Transplant-associated Complications Research Articles

Sintilimab treatment for chronic active Epstein–Barr virus infection and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in children

BackgroundChronic active Epstein–Barr virus infection (CAEBV) and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) are rare but life-threatening progressive diseases triggered by EBV infection. Glucocorticoid/immunosuppressants treatment is temporarily effective; however, most patients relapse and/or progress. Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy; however, there are risks of transplantation-associated complications. Currently there is no standard treatment for CAEBV and EBV-HLH. Programmed death protein 1 (PD-1) inhibitors have achieved a high response in many EBV-related diseases. Sintilimab (a recombinant human IgG4 monoclonal antibody against PD-1) disrupts the interaction between PD-1 and its ligand, leading to T cell reinvigoration.MethodsA retrospective analysis was performed on three children with CAEBV or EBV-HLH in the Children’s Hospital of Soochow University between 12 December 2020 and 28 November 2022. The efficacy of sintilimab was evaluated.ResultsThree patients, including two males and one female, were analyzed. Among them, two children were diagnosed with CAEBV with intermittent fever for more than four years, and one child was diagnosed with EBV-HLH. After sintilimab treatment and a mean follow-up of 17.1 months (range 10.0–23.3 months), patients 1 and 3 achieved a complete clinical response and patient 2 achieved a partial clinical response. All three children showed a > 50% decrease in EBV-DNA load in both blood and plasma. EBV-DNA copies in sorted T, B, and NK cells were also markedly decreased after sintilimab treatment.ConclusionOur data supported the efficacy of PD-1 targeted therapy in certain patients with CAEBV and EBV-HLH, and suggested that sintilimab could provide a cure for these diseases, without HSCT. More prospective studies and longer follow-up are needed to confirm these conclusions.

Indications and Outcomes of Patients Receiving Therapeutic Plasma Exchange under Critical Care Conditions: A Retrospective Eleven-Year Single-Center Study at a Tertiary Care Center.

Background: Therapeutic plasma exchange (TPE) is frequently performed in critical care settings for heterogenous indications. However, specific intensive care unit (ICU) data regarding TPE indications, patient characteristics and technical details are sparse. Methods: We performed a retrospective, single-center study using data from January 2010 until August 2021 for patients treated with TPE in an ICU setting at the University Hospital Zurich. Data collected included patient characteristics and outcomes, ICU-specific parameters, as well as apheresis-specific technical parameters and complications. Results: We identified n = 105 patients receiving n = 408 TPEs for n = 24 indications during the study period. The most common was thrombotic microangiopathies (TMA) (38%), transplant-associated complications (16.3%) and vasculitis (14%). One-third of indications (35.2%) could not be classified according to ASFA. Anaphylaxis was the most common TPE-related complication (6.7%), while bleeding complications were rare (1%). The median duration of ICU stay was 8 ± 14 days. Ventilator support, renal replacement therapy or vasopressors were required in 59 (56.2%), 26 (24.8%), and 35 (33.3%) patients, respectively, and 6 (5.7%) patients required extracorporeal membrane oxygenation. The overall hospital survival rate was 88.6%. Conclusion: Our study provides valuable real-world data on heterogenous TPE indications for patients in the ICU setting, potentially supporting decision-making.

Trends and in-hospital cardiac complications in patients with atrial fibrillation undergoing allogeneic stem cell transplant: A National Inpatient Sample analysis (2002-2019).

Cardiovascular comorbidities increase the risk of transplant-associated complications. However, the impact of atrial fibrillation (AF) as an independent risk factor remains limited. The National Inpatient Sample (NIS) database was queried using the International Classification of Diseases codes to identify patients admitted for allogeneic stem cell transplant (ASCT). The patients were then subclassified into with and without AF. Subsequently, a multivariate logistic regression model was constructed to account for patient demographics, comorbidities, and hospital characteristics to evaluate the impact of AF on the primary outcome of interest: all-cause mortality, and secondary outcomes of interest that included common hospitalization complications. The data for 77 157 cases of ASCT were collected between 2002 and 2019. Among these 5086 (6.6%) cases had concurrent AF. Multivariate logistic regression revealed patients undergoing ASCT with AF had almost a three times higher risk of all-cause mortality (odds ratio = 2.99 [95% confidence interval: 2.73-3.28]; p < .01). AF patients also had a higher risk for cardiac arrest, cardiogenic shock, acute kidney injury, and need for hemodialysis (all p < .01). AF causes a higher risk of death and cardiovascular complications among patients undergoing ASCT. This signifies the importance of pretransplant consultation and optimization for cardiovascular comorbidities to improve hospitalization outcomes.

