Higher Incidence Of Graft Failure Research Articles

A systematic review and meta-analysis of internal thoracic artery harvesting techniques: Skeletonized vs pedicled

ObjectivesThe aim of this meta-analysis was to compare clinical and angiographic outcomes of skeletonized versus pedicled internal thoracic artery for coronary artery bypass grafting. MethodsA comprehensive search on Ovid MEDLINE, Ovid EMBASE and Scopus was performed from inception to December 2022. The primary outcome was follow-up mortality and graft failure. Secondary outcomes were repeat revascularization, cardiovascular death and operative mortality, myocardial infarction, stroke, and sternal wound complications (SWCs). Pooled estimate for follow-up outcomes was summarized as incidence rate ratio (IRR) and 95% confidence interval (CI) while short-term outcomes were pooled as odds ratio (OR) and 95% CI. For all outcomes, inverse variance weighting was used for pooling. ResultsTwenty-eight studies, including 7 randomized trials and 21 observational studies, for a total of 5664 patients in the skeletonized group and 7434 in the pedicled group, were included in the analysis. At a mean weighted follow-up of 4.8 years, there was no difference in mortality between the two groups (IRR 1.14; 95% CI 0.59–2.20). However, the skeletonized group had a higher incidence of graft failure compared to the pedicled group (IRR 1.87, 95% CI 1.33–2.63) but a lower risk of SWCs (OR 0.42; 95% CI 0.30–0.60). There was no difference in short-term outcomes. ConclusionsCompared to the pedicled harvesting technique, skeletonization of the internal thoracic artery is associated with higher rate of graft failure and lower risk of SWCs without mortality difference.

Improved Outcome Following Busulfan-Based Conditioning in Children with Functional Neutrophil Disorders Undergoing Hematopoietic Stem Cell Transplant from HLA-Matched Donors.

Hematopoietic stem-cell transplantation (HSCT) is the only curative treatment for chronic granulomatous disease (CGD) and leukocyte-adhesion deficiency (LAD), but both diseases have high rates of graft failure in transplant and patients with these diseases are often referred to HSCT with significant comorbidity. The intensity of the conditioning regimen should be balanced between the need to ensure durable engraftment and to minimize toxicity when transplanting young children with infections and organ damage. We report on 26 children transplanted at our institution with CGD and LAD over 24years. We found a higher incidence of graft failure in patients receiving treosulfan based conditioning for their first transplant. There was no effect of conditioning regimen on overall survival, as all 8 patients that proceeded to a second busulfan-based HSCT were salvaged. We recommend giving patients with CGD and LAD fully myeloablative conditioning with either a busulfan-based regimen or the combination of treosulfan, fludarabine, and thiotepa.

Abstract 655: Protecting The Saphenous Vein Endothelium During Bypass Surgery

Coronary artery bypass graft surgeries commonly use saphenous vein grafts to revascularize diseased coronary arteries. Despite surgical and pharmacological advancements, graft failure rates remain high. Loss of endothelial cells (EC) during saphenous vein harvest and preservation likely contributes to the high incidence of graft failure. Standard methods of saphenous vein preparation and preservation during surgery include perfusion with heparinized saline solutions, a practice known to induce EC damage. As such, improved methods of saphenous vein storage may be the key to preserving EC and reducing graft failure rates. Here, we assessed the hypothesis that maintaining saphenous veins in autologous heparinized blood would preserve EC coverage and reduce cellular damage compared to standard of care, heparinized saline. To investigate this, saphenous vein tissues from 12 patients undergoing coronary artery bypass graft surgery were split into 2 treatment groups, 1) standard maintenance in heparin-saline (n=6) and 2) maintenance in heparin-blood (n=6). At the end of the surgeries, excess saphenous vein tissues were immediately fixed in 4% PFA to analyze endothelial coverage and DNA damage. In heparin-saline veins, histological analysis by H&E and Movat pentachrome staining revealed a broken or absent luminal layer and exposed lamina matrix, suggesting a loss of endothelial cell coverage. Luminal cell coverage was notably increased in heparin-blood samples. Immunofluorescent staining of endothelial markers VE-cadherin and endothelial nitric oxide identified a significant improvement in endothelial coverage in the heparin-blood group compared to heparin-saline. To determine the health of remaining endothelial cells, DNA damage was measured using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Our data show that most of the endothelium (VE-cadherin positive) in heparin-saline tissues was TUNEL positive compared with heparin-blood. In conclusion, our data indicate that maintaining saphenous vein tissues in solutions containing autologous heparinized blood helps preserve the endothelium and maintains vein graft health which has the potential to improve vein graft patency rates in patients.

