Outcomes In Transplant Patients Research Articles

Immune modulation in transplant medicine: a comprehensive review of cell therapy applications and future directions

Balancing the immune response after solid organ transplantation (SOT) and vascularized composite allotransplantation (VCA) remains an ongoing clinical challenge. While immunosuppressants can effectively reduce acute rejection rates following transplant surgery, some patients still experience recurrent acute rejection episodes, which in turn may progress to chronic rejection. Furthermore, these immunosuppressive regimens are associated with an increased risk of malignancies and metabolic disorders. Despite significant advancements in the field, these IS related side effects persist as clinical hurdles, emphasizing the need for innovative therapeutic strategies to improve transplant survival and longevity. Cellular therapy, a novel therapeutic approach, has emerged as a potential pathway to promote immune tolerance while minimizing systemic side-effects of standard IS regiments. Various cell types, including chimeric antigen receptor T cells (CAR-T), mesenchymal stromal cells (MSCs), regulatory myeloid cells (RMCs) and regulatory T cells (Tregs), offer unique immunomodulatory properties that may help achieve improved outcomes in transplant patients. This review aims to elucidate the role of cellular therapies, particularly MSCs, T cells, Tregs, RMCs, macrophages, and dendritic cells in SOT and VCA. We explore the immunological features of each cell type, their capacity for immune regulation, and the prospective advantages and obstacles linked to their application in transplant patients. An in-depth outline of the current state of the technology may help SOT and VCA providers refine their perioperative treatment strategies while laying the foundation for further trials that investigate cellular therapeutics in transplantation surgery.

Younger unrelated donors may be preferable over HLA match in the PTCy era: a study from the ALWP of the EBMT

AbstractThere is a paucity of information on how to select the most appropriate unrelated donor (UD) in hematopoietic stem cell transplantation (HSCT) using posttransplant cyclophosphamide (PTCy). We retrospectively analyzed the characteristics of 10/10 matched UDs (MUDs) and 9/10 mismatched UDs (MMUDs) that may affect transplant outcomes in patients with acute myeloid leukemia (AML) in first or second complete remission (CR1 or CR2). The primary end point was leukemia-free survival (LFS). Overall, 1011 patients were included with a median age of 54 years (range, 18-77). Donors had a median age of 29 years (range, 18-64); 304 (30%) were females, of which 150 (15% of the whole group) were donors to male recipients, and 621 (61%) were MUDs; 522 (52%) had negative cytomegalovirus (CMV-neg) serostatus, of which 189 (19%) were used for CMV-neg recipients. Donor age older than 30 years had a negative impact on relapse (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.06-1.8), LFS (HR, 1.4; 95% CI, 1.12-1.74), overall survival (HR 1.45; 95% CI, 1.14-1.85) and graft-versus-host disease (GVHD) free, relapse-free survival (HR, 1.29; 95% CI, 1.07-1.56). In addition, CMV-neg donors for CMV-neg recipients were associated with improved LFS (HR, 0.74; 95% CI, 0.55-0.99). The use of MMUD and female donors for male recipients did not significantly impact any transplant outcomes. For patients undergoing HSCT from a UD with PTCy for AML, donor age <30 years significantly improves survival. In this context, donor age might be prioritized over HLA match considerations. In addition, CMV-neg donors are preferable for CMV-neg recipients. However, further research is needed to validate and refine these recommendations.

Pros and Cons of Cryopreserving Allogeneic Stem Cell Products.

The COVID-19 pandemic has precipitously changed the practice of transplanting fresh allografts. The safety measures adopted during the pandemic prompted the near-universal graft cryopreservation. However, the influence of cryopreserving allogeneic grafts on long-term transplant outcomes has emerged only in the most recent literature. In this review, the basic principles of cell cryopreservation are revised and the effects of cryopreservation on the different graft components are carefully reexamined. Finally, a literature revision on studies comparing transplant outcomes in patients receiving cryopreserved and fresh grafts is illustrated.

The role of donor sex on the post-liver transplant outcomes in patients with primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) can result in hepatic decompensation and require liver transplantation (LT). This study investigates the effect of the sex of the donor and recipient as a prognostic risk factor for adverse outcomes after LT in patients with PSC. UNOS registry was used to select LT patients with PSC from 1987 to 2019. The study cohort was stratified based on the sex of the recipient and further subdivided based on the sex of the donor. The primary endpoints of this study were all-cause mortality and graft failure, which were evaluated using a sequential Cox regression analysis. This study included 2829 patients; 906 female recipients were transplanted from 441 male donors and 465 female donors. 1923 male recipients were transplanted from 1194 male donors and 729 female donors. Within the mismatch analyses, the male-to-male recipients also had a significantly reduced hazard ratio of graft failure compared to female-to-male transplants [aHR 0.51, 95% confidence interval (CI) 0.33-0.79, P  = 0.003]. No difference in graft failure was observed in the mismatched female recipient subgroup. The mismatched male recipient group also showed a decreased hazard ratio of mortality from graft rejection and respiratory causes. No differences in specific mortality causes were identified in the mismatched female recipient group. This study demonstrated an increase in the risk of graft failure and mortality secondary to graft failure in male recipients of female donor livers. No differences in mortality or graft failure were identified in female recipients of male livers.

