Post-transplant Complications Research Articles

Hyperacute silicosis after bronchoscopy-induced melanoptysis in a lung transplant patient. A first report in literature.

Silicosis, a fibrotic lung disease caused by crystalline silica inhalation, presents unique challenges in lung transplantation. This case reports an unprecedented complication in a lung transplant recipient with chronic silicosis. A man in his 60 s, post left single-lung transplantation for silica-induced pneumoconiosis, developed acute respiratory deterioration following routine bronchoscopy. Melanoptysis, followed by imaging showing extensive inflammatory involvement in the transplanted lung, required intubation and prone positioning. This case highlights the potential for residual silicotic material to trigger acute post-transplant complications. It underscores the importance of comprehensive pretransplant evaluation of occupational exposures and heightened awareness of silica-related complications in post-transplant care. The report emphasizes gaps in understanding long-term outcomes and optimal management strategies for lung transplant recipients with silicosis.

Five years outcomes of recipients of dual kidney transplantation are better compared to the single kidney transplantation with comparable early post-transplant complications

Five years outcomes of recipients of dual kidney transplantation are better compared to the single kidney transplantation with comparable early post-transplant complications

Impact of Hypothermic Oxygenated Machine Perfusion on Immune Cell Clearance in Liver Transplantation: Enhancing Graft Function and Post-Transplant Outcomes.

Background: Hypothermic oxygenated machine perfusion (HOPE) has emerged as a critical innovation in liver transplantation (LTx), offering significant protection against ischemia-reperfusion injury (IRI). This study focuses on quantifying and characterizing immune cells flushed out during HOPE to explore its effects on graft function and post-transplant outcomes. Materials and Methods: Fifty liver grafts underwent end-ischemic HOPE. Perfusate samples were collected at three time points: at the start of perfusion, after 10 min, and at the end of perfusion. The samples were analyzed to quantify and characterize immune cells, assessing the effectiveness of HOPE in reducing cellular debris and its impact on graft quality. Results: The primary perfusate contained significant concentrations of immune cells, mainly segmented neutrophils, lymphocytes, and monocytes. After 10 min of perfusion, outflow cell concentration decreased by over 95%, and by the end of perfusion, a more than 99% reduction was observed. Conclusions: HOPE effectively reduces immune cell concentrations in liver grafts, suggesting a mechanism for improved graft function and reduced post-transplant complications. These findings support the continued use and optimization of HOPE in LTx.

Post-transplant complications revealed by mycophenolate mofetil related transporters and metabolic enzymes gene polymorphisms in pediatric patients with hematological disorders

BackgroundHaploidentical hematopoietic stem cell transplantation (Haplo-HSCT) serves as an important option for patients without an HLA matched donor in treating hematological disorders, while patients may experience various complications after transplantation. Mycophenolate mofetil (MMF), a cornerstone drug for graft-versus-host disease (GvHD) prophylaxis, effectively reduces the incidence of acute GvHD, and the efficacy of MMF varies among individuals associated with MMF-related transporters and metabolic enzymes single nucleotide polymorphisms (SNPs). However, limited studies have systematically reported the correlations between the MMF-related SNPs and post-transplant complications.MethodsHere, we conducted a retrospective study involving 90 pediatric patients with hematological disorders who underwent haplo-HSCT at a single center. All patients were subjected to MMF-related SNP testing, combined with common clinical characteristics, to be correlated with post-transplant complications.ResultsWe observed that all 15 MMF-related SNPs were in Hardy-Weinberg equilibrium. Based on multivariate Cox regression analysis of post-transplant complications, we discovered that SLCO1B1 (521T > C) variant genotype was an independent protective factor for chronic GvHD (HR = 0.25, 95% confidence interval (CI) (0.08–0.84)). For viral infection, CYP2C8 (1291 + 106T > C) variant genotype was an independent risk factor for cytomegalovirus infection (HR = 2.98, 95% CI (1.18–7.53)). As to hemorrhagic cystitis, SLCO1B1 (1865 + 4846T > C) variant genotype was an independent protective factor, while older age was considered as an independent risk factor (HR = 0.41, 95% CI (0.19–0.85); HR = 2.52, 95% CI (1.14–5.54), respectively). No statistical significance was discovered between common clinical characteristics and MMF-related SNPs with other complications, including grade II-IV/III-IV acute GvHD, Epstein-Barr virus infection, peri-engraftment syndrome, and capillary leak syndrome. We also discovered SLCO1B1 (597 C > T) and SLC29A1 (-162 + 228 A > C) variant genotypes are both independent factors for cumulative incidence of relapse after haplo-HSCT (HR = 4.02, 95% CI (1.42–11.44); HR = 0.18, 95% CI (0.07–0.43), respectively).ConclusionsOur findings highlight the significance of MMF-related transporters and metabolic enzymes SNPs in the development of post-transplant complications, contributing to facilitating personalized risk assessment and improving the clinical management in haplo-HSCT patients.