Successful desensitization of high level donor-specific anti-HLA antibody in patients with hematological diseases receiving haploidentical allografts.

Donor-specific anti-human leukocyte antigen (HLA) antibody (DSA) is associated with a higher incidence of graft failure and mortality in HLA-mismatched allograft settings. However, the optimal protocol of desensitization for patients with positive DSA remains uncertain. We investigated the effectiveness of a desensitization protocol, including rituximab, high-dose intravenous immunoglobulin (IVIG), and a single session of plasma exchange (PE), for haploidentical allograft recipients with a high mean fluorescence intensity (MFI) level of DSA (≥ 5,000). Eleven patients with hematological disease who had positive DSA (median, 11,676, range 5387-20,435) were desensitized by the protocol. All of the patients achieved hematopoietic recovery. The median times for neutrophil and platelet engraftment were 13 (range, 11-26) days and 19 (range, 11-90) days, respectively. Grade II-IV acute graft-versus-host disease (GVHD) was seen in one patient and was controlled completely. Chronic cutaneous GVHD was seen in eight patients. Nine patients are alive with good performance so far. One patient suffered extramedullary relapse, and one patient died of transplantation-associated thrombotic microangiopathy. The 1-year probability of overall survival was 81.8%. These results suggest that successful desensitization could be obtained by a combination of rituximab, high-dose IVIG, and PE for haploidentical allograft recipients with high MFI levels of DSA.

Infusion of haploidentical HSCs combined with allogenic MSCs for the treatment of ALL patients.

Although haploidentical stem cell transplantation (haplo-HSCT) offers almost all acute lymphoblastic leukaemia (ALL) patients an opportunity for immediate transplantation, it exhibits a higher incidence of graft failure and graft versus host disease (GVHD). Mesenchymal stem cells (MSCs) are characterised by their haematopoiesis-promoting and immunomodulatory capacity. Thus, we designed a combination of haplo-HSCT and MSCs for ALL patients. ALL patients (n = 110) were given haploidentical HSCs combined with allogenic MSCs, and ALL patients without MSC infusion (n = 56) were included as controls. The 100-day cumulative incidences of grade ≥2 acute GVHD (aGVHD) and grade ≥3 aGVHD were 40.00% and 9.09% compared to 42.32% (P = 0.79) and 22.79% (P = 0.03) in patients without MSC infusion, respectively. The 3-year cumulative incidences of chronic GVHD (cGVHD) and extensive cGVHD were 22.27% and 10.27% compared to 32.14% (P = 0.19) and 22.21% (P = 0.04) in patients without MSC infusion, respectively. No significant differences in the 3-year relapse incidence, nonrelapse mortality, leukaemia-free survival or overall survival in groups with and without MSC cotransplantation were observed. Multivariate analysis showed that MSC infusion contributed to a lower risk of developing extensive cGVHD. Our data suggested that haplo-HSCT combined with MSCs may provide an effective and safe treatment for ALL patients.

Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome: an EBMT Inborn Errors Working Party analysis

AbstractAllogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for patients affected by Wiskott-Aldrich syndrome (WAS). Reported HSCT outcomes have improved over time with respect to overall survival, but some studies have identified older age and HSCT from alternative donors as risk factors predicting poorer outcome. We analyzed 197 patients undergoing transplant at European Society for Blood and Marrow Transplantation centers between 2006 and 2017 who received conditioning as recommended by the Inborn Errors Working Party (IEWP): either busulfan (n = 103) or treosulfan (n = 94) combined with fludarabine ± thiotepa. After a median follow-up post-HSCT of 44.9 months, 176 patients were alive, resulting in a 3-year overall survival of 88.7% and chronic graft-versus-host disease (GVHD)-free survival (events include death, graft failure, and severe chronic GVHD) of 81.7%. Overall survival and chronic GVHD-free survival were not significantly affected by conditioning regimen (busulfan- vs treosulfan-based), donor type (matched sibling donor/matched family donor vs matched unrelated donor/mismatched unrelated donor vs mismatched family donor), or period of HSCT (2006-2013 vs 2014-2017). Patients aged <5 years at HSCT had a significantly better overall survival. The overall cumulative incidences of grade III to IV acute GVHD and extensive/moderate/severe chronic GVHD were 6.6% and 2.1%, respectively. Patients receiving treosulfan-based conditioning had a higher incidence of graft failure and mixed donor chimerism and more frequently underwent secondary procedures (second HSCT, unconditioned stem cell boost, donor lymphocyte infusion, or splenectomy). In summary, HSCT for WAS with conditioning regimens currently recommended by IEWP results in excellent survival and low rates of GVHD, regardless of donor or stem cell source, but age ≥5 years remains a risk factor for overall survival.