Early pandemic in-hospital outcomes and mortality risk factors in COVID-19 solid organ transplant patients

Background Solid organ transplant (SOT) recipients with COVID-19 have a higher risk of mortality than those without COVID-19. However, it is unclear how SOT patient outcomes compare to the general population without SOT who contract COVID-19. Methods We used the National Inpatient Sample from January to December 2020 to investigate inpatient outcomes seen in SOT recipients after contracting COVID-19 compared to nontransplant patients. We identified our study sample using ICD-10 CM and excluded those <18 years of age and those with dual organ transplants. Inpatient outcomes were compared in SOT and non-SOT COVID cohorts, and we further evaluated predictors of mortality in the SOT with COVID population. Results Out of the 1,416,445 COVID-19 admissions included in the study, 8315 (0.59%) were single SOT recipients. Our analysis that adjusted for multiple baseline characteristics and comorbidities demonstrated that COVID-19 in SOT patients was associated with higher rates of acute kidney injury (adjusted odds ratio [aOR] 2.34, 95% confidence interval [CI] 1.81–3.02, P < 0.01), lower rates of acute respiratory distress syndrome (aOR 0.68, 95% CI 0.54–0.85, P < 0.01), and similar rates of cardiac arrest, pulmonary embolism, circulatory shock, cerebrovascular events, and in-hospital mortality. Age >65 was associated with mortality in SOT patients. Conclusion In this nationally representative sample, SOT patients presenting with COVID-19 experienced similar rates of mortality compared to those without SOT. SOT patients were more likely to develop acute kidney injury. Further research is needed to understand the complex relationship between transplant patient outcomes and COVID-19.

Pulmonary, Hepatic, and Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Telomere Biology Disorders.

This study aimed to summarize evidence and provide consensus-based guidelines for management of transplantation in patients with telomere biology disorders (TBD). Specifically, this review focuses on clinical management of lung, liver, and bone marrow transplantation in TBD patients. TBD patients have specific unique biological vulnerabilities such as T cell immunodeficiency, susceptibility to infections, hypersensitivity to chemotherapy and radiation, and cytopenias. Furthermore, multiple organ involvement at diagnosis makes clinical management especially challenging due to higher degree of organ damage, and stress-induced telomeric crisis. Sequential and combined organ transplants, development of novel radiation and alkylator-free conditioning regimen, and use of novel drugs for graft-versus-host disease prophylaxis are some of the recent updates in the field. Multidisciplinary management is essential to optimize transplant outcomes in patients with TBD. In this review, we provide consensus-based transplant management guidelines for clinical management of transplant in TBD.

Impact of Obesity on Graft-Versus-Host Disease and Transplant Outcomes in Patients Undergoing Allogeneic Hematopoietic Cell Transplant for Hematologic Malignancies

Impact of Obesity on Graft-Versus-Host Disease and Transplant Outcomes in Patients Undergoing Allogeneic Hematopoietic Cell Transplant for Hematologic Malignancies

The Potential Role of NOD2/CARD15 Genotype as a Prognostic Indicator for Bone Marrow Transplantation Outcomes in Patients With Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia: A Systematic Review.

Hematopoietic stem-cell transplantation (HSCT) has emerged as a groundbreaking therapeutic option for acute myeloid leukemia (AML) and specific subtypes of acute lymphoblastic leukemia (ALL). The prognostic significance of the NOD2/CARD15 gene has been explored alongside various factors, encompassing diverse patient cohorts and gene variants. Siblings and unrelated donors used for stem cell transplantation exhibit significant associations between their genetic variations and graft-versus-host disease incidence. The transplantation of stem cells for leukemia patients involves numerous considerations, including patient survival, relapse rates, disease stage, donor and recipient ages, and compatibility. This study delved into research on the NOD2/CARD15 gene and its mutations to assess its suitability as a screening tool. A comprehensive literature search encompassing PubMed, ScienceDirect, and Google Scholararticles yielded 4,840 articles. After removing duplicates and applying inclusion and exclusion criteria, we narrowed the search results to 876 articles. Subsequent screening of abstracts and titles resulted in the selection of 230 relevant articles. Further exclusion of 198 articles unrelated to the research question led to the scrutinizing of 32 full-text articles, which were assessed against inclusion and exclusion criteria. Emphasis was placed on articles that specifically investigated the role of NOD2/CARD15 as a predictive factor for HSCT outcomes, ultimately resulting in the inclusion of 19 articles in this study.Single nucleotide polymorphisms (SNPs) such as NOD2 and CARD15 have demonstrated their potential as reliable genetic markers for predicting post-transplantation relapse and disease outcomes. Patients positive for these genetic markers have exhibited reduced overall survival and event-free survivaland increased transplant-related mortality. Interventions with interferon-gamma and muramyl tripeptide phosphatidylethanolamine have been considered to mitigate the inflammatory effects of these SNPs, thus enhancing the influence of natural killer cells on abnormal cells and potentially extending patient survival. NOD2/CARD15 typing may aid in identifying patients at higher risk for relapse and improving their clinical outcomes after allogeneic stem cell transplant, particularly in ALL patients. However, no remarkable change was observed in AML patients. Additionally, this study underscores the pivotal roles of adaptive and innate immune responses and their interplay in stem cell transplant immunology.

