cytarabine, melphalan) respectively.To identify patients, we used an internal database of auto-HSCT performed between 2005 - 2021. The study group included patients >75 years old. The control group included patients 55-65 years old that were matched to the study group patients by sex and time of transplant. Medical records were reviewed to gather data on demographics, pre-transplant functional status, transplant indication and conditioning regimen, length of stay, admission mortality, 30-day rehospitalization rate, ICU admission, neutropenic fever and infectious workup results, and time to WBC and platelet engraftment.The primary outcomes of the study were admission mortality, length of stay, time to WBC and platelet engraftment incidence, incidence of neutropenic fever, positive blood culture, ICU admission, and 30-day rehospitalization rate.Averages were calculated using medians and IQR. Admission mortality was evaluated using log rank test. P values were calculated using Fisher's test for categorical data and Wilcoxon rank sum test for continuous data. Significance was denoted by α =0.05.Results:We identified 43 patients aged >75 years old who underwent autologous stem cell transplant for multiple myeloma or lymphoma with melphalan or BEAM conditioning at Montefiore Medical Center between 2005-2021.Patient characteristics (Table 1) The earliest transplant in out cohort was in 12/2005 and the latest was in 3/2021. The median time between transplants of patients in the study and cohort groups was 14 [7.5, 24] days. 24 (55.8%) patients were female. The median age in the study group was 77.1 [76.2, 77.9] years old and 61.9 [57.4, 63.0] years old in the control group. Both groups predominantly included patients from minority populations: 55.8 and 46.5% were Spanish/Hispanic/Latino and 25.6% and 14.0% were African American, in study and control groups respectively. Multiple myeloma was the most common indication for auto-HSCT.Primary outcomes (Table 2) Admission mortality did not differ significantly between the groups, with only one death in the control group (p = 0.083). The length of stay was comparable at 18 [17, 22] days and 19 [16, 20] days (p = 0.2) for study and control groups, respectively.Time to WBC engraftment in the study group was 12 [11, 12] days and 11 [11, 12] days in the control group (p = 0.032). Time to platelet engraftment in the study group was 14 [12, 15] days and 12 [11, 14] days in the control group (p = 0.014). Although both time to WBC and platelet engraftment was significantly longer in the study group, the clinical significance of this finding is questionable, especially as it did not seem to prolong length of stay.There was no significant difference between incidence of neutropenic fever, or between incidence of positive blood cultures in patients with neutropenic fever. There was a non-statistically significant increase in the rate of ICU admissions in the study group vs control group 4/43 and 0/43 respectively (p=0.12). 30-day rehospitalization rate was comparable between the two groups.Conclusion:We did not find a statistically significant increase in morbidity or mortality for patients 75-80 years of age undergoing auto-HSCT compared with patients 55-65 years old. To our knowledge this is the largest cohort to date demonstrating the safety of auto-HSCT in this elderly population. [Display omitted] DisclosuresGritsman: iOnctura: Research Funding. Shastri: Onclive: Honoraria; GLC: Consultancy; Kymera Therapeutics: Research Funding; Guidepoint: Consultancy. Verma: Medpacto: Research Funding; Curis: Research Funding; Eli Lilly: Research Funding; Stelexis: Consultancy, Current equity holder in publicly-traded company; Novartis: Consultancy; Acceleron: Consultancy; Celgene: Consultancy; Stelexis: Current equity holder in publicly-traded company; Throws Exception: Current equity holder in publicly-traded company; Incyte: Research Funding; GSK: Research Funding; BMS: Research Funding.

Post-Transplant MRD Status and T Cell Chimerism Predict Outcomes in Patients Allografted for AML/MDS-a Prospective Analysis from the UK NCRI Figaro Trial