High Expression of Leucine-Rich Repeat Neuronal 2 Is the Graft Quality Marker in Living Donor Liver Transplantation

Background: A significant concern in living donor liver transplantation (LDLT) is obtaining good quality and enough size grafts while ensuring donor safety. The indicator of graft quality is not well understood. This study aimed to find a new graft quality marker other than donor age. Methods: We performed PCA analysis based on the gene expression analysis by microarray in cynomolgus macaque among the age group. Results: In PCA analysis, we could identify these macaques into one young group and two subgroups in the elder group based on the expression of 21333 genes. There were two groups in the elder group: one group showed similar gene expression to the young group and the other group showed completely different gene expression. We focused on these genes that differ between elder groups and found that 136 genes differ specially in elder groups. To find a minimum combination of clinically useful biomarkers to indicate liver aging, we performed bioinformatic analysis and found 10 significant genes. We then investigated the expressions of these genes in human donor liver tissue. The recipients who have transplanted the graft with high target gene expression had a higher incidence of graft failure. Multivariate analysis identified that high expression of Leucine-Rich Repeat Neuronal 2 (LRRN2) in donor liver tissue was one of the independent risk factors of graft failure. Conclusions: We searched for novel graft quality markers independent of age and LRRN2 expression may be a useful predictor of graft quality in LDLT.

Post penetrating keratoplasty infectious keratitis: Clinico-microbiological profile and predictors of outcome.

To study the clinico-microbiological profile, outcomes and prognostic factors of post penetrating keratoplasty (PKP) infectious keratitis. Retrospective review of medical records of 78 patients with post PKP infectious keratitis presenting between January 2014 and December 2018. Demographic, clinical and microbiological profile was documented and predictors of treatment and graft success were evaluated using univariate and subsequent multivariate logistic regression analysis. Mean age of patients was 52.17 ± 15.51 years and mean infiltrate size was 19.39 ± 19.68 mm2. Mean duration of presentation with infection post PKP was 11.66 ± 10.65 months. Culture positivity was seen in 64 eyes (82.05%). Bacterial growth was observed in 47 eyes (60.25%), fungal growth in 17 (21.79%) and no microbiological growth in 14 eyes (17.94%). At 3 months the visual acuity (VA) improved in 37 eyes (47.44%), did not change in 27 (34.62%) and deteriorated in 14 (17.95%). Graft failure was noted in 53 eyes (73.08%). Surgical intervention was needed in 47 (60.25%) eyes of which most common was therapeutic PKP in 32 eyes (41.02%). Treatment failure was noted with fungal infection (p = 0.05), poorer vision at presentation (p = 0.02), larger infiltrate area (p = 0.002) and graft infection developing before 1 year (p = 0.02). Graft failure was noted with associated endophthalmitis (p = 0.02), poorer VA at presentation (p = 0.01) and larger infiltrate area (p = 0.02). Post PKP infectious keratitis is a sight threatening ocular condition. It is associated with high incidence of graft failure and frequently requires surgical intervention. Fungal etiology, larger infiltrate size, poorer vision at presentation and associated endophthalmitis carries a poorer prognosis.

Infusion of haploidentical hematopoietic stem cells combined with mesenchymal stem cells for treatment of severe aplastic anemia in adult patients yields curative effects

Background aimsDespite the great advances in immunosuppressive therapy for severe aplastic anemia (SAA), most patients are not completely cured. Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has been recommended as an alternative treatment in adult SAA patients. However, haplo-HSCT presents a higher incidence of graft failure and graft-versus-host disease (GVHD). The authors designed a combination of haplo-HSCT and umbilical cord-derived mesenchymal stem cells (UC-MSCs) for treatment of SAA in adult patients and evaluated its effects. MethodsAdult patients (≥18 years) with SAA (N = 25) were given HLA-haploidentical hematopoietic stem cells (HSCs) combined with UC-MSCs after a conditioning regimen consisting of busulfan, cyclophosphamide, fludarabine and anti-thymocyte globulin and intensive GVHD prophylaxis, including cyclosporine, basiliximab, mycophenolate mofetil and short-term methotrexate. Additionally, the effects of the protocol in adult SSA patients were compared with those observed in juvenile SAA patients (N = 75). ResultsAll patients achieved myeloid engraftment after haplo-HSCT at a median of 16.12 days (range, 11–26). The median time of platelet engraftment was 28.30 days (range, 13–143). The cumulative incidence of grade II acute GVHD (aGVHD) at day +100 was 32.00 ± 0.91%. No one had grade III–IV aGVHD at day +100. The cumulative incidence of total chronic GVHD was 28.00 ± 0.85%. The overall survival was 71.78 ± 9.05% at a median follow-up of 42.08 months (range, 2.67–104). Promisingly, the protocol yielded a similar curative effect in both young and adult SAA patients. ConclusionsThe authors’ data suggest that co-transplantation of HLA-haploidentical HSCs and UC-MSCs may provide an effective and safe treatment for adult SAA.