The influence of socioeconomic deprivation on outcomes in transplant patients infected with SARS‐CoV‐2 in Wales

AbstractIntroductionSARS‐CoV‐2 infection has had a significant impact on vulnerable individuals including transplant patients. Socioeconomic deprivation negatively affects outcomes of many health conditions. The aim of this study was to evaluate the effect of socioeconomic deprivation on the incidence and severity of SARS‐CoV‐2 infection among Welsh transplant patients.MethodsThis study is a retrospective, cross‐sectional study on the transplant population of Wales. The Welsh Index of Multiple Deprivation (WIMD) was used to assess the influence of socioeconomic deprivation on outcomes of Welsh transplant patients who developed SARS‐CoV‐2 infection. Outcome measures were the incidence of SARS‐CoV‐2 infection, rates of hospital and ICU admission, development of acute kidney injury (AKI) and mortality. A logistic binomial regression analysis was used to correlate the various risk factors with the incidence of SARS‐CoV‐2 infection.ResultsTwo hundred and sixty‐six (25%) of regular follow up patients had SARS‐CoV‐2 infection; of these 55 (20.7%) were admitted, 15 (5.6%) to ICU, 37 (13.9%) developed AKI, and 23 (8.6%) died. In a regression analysis, patients of younger age were associated with more (p = .001) and those with SPK (simultaneous pancreas kidney) transplant less chance of infection (p = .038), whereas social deprivation was not associated with the chance of infection (p = .14). In regression analysis increased social deprivation was associated with higher chance of AKI post SARS‐CoV‐2 (p = .049).ConclusionsSocioeconomic deprivation did not affect the rates or severity of SARS‐CoV‐2 infection apart from the degree of AKI in Welsh Transplant patients. Adherence to the preventive measures for this high‐risk population must continue to remain a priority.

Referral and evaluation for kidney transplantation among patients with lupus nephritis-related end-stage kidney disease.

For the majority of patients with lupus nephritis-related end-stage kidney disease (LN-ESKD), kidney transplant is associated with better outcomes than dialysis. Access to kidney transplant requires an initial referral to a transplant center and medical evaluation prior to waitlisting. The study's objective was to examine access to these early steps in the kidney transplant process among patients with LN-ESKD. Adults who began treatment for ESKD in the Southeast, Northeast, New York, or Ohio River Valley U.S. regions from 1/1/2012 to 12/31/2019, followed through 6/30/2021, were identified from the United States Renal Data System. Referral and evaluation start data were collected from 28 of 48 transplant centers across these regions. The exposure was primary cause of ESKD (LN-ESKD vs other-ESKD). The outcomes were referral and evaluation start at a transplant center. Cox models quantified the association between LN-ESKD (vs other-ESKD) and referral and evaluation start. Among 192,318 patients initiating treatment for ESKD, 0.4% had LN-ESKD. Over half (58%) of LN-ESKD patients were referred before study end, and among those referred, 66% started the evaluation. In adjusted analyses, patients with LN-ESKD were referred (HR: 1.09, 95% CI: 0.99, 1.19) and started the transplant evaluation (HR: 1.13, 95% CI: 1.00, 1.28) at a higher rate than patients with other-ESKD. Among referred patients with LN-ESKD, the median time from ESKD start to referral was 2.9months (IQR: <1 to 11.7months), which is similar to patients with other-ESKD (median 2.6months, IQR: <1 to 8.8months). Among incident patients with ESKD, having a primary diagnosis of LN-ESKD versus other-ESKD is associated with higher rates of early transplant access outcomes. Despite this, patients with LN-ESKD (vs other-ESKD) are less likely to be preemptively referred (i.e., referred prior to ESKD start) for kidney transplant. While providers may no longer be delaying the early steps in the kidney transplantation process among this patient population, there is still room for improvement in the rates of preemptive referral. Access to kidney transplant referral prior to ESKD could result in increased transplant rates and better transplant outcomes for patients with LN-ESKD.

A Multicenter Analysis of Allogeneic Transplant Outcomes in Patients with Philadelphia-like (Ph-like) Acute Lymphoblastic Leukemia (ALL)