Sonography of Renal Transplant-Associated Complications: A Primer

The advent of renal transplantation has significantly improved the quality of life and mortality of patients with end-stage renal disease. Unfortunately, transplant-associated complications (TACs) are common and pose a significant risk to both the allograft and the patient. A major advancement in the care of transplant recipients is the implementation of renal ultrasound, which allows for a more detailed assessment of the renal allograft and facilitates the distinction of different TAC manifestations such as perinephric fluid collections, vascular disease, and parenchymal disease. A better understanding of the clinical and sonographic features of TACs will help guide TAC management and promote better outcomes for renal transplant recipients.

Sonography of Renal Transplant-Associated Complications: A Primer

Contemporary Diagnostic Radiology 45(24):p 7-8, November 30, 2022. | DOI: 10.1097/01.CDR.0000897428.66301.09

Pretransplant Systemic Lipidomic Profiles in Allogeneic Stem Cell Transplant Recipients

Simple SummaryStem cell transplantation is used in the treatment of aggressive hematological malignancies and consists of initial high-dose and potentially lethal chemotherapy, followed by rescue with the transplantation of hematopoietic stem cells. Transplantation with stem cells from a healthy donor (i.e., allogeneic stem cells) has the strongest anti-cancer effect, but also the highest risk of severe toxicity. Furthermore, the clinical status at the time of transplantation (inflammation, fluid overload) is associated with posttransplant mortality, and immune-mediated acute graft-versus-host disease (GVHD) is a potential lethal complication. Finally, lipid metabolism regulates the proliferation and survival of both malignant hematological cells and immunocompetent cells that cause GVHD. Our study shows that the pretransplant lipid profiles differ between allotransplant recipients and can be used for the subclassification of patients and possibly to identify patients with an increased risk of death due to disease relapse or treatment toxicity. The therapeutic targeting of lipid metabolism should therefore be further explored in these transplant recipients.Allogeneic stem cell transplantation is used in the treatment of high-risk hematological malignancies. However, this treatment is associated with severe treatment-related morbidity and mortality. The metabolic status of the recipient may be associated with the risk of development of transplant-associated complications such as graft-versus-host disease (GVHD). To better understand the impact of the lipidomic profile of transplant recipients on posttransplant complications, we evaluated the lipid signatures of patients with hematological disease using non-targeted lipidomics. In the present study, we studied pretransplant serum samples derived from 92 consecutive patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). A total of 960 lipid biochemicals were identified, and the pretransplant lipidomic profiles differed significantly when comparing patients with and without the risk factors: (i) pretransplant inflammation, (ii) early fluid overload, and (iii) patients with and without later steroid-requiring acute GVHD. All three factors, but especially patients with pretransplant inflammation, were associated with decreased levels of several lipid metabolites. Based on the overall concentrations of various lipid subclasses, we identified a patient subset characterized by low lipid levels, increased frequency of MDS patients, signs of inflammation, decreased body mass index, and an increased risk of early non-relapse mortality. Metabolic targeting has been proposed as a possible therapeutic strategy in allotransplant recipients, and our present results suggest that the clinical consequences of therapeutic intervention (e.g., nutritional support) will also differ between patients and depend on the metabolic context.

Risk and Predictive Factors for Candidemia After Allogeneic Hematopoietic Cell Transplantation: JSTCT Transplant Complications Working Group

Although antifungal prophylaxis that covers Candida species is a standard of care in allogeneic hematopoietic cell transplantation (HCT), candidemia mainly caused by non-albicans Candida species still occurs and is associated with a high mortality rate. This study aimed to evaluate the risk factors for candidemia after allogeneic HCT. Particularly, we evaluated the impact of patient factors such as hematopoietic cell transplantation–specific comorbidity index (HCT-CI) and performance status (PS) in addition to well-recognized risk factors including donor type, delayed engraftment, and graft-versus-host disease (GVHD). By using data from a Japanese transplant registry database, we analyzed 26,236 pediatric and adult patients with hematological malignancies who underwent their first allogeneic HCT. The posttransplant period was divided into early (days 0-40), late (days 41-100) and very late (days 101-365) phases. The 1-year cumulative incidence of candidemia was 1.8%. When we analyzed pretransplantation factors, age ≥40 years (hazard ratio [HR] 1.85), male (HR 1.34), HCT-CI (HCT-CI 1-2, HR 1.56; HCT-CI ≥ 3, HR 2.21), PS ≥ 2 (HR 2.01), high-risk disease (HR 1.78) and donor type including HLA-mismatched related donor (MMRD) (HR 1.96), HLA-mismatched unrelated donor (HR 2.05), and cord blood (CB) (HR 2.85) were significantly associated with an increased incidence of candidemia. Focusing on the early phase (days 0-40), HCT-CI, PS, high-risk disease and CB transplantation together with engraftment and severe acute GVHD significantly affected the development of candidemia. In the late phase (days 41-100), higher HCT-CI, male, and donor type including MMRD, and CB were associated with the occurrence of candidemia together with acute GVHD and disease relapse. In the very late phase (days 101-365), HCT-CI ≥ 3 and high-risk disease significantly affected the occurrence of candidemia together with acute and chronic GVHD, and disease relapse. In addition to well-recognized risk factors including donor type, engraftment and GVHD, patient factors such as HCT-CI and PS were associated with the development of candidemia, which suggests that severely ill patients with transplantation-associated complications are more likely to develop candidemia.