Is There a Higher Incidence of Graft Failure or Delayed Time to Engraftment in Patients Undergoing Autologous Stem Cell Transplantation Who Receive Olanzapine for Anti-Emetic Prophylaxis?

Olanzapine has been shown to significantly decrease nausea and emetic episodes associated with chemotherapy in patients undergoing hematopoietic stem cell transplant (Monson, Greer, Kreikemeier, & Liewer, 2020). Additionally, Olanzapine has been shown to improve clinical outcomes in autologous stem cell transplant patients when added to triplet anti-emetic therapy of ondansetron, fosaprepitant and dexamethasone without any negative effects on time to engraftment (Clemmons, et al., 2018). Although this study did not show any delay in time to engraftment, there is only a small amount of data looking at this question, including Clemmons et al. (2016) and Trifilio et al. (2017). Other studies (Navari et al., 2016) demonstrated a decrease in chemotherapy related nausea and vomiting in patients receiving Olanzapine, but did not provide data on engraftment times as this was in standard chemotherapy recipients.At Colorado Blood Cancer Institute (CBCI), Olanzapine was used for a period of time for anti-emetic prophylaxis both pre and post autologous stem cell transplant. There was concern regarding whether or not Olanzapine was causing delays in time to engraftment or even potentially graft failure and use of the drug in transplant anti-emetic regimens was discontinued.We hypothesized that Olanzapine does not cause higher incidence of graft failure, as compared to patients who do not receive Olanzapine as part of their anti-emetic regimen during the pre and post autologous stem cell transplant period. A retrospective analysis (n = 272) was conducted on patients who underwent autologous stem cell transplant between 2019 and 2020. 134 of these patients received Olanzapine during conditioning and up until time of engraftment, and 138 patients had no Olanzapine exposure throughout their conditioning and transplant. Conditioning regimens were equal between the two groups (Table 1). The average number of days on Olanzapine was 10.7, and the average dose was 7.5mg daily. For the purposes of this study engraftment was defined as the first day post stem cell infusion that the patient had an absolute neutrophil count (ANC) of greater than or equal to 500.Findings showed that the mean day of engraftment in the patients with Olanzapine exposure was 14.69; in the non-Olanzapine group, the mean day of engraftment was 12.64 (Table 2). Using the two-sample t-test, this difference (2.05 days, 95% CI (1.60-2.51)) is significant (p<.0001).Based on our findings, there is evidence to support Olanzapine causing a slightly delayed time to engraftment in autologous stem cell transplant patients, but not a higher incidence of graft failure, although a randomized controlled trial would be needed to fully investigate. There is clear data showing increased ability to manage chemo therapy induced nausea and vomiting. While a randomized controlled trial would be needed to fully investigate, given there is not a proven increase in graft failure, Olanzapine should be considered as a desirable option to treat and prevent chemotherapy induced nausea and vomiting in autologous stem cell transplant patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare. OffLabel Disclosure:Olanzapine (Zyprexa) - Used off-label for the treatment and prevention of chemotherapy induced nausea and vomiting

Promising Results at 1 Year Follow-up Following Familial Haploidentical (FHI) T-Cell Depleted (TCD) with CD34 Enrichment and T-Cell (CD3) Addback Allogeneic Stem Cell Transplantation in Patients with High-Risk Sickle Cell Disease (SCD) (IND 14359)