▪Allogeneic stem-cell transplantation is an important curative strategy in acute myeloid leukaemia (AML) consequent upon the development of a graft-versus-leukaemia (GVL) effect. Disease relapse is the major cause of transplant failure and novel therapeutic strategies are required in patients with measurable residual disease (MRD) post-transplant. Recognizing that full donor T cell chimerism serves as a biomarker of GVL and that mixed donor T cell chimerism reflects the presence of bi-directional tolerance, we report the first prospective correlation of the impact of post-transplant T cell chimerism and MRD in patients allografted for AML/MDS.Methods: 186 patients from FIGARO, a prospective randomized trial of reduced intensity conditioning regimens in AML/MDS, were alive and relapse free, at the first MRD timepoint and provided post-transplant bone marrow samples for flow cytometric MRD monitoring (day+42, month+3/+6/+9/+12) and peripheral blood samples for T cell chimerism analysis (3-monthly during the first year). Results were not available to clinicians. Flow cytometric MRD incorporating an unsupervised immunophenotypic analysis approach was used on 778 sequential samples. The prognostic significance of post-transplant MRD from each sampling timepoint was assessed by landmark analysis.Results: 29 (15.6%) patients were MRD+ at one or more timepoints in the first year after transplant. The presence of post-transplant MRD was associated with reduced OS (HR:2.19, p=0.0026) and RFS (HR:5.36, p<0.0001), when analyzed as a time varying Cox variable. We, and others, have shown that pre-transplant MRD status is an important determinant of post-transplant survival. We therefore performed a multivariate analysis of factors that may determine the prognoses of patients with pre-transplant MRD+ disease. This demonstrated that the presence of detectable post-transplant MRD was the only independent determinant of RFS in this group of patients (HR 9.05 (95%CI:1.70-48.2), p=0.0099), even when adjusted for cytogenetics, FLT3-ITD and GVHD. The highest frequency of post-transplant MRD positivity occurred at day+42/month+3. The 2yr OS of day+42 MRD+ patients (n=13/158) was 30.8% (95%CI 9.5-55.4) compared to 67.1% (95%CI 58.5-74.2) in MRD negative patients (p<0.001); and 2yr CIR in day+42 MRD+ patients was 92.3% (95% CI:35.8-99.4) versus 22.8%% (95%CI:16.3-29.9) when MRD negative (p<0.001). Day+42 MRD was associated with more rapid relapse kinetics (median RFS of 2 months) compared to when MRD was first detected at later timepoints.Next, we examined the impact of T-cell chimerism, and post-transplant MRD on outcomes. In patients with mixed-donor T-cell chimerism (MDTC) at month+3 or +6, the presence of post-transplant MRD (preceding or at time of first MDTC) was associated with decreased OS (p=0.001) and RFS. Specifically, 2yr RFS in MRD+ patients was 23.1% (95%CI:5.6-47.5), compared to 63.6% (95%CI:44.9-77.5) in patients who were MRD negative (p=0.004) (Figure). In contrast, in 48 patients with full donor T-cell chimerism (FDTC) at months 3 and 6, only 5 patients were MRD+ post-transplant and their outcomes were equivalent to patients who were MRD negative (FDTC/MRD negative 2yr RFS: 80.9% (95% CI:65.3-90.0)).Downregulation of HLA class II molecules on AML blasts after transplant may result in immune evasion from GVL: we examined whether this had an additional impact on outcome in post-transplant MRD+ patients. Both RFS and OS were significantly lower in MRD+ patients when MRD+ blasts had down-regulated HLA-DR expression. In MRD+ patients, 2yr OS was 20.0% (95%CI:3.1-47.5) in those with HLA-DR down-regulation, versus 57.9% (95%CI 33.2-76.3) in those without (p=0.001).Conclusion We demonstrate that dynamic assessment of post-transplant MRD is an important predictor of outcome in patients allografted for AML/MDS, with additional prognostic value to pre-transplant MRD assessment. Post-transplant MRD and T-cell chimerism results are most informative when combined, underlining the importance of a GVL effect in AML/MDS. This suggests post-transplant strategies which result in FDTC may improve outcomes in patients allografted for AML/MDS. Our data also supports the clinical relevance of monitoring for leukemic immune escape as HLA-DR down-regulation identifies a post-transplant MRD positive subgroup at risk of almost inevitable relapse. [Display omitted] DisclosuresLoke: Novartis: Other: Travel; Janssen: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Daichi Sankyo: Other: Travel. Protheroe: Jazz Pharmaceuticals: Honoraria; Astellas: Honoraria; Kite Gilead: Honoraria. Dillon: Amgen: Other: Research support (paid to institution); Astellas: Consultancy, Other: Educational Events , Speakers Bureau; Jazz: Other: Education events; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: educational events; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Session chair (paid to institution), Speakers Bureau; Menarini: Membership on an entity's Board of Directors or advisory committees; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Research Support, Educational Events. Craddock: Novartis Pharmaceuticals: Other: Advisory Board ; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Risk Factors and Prognosis Analysis of Patient-Specific HLA Genomic Loss Relapse Following ATG-Based T-Cell-Replete Haploidentical Hematopoietic Stem Cell Transplantation