Post-transplant complications in alcohol- and metabolic-associated steatotic liver disease

Alcohol-associated liver disease (ALD) and metabolic-associated steatotic liver disease (MASLD)/metabolic-associated steatohepatitis (MASH) are severe liver diseases, with liver transplant being the primary curative treatment option. Transplant recipients with ALD suffer from alcohol use disorder (AUD) and poor drug compliance, which can result in graft injury and even graft loss. Relapse of alcohol consumption, lack of drug compliance, and smoking negatively impact the graft and clinical outcome of ALD-related transplantation patients. Furthermore, these patients are at a higher risk of developing non-hepatic complications such as malignancies, cardiovascular diseases, and other metabolic conditions. The management of these conditions requires pharmacological and behavioral strategies to manage complications as soon as they arise. Critical monitoring of these conditions is also advocated. In patients undergoing transplants for MASLD/MASH, early complications arise in obese and diabetic patients. Late post-transplant complications such as cardiovascular diseases, chronic kidney disease, recurring MASLD/MASH, immunosuppression, and arterial hypertension are reported. Integrating behavioral strategies with diet modification and physical activity is crucial to balance underlying metabolic disorders and improve clinical outcomes. Early steroid withdrawal and low calcineurin inhibitor doses can decrease the risk of post-transplant diabetes, hypertension, and dyslipidemia. Lifestyle modifications and tailored immunosuppression are helpful in the prevention and management of post-transplant recurrent MASLD/MASH.

Liver Transplantation for Autoimmune Hepatitis: 20 Years of Tertiary Centre Experience.

We analyzed the frequency of complications and survival rates in patients with autoimmune hepatitis (AIH) who underwent liver transplantation at a high-volume transplant center. Patients who underwent transplantation for AIH at the xxx University Liver Transplantation Institute between January 2002 and December 2021 were included. Patients with a confirmed diagnosis of AIH, without concomitant chronic liver disease, were included in the study. We included 51 patients (31 female) with a median age of 38.5 years (18-65 years). The 12-month and 60-month survival rates were 86.3% and 80.9%, respectively. During a median 2.22 years follow-up, 9 patients died. Six patients died due to systemic infection, 1 due to biliary complications, and 2 patients due to graft rejection. Autoimmune hepatitis recurrence developed in 6 (11%) patients. Overall, biliary complications developed in 56% (28/51) of patients following liver transplantation, and graft rejection occurred in 22% (11/51) of patients. Our results suggest that the outcome of AIH following liver transplantation is good, with a survival rate of up to 80%. Posttransplant biliary complications are common; therefore, close follow-up is necessary.

Clinical Characteristics and Risk Factors for Persistent Thrombocytopenia among Pediatric Patients after Bone Marrow Transplant in Saudi Arabia: A 3-Year Retrospective Observational Analysis from Tertiary Hospital

Background Bone marrow transplantation (BMT) is a crucial treatment for pediatric patients with various hematological, oncological, and genetic diseases. However, persistent thrombocytopenia (PT) post-transplantation poses a significant challenge, affecting recovery and prognosis. Purpose This study aimed to identify the clinical characteristics and risk factors associated with PT in pediatric patients post-BMT, specifically in Saudi Arabia. Methods A retrospective cohort study design was employed, involving pediatric patients who underwent BMT between January 2020 and January 2023. Clinical characteristics, laboratory results, treatment data, and outcomes were collected from electronic medical records. Logistic regression analyses were conducted to identify risk factors associated with PT. Results Among the 77 pediatric patients in the study, no significant differences were observed in demographic characteristics, transplant types, or treatment modalities between early-onset and late-onset thrombocytopenia groups. However, the duration of thrombocytopenia post-transplant differed significantly between the groups, with early-onset cases experiencing shorter durations. Infections and graft-versus-host disease were common post-transplant complications. Chemotherapy and antiviral therapy were frequently administered treatments. Pediatric patients undergoing BMT are susceptible to PT, with varying durations based on the onset timing. Conclusion The study emphasizes the importance of risk assessment and tailored management to mitigate thrombocytopenia in pediatric BMT patients. Further research is needed to elucidate the underlying mechanisms and optimize therapeutic interventions for thrombocytopenia in this population.

Outcome of Liver Retransplantation in Patients With Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is among the most common indications for liver transplantation in the Nordic countries and with an increasing trend in Europe and North America. Due to post-transplant complications and high prevalence of disease recurrence this group is at risk of requiring retransplantation (re-LTX). Results from re-LTX for PSC are not extensively studied and there is a lack of knowledge regarding prognosis after re-LTX in this population. Graft and patient survival after re-LTX for patients with PSC and a comparable comparison group from the Nordic liver transplant registry were analysed. One-hundred and eighty-five patients with PSC and 208 patients in the comparison group were included. The graft and patient survival were better for patients with PSC compared to the comparison group (p < 0.001). Re-LTX for recurrence of PSC (rPSC) compared to other aetiologies had similar and better outcomes for graft and patient survival (p = 0.093 and p = 0.023, respectively). Moreover, re-LTX for rPSC compared to the comparison group had a lower 30-day and 5-year mortality (p < 0.001 and p = 0.041, respectively). Outcomes after retransplantation for PSC were similar or better compared to the comparison group. Retransplantation represents a treatment option with the potential for excellent outcomes in patients with PSC and should be considered in transplanted PSC patients with graft failure.