AlloSCT from HLA-matched MSD has been successful for high-risk SCD, and is the only known curative therapy (Talano/Cairo et al EJH, 2014). We have recently demonstrated 100% EFS and absence of sickle cell symptoms following reduced toxicity conditioning in HLA matched sibling donor (MSD) or cord blood AlloSCT (Bhatia/Cairo et al BMT, 2014). However, 5 out of 6 children lack an HLA MSD without SCD. Only 19% of recipients of African descent will identify a well-matched unrelated donor (MUD) and results after unrelated UCBT are poor (Radhakrishnan/Cairo et al BBMT, 2013). Recent results utilizing matched unrelated donors in a multi-center trial showed unacceptable rates of cGVHD at 62% (95% CI 41-77) (Shenoy et al Blood, 2016). We demonstrated CD34+ selection followed by T-cell addback from MUD in pediatric recipients led to 100% engraftment with minimal aGVHD (Geyer/Cairo et al BJH, 2011). Limitations in the past of various T-cell depletion methods have included a higher incidence of graft failure, delayed immune reconstitution, opportunistic fungal infection and higher incidence of cGVHD. FHI TCD AlloSCT utilizing the approach of CD34+ enrichment and T-cell addback could expand the donor pool and improve outcomes for patients with high risk SCD and have similar outcomes to AlloSCT from HLA MSD.This SCD consortium trial (www.sicklecelltransplantconsortium.org) (NCT01461837) is investigating the safety, feasibility, EFS, donor chimerism, graft failure, aGVHD and cGVHD after FHI TCD AlloSCT in high-risk SCD patients.High risk included: ≥1 CVA, ≥2 ACS, ≥3 VOC in past 2 years, or 2 abnormal TCDs. Patients (2-<21 yrs) who have ≥1 high-risk SCD features were eligible. Patients received hydroxyurea and azathioprine, day -59 - day -11, fludarabine (150mg/m2), busulfan (12.8mg/kg) (targeted trough Css of 600-900), thiotepa (10 mg/kg), cyclophosphamide (200mg/kg), R-ATG (8mg/kg), and TLI (500cGy) followed by FHI T-cell depleted AlloSCT. AGVHD prophylaxis: tacrolimus. We utilized the CliniMACS to enrich for peripheral blood HPC's; target dose of 10 x 106 CD34+ cells/kg with a fixed dose of 2 x 105 CD3+ T cells/kg. The Child Health Rating Inventories (CHRIs) was used to serially collect parent proxy-rated health-related quality of life (HRQL).Twenty-one patients have been enrolled. Nineteen patients have received AlloSCT to date. Fifteen patients utilized maternal donors and 4 patients utilized paternal donors. Two donors encountered thrombocytopenia that resolved spontaneously. The mean ± SD CD34+ enrichment prior to cryopreservation was 12.66 ± 3.3 x 106/kg and log T-cell depletion was 4.8 ± 0.58. Evaluable pts had early neutrophil engraftment (median day +9), and ≥95% whole blood and RBC (CD71) donor chimerism at 1yr. Probability of aGVHD n=17, 7.1% (CI95: 0-70.0); cGVHD n=17, 20% (CI95: 0.7-59.6) (Figure 1A and 1B). Probability of 1-Year Overall Survival (OS) n=17; 88.2% (CI95: 60.6-96.9) (Figure 1C). Immune reconstitution was robust with 1 yr NK, CD3, CD4 and CD8 204±37 cells/μL, 795±168 cells/μL, 408±102 cells/μL and 375±90 cells/μL, respectively. Two-yr PFT results were also robust with % predicted FVC, FEV1, TLC and DLCO of 89%, 84%, 82%, and 68%, respectively. All survivors are free of SCD symptoms and without signs of progression of multi-organ toxicity. One patient developed late hepatic SOS and died at day +59; one patient died at day +390 due to complications of CGVHD, and one patient died at day +141 of steroid refractory aGVHD, the remainder are alive and free of SCD symptoms with a median follow-up of +711 days (range, +231 to +1684 days). Most importantly, mean + SD HRQL score (0-100) reported at 1 yr for emotional, physical functioning, role, and global scores were 82.9±9.7 points, 82.8±15.8 points, 89.6±13.3 points, and 86±8.2 points, respectively.Early results indicate promising results in 1 yr OS, stable donor chimerism, and low incidence of acute and/or cGVHD after FHI HCT utilizing CD34 enrichment and CD3/MNC addback in high-risk SCD patients who lack a MSD or URD. A longer term follow-up is needed to assess long-term safety and outcomes. This research was supported by RO1FD004090-01A1. [Display omitted] DisclosuresWalters:AllCells, Inc: Other: Medical Director; bluebird bio: Research Funding; Sangamo Therapeutics: Consultancy; ViaCord Processing Lab: Other: Medical Director. Cairo:Jazz Pharmaceuticals: Speakers Bureau.