Graft-Versus-Host Disease Prophylaxis with Posttransplantation Cyclophosphamide and Ruxolitinib in Patients with Myelofibrosis

Introduction. Allogeneic stem cell transplantation (alloHSCT) is currently the only treatment modality with curative potential in patients with myelofibrosis (MF), although transplant-associated complications and relapses significantly reduce the application of this method. JAK1/JAK2 inhibitor ruxolitinib is effective in reducing symptomatic splenomegaly and myelofibrosis-related symptoms. At the same time it has significant immunomodulatory effect and is used for the treatment of steroid-refractory acute and chronic graft-versus-host disease (GVHD). This study evaluated calcineurin inhibitor free GVHD prophylaxis regimen with ruxolitinib in combination with posttransplant cyclophosphamide (PTCy).Patients and methods. Pilot prospective study (NCT02806375) so far enrolled 13 patients with primary or secondary MF. One patient had post-essential thrombocythemia MF, 3 -post-polycythemia vera MF, 9 - primary MF. 11 patients had intermediate-2 risk and 2 had high risk according to DIPSSplus. Median age was 50 years (range 32-64). Nine patients were JAK2V617F positive, 1 patient MPL -positive, 2 patients CALR -positive before alloHSCT. 5 patients had pre-transplant splenectomy. Reduced intensity conditioning was performed with fludarabine 180 mg/m2 and busulfan 10 mg/kg (N Kröger et al., 2009). GVHD prophylaxis included PTCy 50 mg/kg at day +3, +4 and ruxolitinib 45 mg/day at days -7 to -2, and 15 mg/day at days +5 to +100. 4 patients were grafted from matched related donor, 6 from 10/10-matched unrelated donor, 1 from 9/10 matched unrelated donor and 2 from haploidentical donor. Peripheral blood stem cells were used as a graft source in 12/13 patients.Results. Median folow-up was 192 days (range 49-676). Engraftment was documented in all patients. Median time to neutrophil engraftment was 25 days (range 16-57 days), to platelet engraftment - 42 days (15-345). In two cases stem cell “boost” was administered due to poor graft function. Dose reduction of ruxolitinib to 10 mg/day due to poor graft function was performed in all but two patients. 12/13 are alive and with full donor chimerism. One died of Pseudomonas aeruginosa sepsis. In 5 patients near complete bone marrow fibrosis resolution (grade 1-0) was observed. No hematologic relapses of MF were documented.Two patients developed grade III acute GVHD and one grade II acute GVHD. 4/13 patients developed chronic GVHD, in two cases it was classified as moderate (NIH). In all but one patient, who required systemic steroids, GVHD was successfully treated with cyclosporine A.The regimen was well tolerated. Grade 3-4 toxicities included only toxic hepatitis in 3 and sepsis in 3 patients. Mild veno-occlusive disease was observed in one patient. Viral reactivations were relatively frequent, including CMV in 62%, HSV type 1,2 in 100%, HSV type 6 in 8% and BK virus in 23% of patients. Moderate hemorrhagic cystitis developed in 2 patients.Conclusion. GVHD prophylaxis with combination of PTCy and ruxolitinib is associated with good acute and chronic GVHD control and seems promising modality at least for MF patients. Further recruitment of patients and longer follow-up is required to draw more solid conclusions. DisclosuresNo relevant conflicts of interest to declare.