Clinical and molecular profile of 20 patients with DOCK8 deficiency-a single-center experience from Southern India.

DOCK8 deficiency is the most common cause of autosomal recessive hyper-IgE syndrome (AR-HIES). The clinical spectrum is wide resulting in combined immunodeficiency, atopy, autoimmunity, and malignancies. To study the clinical and molecular profile of 20 patients with DOCK8 deficiency. Four hundred and eight patients with various inborn errors of immunity (IEIs) were diagnosed in the Pediatric Immunology Unit of our hospital during the study period of February 2017 to August 2023. Based on the clinical and immunological phenotype, DOCK8 deficiency was suspected in 31 patients. Genetic studies confirmed DOCK8 deficiency in 20 patients, and their profile was analyzed in detail. Twenty patients from 17 kindreds were diagnosed with DOCK8 deficiency. The female-to-male ratio was 1.2:1. The mean age at onset of symptoms and diagnosis was 9.8 and 69.8 months, respectively. Thirteen out of 17 families (76%) reported consanguinity. Eczema was the presenting manifestation in 19 patients (95%). Mucocutaneous manifestations included oromucosal hyperpigmentation (n = 8), scalp seborrhoea (n = 2), psoriasis (n = 2), and alopecia (n = 1). The spectrum of infections included pneumonia (n = 14), otitis media (n = 6), gastrointestinal infections (n = 6), cutaneous viral infections (n = 5), oral candidiasis (n = 4), and meningoencephalitis (n = 2). Three patients had developed bronchiectasis. Four patients had autoimmune manifestations including autoimmune hemolytic anemia (n = 2) and vasculitis (n = 2). The whole exome sequencing showed deletions (8 kindreds) as the most common mutation in the DOCK8 gene. Overall, 11 of these mutations were novel. Ten patients were on monthly intravenous immunoglobulin therapy and antibiotic prophylaxis at the time of writing this paper. Three patients underwent hematopoietic stem cell transplants elsewhere, two of whom succumbed to post-transplant complications and one is doing well. Nine patients died during the study period. We present one of the largest single-center experiences on DOCK8 deficiency from India. A significant delay in the diagnosis contributed to poor outcomes in our cohort.

Compassionate access to virus-specific T cells for adoptive immunotherapy over 15 years

Adoptive T-cell immunotherapy holds great promise for the treatment of viral complications in immunocompromised patients resistant to standard anti-viral strategies. We present a retrospective analysis of 78 patients from 19 hospitals across Australia and New Zealand, treated over the last 15 years with “off-the-shelf” allogeneic T cells directed to a combination of Epstein–Barr virus (EBV), cytomegalovirus (CMV), BK polyomavirus (BKV), John Cunningham virus (JCV) and/or adenovirus (AdV) under the Australian Therapeutic Goods Administration’s Special Access Scheme. Most patients had severe post-transplant viral complications, including drug-resistant end-organ CMV disease, BKV-associated haemorrhagic cystitis and EBV-driven post-transplant lymphoproliferative disorder. Adoptive immunotherapy is well tolerated with few adverse effects. Importantly, 46/71 (65%) patients show definitive clinical improvement including reduction in viral load, clinical symptoms and complete resolution of end-organ disease. In addition, seven high-risk patients remain disease free. Based on this long-term encouraging clinical experience, we propose that a dedicated nationally funded centre for anti-viral cellular therapies should be considered to provide T cell therapies for critically ill patients for compassionate use.

Enhancing lung transplantation with ECMO: a comprehensive review of mechanisms, outcomes, and future considerations.

Lung transplantation (LTx) is a critical intervention for patients with end-stage lung disease. However, challenges such as donor organ scarcity and post-transplant complications significantly affect its success. Recent advancements in Extracorporeal Membrane Oxygenation (ECMO) have shown promise in improving the outcomes and expanding eligibility for LTx. A comprehensive literature review was conducted, focusing on studies that explore the use of ECMO in lung transplantation. A thorough search of relevant studies on ECMO and LTx was conducted using multiple scholarly databases and relevant keywords, resulting in 73 studies that met the inclusion criteria. Sources included peer-reviewed journals and clinical trial results, with emphasis on articles captured recent advancements in ECMO technology and techniques. ECMO has been crucial in supporting patients before, during, and after LTx. It serves as a bridge to transplantation by maintaining pulmonary and circulatory stability in critically ill patients awaiting donor organs. ECMO also aids in the evaluation of marginal donor lungs and supports patients through acute post-transplant complications. Recent technological advancements have improved the safety and efficacy of ECMO, further solidifying its role in LTx. In conclusion, this review underscores ECMO's critical role in enhancing outcomes across all stages of lung transplantation. Its various configurations and strategies have shown promise in stabilizing critically ill patients and improving transplant success rates. Looking ahead, it's important to gather more information about the long-term outcomes and potential complications associated with ECMO use. More research and data collection will help us understand the benefits and risks better, leading to improved decision-making and patient care in this field.