Background: Ph-like ALL is a high-risk subset of B-lineage ALL that responds poorly to standard chemotherapy regimens. While allogeneic hematopoietic cell transplantation (HCT) is routinely recommended for patients with Ph-like ALL, large multicenter data addressing its role is limited. Here, we conducted a multicenter study to evaluate the role of HCT in adolescent and young adult (AYA) and adult patients (pts) with Ph-like ALL and compare their outcomes to pts with Ph-pos and Ph-neg (non-Ph-like) ALL. Methods: The study included pts (age ≥18) with B-lineage ALL who received HCT in first complete remission (CR1) at 3 academic centers (MD Anderson Cancer Center, City of Hope and Mayo Clinic) between 2006 and 2021. Pts were divided into 3 main subgroups: Ph-like, Ph-pos and Ph-neg ALL. Ph-like ALL cases were identified using cumulative data obtained by targeted RNA sequencing, conventional cytogenetics, FISH studies, whole genome chromosomal microarray and flow cytometry. Measurable residual disease (MRD) prior to HCT was measured using flow cytometry with a sensitivity of 0.01% for Ph-neg and Ph-like ALL, and with a PCR assay for BCR::ABL1 for Ph-pos ALL. MRD-negativity was defined as &amp;lt;0.01%. Predictors of relapse were evaluated in univariate and multivariate analysis using Fine-Gray sub-distribution hazard models considering non-relapse mortality (NRM) as a competing risk. Results: 673 patients were identified, 83 (12.3%) had Ph-like ALL, of which 73% had CRLF2-alterations. The remaining patients were classified either as Ph-pos (N=271, 40.3%) or Ph-neg ALL (N=319, 47.4%). Patients with Ph-like ALL were younger (median age 40 years vs 48 and 46 years for Ph-pos and Ph-neg ALL, respectively, p=0.01), more likely to be of Hispanic ethnicity (69% vs 32% and 48% for Ph-pos and Ph-neg ALL respectively, p&amp;lt;0.001). Patients with Ph-like ALL were also more likely to have induction failure (24% vs 2% and 11% for Ph-pos and Ph-neg ALL, respectively, p=0.001). A summary of pts characteristics for each subgroup can be found in Table 1. The median follow-up was 30, 52 and 48 months for patients with Ph-like, Ph-pos and Ph-neg ALL, respectively. In univariate analysis, 3-yr OS and PFS did not differ significantly (66% and 59% vs 59% and 54%, p=0.1) between patients with Ph-like and Ph-neg ALL, respectively. Similarly, the cumulative incidence of relapse was comparable between patients with Ph-like and Ph-neg ALL (22% vs 20%, respectively, p=0.7). In contrast, the 3-yr OS (75%, p&amp;lt;0.001) and PFS (70%, p=0.001) were significantly higher and relapse rate significantly lower (12%, p=0.003) in pts with Ph-pos ALL compared with Ph-like or Ph-neg ALL (Figure 1). The inferior survival in patients with Ph-like and Ph-neg ALL was likely attributable to higher relapse rates (22% and 20% vs 12%, respectively, p=0.003) compared to Ph-pos ALL. Finally, the 3-yr NRM rate in patients with Ph-like ALL was comparable (20% vs 18% and 23%, respectively, p&amp;gt;0.1) to Ph-pos and Ph-neg ALL. We confirmed that the relapse rate in patients with Ph-like ALL was comparable to the rate in pts with Ph-neg ALL (HR=1.02, 95% CI 0.6-1.8, p=0.9) on multivariate analysis (MVA). Ph-pos ALL was associated with a significantly lower relapse rate compared with Ph-neg ALL (HR=0.4, 95% CI 0.3-0.7, p&amp;lt;0.001). MRD positivity prior to allo-HCT was the only additional significant predictor for relapse on MVA (HR=2.9, 95% CI 1.8-4.7, p&amp;lt;0.001). Conclusions: HCT appears to overcome the poor prognosis of patients with Ph-like ALL. Despite higher induction failure rates, patients with Ph-like ALL undergoing HCT in CR1 had similar outcomes to other Ph-neg ALL subsets. The impact of effective salvage therapy leading to MRD-negativity in CR1 in this group is under investigation and will be reported. Further studies are needed to assess the impact of different Ph-like alterations on HCT outcomes. Outcomes for patients with Ph-pos ALL are significantly better than other groups, likely due to the use of TKIs pre- and post-HCT.

Deciphering the Impact of Donor Telomere Length on Allogeneic Transplantation Outcomes: Telomere Length Matters More Than Age

Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for acute leukemia. The success of transplantation relies significantly on optimal donor selection, with the donor's age being a critical factor affecting recipient survival post allo-HSCT. Telomeres play a vital role in safeguarding genetic information and are considered biomarkers for biological aging. In patients with severe aplastic anemia undergoing allo-HSCT, shorter telomere length is strongly associated with adverse outcomes. However, the relationship between telomere length and transplant outcomes in patients with acute leukemia remains unexplored. Thus, this study aims to investigate the impact of donor telomere length on clinical outcomes following allo-HSCT. Methods This post hoc analysis included 863 patients with acute leukemia who underwent allo-HSCT at the First Affiliated Hospital of Zhejiang University between June 6, 2016, and March 4, 2022. The inclusion criteria were as follows: (1) patient age ≥ 10 years; (2) diagnosis of acute leukemia, including acute myeloid leukemia, acute lymphoblastic leukemia, and mixed phenotype acute leukemia; (3) availability of a pre-transplant blood sample from the donor before mobilization. Peripheral mononuclear cells were sorted and analyzed uniformly for telomere length using qPCR. Based on the quartiles of donor telomere length, patients were categorized into the shortest telomere group (Q1), intermediate length telomere group (Q2, Q3), and longest telomere group (Q4), and the transplant outcomes were compared among the different telomere length groups. Results Out of the 863 eligible patients, 137 underwent allo-HSCT with matched sibling donors, 88 with unrelated donors, and 638 with haploidentical related donors. There were 546 donors aged &amp;lt; 40 years and 317 donors aged ≥ 40 years. An inverse linear correlation was observed between donor age and telomere length (P &amp;lt; 0.001, Figure 1A). However, this age-dependent association was mainly evident in younger donors (age &amp;lt; 40 years, P = 0.021), while in donors aged ≥ 40 years (elderly donors), it did not reach statistical significance as observed in the younger donor group (P = 0.36). In patients receiving grafts from younger donors, there was no significant correlation between telomere length and engraftment, acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), non-relapse mortality (NRM), relapse, relapse-free survival (RFS), or overall survival (OS). In patients receiving grafts from elderly donors, the shortest telomere length was associated with an elevated incidence of aGVHD, while aGVHD incidence was similar between intermediate and longest telomere groups (49.4%, 38.5%, and 34.2% for shortest, intermediate, and longest, respectively, P = 0.06). Moreover, the intermediate telomere group exhibited improved OS (3-year OS for shortest, intermediate, and longest was 59.2%, 75.6%, and 59.9%, respectively, P = 0.07, Figure 1B) and prolonged RFS (3-year RFS for shortest, intermediate, and longest was 58.8%, 74.1%, and 55.1%, respectively, P = 0.06, Figure 1C). While the donor age has on impact on OS and RFS (P &amp;gt; 0.05). Even after adjusting for prognostic factors such as patient age, pre-transplant disease status, disease risk index stratification, and transplantation type, the multivariate analyses consistently indicated that intermediate telomere length remained an independent protective factor for OS (HR = 0.549, 95% CI, 0.328-0.920, P = 0.023, Figure 1D) and RFS (HR = 0.591, 95% CI, 0.361-0.967, P = 0.036, Figure 1E). Notably, elderly donors with the longest and shortest telomeres showed significantly inferior OS compared to younger donors ( Figure 1F). However, those elderly donors with intermediate telomere lengths demonstrated comparable OS to younger donors ( Figure 1G). Conclusion This study has significantly advanced our comprehension of telomeres, revealing that both excessively long and short telomeres are linked to adverse clinical outcomes in allo-HSCT for acute leukemia. Remarkably, elderly donors with intermediate-length telomeres demonstrate comparable outcomes to younger donors, challenging the conception that “young donors are superior to elderly donors.” These findings underscore the paramount importance of donor telomere length more than donor age, emphasizing its pivotal role in allo-HSCT success.

Sequential Conditioning Does Not Improve Outcomes of Allogeneic Stemcell Transplantation in CMML Patients

Background: Allogeneic stem cell transplantation (SCT) is potentially curative therapy for patients with CMML. Data on optimal allo-SCT conditioning in CMML Patients is scarce. Methods: This retrospective study from the Department of Stem Cell Transplantation at the University Medical Center Hamburg, Germany, compared allo-SCT outcomes in CMML patients across three conditioning regimes: Thiotepa-Busulfan (TB), Sequential FLAMSA-Busulfan Fludarabine (FLAMSA-FB), and Treosulfan-Fludarabine (Treo-Flu). TB consisted of Thiotapa ( 5mg/Kg; a total dose of 10mg/Kg) on day -6 and -5 and Busulfan (3.2mg/Kg; total dose 6.4mg/Kg or 9.6mg/Kg) on days -4 and -3 or -4 to -2. FLAMSA-FB regimen consists of fludarabine (30 mg/m 2 ; total dose 120 mg/m 2 ), amsacrine (100 mg/m 2 ; total dose 400 mg/m 2 ), and cytarabine (1 g/m 2 ; total dose 4 g/m 2 ) therapy from days -11 to minus -8, followed by a three-day interval without therapy and Busulfan from day -4 to -2 with a total dose of 6.4mg/Kg and Fludarabine on day -4 and -3 (30 mg/m 2, total dose 60mg/m 2 ).Treo-Flu regimen consisted of Treosulfan (12 g/m 2 , total dose 36 mg/m 2 ) on days-6 to -4 and fludarabine (30 mg/m 2 ; total dose 150 mg/m 2 ) on days -6 to -2. Results Sixty-nine consecutive patients with CMML who underwent allo-SCT between the years 2006-2022. Twenty-two received TB, 27 received FLAMSA-FB, and 20 received Treo-Flu conditioning. Transplant sources included matched related donors (MRD, 8 patients), mismatched related donors (MMRD, 8 from TB), matched unrelated donors (MUD, 31), and mismatched unrelated donors (MMUD, 23) with significant group variations (p&amp;lt;0.001). Most Patients received ATLG for GVHD prophylaxis (TB 68%, FLAMSA-FB 93%, Treo-Flu 85%, p=0.08). Regarding CPSS-mol scores, the TB group exhibited a significantly higher proportion of high (46%) and intermediate-2 scores (32%) than FLAMSA-FB (11% high, 7% intermediate-2) and Treo-Flu (40% high, 20% intermediate-2) (p=0.001). One TB patient experienced primary graft failure, but engraftment times were comparable across groups. Although not statistically significant (p=0.07), the TB group showed a trend towards improved 3-year OS rates (84%) compared to FLAMSA-FB (37%) and Treo-Flu (49%). The TB group also displayed significantly higher 3-year PFS rates (79%) compared to FLAMSA-FB and Treo-Flu (both 30%), (p=0.03). (Figure 1) No significant differences were observed in 3-year non-relapse mortality (NRM) across the TB (17%), FLAMSA-FB (30%), and Treo-Flu (26%) groups (p=0.7). Interestingly, no TB patients relapsed at 3 years, contrasting with the FLAMSA-FB (41%) and Treo-Flu groups (43%, p=0.02). Lastly, cumulative incidences of acute GVHD grade II-IV (TB 41%, FLAMSA-FB 35%, Treo-Flu 30%, p=0.75) and all-grade chronic GVHD (TB 50%, FLAMSA-FB 65%, Treo-Flu 40%, p=0.35) were similar across groups. Conclusion Our study suggests that sequential conditioning with FLAMSA-FB does not improve Transplant outcomes in patients undergoing allo-SCT for CMML.