Potential Benefit of Soluble Thrombomodulin in Coping with COVID-19/SARS-CoV-2-Induced Coagulopathy

Researchers should investigate the coagulopathy that accompanies Coronavirus Disease 2019 (COVID-19), as the incidence, as well as the mortality associated with coagulopathy, is higher than expected in COVID-19 patients. We read with interest the article published by Tang N et al. suggesting that elevated plasma levels of the fibrin degradation product D-dimer might be a predictive marker for mortality of patients with COVID-19 [1]. The same authors also reported that the use of heparin improved the prognosis of COVID-19 patients with severe coagulopathy and D-dimer levels &gt;6-fold of the normal upper limit [2]. The high plasma levels of D-dimer suggest that the fibrinolytic system is not inhibited; nonetheless, thrombotic events are frequently noted in COVID-19 patients transferred to intensive care units [3]. Curiously, severe cases of COVID-19 are complicated by cytokine release syndrome in conjunction with Hemophagocytic Lymphohistiocytosis (HLH) [4], suggesting that extremely exaggerated hypercoagulability is induced in COVID-19. The pathophysiology of COVID-19-induced coagulopathy has not been fully elucidated. However, recently, postmortem examination of patients with COVID-19 who died of respiratory failure found thrombi in parallel with the deposition of the C5b-9 complex in the microvasculature, indicating terminal complement activation [5]. These pathological findings are reminiscent of the pathogenesis of Transplant-Associated Thrombotic Microangiopathy (TA-TMA) and atypical Hemolytic Uremic Syndrome (aHUS), in which activation of the complement system plays a role. Other possible factors involved in the pathogenesis of COVID-19-induced coagulopathy may be related to the tropism of Severe Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the pathogen that causes COVID-19, to vascular endothelial cells [6]. SARS-CoV-2 infects vascular endothelial cells via the Angiotensin-Converting Enzyme 2 (ACE2) receptor, leading to vascular derangement, so-called endotheliitis, which may result in coagulopathy and TMA. Thrombomodulin (TM) is a cell-surface expressed glycoprotein comprising six distinct domains, including an NH2-terminal lectinlike region, six tandem Epidermal Growth Factor (EGF)-like structures, an O-glycosylation site-rich domain, a transmembrane domain, and a cytoplasmic tail domain [7]. TM binds to thrombin via its EGF-like region and Converts Protein C (PC) to Activated PC (APC), which inhibits coagulant factors FVIIIa and FVa in the presence of protein S, thereby inhibiting further thrombin generation. Interestingly, TM has an anti-inflammatory effect; the lectin-like domain of TM binds and degrades High Mobility Group Box-1 (HMGB1) and attenuates inflammation. Additionally, after interacting with thrombin, TM converts carboxypeptidase Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) to activated TAFI (TAFIa), which inactivates C3 and C5. Furthermore, the fifth domain of EGF-like region of TM (TME5) interacts with the cell-surface chemokine receptor G protein-coupled receptor protein 15 (GPR15) and then exerts cytoprotective effects on vascular endothelial cells in association with upregulation of antiapoptotic MCl-1 proteins, which is mediated by the activation of extracellular signal-regulated kinase [7]. Recombinant human soluble TM (rhTM) comprises extracellular domains of TM. A clinical trial comparing the efficacy and safety of rhTM with Unfractionated Heparin (UFH) in patients with Intravascular Coagulation (DIC) caused by hematological malignancies or infection found that a greater number of patients treated with rhTM recovered from DIC with acceptable toxicity profiles than those who received UFH. Based on these results, the use of rhTM has been approved for the treatment of DIC in Japan since 2008. The use of rhTM effectively treated many patients with DIC with various types of underlying diseases, including transplant-associated complications such as TA-TMA, hepatic sinusoidal obstruction syndrome/veno-occlusive disease and engraftment syndrome [8]. Importantly, endothliitis plays a role in the development of all of these conditions, suggesting the possible cytoprotective roles of rhTM in vascular endothelial cells. Moreover, prompt improvement of DIC caused by HLH developed in association with immune reconstitution syndrome after initiation of highly active antiretroviral therapy for acquired immunodeficiency syndrome was noted in the individual who received rhTM [9]. Thus, the use of anticoagulant rhTM with additional activities for immune systems and vascular endothelial cells could counteract severe COVID-19 with coagulopathy, although a systematic review and meta-analysis of rhTM therapy for sepsis-induced coagulopathy failed to prove the significant improvement of clinical outcomes of patients with sepsis-induced coagulopathy [10].