Dual hypothermic oxygenated machine perfusion of the liver reduces post-transplant biliary complications: a retrospective cohort study.

Corroborating evidence for the use of hypothermic oxygenated machine perfusion (HOPE) prior to orthotopic liver transplantation (OLT) suggests a beneficial effect in regard to biliary complications. Here, the authors aim to evaluate whether perfusion via portal vein alone (sHOPE) or via additional perfusion of the hepatic artery (dHOPE) have diverging impact on outcomes after OLT when compared to the use of static cold storage (SCS). Consecutive patients undergoing OLT at the Medical University of Vienna (2018-2023) were retrospectively analyzed. Donor organs were procured using SCS, or subjected to end-ischemic sHOPE or dHOPE. The severity of biliary complications was classified according to the degree of therapeutic intervention (endoscopic retrograde cholangiopancreatography or surgical revision). Two hundred forty-seven patients were included (69 SCS, 76 sHOPE, and 102 dHOPE). Hospitalization was shorter for patients after HOPE (median in days: SCS=25 vs HOPE=20, P =0.019). Biliary complications were less frequent in patients after HOPE (SCS=37.7% vs HOPE=22.5%, P =0.015). A significantly lower incidence of surgical revisions for biliary complications was observed in the HOPE cohort (24.6% vs 11.8%, P =0.012). When evaluating outcome according to HOPE-modality, a significant reduction in biliary complications ( P =0.006) and surgical revisions ( P =0.002) was only observed in dHOPE patients in comparison to SCS. Further, only dHOPE was significantly associated with a reduced need for surgical revision for biliary complications upon univariable and multivariable logistic regression (odds ratio=0.336, P =0.011). HOPE leads to a reduction of biliary complications and associated surgical revisions. This effect seems to be primarily associated with use of dHOPE, while both methods appear as feasible options for preconditioning of donor grafts prior to OLT.

Severe Abdominal Complications in Lung Transplant Recipients.

Lung transplant is a complex procedure with potential for substantial postoperative complications, including abdominal issues. Although previous studies have suggested that preexisting gastrointestinal conditions may be associated with a high risk of posttransplant complications, the evidence remains inconsistent. We aimed to explore the incidence rates, risk factors, and outcomes of abdominal complications within the first year following lung transplant. We conducted a retrospective cohort study at the University Hospital Zurich of 68 lung transplant recipients who experienced abdominal complications within 1 year after transplant. Data were collected from medical records on baseline demographic and clinical characteristics, including pretransplant gastrointestinal and hepatobiliary diseases. We used descriptive statistics (Fisher exact test, chi-square test, and Cramer V test) to assess outcome details, such as the timing and type of abdominal complications, surgical interventions, and associations with pretransplant conditions. Abdominal complications occurred at a mean of 43 days posttransplant, with bowel ischemia and perforation as the most common reasons for posttransplant surgical intervention. Symptoms leading to surgery included nausea and abdominal pain, and 1 of 8 patients with abdominal surgery (12.5%) died after surgery. Notably, no significant associations were found between pretransplant factors (ie, gastrointestinal disease, hepatobiliary disease, body mass index >24, smoking status, peripheral vascular disease, and diabetes) and the occurrence of posttransplant abdominal surgery. Effect size analyses indicated very weak associations, suggesting that these pretransplant conditions are not strong predictors of postoperative abdominal complications. Our results showed that preexisting gastrointestinal and hepatobiliary conditions, along with other common pretransplant factors, were not significant predictors of abdominal complications following lung transplant. Future studies should focus on intraoperative and immediate postoperative factors and should explore the role of minimally invasive surgical techniques and potential benefits of earlier or more comprehensive pretransplant screening.

Modeling and simulation of dielectrophoretic sorting of tenogenically differentiating mesenchymal stem cells for high throughput