BackgroundDevelopments in related haploidentical hematopoietic stem cell transplantation (haplo-HSCT) have made two immune systems with incompatible human leukocyte antigens (HLA) adaptable, greatly reducing transplantation-related toxicity. In the haploidentical transplantation system, patient-specific HLA antigens are a primary way in which donor immune cells exert their graft-versus-leukemia effects by alloreactivity, and therefore patient-specific HLA genomic loss is often considered a mechanism of leukemia relapse. Although the incidence and characteristics of HLA loss have been investigated in patients with myeloid leukemia who relapsed after transplantation, patient-specific HLA genomic loss in lymphoid conditions and under different transplantation regimes remain enigmatical. We herein provide the data for HLA loss relapse in lymphoid disease, as well as offer data in myeloid disease based on antithymocyte globulin (ATG) T-cell-replete conditioning.MethodsBetween May 2012 and May 2021, 106 patients were enrolled in this study, including 104 had hematological relapse and 2 had minimal residual disease (MRD) recurrence after haplo-HSCT. All data were collected from centers within the Zhejiang Provincial Workgroup of HSCT. Firstly, the patients were divided into two groups according to the type of disease: myeloid and lymphoid conditions, and secondly, they were divided into the Classic Group and the Loss Group according to whether the patients had unshared HLA genomic loss at the time of relapse or not. A two-tailed P value of 0.05 was considered statistically significant. Univariate analysis is performed using the χ2 test, Fisher exact test, and Student t test, as appropriate. A multivariate model was used to calculate the odds ratio (OR) with a 95% confidence interval (CI). Post relapse overall survival (prOS) was estimated and plotted using the Kaplan-Meier method.ResultsOf all patients, HLA loss was detected in 50.9% (54/106) patients and the occurrence was not related to disease type (P=0.44). Patients having either myeloid malignancies or lymphoid malignancies with HLA loss experienced relapse later than those with classic relapse. The demographic and baseline characteristics of patients were summarized in Table 1, and the post-relapse parameters were presented in Table 2.We next determined what factors correlating with HLA loss at relapse by multivariate analysis. For patients with myeloid malignancies, a pre-transplant underweight status based on body mass index (BMI) was a factor strongly correlated with classic type when relapse (OR=0.095, 95%CI: 0.015~0.604, P=0.013); patients suffering de novo aGVHD had an OR of 4.844 (95%CI: 1.143~20.530, P=0.032) (Figure 1). As for lymphoid conditions, patients who experiencing MRD-positivity before hematological relapse (OR=22.623, 95% CI: 1.597~320.532, P=0.021), and >180 days from HSCT to relapse (OR=5.695, 95% CI: 1.073~30.211, P=0.041) were more likely to lose unshared HLA at relapse. Yet male patients (OR=0.037, 95% CI: 0.003~0.411, P=0.037) were inclined to have classic one when relapse (Figure 1).For prognosis, in patients with myeloid conditions, the median prOS was 217 days and 215 days in the Loss Group and Classic Group, respectively (P=0.34). In the Loss Group, the white blood cell (WBC) at diagnosis was related to prOS (>50ⅹ10 9/L vs. ≤50ⅹ10 9/L: median: 157 vs. 261 days, P=0.037). For patients having male donors, patient gender was related to prOS: median prOS was 386 days for male patients and 124 days for female patients (P=0.008). For patients with lymphoid malignancies, the median prOS was 285 days and 244 days in the Loss Group and Classic Group, respectively (P=0.24). The results of the univariate analysis from the Loss Group showed that male patients (median: 40 vs. 194 days; P=0.036) and cGVHD fare (median: 114 vs. 468 days; P=0.002) were related to inferior prOS.ConclusionThe occurrence of patient-specific HLA genomic relapse after haplo-HSCT appears later than classic relapse. In myeloid malignancies, the patient pre-transplant BMI and aGVHD fare are associated with the relapsed type. In lymphoid conditions, patient sex, presence of MRD-positive results before relapse, and the time from transplantation to relapse correlate with HLA loss at relapse. Yet this study is based on a limited number of patients, further validation in other centers is warranted. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Major ABO Incompatibility Significantly Influences the Survival and Outcomes after Allogeneic Hematopoietic Cell Transplantation in Leukemia - CIBMTR Analysis

Background: Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). While many factors influence the outcomes of allo-HCT in these leukemias, the independent impact of ABO mismatching between the patient and donor remains unclear.Methods: Using the CIBMTR database, we identified adults aged ≥18 years with AML or ALL who underwent allo-HCT from HLA-matched sibling donor (MSD) or 8/8 matched unrelated donor (MUD) between 2008-2018. We excluded patients who underwent transplant from a mismatched donor source or who received an ex-vivo T-cell depleted graft. Patients were stratified into cohorts based on ABO status (match, minor mismatch, major mismatch, bidirectional mismatch). Outcomes such as overall survival (OS), disease free survival (DFS), non-relapse mortality (NRM), relapse, incidence of acute graft versus host disease (GVHD), chronic GVHD, neutrophil engraftment, platelet engraftment and graft failure were evaluated. Survival analysis was done using Kaplan-Meier method and significant predictors were evaluated using Cox-proportional hazard regression method. Multivariate regression model included main effect (ABO status) and covariates (patient age, gender match, disease type, disease status, HCT-CI, Karnofsky performance status, donor type, conditioning intensity/use of TBI, stem cell source, GVHD prophylaxis, ATG/alemtuzumab use, transplant year).Results: Of 4946 patients who met the study criteria, 2741 patients (55.4%) were ABO matched, 1030 patients (20.8%) had minor ABO mismatch, 899 patients (18.1%) had major ABO mismatch and 276 patients (5.6%) had bidirectional ABO mismatch. Graft manipulation for ABO incompatibility was performed in 900 patients (minor ABO mismatch=532; major ABO mismatch=226; bidirectional mismatch=142), however, the information on individual graft manipulation techniques was limited. In multivariable analysis (table 1), major ABO mismatch significantly affected the OS, platelet engraftment and primary graft failure. Compared to ABO matched allo-HCT, major ABO mismatched allo-HCT was associated with worse OS (major mismatch - HR 1.16, 95% CI 1.05-1.29; p=0.005), inferior platelet engraftment (HR 0.83, 95% CI 0.77-0.90; p=<0.001), and higher risk of primary graft failure [4.5% (major mismatch) vs. 3.2% (ABO matched) - HR 1.60, 95% CI 1.12-2.30, p=0.01]. There was a significant interaction between the ABO status and graft type (peripheral blood vs. bone marrow) for the acute GVHD grades 2-4 model, and they are presented separately (table 1). Bidirectional ABO mismatch also significantly impacted the outcomes such as acute GVHD grades 2-4 (in bone marrow stem cell subgroup, HR 0.50, 95%CI 0.27-0.93, p=0.02) in addition to a trend towards inferior survival and NRM (p-value not significant). Other outcomes such as relapse (p=0.41), acute GVHD grades 3-4 (p=0.13), and chronic GVHD (p=0.30) were not significantly influenced by the ABO status.Conclusions: Our study demonstrates that pre-transplant ABO status is an independent predictor of survival and other post-transplant outcomes in a large cohort of patients with AML and ALL undergoing allo-HCT in the recent era. This demonstrates the importance of considering ABO status in the donor selection algorithms and potential strategies to mitigate its adverse impact. Due to the limited information available on graft manipulation strategies, the impact of graft manipulation techniques on the outcomes could not be evaluated and needs to be investigated in future studies. [Display omitted] DisclosuresGuru Murthy: Techspert: Consultancy; Guidepoint: Consultancy; Cancerexpertnow: Honoraria; Qessential: Consultancy; TG therapeutics: Other: Advisory board; Cardinal Health Inc.: Honoraria. Devine: Magenta Therapeutics: Current Employment, Research Funding; Tmunity: Current Employment, Research Funding; Sanofi: Consultancy, Research Funding; Johnsonand Johnson: Consultancy, Research Funding; Orca Bio: Consultancy, Research Funding; Be the Match: Current Employment; Vor Bio: Research Funding; Kiadis: Consultancy, Research Funding. Farhadfar: Incyte: Consultancy. Sharma: Vertex Pharmaceuticals/CRISPR Therapeutics: Other: Salary support paid to institution; Novartis: Other: Salary support paid to institution; Spotlight Therapeutics: Consultancy; Medexus Inc: Consultancy; CRISPR Therapeutics: Other, Research Funding; Vindico Medical Education: Honoraria. Stefanski: Novartis: Honoraria. Pulsipher: Equillium: Membership on an entity's Board of Directors or advisory committees; Adaptive: Research Funding; Jasper Therapeutics: Honoraria. Shaw: mallinkrodt: Other: payments; Orca bio: Consultancy.