Potential of ultrasound in allogeneic stem cell transplantation andtransplant-related complications

Allogeneic hematopoietic stem cell transplantation (HCT) is a complex therapeutic procedure causing significant morbidity and mortality, including the gastrointestinal tract. Early diagnosis and treatment of HCT-associated complications are, therefore, of utmost importance to improve overall HCT outcome. Sonography can be a powerful diagnostic tool and is easily accessible at the bedside of HCT patients. In the hands of a sonography-experienced physician, it allows for instant diagnosis and can also rule out several important transplant-associated complications. Here we review available evidence on the diagnostic and clinical value of ultrasound prior, during and after HCT.

The clinical role of the gut microbiome and fecal microbiota transplantation in allogeneic stem cell transplantation.

Outcomes of allogeneic hematopoietic stem cell transplantation (allo- HSCT) have improved in the recent decade; however, infections and graft-versus-host disease remain two leading complications significantly contributing to early transplant-related mortality. In past years, the human intestinal microbial composition (microbiota) has been found to be associated with various disease states, including cancer, response to cancer immunotherapy and to modulate the gut innate and adaptive immune response. In the setting of allo-HSCT, the intestinal microbiota diversity and composition appear to have an impact on infection risk, mortality and overall survival. Microbial metabolites have been shown to contribute to the health and integrity of intestinal epithelial cells during inflammation, thus mitigating graft-versus-host disease in animal models. While the cause-andeffect relationship between the intestinal microbiota and transplant-associated complications has not yet been fully elucidated, the above findings have already resulted in the implementation of various interventions aiming to restore the intestinal microbiota diversity and composition. Among others, these interventions include the administration of fecal microbiota transplantation. The present review, based on published data, is intended to define the role of the latter approach in the setting of allo-HSCT.

The gut microbiome in solid organ transplantation.

Despite ground-breaking advances in allogeneic transplantation, allograft rejection and immunosuppressant-specific complications remain a major challenge in transplant medicine. Growing evidence suggests the human gut microbiome as a potential contributor to transplant outcome and patient health. After breakthrough findings in haematopoietic stem cell transplantation (HSCT), the relevance of the microbiome in solid organ transplantation (SOT) is becoming increasingly clear. Here, we review the role of the microbiome in SOT focusing on its significance for transplant-associated complications such as allograft rejection and infections, and highlight its potential impact on immunosuppressive treatment. Moreover, we shed light on the emerging role of the microbiome as a diagnostic biomarker and therapeutic target and discuss current microbial intervention strategies. In addition, this review includes some practical considerations in designing clinical microbiome trials and offers some advice for the interpretation of the resulting data. Further investigation of the gut microbiome harbours countless clinical application possibilities and holds great promise of having a lasting impact on transplant medicine.

A Preliminary Investigation towards the Risk Stratification of Allogeneic Stem Cell Recipients with Respect to the Potential for Development of GVHD via Their Pre-Transplant Plasma Lipid and Metabolic Signature.

The clinical outcome of allogeneic hematopoietic stem cell transplantation (SCT) may be influenced by the metabolic status of the recipient following conditioning, which in turn may enable risk stratification with respect to the development of transplant-associated complications such as graft vs. host disease (GVHD). To better understand the impact of the metabolic profile of transplant recipients on post-transplant alloreactivity, we investigated the metabolic signature of 14 patients undergoing myeloablative conditioning followed by either human leukocyte antigen (HLA)-matched related or unrelated donor SCT, or autologous SCT. Blood samples were taken following conditioning and prior to transplant on day 0 and the plasma was comprehensively characterized with respect to its lipidome and metabolome via liquid chromatography/mass spectrometry (LCMS) and gas chromatography/mass spectrometry (GCMS). A pro-inflammatory metabolic profile was observed in patients who eventually developed GVHD. Five potential pre-transplant biomarkers, 2-aminobutyric acid, 1-monopalmitin, diacylglycerols (DG 38:5, DG 38:6), and fatty acid FA 20:1 demonstrated high sensitivity and specificity towards predicting post-transplant GVHD. The resulting predictive model demonstrated an estimated predictive accuracy of risk stratification of 100%, with area under the curve of the ROC of 0.995. The likelihood ratio of 1-monopalmitin (infinity), DG 38:5 (6.0), and DG 38:6 (6.0) also demonstrated that a patient with a positive test result for these biomarkers following conditioning and prior to transplant will be at risk of developing GVHD. Collectively, the data suggest the possibility that pre-transplant metabolic signature may be used for risk stratification of SCT recipients with respect to development of alloreactivity.