Mesenchymal stem cell (MSC)-based regenerative therapies are promising for healing tendon injuries and tears, due to their potential to differentiate into tenogenic cells. However, generating homogeneous populations of tenogenically differentiated stem cells remains a big challenge, as non-differentiated cells can lead to post-transplantation complications. Therefore, a homogenous sample of tenogenically differentiated MSCs is critical for advancing tendon therapies and avoiding uncontrolled cell growth or non-tendon tissue formation (e.g., ectopic bone). This work is focused on designing and simulating a dielectrophoretic (DEP)-based label-free, microfluidic platform to selectively sort and enrich tenogenically differentiated MSCs (tMSCs) from undifferentiated MSCs. Using particle tracing, creeping flow (transport of diluted species model), and electric current physics modules in the COMSOL Multiphysics simulation software package, the sorting was simulated within a two-stage microfluidic device operating at a sinusoidal frequency of 160 kHz. The optimal separation efficiency and purity are achieved at an inlet velocity of 400–1000 μm/s, with specific voltage configurations, enabling recovery of one million tMSCs in ∼3 h. Results demonstrate a near-linear relation between recovery time and particle count at the outlet boundaries and selected surfaces, indicating consistent throughput across varying conditions. This study demonstrates that DEP can offer a scalable, efficient, and label-free method for enriching tMSC populations with high selectivity, enhancing more prospects for MSC-based tendon therapies and advancing the development of microfluidic sorting devices for regenerative medicine applications.

Outcomes within 100 days of hematopoietic cell transplantation in pediatric patients: insights from an intensive care unit in Colombia.

Hematopoietic cell transplantation (HCT) has become an essential therapeutic modality for pediatric patients with malignant and non-malignant conditions. Despite its effectiveness, many patients experience post-transplant complications often leading into life-threatening conditions requiring specialized care in a Pediatric Intensive Care Unit (PICU). This study aims to describe clinical characteristics associated with mortality in pediatric HCT patients who needed PICU care within 100 days post-transplant in a resource-limited country. A retrospective cohort study was conducted involving pediatric HCT patients (<18 years old) admitted to our PICU from January 2012 to December 2021. Variables were characterized according to their nature, employing appropriate measures of central tendency and dispersion. The relationship between mortality and patient clinical characteristics was assessed using the Chi-square test or the Mann-Whitney U test, as applicable. A p-value of <0.05 was considered statistically significant. A Kaplan Meier survival curve was performed considering the days from HCT to death during PICU admission and a Cox regression analysis was conducted to analyze the association between PRISM III score and risk of death. Data analysis was executed utilizing the STATA SE v18 statistical software package. Of 316 HCTs, 69 patients required admission to the PICU. Haploidentical transplants from related donors were performed in 72.5% of these patients. The primary cause of PICU admission was infection, accounting for 68.1% (n = 47) of cases. Factors significantly associated with mortality included a PRISM III score > 20 (p < 0.002), mechanical ventilation (p < 0.007), renal replacement therapy (p < 0.002) and vasoactive support (p < 0.001). A total of 27 patients succumbed during their PICU stay. Kaplan Meier curve showed a survival rate of 51.6% at100-days post-transplant. A PRISM III score higher than 20 points was related with mortality (Hazard ratio 5.71 CI 95% 2.09-15.5). This study examines critical factors associated with mortality in pediatric HCT recipients who required admission to our PICU within the first 100 days post-transplant. Our findings indicate that infectious complications, alongside the need for advanced cardiovascular, respiratory, and renal support are strongly correlated with mortality. These results underscore the importance of early risk factor identification and targeted interventions to optimize patient outcomes.

Comparison of Two Myeloablative Total-Body Irradiation (MAC-TBI) Regimens: 1200 Cgy Vs 800 Cgy of TBI for Allogeneic Stem Cell Transplantation in Adults with Hematological Malignancies