Negative MRD at Day 100 after Allogenic Hematopoietic Stem Cell Transplant (HSCT): The Grail to Reach in Acute Myeloid Leukemia (AML)

INTRODUCTIONHSCT remains the best curative treatment in eligible AML patients with adverse or intermediate cytogenetics according to the ELN classification, and for those with unfavorable molecular markers at diagnostic or with a positive measurable residual disease (MRD) after intensive chemotherapy. MRD-positivity after HSCT confers an inferior outcome and a recently published study demonstrated that the evaluation of WT1 MRD before HSCT or 3 months after HSCT is highly predictive of post-transplant relapse. Besides, the impact and the kinetics of MRD positivity on prognosis are still unclear. Here we assess the impact of both pre- and post-transplant MRD on long term survival and incidence of relapse among a real-life cohort of 117 AML patients who underwent HSCT. PATIENTS AND METHODFrom November 7, 2012 to December 17, 2019, 117 patients diagnosed with AML and aged over 18 years underwent HSCT in Amiens University Hospital Center. MRD status was assessed using RQ-PCR (sensitivity 10 -4 to 10 -5) or multiparametric flow cytometry (sensitivity 10 -3 to 10 -4) before HSCT, depending on the markers available at diagnosis, at day 30, day 100 and a year after HSCT. Overall survival (OS) and cumulative incidence of relapse (CIR) were evaluated at the same time-points in landmark analysis for patients surviving beyond d100 to reduce the impact of early death on CIR. Statistical analyses were performed with SPSS Statistics 20 (IBM). RESULTSMedian age was 55 years (range 18-72) with 67/117 males. 85% patients had de novo AML. Cytogenetic ELN risk stratification was favorable for 15 (13%), intermediate for 72 (62%) and adverse for 28 (25%). At the time of HSCT, 76% were in complete remission (CR) after intensive chemotherapy. 30 patients (25%) had myeloablative conditioning (MAC) or toxicities-reduced regimens (TRC), 34 patients (30%) had reduced-intensity regimens (RIC) and 53 patients (45%) underwent sequential-based conditioning regimens (Seq). For the 100 patients who survived beyond d100, median time follow-up was 23.5 months (3.0-85.0). OS at 1 and 3 years was respectively 80% (75.9-84.1) and 61.7% (56.1-67.3) and CIR at same time-points was 19,3% (15.2-23.4) and 29,8% (24.6-35.0). No OS and CIR differences were observed according to the conditioning regimen, stem cell source and ELN score. A progressive disease before HSCT increased the risk of relapse but didn't worsen the OS. Before HSCT, MRD was positive in 48 patients (58.5%) with analyzable markers, either at molecular or flow cytometry level. OS and CIR were not impacted by the pre-HSCT MRD. Strikingly, performing HSCT resulted in MRD negativation at day 100 for 85.4% of patients with previous positive MRD, significantly improving OS and CIR (p<.001 for both, Figure 1A and B). Beyond day 100, achieving a negative MRD limited the 5-year CIR to 20%. In multivariate analysis, OS was significantly inferior, in patients with acute GVHD > grade 2 (HR=5.4, 95CI=1.8-16.1; p=.002) and positive MRD at day 100 (HR=19.2, 95CI=6.0-61.1; p<.001). Positive MRD at day 100 was the only significant predictor of adverse CIR (HR=17.5, 95CI=5.6-55.3; p<.001).DISCUSSION/CONCLUSIONIn this real-life cohort of patients diagnosed with AML, we show that HSCT procedure consistently allows MRD negativation, subsequently improving the outcome of patients surviving beyond d100. Persistence of positive MRD after HSCT was the main predictor of long-term adverse outcome after transplant. Our data highlight the importance of MRD negativation at day 100 regardless of pre-transplant status, conditioning regimen or initial ELN classification. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Circulating Tumor Cell Is a Clinical Indicator of Pretransplant Radiofrequency Ablation for Patients with Hepatocellular Carcinoma.