PF775 MONOSOMY 7 ALONE OR WITH OTHER CHROMOSOMAL ABNORMALITIES SIGNIFICANTLY AFFECT SURVIVAL OF SECONDARY AML PATIENTS TREATED WITH ALLOGENEIC- SCT

Background: T-cell replete Haploidentical stem cell transplantation (Haplo-SCT) with high dose post-transplant cyclophosphamide (PT-Cy) is being increasingly used for patients when a HLA identical sibling or a matched related donor is not available. With regard to inborn errors of metabolism (IEM) or primary immunodeficiency which need a hematopoietic stem cell transplantation (HSCT) for cure, haplo-SCT could be an alternative option. However, there is insufficient data on the efficiency and safety of the procedure of haplo-SCT with PT-Cy in patients with nonmalignant genetic diseases. Aims: The aim of the present study is to evaluate the feasibility and safety of haplo-SCT with PT-Cy in patients with nonmalignant genetic diseases compared with HLA matched donor transplantation. Methods: We retrospectively analyzed 16 patients (Haplo group) receiving Haplo-SCT with PT-Cy from peripheral blood graft source, and 20 patients (Matched group) receiving HSCT from related matched (n = 4), unrelated 9–10/10 matched donors (n = 16) between Jan 2014 and Feb 2018 at Seoul National University Children's Hospital. Three chronic granulomatous disease (CGD), 5 adrenoleukodystrophy (ALD), 4 Krabbe disease, and 4 others were included in Haplo group, whereas 11 CGD, 1 ALD, 1 Krabbe disease, 3 congenital neutropenia, and 4 other diseases in Matched group. We used an intensive daily pharmacokinetic monitoring method for busulfan dosing for effective myeloablation and to reduce toxicity. The total target area under the curve (AUC) of busulfan was set at 74,000 to 76,000 μg × h/L. Targeted busulfan, fludarabine were used in both groups for the conditioning regimen, while cyclophosphamide was included in Haplo group, and anti-thymocyte globulin in Matched group. Results: The outcomes of haplo group and Matched group, respectively, are discussed. The median follow-up time were 27.6 months (range, 11.9–60.8), and 34.2 months (range, 12.5–59.9), respectively. The cumulative incidence (CI) rates of neutrophil engraftment in haplo and control groups were 93.8% and 95.0%. The median days of neutrophil engraftment were 14 days and 11 days, and those of platelet engraftment were 34 days and 17 days, respectively. The both groups did not differ in terms of transplantation-associated complications (hepatic veno-occlusive disease, CMV reactivation, hepatic toxicity, hemorrhagic cystitis). For 13 patients with IEM, the post-HSCT brain MRI findings were reported as similar to the pre-HSCT one. In particular, 2 ALD patients in Haplo group who did not showed neurologic symptom before HSCT (pre-HSCT Loes scores were 0 and 2, respectively) are still normal with regard to neurologic status at median follow-up time 41 months and 18 months, respectively. The CI rates of grade II–IV, grade III-IV acute and extensive chronic graft versus host disease were 45.0% versus 40.0% (P = 0.68), 6.0% versus 20.0% (P = 0.263) and 13.3% versus 26.7% (P = 0.335), respectively. The event-free survival rates at 2 years (93.8% versus 95.0%, P = 0.856) were similar and the overall survival rates were 100% in both groups. Summary/Conclusion: The present study shows that haplo-SCT using PT-Cy, along with a targeted busulfan-based myeloablative conditioning regimen, is a safe and promising therapeutic option for patients with nonmalignant genetic diseases. In particular, it could be useful for patients in urgent need of HSCT who lack a sibling donor or do not have enough time to find a suitable unrelated donor.

Kasai procedure improves nutritional status and decreases transplantation-associated complications.

The aim of this study was to retrospectively investigate whether Kasai Procedure (KP) improves nutritional status and whether KP decreases liver transplantation (LT)-associated complications in children with biliary atresia (BA). From March 1st 2014 to February 28th 2015, 103 patients underwent LT and the other 17 without prior KP died during the waiting period. In 103 patients undergoing LT, 58 patients received KP previously (Group A), and 45 only underwent primary LT (Group B). The nutritional status, liver function and LT-related short-term complications were analyzed. Compared to Group B, patients in Group A had significantly increased time interval when undergoing LT (p < 0.05). Persistently, the bodyweight, albumin and hemoglobin in Group A were significantly increased compared to Group B (all, p < 0.0001). The bilirubin, ALT/AST and PELD score in Group A were all decreased compared to Group B (p < 0.05) prior to LT. The incidences of post-LT severe infection and hypoalbuminemia in Group A were significantly lower than those of Group B (p < 0.05). KP improves the nutritional status, preserves liver function for patients who finally undergo LT, and decreases the incidence post-LT severe infection and hypoalbuminemia. Mental health can be improved in parents whose children underwent previous KP.