Introduction: Total body irradiation (TBI) is a commonly used conditioning regimen for allogeneic hematopoietic cell transplantation (alloHSCT). TBI 1200 cGy (TBI1200) has been associated with short- and long-term toxicities, while TBI 800 cGy (TBI800) regimens have been primarily used for benign hematologic disorders. Comparisons of these approaches are lacking. Methods: We retrospectively reviewed 23 consecutive patients with hematologic malignancies undergoing their first allogeneic transplant receiving TBI-MAC between June 2016 and January 2024, of whom 12 (52%) received 800 cGy and 11 (48%) received 1200 cGy. We evaluated immediate (≤90 days post-transplant) and late (&amp;gt;90 days) complications as well as survival data. Post-transplant complications between TBI800 vs TBI1200 groups were compared using Fisher's exact test. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). The Fine-Gray model was used to correlate acute graft-versus-host disease (aGVHD) with clinical factors. Results: Twelve patients (52.2%) received fludarabine and TBI800, 9 patients (39.1%) received cyclophosphamide (Cy) and TBI1200, and 2 patients (8.7%) received fludarabine and TBI 1200 cGy. GVHD prophylaxis included: post-transplant Cy, mycophenolate mofetil, and tacrolimus in 5 patients (21.7%) and methotrexate and tacrolimus in 18 patients (78.3%). Palifermin was administered to 43.5% patients (25% in the TBI800 group vs 63.6% in the TBI1200 group, p=0.1). Donor sources included: matched-related donors (9, 39.1%), matched-unrelated donors (11, 47.8%), and haploidentical or mismatched-related donors (3, 13%). PBSC were used in 19 patients (82.6%) and bone marrow in 4 (17.4%). Diagnoses were AML (3, 13%), B-cell ALL (13, 56.5%), T-cell ALL (3, 13%), mixed phenotype leukemia (2, 8.7%), MPN (1, 4.4%), and NHL (1, 4.4%), p=0.51. There were similar baseline demographics between the two groups, except for remission status (TBI800 vs TBI1200 groups: CR1 41.7% vs 72.7%, CR2 and beyond 58.3% vs 9.1%, active disease 0 vs 18.2%, p=0.02, respectively). Among the patients in the TBI800 and TBI1200 groups, time to neutrophil and platelet engraftment (16 vs 14 days, p=0.38; and 20 vs 17 days, p=0.07), incidence of engraftment syndrome (8.3% vs 9.1%, p=1.0), use of total parenteral nutrition (0 vs 9.1%, p=0.48) and patient-controlled analgesia (16.7% vs 18.2%, p=1.0), and presence of full chimerism at D+30 (77.8% vs 70%, p=1.0) were similar. The need for intensive care unit admission (≤90 days) was also comparable (8.3% vs 9.1%, p=1.0). Except for grade 2 diarrhea (66.7% vs 18.2%, p=0.05), there was a similar incidence of immediate adverse events among the patients who received TBI800 vs TBI1200: grade 1 radiation dermatitis (0 vs 9.1%, p=0.48), grade 3 febrile neutropenia (66.7% vs 54.6%, p=0.68), grade 2 lung infection (8.3% vs 0, p=1.0), ≥ grade 3 mucositis (16.7% vs 36.4%,p=0.91), and grade 3 nausea (0 vs 9.1%, p=0.8). Rates of late adverse events were also comparable among the two groups, with similar incidence of grade 2 cataracts (25% vs 0, p=0.22), grade 1 osteoporosis (8.3% vs 0, p=1.0), grade 2 hyperlipidemia (0 vs 9.1%, p=0.48), grade 3 hyperglycemia (8.3% vs 0, p=1.0), and grade 3 LVEF dysfunction (8.3% vs 9.1%, p=1.0). Despite the TBI800 group having more patients with advanced disease (CR2 and beyond), survival outcomes were comparable. After a median follow-up of 22.2 months (range, 3.3 - 94.3 months), the 1-yr OS, PFS, and CIR for TBI800 vs TBI1200 were: 91.7% vs 77.9%, p=0.67; 81.5% vs 80.8%, p=0.48; 18.5% vs 19.2%, p=0.78, respectively. Day +100 mortality was comparable at 8.3% vs. 9.1%, p=1.0. Only one case of NRM was reported in the TBI800 group (related to infection with COVID-19), and none in the TBI1200 group. The Multivariable Fine-Gray Model showed a higher risk of aGVHD, particularly grade I-II, in the TBI1200 group (HR 6.66, 95% CI: 2.07-21.38). Conclusion: TBI800 vs TBI1200 led to similar relapse incidence, with a lower risk of aGVHD and decreased grade 3-4 mucositis rate in the TBI800 group. Studies on a larger scale are required to establish the safety and efficacy of TBI800.

Immune Reconstitution after Allogenic Stem Cell Transplantation in Patients with Myelofibrosis