Allogeneic hematopoietic cell transplantation with cord blood versus mismatched unrelated donor with post-transplant cyclophosphamide in acute myeloid leukemia

BackgroundAllogeneic hematopoietic cell transplantation (allo-HCT) using a mismatched unrelated donor (MMUD) and cord blood transplantation (CBT) are valid alternatives for patients without a fully human leukocyte antigen (HLA)-matched donor. Here, we compared the allo-HCT outcomes of CBT versus single-allele-mismatched MMUD allo-HCT with post-transplant cyclophosphamide (PTCy) in acute myeloid leukemia.MethodsPatients who underwent a first CBT without PTCy (N = 902) or allo-HCT from a (HLA 9/10) MMUD with PTCy (N = 280) were included in the study. A multivariate regression analysis was performed for the whole population. A matched-pair analysis was carried out by propensity score-based 1:1 matching of patients (177 pairs) with known cytogenetic risk.ResultsThe incidence of grade II–IV and grade III–IV acute graft-versus-host disease (GVHD) at 6 months was 36% versus 32% (p = 0.07) and 15% versus 11% (p = 0.16) for CBT and MMUD cohorts, respectively. CBT was associated with a higher incidence of graft failure (11% vs. 4%, p < 0.01) and higher 2-year non-relapse mortality (NRM) (30% vs. 16%, p < 0.01) compared to MMUD. In the multivariate analysis, CBT was associated with a higher risk of, NRM (HR = 2.09, 95% CI 1.46–2.99, p < 0.0001), and relapse (HR = 1.35, 95% CI 1–1.83, p = 0.05), which resulted in worse leukemia-free survival (LFS) (HR = 1.68, 95% CI 1.34–2.12, p < 0.0001), overall survival (OS) (HR = 1.7, 95% CI 1.33–2.17, p < 0.0001), and GVHD-free, relapse-free survival (GRFS) (HR = 1.49, 95% CI 1.21–1.83, p < 0.0001) compared to MMUD. The risk of grade II–IV acute GVHD (p = 0.052) and chronic GVHD (p = 0.69) did not differ significantly between the cohorts. These results were confirmed in a matched-pair analysis.ConclusionsCBT was associated with lower LFS, OS, and GRFS due to higher NRM, compared to MMUD allo-HCT with PTCy. In the absence of a fully matched donor, 9/10 MMUD with PTCy may be preferred over CBT.

Optical Iridectomy as An Alternative Clear Visual Axis for Peters Anomaly

&#x0D; &#x0D; &#x0D; Introduction and objective: Peters anomaly is a rare congenital disease presented with central leukoma, iridocorneal adhesion, and with or without a cataractous lens. The presence of central leukoma will block the visual axis and lead to a disruption in normal visual development. Therefore, optical iridectomy, which can overcome the high incidence of graft failure in penetrating keratoplasty (PK), has been proposed as the alternative treatment to clear the visual axis. This study aims to show the outcome of optical iridectomy in patients with Peters’ anomaly. &#x0D; Method: Systematic literature searched in Pubmed, Google Scholar, and Cochrane from their inception to August 2020 was conducted using keywords “iridectomy” and “Peters’ anomaly”. Full- text articles in English that report the outcome of iridectomy in Peters’ anomaly were included, and a manual review of article bibliographies was done. Outcome measures were analyzed using the following clinical questions: indication, age, visual acuity (VA), and intraocular pressure (IOP). Result: One case series and two case reports demonstrating the use of optical iridectomy in Peters anomaly were identified. In total, 26 patients aged one week to 7.7 years received optical iridectomy to establish a clear visual axis. All studies showed an improvement in visual acuity through clinical findings, and one of the studies showed a better postoperative VA in bilateral cases. Studies showed good control of IOP. &#x0D; Conclusion: Optical iridectomy can be used as a safe procedure to improve visual acuity in Peters anomaly patient. &#x0D; &#x0D; &#x0D;

Impact of donor smoking history on post heart transplant outcomes: A propensity-matched analysis of ISHLT registry.