Bispecific T-Cell Engagers for B-Cell NON-Hodgkin Lymphoma Patients before Allogeneic Stem Cell Transplantation. a Study on Behalf Od Geth-TC

Background: Bispecific T-cell engagers antibodies (BiTEs) have shown promising efficacy across B-cell non-Hodgkin lymphoma (BCL) subtypes. If a response is observed, consolidation with allogeneic hematopoietic cell transplantation (alloHCT) could be reasonably pursued for high risk patients. To date, no data are available regarding BiTEs exposure prior to an alloHCT. Our aim was to describe patient characteristics, response, survival outcomes and treatment-related toxicities of patients treated with anti CD20-CD3 BiTE before alloHCT. Methods: We performed a multicentric, retrospective study including adult patients (&amp;gt;18 years old) who received an alloHCT as consolidative therapy following anti-CD20-CD3 BiTE treatment for relapsed/refractory (R/R) BCL between February 2018 and March 2023. The primary endpoint was non-relapse mortality (NRM). Secondary endpoints were overall survival (OS), progression-free survival (PFS), relapse/progression of disease (Rl/POD), cumulative incidence of acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD), and hematological recovery. Probabilities of OS and PFS were calculated using Kaplan-Meier estimator method, and NRM, RI/POD, GVHD and hematological recovery as cumulative incidences. Results: A total number of 29 patients were included in the analysis. Patient's characteristics are described in Table 1. Median age was 57 (range 22-67) and 62.1% of patients were males. Twenty-four (82.8%) patients had stage III-IV at diagnosis and 21 (72.4%) were primary refractory. Nine (31%) patients had received an autologous transplant and 10 (34.5%), anti-CD19 CART prior to BiTE. Median number of lines at alloHCT were 4 (range 3-11). Median time from diagnosis to alloHCT was 39 (range 9 -208) months. Epcoritamab (n=16) was administered in monotherapy. Glofitamab (n= 13) was given in either monotherapy (n=2) or combination with either atezolizumab (n=2), polatuzumab (n=3) or englumafusp (n=6). The median number of BiTE's administered doses was 10 (range 4-20). The median time between BiTE's last dose and alloHCT was 44 (range 13 - 203) days. Median follow-up among survivors was 21.9 months (range 3.3 - 52.6 months). At 18-months, OS, PFS, NRM and RI/POD were 66% (95% confidence interval [CI]: 45-81%), 62% (95% CI: 40-78%), 33% (95% CI: 15-53%), and 4% (95% CI: 0-12%), respectively. Causes of death were 1 relapse and 9 transplant toxicities (7=infections, 1=cGVHD, 1=cerebrovascular disease). Fifty-five percent of toxicity-related deaths were observed during the first 3 months from transplant. The cumulative incidence of neutrophil and platelet engraftment at day +30 was 90% (95% CI, 78-100%) and 68% (95% CI, 50-86%), respectively. The cumulative incidence of all grade and grade II-IV aGVHD at day +100 was 31% (95% CI: 13-49%) and 22% (95% CI: 7-37%), respectively. The cumulative incidence of all grade cGVHD at 18 months was 16% (95% CI: 2-30%), with only 1 patient presenting with moderate cGVHD. On univariate analysis, no prognostic factors were found in terms of OS, PFS, RI/POD and NRM. A comparison with a contemporary cohort of alloHCT recipients for BCL (N=101) from the Grupo Español de Trasplante y Terapia Celular (GETH-TC) who were not exposed to BiTE was performed ( figure 1). Propensity score matching using most significant patient, disease and alloHCT characteristics was performed to reduce cohort's heterogeneity ( Table 1). In the final 1:1 matched population (n=58; 29 patients treated with BiTE prior alloHCT and 29 patients who did not receive BiTE prior alloHCT), no differences in terms of OS, PFS, RI/POD and NRM at 18 months were observed (66% [95% CI, 45-81%] vs 48% [95% CI, 29-65%] [p=0.18]; 62% [95% CI, 40-78%] vs 45% [95% CI, 27-62%] [p=0.17]; 33% [95% CI, 14-52%] vs 41% [95% CI, 22-60%] [p=0.35] and 4% [95% CI, 0-10%] vs 10% [95% CI, 0-20%] [p=0.24]. Conclusions: We describe for the first time the results of BiTE exposure before alloHCT in terms of safety and efficacy. AlloHCT as consolidation therapy is feasible and does not seem to be detrimental for transplant outcomes in patients with R/R BCL with expected toxicity and surprisingly low relapse rate.