Introduction It is of great significance to confirm reliable indicators for the guidance of pretransplant radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). In this study, we aim to investigate whether circulating tumor cell (CTC) status is a clinical indicator for RFA before liver transplantation (LT) in HCC patients. Method CTC analyses were measured in 79 HCC patients. Clinical outcomes including progression-free (PFS) and overall survival (OS) were compared and analyzed between patients with and without pretransplant RFA. Result Forty-two patients were detected as CTC-positive and 18 patients received pretransplant RFA. Recurrence was correlated with CTC count (P=0.024), tumor number (P=0.035), liver cirrhosis (P=0.001), Milan criteria (P=0.003), and University of California San Francisco (UCSF) criteria (P=0.001). Kaplan–Meier analysis revealed that patients with CTC-positive had a lower PFS rate (P=0.0257). For CTC-positive patients, the PFS rate of the pretransplant RFA group was significantly higher than the non-pretransplant RFA group (100% vs. 46.7%, P=0.0236). For CTC-negative patients, both PFS rate and OS rate were similar and without significant differences. In multivariate analysis, pretransplant RFA was the independent factor for PFS (P=0.025). Conclusion Pretransplant CTC status can guide the administration of pretransplant RFA in HCC patients which can improve PFS in CTC-positive HCC patients.

Allo-HSCT for acute myeloid leukemia with myelodysplastic-related changes: a clinical analysis

目的评价异基因造血干细胞移植（allo-HSCT）治疗急性髓系白血病伴骨髓增生异常相关改变（AML-MRC）的疗效及预后因素，分析AML-MRC患者基因突变谱系并探讨影响移植预后的分子生物学特征。方法对2006年至2020年于中国医学科学院血液病医院接受allo-HSCT的75例AML-MRC患者进行回顾性分析。将75例患者分为：H组［既往有骨髓增生异常综合征（MDS）或MDS/骨髓增殖性肿瘤（MPN）病史］、C组（新诊断的AML-MRC伴MDS相关细胞遗传学异常）和M组（新诊断的AML-MRC伴多系发育异常），分析三组患者临床特征差异以及对移植预后的影响。对43例患者行骨髓靶向二代测序（137个基因）。结果①75例AML-MRC患者，男41例，女34例，中位年龄41（18～56）岁，中位随访时间为35（95％ CI 30～49）个月，中位总生存（OS）时间为78个月（95％CI 23个月～未达到）。移植后3年OS率为57.1％（95％CI 45.6％～71.4％），无事件生存（EFS）率为52.0％（95％CI 40.8％～66.1％），累积复发率（CIR）为26.8％（95％CI 16.6％～30.0％），移植相关死亡率（TRM）为22.7％（95％ CI 13.2％～33.8％）。多因素分析显示，移植前处于非第1次完全缓解（CR1）状态是移植后OS和EFS的独立危险因素。影响OS的独立危险因素还包括−5/5q−染色体核型异常、移植后未发生慢性移植物抗宿主病（慢性GVHD）。②75例患者中H组59例（78.7％），其中20例转化为白血病（转白）前曾接受去甲基化药物治疗；C组9例（12.0％），M组7例（9.3％）。M、H、C组移植后3年OS率分别为71.4％（95％CI 44.7％～100.0％）、55.0％（95％CI 41.8％～72.5％）、55.6％（95％ CI 31.0％～99.7％）（P＝0.700），EFS率分别为71.4％（95％CI 44.7％～100.0％）、46.5％（95％CI 34.0％～63.8％）、55.6％（95％CI 31.0％～99.7％）（P＝0.600）；原发性AML-MRC与继发性AML-MRC相比，移植后3年OS、EFS率差异无统计学意义［61.9％（95％CI 41.9％～91.4％）对55.0％（95％ CI 41.8％～72.5％），P＝0.600；61.9％（95％CI 41.9％～91.4％）对46.5％（95％CI 34.0％～63.8％），P＝0.400］。转白前接受去甲基化治疗（20例）与未接受去甲基化治疗（39例）患者比较，转白时间差异无统计学意义［195（16～937）d对162（9～3167）d，P＝0.804］，且两组患者OS和EFS差异无统计学意义（P＝0.400，P＝0.700）。③对43例（57.3％）患者骨髓样本行二代基因测序，共发现73个突变类型，检出率最高的是U2AF1（11例，25.6％），其他检出率>10％的突变包括RUNX1（10例，23.3％）、NRAS（10例，23.3％）、ASXL1（6例，14.0％）、PTPN11（5例，11.6％）、TET2（5例，11.6％）。单因素分析显示U2AF1［P＝0.875，HR＝1.110（95％ CI 0.295～4.195）］、RUNX1［P＝0.685，HR＝0.728（95％ CI 0.157～3.375）］、NRAS［P＝0.919，HR＝0.923（95％CI 0.196～4.334）］突变对移植后OS没有影响。结论−5/5q−染色体异常、未发生慢性GVHD、移植前非CR1状态是影响AML-MRC患者移植后OS的独立危险因素；MHC亚组分类不是影响移植预后的因素；去甲基化药物治疗可能无助于延缓MDS患者转白以及延长移植后OS期。