Smoking is a major public health issue, and its effect on cardiovascular outcomes is well established. This study evaluates the impact of donor smoking on heart transplant (HT) outcomes. HT recipients between January 1, 2005, and December 31, 2016, with known donor smoking status were queried from the International Society of Heart and Lung Transplantation (ISHLT) registry. The primary outcome was all-cause mortality, and secondary endpoints were graft failure, acute rejection, and cardiac allograft vasculopathy. We utilized propensity-score matching to identify cohorts of recipients with and without a history of donor smoking. Hazard ratios for post-transplant outcomes for the matched sample were estimated from separate Cox proportional hazard models. Of 26390 patients in the cohort, 18.9% had history of donor smoking. Donors with history of smoking were older, predominantly male and had higher incidence of diabetes, hypertension, cocaine use, and "high-risk" status. In propensity-matched analysis, recipients with a history of donor smoking had increased risk of death (HR 1.11, 95% CI 1.03-1.20) and higher risk of graft failure (HR 1.11, 95% CI 1.03-1.20). Donor smoking was associated with increased mortality and higher incidence of graft failure following HT. Consideration of donor smoking history is warranted while evaluating donor hearts.

Outcomes of Allogeneic Hematopoietic Cell Transplantation with Cord Blood Versus Mismatched Unrelated Donor with Post-Transplant Cyclophosphamide in Acute Myeloid Leukemia: An Analysis from the ALWP of the EBMT

Outcomes of Allogeneic Hematopoietic Cell Transplantation with Cord Blood Versus Mismatched Unrelated Donor with Post-Transplant Cyclophosphamide in Acute Myeloid Leukemia: An Analysis from the ALWP of the EBMT

A study of human leukocyte antigen-haploidentical hematopoietic stem cells transplantation combined with allogenic mesenchymal stem cell infusion for treatment of severe aplastic anemia in pediatric and adolescent patients.

The clinical applications of human leukocyte antigen (HLA) haploidentical hematopoietic stem cells transplantation (haplo‐HSCT) have offered most of the young severe aplastic anemia (SAA) patients an opportunity to accept curative therapy at the early stage of bone marrow lesions. However, the outcome of juvenile SAA patients received haplo‐HSCT remain to be improved due to high incidence of graft failure and graft vs host disease (GVHD). Mesenchymal stem cells (MSCs) have been characterized by their hematopoiesis‐supporting and immunomodulatory properties. In the current study, we designed a combination of haplo‐HSCT with allogenic MSC for treatment of SAA in pediatric and adolescent patients and evaluated its effects. Juvenile patients (<18 years) with SAA (n = 103) were given HLA‐haploidentical HSC combined with allogenic MSC after a conditioning regimen consisting of busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin and an intensive GVHD prophylaxis, including cyclosporine, short‐term methotrexate, mycophenolate mofetil, and basiliximab. Neutrophil engraftment was achieved in 102 of 103 patients in a median time of 14.3 days (range 9‐25 days). The median time of platelet engraftment was 25.42 days (range 8‐93 days). The cumulative incidence of II‐IV acute GVHD at day +100 was 26.32% ± 0.19% and III‐IV acute GVHD was 6.79% ± 0.06% at day +100, respectively. The cumulative incidence of chronic GVHD was 25.56% ± 0.26%. The overall survival was 87.15% ± 3.3% at a median follow‐up of 40 (1.3‐98) months. Our data suggest that cotransplantation of HLA‐haploidentical HSC and allogenic mesenchymal stem cell may provide an effective and safe treatment for children and adolescents with SAA who lack matched donors.

Impact of Donor Smoking History on Post Heart Transplant Outcomes: A Propensity Matched Analysis of the ISHLT Registry

Tobacco smoking is a major public health issue and its adverse impact on cardiovascular outcomes is well documented. However, the impact of donor tobacco smoking on post heart transplant (HT) outcomes is unclear. This study aims to compare long term outcomes between adult HT recipients based on the history of donor smoking. All primary adult HT recipients (age ≥18y) transplanted between January 1, 2005 and December 31, 2016, with known donor smoking status were queried in the ISHLT thoracic transplant registry. Primary outcome was overall patient survival and secondary endpoints were graft failure, acute rejection and cardiac allograft vasculopathy (CAV). We derived propensity score matching to reduce bias using a greedy algorithm to identify a matched cohort with no history of donor smoking. Hazard ratios for post-transplant outcomes for the propensity matched sample were estimated from separate Cox proportional hazard models using robust sandwich covariance matrix estimates. Of the 26,390 HT patients in the cohort, 18.9% (N=4664) had history of donor smoking. Donors with history of smoking were older, predominantly male and had higher incidence of diabetes, hypertension, cocaine use and 'high risk' status as compared to non-smokers. Propensity score matching identified 4,572 HT patients with similar propensity scores. In the propensity matched analysis, HT patients with a history of donor smoking had worse 10 year survival (HR 1.11, 95% CI 1.03-1.20) (Figure 1), and a higher incidence of graft failure (HR 1.11, 95% CI 1.03-1.20). Rates of CAV and acute rejection were not statistically different between groups (Table 1). Donor smoking was independently associated with increased long term mortality, and higher incidence of graft failure after HT, independent of rejection and CAV. Careful consideration of donor smoking history is needed while evaluating donor hearts prior to HT.