Score to Guide Donor Choice in Haploidentical Stem Cell Transplant Using Post-Transplant Cyclophosphamide for Patients with Acute Myeloid Leukemia: A Study from the Acute Leukemia Working Party of the EBMT

Introduction: There is paucity of information to guide selection of the most appropriate stem cell donor for haploidentical (Haplo) hematopoietic stem cell transplant (HSCT). Patients and Methods: We retrospectively analyzed the characteristics of haploidentical family donors that may affect transplant outcomes in patients with acute myeloid leukemia (AML) who received graft-versus-host disease (GVHD) prophylaxis with postransplant cyclophosphamide (PTCy) registered in the EBMT database. The primary endpoint was GVHD and relapse-free survival (GRFS). Results: Overall, 2200 patients were included with a median age of 56 years (range, 18-75); 1742 (79%) were in complete remission and 1246 (56.6) received reduced intensity conditioning. Regarding donors, the median age was 37 years (range, 8-71), 820 (37%) were females of which 458 (21%) were used for male recipients, 1252 (57%) had positive CMV serostatus, 1631 (74%) donated peripheral blood (PB) and 1638 (75%) had ≥ 4/8 HLA mismatch with the recipient. 100-day acute GVHD grade II-IV and III-IV and 2-year chronic and chronic extensive GVHD were 28% (95% CI 26-30), 11% (95% CI 10-12), 33% (95% CI 31-35) and 14% (95% CI 12-15), respectively. After median follow-up of 24 months, the cumulative incidence of relapse and non-relapse mortality (NRM) and the probability of leukemia-free survival (LFS), overall survival (OS) and GRFS were 26% (95% CI 24-28), 22% (95% CI 20-24), 52% (95% CI 50-55), 57% (95% CI 55-60) and 41% (95% CI 39-43), respectively. In multivariable analysis, donor-related risk factors with a negative impact on GRFS were older age (HR 1.1; 95% CI 1.04-1.15), use of PB (HR 1.19; 95% CI 1.04-1.37), and female donors to male recipients (HR 1.25; 95% CI 1.09-1.43). We further developed a score that distinguished 4 groups with 0 (241), 1 (913), 2 (863) or 3 (183) donor-related risk factors. GRFS was 57% (95% CI 50-63), 43% (95% CI 39-46), 37% (95% CI 33-40), and 30% (95% CI 23-38), respectively (P &amp;lt; 0.001) (Figure 1). The score was also able to stratify risk groups for acute and chronic GVHD, NRM, LFS and OS. Conclusion: Donor variables have an important impact on AML patient's outcome after Haplo-HSCT using PTCy. With three simple donor characteristics, age, gender and stem cell source, we were able to generate a score that may help to select the most appropriate donor in clinical practice.

Outcomes of Allogeneic HSCT in Elderly Patients (70 years old and above) -a Canadian Experience

Introduction: Allogeneic hematopoietic cell transplant (alloHCT) in elderly patients is a challenge, as with increasing age, there is higher incidence of co-morbidities and pre-frail status. In our recent study on alloHCT in patients 60 years (y) or older, those who were 70y or more had worse outcome and high 2-y non-relapse mortality (NRM) of 53% (Al-Shaibani E et al. Ann Hematol, 2023, 102: 917-926). We therefore implemented a number of changes to improve outcomes in elderly patients undergoing alloHCT. In this study, we analyze transplant outcomes in patients ≥ 70 y, and compare the earlier cohort with the more recent cohort. Methods: This is a retrospective analysis of all consecutive patients 70y or older, who had an alloHCT from Jan 2015 to Dec 2022. We compared those who underwent an alloHCT from 2015-2019 (Cohort A, n=44) with those who had a transplant from 2020-2022 (Cohort B, n=40). The median age of the patients was 71y (range 70-76). The underlying diagnosis was mainly a myeloid malignancy (AML, MDS, MPN, CMML, n=82; lymphoid (ALL, TPLL, n=2). There were 54 males. Stages of disease at transplant were in CR1 (n=51), CR2 (n=4) or stable disease (n=15, MDS, MPN or CMML pts). All patients received RIC regimens for conditioning including Flu4/Bu2/TBI200 (n=73), Flu4/Treo30 (n=7) and Flu/Treo42 (n=3). The GVHD prophylaxis regimens used included ATG2/PTCy/CSA (n=32), ATG4.5/PTCy/CSA (n=35), ATG4.5/CSA/MTX (n=7), ATG2/CSA/MTX (n=3). The donors were either matched related (n=10), matched unrelated (including minor mismatch) (n=57) or haploidentical (n=16). Graft source was peripheral blood in all except one who received bone marrow. (Details in Table). The overall survival (OS), event free survival (EFS), NRM, cumulative incidence of relapse (CIR), incidence of acute and chronic GVHD, length of transplant hospitalization and the number of hospital re-admissions in first 6 months were assessed. The Kaplan Meier curves were plotted for OS and EFS for the overall sample, as well as stratified by the two eras (cohort A and B) and the differences assessed using log-rank tests. Cumulative incidence curves for NRM and CIR were generated, and differences assessed using Gray's K-sample. Results: For all patients transplanted in 2015-2022, the 1-year OS was 53%, the 1-year EFS was 45% and the 1-year NRM was 35%. The median number of days of transplant hospitalization for the whole population was 33.5 days (range 16 - 116). The incidence of grade I-II aGVHD was 32%, and grade III-IV aGVHD was 9.5%; mild to moderate cGVHD was 14% and severe cGVHD was 2%. The 1-year CIR was approximately 18%. Comparing the two cohorts A and B, the 1y OS was 45% vs 62% (p=0.10) respectively; the 1-year EFS was 37% vs 58% (p=0.07) respectively and the 1-year NRM was 45% vs 23% (p=0.04) respectively (Figures attached). The incidence of GVHD and CIR were similar in both cohorts, despite reducing the ATG dose in cohort B. Conclusions: Our study shows that there were statistically significant improvements in NRM and a trend towards improvement in the OS and EFS in the patients transplanted during 2020-2022 compared to patients undergoing alloHCT from 2015-2019. This improvement may be due to one or more changes implemented in recent years, although it is not possible to identify a single factor. These changes were (a) introduction of Frailty testing in all patients (Salas MQ et al. BMT. 2021; 56:60-69). (b) capping the CD34 cell dose in grafts (c) introduction of Treosulfan for selected indications (MDS/CMML) (Pasic I et al. Leuk Res 2023, 128: 107131). (d) Letermovir for CMV prophylaxis (e) reducing ATG dose for GVHD prophylaxis and (f) focus on diet, nutrition, exercise. While alloHCT should be offered to medically eligible elderly patients, there is a special need to minimize the risks that are part of age related vulnerabilities.