Background Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the only curative treatment for patients (pts) diagnosed with myelofibrosis (MF). Despite several improvements over time, post-transplant complications can still be severe and significantly affect pts' survival. Inflammation and bone marrow fibrosis may hinder immune reconstitution (IR) in MF pts, but there is limited data available. This study aimed to evaluate IR in MF pts undergoing alloHSCT and its impact on their outcomes. Methods We retrospectively evaluated IR in MF pts who underwent alloHSCT at the Bone Marrow Transplantation Unit of Spedali Civili di Brescia between April 2017 and April 2024. Absolute lymphocyte counts (ALC) and lymphocyte subtypes were assessed at +3, +6, +9, +12, +18, and +24 months (M) post-transplant. IR was evaluated by flow cytometry using fresh whole blood samples. Monoclonal antibodies were employed to evaluate main lymphocyte populations, CD4/CD8 ratios, and T-cell subset (CD45RA; CD45RO). Lymphocyte recovery was defined as ALC &amp;gt;500/uL at M+3, and ALC &amp;gt;750/uL from M+6 onward. The recovery of subtypes CD3+CD4+, CD3+CD8+ and CD19+ was classified as absolute counts &amp;gt;200/uL. Results Since April 2017, 33 MF pts were transplanted at our Institution. The median age was 60.7 years (range 44-71), with 76% (25) being male. Seventeen out of 29 evaluable pts (59%) had an unfavorable karyotype. Twenty-four pts were JAK2 mutated, while 8 were CALR+ and 1 MPL+. Overall, 13 on 28 evaluable pts harbored a high molecular risk mutation. Five pts had DIPSS intermediate-1, 20 pts had intermediate-2, and 8 had high risk. Twenty-eight pts received JAK2 inhibitor before alloHSCT. Regarding transplant features, 16 pts received a myeloablative conditioning, and 27 received double-alkylators regimens (Thiothepa-Busulfan-Fludarabine). Donors were sibling, unrelated or haploidentical in 18.2%, 48.5% and 33.3% of cases, respectively. HCT-CI was high in 15 pts. Almost all pts (85%) received peripheral blood stem cell grafts. In haploidentical alloHSCT, pts received post-transplant cyclophosphamide, while the other pts received GvHD prophylaxis with cyclosporine and methotrexate (or mycophenolate); 21 pts received rabbit antithymocyte globulin (ATG). After a median follow-up of 15.9 months (IQ 8-43), 12 pts had died (5 relapse, 4 infections, 3 acute GVHD) for a 5-year CIR, NRM and OS of 27.2% (95%CI 10.8-46.7), 19% (95%CI 7.5-34.6) and 54.3% (95%CI 28.5-74.4), respectively. Serial ALC assessments showed a gradual increase from M+3 to M+18. Median counts reached 426/uL (115-1758) at M+3, 587/uL (254-2794) at M+6, 891/uL (148-3181) at M+9, and 1643/uL (438-4978) at M+18, representing 41%, 42%, 53% and 83% of recovered pts, respectively. Similarly, CD4+ recovery improved over time, with median CD4+ counts surpassing 200/uL only at M+9. CD4+ reconstitution at M+3 varied significatively according to donor type: haploidentical alloHSCT had a median of 104/uL, whereas sibling and MUD transplants were 171/uL and 142/uL, respectively (p 0.01). ATG treatment was not related to CD4+ reconstitution. CD4+CD45RA+ cells, more likely naïve cells, significatively increase at each time point, peaking at 37.7/uL at M+18. Conversely, CD3-CD56+/CD16+ NK cells significatively decreased from M+3 to M+24. Pts not reconstituting CD4+ and ALC at M+9 were associated with a higher relapse rate (p 0.05) and showed a trend towards worse overall survival. At M+24, the cumulative incidence of relapse was 33% in pts with less than 200 CD4+/uL at M+9, compared to 0% in those with recovered CD4+ counts (p 0.05). Similarly, pts not recovering ALC at M+9 had relapse CI of 40% at M+24, compared to 0% in those with recovered ALC. ALC and CD4+ recovery at M+9 also impacted the maintenance of chimerism (p 0.05). CD4+ recovery at M+3 and M+6 was associated with a trend towards fewer infections. Additionally, not achieving CD4+ recovery at M+3 was linked to a higher risk of chronic GVHD. Conclusion MF pts exhibit slow immune reconstitution after alloHSCT, with median CD4+ count exceeding 200/uL only after 9 months, and CD4CD45RA+ counts peaking at 18 months. ALC and CD4+ recovery at 9 months is associated with lower late-relapse rates and lower chimerism loss. Despite being influenced by various factors (e.g., donor type), IR after alloHSCT in MF pts can be a valuable tool for assessing the risk of infections, GVHD development, and relapse.

Impact of Systemic Antibiotics Use on Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: Post-transplant complications lead to significant morbidity and mortality in the management of patients undergoing allogeneic hematopoietic stem cell transplant (allo-HCT). Broad-spectrum systemic antimicrobials and better prophylaxis strategies have reduced infection-related morbidity and mortality in allo-HCT patients. However, broad-spectrum antibiotic use disrupts the microbiome and immunome, which may result in poor post-transplant outcomes. We aimed to evaluate the impact of systemic antibiotics on allo-HCT outcomes. Methods: A retrospective multicenter analysis was conducted, including allo-HCT patients in the publicly available Center for International Blood and Marrow Transplant (CIBMTR) registry from 2013 to 2018 using P5646 data by Ramathan et al. Chi-square and t-tests were used to compare categorical and continuous baseline demographics. Multivariate Cox regression analyses were used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for overall survival (OS), disease-free survival (DFS), relapse, non-relapse mortality (NRM), acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD), engraftment, and infection-related mortality between the two groups. Statistical analysis was conducted using R version 4.16, with statistical significance defined as p &amp;lt;0.05. Results: Among 7524 allo-HCT patients, 5779 were administered broad-spectrum systemic antibiotics (SA) while 1745 were not given systemic antibiotics (NSA). The median age was 58.58 years (range: 2.03-82.67) in the SA group and 56.18 years (range: 2.00 - 77.86) in the NSA group, and 58% were men in both groups. Ethnicities were Caucasian (76%), Hispanic (8%), African American (6%), and others (10%). The primary disorders included acute myeloid leukemia (47%), myelodysplastic syndrome (35%), and acute lymphoblastic leukemia (18%). Myeloablative conditioning was used in 53% of patients. Donor types were matched unrelated (49.5%), matched related (34%), and cord blood (16%). Graft sources were bone marrow (15%), peripheral blood stem cells (68%), and cord blood (16%). GVHD prophylaxis regimens included Tacrolimus and Cyclosporine-based (77%), post-transplant Cyclophosphamide-based (9%), Ex vivo T-cell depletion or CD34 selection (3%), and others (11%). In the multivariate regression analyses, systemic antibiotics independently predicted poor OS (55% SA vs 57% NSA; HR 1.13, 95% CI 1.01-1.22, p=0.026). Higher incidence of NRM (19% SA vs 15% NSA; HR 1.32, 95% CI 1.12-1.55, p=0.001), grade 2-4 aGVHD (41% SA vs 34% NSA; HR 1.24, 95% CI 1.12-1.38, p&amp;lt;0.001), and cGVHD (40% SA vs 39% NSA; HR 1.12, 95% CI 1.01-1.24, p=0.040) were observed with SA use. The two groups had no significant difference in DFS, relapse, infection-related mortality, and engraftment rates. The outcomes analyses were adjusted for the significant predictors identified in the univariate analyses. Conclusion: Systemic antibiotics use in allo-HCT patients is associated with higher morbidity and mortality. Judicious use and de-escalation of systemic antibiotics when safe may help to improve post-transplant outcomes. Future research exploring microbiome restoration could result in better post-transplant outcomes.