Deregulation of the Purine Pathway in Pre-Transplant Liver Biopsies Is Associated with Graft Function and Survival after Transplantation

The current shortage of livers for transplantation has increased the use of marginal organs sourced from donation after circulatory death (DCD). However, these organs have a higher incidence of graft failure, and pre-transplant biomarkers which predict graft function and survival remain limited. Here, we aimed to find biomarkers of liver function before transplantation to allow better clinical evaluation. Matched pre- and post-transplant liver biopsies from DCD (n = 24) and donation after brain death (DBD, n = 70) were collected. Liver biopsies were analysed using mass spectroscopy molecular phenotyping. Discrimination analysis was used to parse metabolites differentiated between the two groups. Five metabolites in the purine pathway were investigated. Of these, the ratios of the levels of four metabolites to those of urate differed between DBD and DCD biopsies at the pre-transplantation stage (q < 0.05). The ratios of Adenosine monophosphate (AMP) and adenine levels to those of urate also differed in biopsies from recipients experiencing early graft function (EGF) (q < 0.05) compared to those of recipients experiencing early allograft dysfunction (EAD). Using random forest, a panel consisting of alanine aminotransferase (ALT) and the ratios of AMP, adenine, and hypoxanthine levels to urate levels predicted EGF with area under the curve (AUC) of 0.84 (95% CI (0.71, 0.97)). Survival analysis revealed that the metabolite classifier could stratify six-year survival outcomes (p = 0.0073). At the pre-transplantation stage, a panel composed of purine metabolites and ALT could improve the prediction of EGF and survival.

Enhancing the Efficacy of Stem Cell Therapy with Glycosaminoglycans.

SummaryHuman mesenchymal stem cell (hMSC) therapy offers significant potential for osteochondral regeneration. Such applications require their ex vivo expansion in media frequently supplemented with fibroblast growth factor 2 (FGF2). Particular heparan sulfate (HS) fractions stabilize FGF2-FGF receptor complexes. We show that an FGF2-binding HS variant (HS8) accelerates the expansion of freshly isolated bone marrow hMSCs without compromising their naivety. Importantly, the repair of osteochondral defects in both rats and pigs is improved after treatment with HS8-supplemented hMSCs (MSCHS8), when assessed histologically, biomechanically, or by MRI. Thus, supplementing hMSC culture media with an HS variant that targets endogenously produced FGF2 allows the elimination of exogenous growth factors that may adversely affect their therapeutic potency.

Improvement of Early Mortality in Single-Unit Cord Blood Transplantation for Adults During 20 Years: A Retrospective Cohort Study

Background: The major limitation of cord blood transplantation (CBT) for adults remains the delayed hematopoietic recovery and higher incidence of graft failure, which result in a higher risk of early mortality in CBT. Methods: We evaluated early overall survival (OS), non-relapse mortality (NRM), neutrophil engraftment, acute graft-versus-host disease, and cause of early death among 9678 adult patients who received single-unit CBT in Japan between 1998 and 2017. Findings: The probability of OS at 100 days was 61.8%, 64.7%, 71.7%, and 78.9% for the periods 1998 to 2002, 2003 to 2007, 2008 to 2012, and 2013 to 2017, respectively (P<0.001). The cumulative incidences of NRM at 100 days during the same period were 33.2%, 27.6%, 20.8%, and 14.6%, respectively (P<0.001). The cumulative incidences of neutrophil engraftment were also improved during the same period (P<0.001). The most common cause of death within 100 days after CBT was bacterial infection in 1998 to 2002 and primary disease in the latter three time periods. Across the four time periods, the proportions of deaths from bacterial and fungal infection, graft failure, hemorrhage, sinusoidal obstructive syndrome, and organ failure decreased in a stepwise fashion. Landmark analysis of OS and NRM after 100 days showed that OS and NRM did not change over time in the multivariate analysis. Interpretation: Our registry-based data demonstrated a significant improvement of early NRM after CBT for adults over the past 20 years. The landmark analysis suggested that improvement of early mortality could lead to an improvement of long-term OS after CBT. Funding Statement: Japan Agency for Medical Research and Development. Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: This retrospective study complied with the Declaration of Helsinki and was approved by the institutional review board at the Institute of Medical Science, The University of Tokyo, where this study was carried out (30-70-B0128).