Kidney Transplant Outcomes in Patients With Scleroderma an Experience at Northwestern Memorial Hospital, Chicago, Illinois

Scleroderma renal crisis (SRC) is a devastating complication of diffuse cutaneous systemic sclerosis (dcSSc) that occurs in 5% to 20% of patients in this population. End-stage kidney disease develops in 25% to 40% of SRC, and mortality occurs in 50% at 5 years. Kidney transplantation (KT) is a viable option, but little data exist on outcomes. We performed a retrospective study of all patients with dcSSc who underwent KT at Northwestern Hospital between 2000 and 2020. The objective of this study was to determine graft and patient survival at years 5 and 10 post-transplant. Both patient and graft survival were 78% and 100% at 5 and 10 years, respectively. Kidney transplantation is associated with favorable outcomes in patients and graft survival at 5 and 10 years in patients with dcSSc.

Utility of the Stanford Integrated Psychosocial Assessment for Transplant in predicting outcomes before and after lung transplantation

Optimizing donor use and achieving maximal survival following lung transplantation (LTx) requires a pre-transplant assessment that identifies clinical, physiological and psychosocial patient factors associated with both poor and optimal post-LTx survival. We examined the utility of a psychosocial tool, the Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) to identify patient suitability for LTx, as well as its association with clinical outcomes before and after LTx. Retrospective single center study analysing LTx assessment clinical variables (age, gender, diagnosis, functional capacity, nutrition, renal function), with a particular focus on the utility of the SIPAT score, to predict patient suitability for LTx. The same variables were analysed against LTx wait-list mortality, as well as post-LTx survival. Over an 8-yr period dating from December 2012, 914 patients (male 54.4%, mean age 55.2 yrs) underwent LTx assessment. Patients declined for LTx (n = 152, 16.6%) were older and had reduced functional capacity, nutritional markers and renal function, but had a higher SIPAT score. Once listed for LTx, a higher SIPAT score was not associated with wait-list mortality or reduced post-LTx survival. The SIPAT tool measures psychosocial suitability for transplantation that can be incorporated into a standardized assessment of LTx suitability. While patients with higher SIPAT score were more likely to be declined for LTx, the SIPAT score did not predict outcome in transplanted patients. A subgroup of patients with high SIPAT scores were successfully transplanted suggesting that unfavorable psychosocial variables are potentially modifiable with a well-resourced multidisciplinary LTx team.

Renal Transplantation in Patients With Tuberculosis: A Single-center Experience From an Endemic Region.

Despite being a common infection in end-stage kidney disease patients, there are no evidence-based guidelines to suggest the ideal time of transplantation in patients on antitubercular therapy (ATT). This study aimed to examine the outcome of transplantation in patients while on ATT compared with those without tuberculosis (TB). This was a retrospective study. Renal transplant recipients transplanted while on ATT were compared with a 1:1 matched group (for age, sex, diabetic status, and type of induction agent) of patients without TB at the time of transplant. Patient outcomes included relapse of TB and graft and patient survival. There were 71 patients in each group. The mean duration for which ATT was given pretransplant was 3.8 ± 2.47 mo. The average total duration of ATT received was 12.27 ± 1.25 mo. Mortality in both the groups was similar (8.4% in the TB group versus 4.5% in the non-TB group; P = 0.49). None of the surviving patients had recurrence of TB during the follow-up. Death-censored graft survival (98.5% in the TB group versus 97% in the non-TB group; P = 1) and biopsy-proven acute rejection rates (9.86% in the TB group versus 8.45% in the non-TB group; P = 1) were also similar in both the groups. Successful transplantation in patients with end-stage kidney disease on ATT is possible without any deleterious effect on patient and graft survival and no risk of disease recurrence. Multicentric prospective studies are needed.

S1518 Effect of Inflammatory Bowel Disease Activity on Liver Transplantation Outcome in Patients With Primary Sclerosing Cholangitis

S1518 Effect of Inflammatory Bowel Disease Activity on Liver Transplantation Outcome in Patients With Primary Sclerosing Cholangitis