Postrenal Transplant Allograft "Page Kidney" Identified and Salvaged using 99mTc-diethylenetriaminepentaacetic acid Renogram and Single-photon Emission-computed Tomography.

99mTc diethylenetriaminepentaacetic acid (DTPA) renogram is a commonly performed evaluation postrenal transplant to assess graft function and for early detection of suspected immediate and late transplant-associated complications. Although several modalities can be utilized to detect perinephric collection in posttransplant period, the utility of 99mTc DTPA single-photon emission-computed tomography (SPECT-CT) is not recognized. Herein, we discuss the incremental role of seldom considered SPECT-CT in early detection, leading to timely appropriate management and graft salvage in a case of posttransplant deteriorating renal allograft as a result of subcapsular hematoma.

Hematopoietic Stem Cell Transplantation for Patients with Mucopolysaccharidosis II

There is limited information regarding the long-term outcomes of hematopoietic stem cell transplantation (HSCT) for mucopolysaccharidosis II (MPS II). In this study, clinical, biochemical, and radiologic findings were assessed in patients who underwent HSCT and/or enzyme replacement therapy (ERT). Demographic data for 146 HSCT patients were collected from 27 new cases and 119 published cases and were compared with 51 ERT and 15 untreated cases. Glycosaminoglycan (GAG) levels were analyzed by liquid chromatography tandem mass spectrometry in blood samples from HSCT, ERT, and untreated patients as well as age-matched controls. Long-term magnetic resonance imaging (MRI) findings were investigated in 13 treated patients (6 ERT and 7 HSCT). Mean age at HSCT was 5.5 years (range, 2 to 21.4 years) in new patients and 5.5 years (range, 10 months to 19.8 years) in published cases. None of the 27 new patients died as a direct result of the HSCT procedure. Graft-versus-host disease occurred in 8 (9%) out of 85 published cases, and 9 (8%) patients died from transplantation-associated complications. Most HSCT patients showed greater improvement in somatic features, joint movements, and activity of daily living than the ERT patients. GAG levels in blood were significantly reduced by ERT and levels were even lower after HSCT. HSCT patients showed either improvement or no progression of abnormal findings in brain MRI while abnormal findings became more extensive after ERT. HSCT seems to be more effective than ERT for MPS II in a wide range of disease manifestations and could be considered as a treatment option for this condition.

Thrombotic complications after hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) involves some serious transplant-associated complications (TACs) or vascular disorders, such as veno-occlusive disease (VOD), thrombotic microangiopathy (TMA), and graft-versus-host disease (GVHD). VOD is related to a clinical syndrome characterized by tender hepatomegaly, jaundice, fluid retention, and unexplained weight gain. When TMA is described in patients who have undergone HSCT, it is often implied that the clinical diagnosis of TMA is similar to that of thrombotic thrombocytopenic purpura. Therefore, levels of cytokines, chemokines, and soluble molecules are useful biomarkers for VOD and TMA after HSCT. Acute GVHD (aGVHD) occurs in the early period after transplantation and is initiated by alloreactive donor T cells. The mechanisms whereby immune responses trigger this post-transplantation condition remain unclear, but endothelial cell function might play a role in this. The authors investigated the expression of endothelial cell activation markers such as sE-selectin, sVCAM-1, PAI-1, and microparticle in patients undergoing allogeneic HSCT. Levels of endothelial cell activation markers were significantly higher in 143 patients who developed aGVHD than in those who did not develop aGVHD. Moreover, patients who received rTM exhibited a significantly lower frequency of aGVHD and reduced levels of endothelial cell activation markers. These findings suggest that endothelial cell activation might be linked to TAC and that rTM may, at least in part, act to prevent TAC through its effect on endothelial cells.

Comparison of Disposition and Complications in Geriatric (≥ 65 years) and Non-Geriatric (50-64 years) Cancer Patients Receiving Hematopoietic Stem Cell Transplantation