Prognostic Factors Affecting Day+100 Survival in Patients Undergoing Allogeneic Haematopoietic Stem Cell Transplantation for Acute Leukaemia - A Single Centre Experience.

To determine the factors affecting the first 100 days of survival in acute leukaemia patients undergoing allogeneic haematopoietic stem cell transplantation (Allo-HSCT). Descriptive study. Place and Duration of the Study: Bone Marrow Transplant Centre, Rawalpindi, Pakistan, from March 2016 to February 2022. Patients with acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL) in complete remission (CR) undergoing Allo-HSCT were included. Data were collected on patient demographics, diagnosis, remission status, pre-transplant analysis, donor compatibility, conditioning regimen, GVHD prophylaxis, engraftment times, post-transplant complications, mortality causes, and overall survival (OS) at 100 days. Among 101 transplant recipients (mean age of 24 ± 11.05 years; n = 76 males, n = 25 females), 41 had AML and 60 had ALL. Ninety patients underwent matched sibling donor (MSD)-HSCT, while 11 had haplo-identical sibling-HSCT. Patients ≤13 years had higher survival rates than older patients (94.4% vs. 67.5%, p = 0.03). High pre-transplant serum ferritin levels (>2500 mg/dl) predicted lower OS (48.9% vs. 100% in ferritin <1000 mg/dl, p <0.01). AML patients had a survival advantage over ALL patients (82.9% vs. 65%, p = 0.05). Early neutrophil engraftment within 14 days correlated with better survival (96.4% vs. 54.3%, p <0.01). Lastly, severe mucositis also adversely affected survival (60% in Grade III vs. 9.5% in Grade IV, p <0.01). Identifying modifiable factors can improve long-term support and follow-up, enhancing the patient outcomes in underdeveloped nations. Haematopoietic stem cell transplant, Day + 100 survival, Acute leukaemia, Pakistan.

Prognostic Factors Affecting Day+100 Survival in Patients Undergoing Allogeneic Haematopoietic Stem Cell Transplantation for Acute Leukaemia - A Single Centre Experience.

To determine the factors affecting the first 100 days of survival in acute leukaemia patients undergoing allogeneic haematopoietic stem cell transplantation (Allo-HSCT). Descriptive study. Place and Duration of the Study: Bone Marrow Transplant Centre, Rawalpindi, Pakistan, from March 2016 to February 2022. Patients with acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL) in complete remission (CR) undergoing Allo-HSCT were included. Data were collected on patient demographics, diagnosis, remission status, pre-transplant analysis, donor compatibility, conditioning regimen, GVHD prophylaxis, engraftment times, post-transplant complications, mortality causes, and overall survival (OS) at 100 days. Among 101 transplant recipients (mean age of 24 ± 11.05 years; n = 76 males, n = 25 females), 41 had AML and 60 had ALL. Ninety patients underwent matched sibling donor (MSD)-HSCT, while 11 had haplo-identical sibling-HSCT. Patients ≤13 years had higher survival rates than older patients (94.4% vs. 67.5%, p = 0.03). High pre-transplant serum ferritin levels (>2500 mg/dl) predicted lower OS (48.9% vs. 100% in ferritin <1000 mg/dl, p <0.01). AML patients had a survival advantage over ALL patients (82.9% vs. 65%, p = 0.05). Early neutrophil engraftment within 14 days correlated with better survival (96.4% vs. 54.3%, p <0.01). Lastly, severe mucositis also adversely affected survival (60% in Grade III vs. 9.5% in Grade IV, p <0.01). Identifying modifiable factors can improve long-term support and follow-up, enhancing the patient outcomes in underdeveloped nations. Haematopoietic stem cell transplant, Day + 100 survival, Acute leukaemia, Pakistan.