AML-267: Minimal Residual Disease Predicts the Outcome of Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia in the First Remission

Context: The independent influence of pre-transplant MRD status on the results of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is now being widely reported. The genetic and immunophenotypic diversity of AML is a problem for monitoring MRD in daily clinical practice. The most widely used methods for assessing MRD are multiparametric flow cytometry (MFC) and PCR. Objective: To assess the impact of pre-transplant MRD status determined by MFC or PCR on the long-term results of allo-HSCT. Patients and Methods: The study included 106 patients with AML in the 1st CR who underwent allo-HSCT in our center from September 2015 to December 2020. The median follow-up was 19.5 (1–50) months. Eleven-color MFC was performed on bone marrow samples obtained before allo-HSCT. In 46 out of 106 patients who had molecular markers (NPM1, FLT3, RUNX1-RUNX1T1, MLL, or CBFβ-MYH11), the MRD status was determined using PCR also. Cox proportional hazards models were used to assess the influence of various independent factors on the probability of relapse (PR). The factors included in the model were ELN risk, donor type, conditioning regimen, graft source, pre-transplant MRD status, and age. The probabilities of DFS and relapse were estimated using the Kaplan-Meier method. Results: Out of 106 patients, 22 were identified as MRD+ MFC, 84 patients were MRD- MFC, 16 patients were MRD+ PCR, and 30 patients were MRD- PCR. Statistical analysis revealed significant differences between MRD+ and MRD- patients, regardless of the research method: patients with MRD+ status had the worst DFS (MFC: 24% versus 64%, p 40 y (HR=7.006) were independent factors influencing the probability of relapse. Conclusions: MRD, regardless of whether it is determined by MFC or PCR, ELN risk, and older age are independent predictors of disease recurrence risk. The study of MRD in AML patients before allo-HSCT can be used to stratify the risk of allo-HSCT and identify patients who need prophylactic post-transplant therapy to prevent disease relapse.

AML-282: Prognostic Values of D816V KIT Mutation and Peri-Transplant CBFB-MYH11 MRD Monitoring on Acute Myeloid Leukemia with CBFB-MYH11

<h3>Context:</h3> Controversies exist in the prognostic value of KIT mutations and the optimal thresholds and time points for measurable residual disease (MRD) monitoring for acute myeloid leukemia (AML) with CBFB-MYH11. <h3>Objective:</h3> This study aimed to evaluate the prognostic value of different types of KIT mutations and CBFB-MYH11 quantification in AML patients with CBFB-MYH11 who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) or autologous HSCT (auto-HSCT) and the clinical relevance of each transplant strategy in each risk group. <h3>Design:</h3> We retrospectively evaluated 88 patients who underwent allo-HSCT (n=60) or auto-HSCT (n=28). <h3>Setting:</h3> A referral center. <h3>Patients:</h3> Ninety-six consecutive AML patients with CBFB-MYH11 in remission who underwent HSCT at the Catholic Hematology Hospital between 2009 and 2019. After excluding two patients who underwent second HSCT and four patients without data for KIT mutations or pre-transplant CBFB-MYH11 MRD data, 88 patients were finally included in this study. <h3>Interventions:</h3> Not applicable. <h3>Main Outcome Measures:</h3> We retrospectively compared survival outcomes according to different types of KIT mutations and CBFB-MYH11 MRD levels. <h3>Results:</h3> The D816V KIT mutation was significantly associated with post-transplant relapse, contrasting with other types of mutations in KIT. Pre- and post-transplant (3 months after transplant) CBFB-MYH11 MRD assessments were useful for predicting post-transplant relapse and poor survival. The optimal threshold was determined as a 2-log reduction at both time points. In multivariate analysis, the D816V KIT mutation and CBFB-MYH11 MRD assessments were independently associated with post-transplant relapse and survival. Stratification by D816V KIT and pre-transplant CBFB-MYH11 MRD status further distinguished the risk of relapse and survival. Auto-HSCT was superior to allo-HSCT in MRD-negative patients without D816V KIT, while allo-HSCT trended to be superior to auto-HSCT in patients with MRD positivity or the D816V KIT mutation. <h3>Conclusions:</h3> This study demonstrated the differentiated prognostic value of the D816V KIT mutation in AML with CBFB-MYH11 and clarified the optimal time points and thresholds for CBFB-MYH11 MRD monitoring in the setting of HSCT.