Background:.The disposition and complications of hematopoietic stem cell transplant (HSCT) in the geriatric population has not been extensively studied and compared with younger patients. We have analyzed a database with nationwide representation for outcomes of HSCT in these patients over a 12 year period.Methods: Data regarding patients who underwent HSCT was extracted from the Nationwide Inpatient Sample (NIS) from 2000 to 2011 using ICD-9-CM codes. HSCT hospitalizations were classified into allogeneic transplantation, autologous transplantation, subsequent hospitalization (s/p transplant) with graft versus host disease (GVHD) and subsequent hospitalization (s/p transplant) with other complications. NIS variables were used to identify in-hospital complications and discharge disposition. Chi square test and Wilcoxon rank test were used to compare categorical and continuous variables respectively.Results: The proportion of elderly patients (≥ 65 years) receiving autologous transplants and being discharged to nursing homes has increased over the past decade when compared to a younger patient population. Notably, the rate of major complications: mechanical ventilation, tracheostomy and requirement of new dialysis are similar in both the patient populations. The trends from 2000 to 2011 are summarized in Table 1.Conclusion: Although the rate of transplant-associated complications are similar in geriatric and non-geriatric populations, a higher percentage of geriatric cancer patients who receive HSCT are discharged to nursing homes. These rates have not significantly changed over the past decade (p > 0.05). More medical services and resources will be required to support the growing elderly population undergoing HSCT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

External Validation of the Revised PAM Score for Patients with AML Scheduled for Allogeneic Hematopoietic Stem Cell Transplantation

PurposeCounselling of patients with AML about allogeneic hematopoietic stem cell transplantation (alloHSCT) is still an ambitious task in the light of the potential curative perspective after alloHSCT, poor outcomes after non-transplant approaches but a high risk of transplant-associated complications and still a significant risk of relapse even after HSCT. Several scores have been developed to predict outcome after HSCT, such as the HCT-CI and the Pre-transplant Assessment of Mortality (PAM) score. The PAM score has been revised recently, thereby acknowledging the shift to more frequently used reduced intensity conditioning. This score utilizes information on pts.age, donor type, disease risk, theserostatus for the CMV of pts.and donor, and the forcedexspiratory volume in the 1 second (FEV1). The aim of this study was to analyze the predictive power of the PAM score in an independent, large cohort of AML pts.who receivedalloHSCT within the last 12 years.Patients and MethodsWe selected all adult AMLpts.whoreceived the firstalloHSCTat the University Hospital of Dresden, a tertiary care hospital with a large transplant program, from January, 1, 2003 to July, 1, 2015.Pts.withhaplo-identical donors or after cord-blood transplantation were excluded. All patients gave their informed consent on analysing data. The PAM score was calculated as published (Au et al., BBMT 2015) and stratified into 4 groups: scores <17,scores17 to <24, scores 24 through 30, and scores >30.Overall survival (OS), event-free survival (EFS), cumulative incidence of relapse (CIR) and non-relapse-mortality (NRM) after alloHSCTwereanalyzed according to several factors known to impact outcome using the log-rank test for univariate comparison. Age, AML type (de novo vs. sAMLvs. t-MN), sex match (female donor/male recipient vs. all other), CMV match (negative/negative vs. all other), donor type (sibling vs. matched unrelated vs. mismatched unrelated), ELN risk classification, type of conditioning (RIC vs. MAC), disease stage (CR1 vs. primary induction failure vs. >= first relapse) and the PAM score as a continuous variable were selected a priori for multivariate Cox regression analyses.ResultsOverall, 544 pts.metthe inclusion criteria and were analyzed,the median age was 57 years (range, 18 to 76). Two-hundred-three pts.(37%) were treated with standard myeloablative conditioning (MAC) regimens while the remaining pts. received reduced intensity conditioning (RIC). Donors were siblings in 120 (22%), matched unrelated in 295 (54%) and mismatched unrelated donors in 129 (24%) pts. With a median follow up of 47 months (range, 1 to 161), the estimated OS for the whole cohort at five years was 43%, with a CIR of 30% and a NRM of 31% up to that time-point. The probability for OS at five years for pts.in PAM score group 0, 1, 2, and 3 was 65%, 50%, 33%, 22%, respectively (log-rank test, p= <.001). Both the CIR and NRM increased with increasing PAM scores (gray-tests, p= .005 and p= <.001, respectively). Notably, the PAM score contributed significantly to the prediction of OS even when added to a multivariate regression model which contained the single components of the score. In the final multivariate model, age (HR 1.02 per year, p= .004), disease stage (primary induction failure versus CR1, HR 1.5, p= .03), and the PAM score (HR 1.04, p= .03) had a significant impact on OS.ConclusionWe validated the revised PAM for the prediction of OS after HLA-compatiblealloHSCTin a large, well characterised cohort of AMLpts.treatedat a large German transplantcenter. To the best of our knowledge, this is the first external validation of the revised PAM score. OS prediction based on this tool will be useful for counselling of futurepts.withAML. [Display omitted] DisclosuresMiddeke:Sanofi: Honoraria. Thiede:AgenDix: Employment, Other: Ownership. Schetelig:Sanofi: Honoraria.