CT-374: Outcomes of Allogeneic SC Transplant in Hematological Malignancy Patients Using a Busulfan 3 (9.6 mg/kg)-Based Conditioning Regimen

Introduction Busulfan is often used in a myeloablative conditioning regimen at an IV dose of 12.8 mg/kg (BU4). A reduced intensity regimen using 6.4 mg/kg (BU2) is commonly used in older patients or those with comorbid diseases. Data on use of BU3 (9.6 mg/kg) based regimen are limited. At KFSHRC, the busulfan-based MAC regimen’s IV-BU dose is 12.8 mg/kg (BU4), but for those who do not tolerate the full MAC, BU can be reduced to 9.6 mg/kg (BU3). Objective To study the outcomes of hematological malignancy patients who received allo-HCT using BU3-based conditioning from matched related or unrelated donors. Methods A retrospective analysis of the KFSHRC-BMT Database for patients who received allo-HCT between October 2005 and December 2019. Results A total of 65 patients were identified: 47 AML (72.3%), 8 MDS (12.3%), 8 myelofibrosis (12.3%), and 2 CML (3.1%) patients. Median age was 52 years (16–66), and 35 (54%) were males. Pre-transplant status showed 57% were in CR1, 17% in CR2, and 3% not in CR. Fifty-seven (88%) patients received PBSC, 6 (9%) received BM source, and 2 (3%) received both PBSC and BM from HLA-matched related [N= 61 (93%)] or unrelated [N=4 (7%)] donors. Forty (61.5%) patients received Bu/Flu as a conditioning regimen, 14 (21.5%) received Bu/Cy, 7 (10.8%) received Bu/Flu/ATG, and 4 (6.2%) received Bu/Cy/ATG. GVHD prophylaxis consisted of cyclosporine and methotrexate for all patients. Fifty-two (80%) patients had comorbidities with comorbidity index between 1–2 in 29 (44.6%) patients and more than 2 in 23 (35.4%). Sixty-two (95%) patients engrafted; median ANC and platelet engraftment were 18 days. Acute GvHD grade II–IV and III–IV occurred in 29% and 14%, respectively. Chronic GvHD occurred in 55% and was extensive in 24% of patients. With median follow-up of 60.5 months, the 2 year- and 5 year-OS were 58.5% and 44.1% respectively. The 2 year- and 5 year-DFS were 52.9% and 44.5%, respectively. Cumulative incidence of relapse and NRM at 2 years were 29.5% and 17.4%, respectively. Day +100 TRM was 10.7%. Conclusions Allogeneic SCT using BU3-based regimen appears feasible to use in patients who are not suitable for a fully myeloablative (BU4) regimen. TRM, DFS, and OS rate were comparable to reports from studies using a BU4-based regimen, warranting prospective studies in these patients.

The Impact of Performance Status on Length of Hospital Stay and Clinical Complications Following Liver Transplantation.

Impaired pretransplant performance status (PS) is associated with chronic liver disease (CLD). We studied its impact on hospital length of stay (LOS), complications, and readmissions in the first year after liver transplantation. The Standard National Liver Transplant Registry was linked to a hospital administrative dataset, and all first-time liver transplant recipients with CLD aged ≥18 years in England were identified. A modified 3-level Eastern Cooperative Oncology Group score was used to assess PS. Linear- and logistic-fixed effect regression models were used to estimate the effect of specific posttransplant complications and readmissions in the first year after transplantation. Six thousand nine hundred sixty-eight recipients were included. Impaired PS was associated with an increased LOS in the initial posttransplant period (comparing ECOG 1-3, adjusted difference 7.2 d; 95% confidence [CI], 4.8-9.6; P < 0.001) and in time spent on the ITU (adjusted difference 1.2 d; 95% CI, 0.4-2.0; P < 0.001). There was no significant association between ECOG status and total LOS of later admissions (adjusted difference, 2.5 d; 95% CI, -0.4-5.5; P = 0.23). Those with a poorer ECOG status had an increased incidence of renal failure (odds ratio, 1.5; 95% CI, 1.1-2.0; P = 0.004) and infection (odds ratio, 1.2; 95% CI, 1.1-1.4; P = 0.02) but not an increased incidence of readmission (odds ratio, 1.2; 95% CI, 0.9-1.5; P = 0.13). In liver transplant recipients with CLD, impaired pretransplant PS is associated with prolonged LOS in the immediate posttransplant period but not with LOS of later admissions in the first year after transplantation. Impaired PS increased the risk of renal failure and infection.

Human Leukocyte Antigen Antibody Sampling in Ventricular Assist Device Recipients: Are We Talking?

Ventricular assist devices (VADs) are commonly used as a bridge to transplantation but may yield HLA sensitization. We evaluated the prevalence of HLA antibody (Ab) sampling pre- and post-VAD placement in pediatric and adult patients and notification of VAD status to the HLA laboratory. All pediatric and adult patients who received a first-time VAD between 2005 and 2013 were included in this single-center retrospective review. Data were collected from the University of Alberta Hospital histocompatibility laboratory's information system and a local VAD database. In total, 106 patients were included (40 pediatric, median 3.0 years [interquartile range, 0.3-10.7]; 66 adult, 55.0 years [46.8-61.2]). HLA Ab sampling within 1-month pre-VAD occurred in 70% of pediatric and 79% of adult recipients (P=.215). Testing within 1 month of VAD placement occurred in 89% of pediatric and 67% of adult recipients (P=.012). For those with HLA Ab sampling within 30 days postimplant, notification to the HLA laboratory of VAD status occurred in 19 of 27 (70%) pediatric and 24 of 33 (73%) adult patients (P=.533). Of patients transplanted post VAD with HLA Ab samples collected, 12 of 28 (43%) and 13 of 38 (34%) adult recipients did not have notification of VAD status to the HLA laboratory (P=.322). There were inconsistencies in HLA Ab sampling and communication to the HLA laboratory surrounding VAD placement. Standardization of both HLA Ab assessment frequency after VAD implantation and communication regarding changes in clinical status and the occurrence of key sensitizing events such as VAD placement are imperative as patients await transplantation.

Antibodies to human leukocyte antigens and their association with blood product exposures in pediatric patients undergoing cardiac transplantation

Previous blood product exposures may result in the development of antibodies to human leukocyte antigens (HLA). Pediatric heart transplant recipients who have these antibodies experience increased morbidity and mortality after transplantation. In this study, our aims were to confirm the association of previous allogeneic blood product exposures with the formation of anti-HLA antibodies, determine which blood components pose the greatest risk of developing antibodies, and assess differences in outcomes after transplantation between patients who had anti-HLA antibodies and those who did not. This retrospective investigation included all children who underwent cardiac transplantation at Children's Healthcare of Atlanta from January 1, 2015 through December 31, 2018. Chart reviews were performed to collect pertinent data. Anti-HLA antibodies were detected by single antigen bead testing. Antibody burden was tabulated using the calculated panel reactive antibody (cPRA) score immediately prior to transplantation. Statistical analyses were conducted to examine differences based on HLA antibody status and identify associations with outcomes of interest. Our results show a significant association between pretransplant blood product exposures and HLA antibody status. Children with a pretransplant blood product exposure had 7.98 times the odds of developing an anti-HLA antibody compared to those without a pretransplant blood product exposure (p=.01). We also found a significant association between a previous red blood cell (RBC) exposure and HLA antibody status (p=.01) which was not found for other blood component exposures. Patients who were HLA antibody positive were more likely to develop a donor-specific antibody (DSA) after transplantation (p=.04). Exposure to previous allogeneic blood products affects the development of anti-HLA antibodies in children presenting for heart transplantation. Previous RBC exposures resulted in HLA antibody positivity more than other blood component exposures. Importantly, the presence of HLA antibodies was associated with the development of DSAs post-transplantation. Developing transfusion strategies to reduce allogeneic blood product exposures in children who may need future cardiac transplantation should be a high priority.

Prognostic value of measurable residual disease at allogeneic transplantation for adults with core binding factor acute myeloid leukemia in complete remission.

Pretransplant measurable residual disease (MRD) has been shown to be associated with relapse incidence following allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML). However, it remains less clear whether pretransplant MRD status affects transplant outcomes in core binding factor AML (CBF-AML). We retrospectively evaluated the effect of pretransplant MRD, which was measured by a polymerase chain reaction of RUNX1-RUNX1T1 or CBFB-MYH11 fusion transcripts, on transplant outcomes for a cohort of 959 adult patients with t(8;21) or inv(16) AML treated by allogeneic HCT during complete remission (CR), between 2000 and 2018. Multivariate analysis showed the absence of pretransplant MRD was significantly associated with lower relapse (hazard ratio [HR], 0.46; P < 0.001), treatment failure (HR, 0.66; P = 0.004), and overall mortality (HR, 0.72; P = 0.037) among patients with t(8;21). However, pretransplant MRD negativity was not associated with relapse (HR, 0.73; P = 0.420), treatment failure (HR, 0.64; P = 0.063), or overall mortality (HR, 0.69; P = 0.149) among patients with inv(16). In subgroup analysis, pretransplant MRD status significantly affected relapse and LFS only in patients with t(8;21) undergoing allogeneic HCT during CR2. In conclusion, our data demonstrate the different prognostic values of pretransplant MRD for CBF-AML, highlighting the need to develop effective therapeutic strategies for such MRD-positive patients.

Post-transplant allograft outcomes according to mismatch between donor kidney volume and body size of recipients with pre-transplant diabetes mellitus

AimsThe aim of this study was to investigate allograft outcomes when relatively small kidneys were donated to patients with pre-transplant diabetes mellitus (DM). MethodsFrom January 2010 to December 2018, 788 cases of non-sensitized living donor kidney transplant recipient and donor pairs were enrolled. The subjects were divided into four groups according to the relative size of kidney and pre-transplant DM status: non-DM large kidney, non-DM small kidney, DM large kidney, and DM small kidney. We compared allograft outcomes between these four groups. ResultsThe four groups did not show differences in the development of de novo donor-specific antibody and acute rejection. However, a significantly greater decline of allograft function and increased proteinuria were observed in the DM small kidney group. The highest death-censored graft loss rate (P = 0.008) was also observed in this group and the combination of relatively small kidney size and pre-transplant DM was an independent risk factor for death-censored graft loss. In addition, the relatively small kidney and pre-transplant DM showed significant interaction with each other. ConclusionsThe size mismatch between donated kidney volume and recipient body size should be considered in donor selection of patients with pre-transplant DM.