A Four Protein Plasma Fingerprint of Acute Graft Versus Host Disease (GVHD) Predicts Long Term Survival.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 38-38 ◽  
Author(s):  
Sophie Paczesny ◽  
Sung Choi ◽  
Thomas Braun ◽  
Carrie Kitko ◽  
Krijanovski Oleg ◽  
...  

Abstract There are no independent laboratory diagnostic tests for acute GVHD. We first identified 7 potential plasma biomarkers (IL-2R-α, CRP, IL-8, TIMP-1, TNFR1, HGF, CA-19.9) of acute GVHD using a combination of proteomic approaches and antibody microarrays. We next conducted a retrospective analysis using plasma samples from 424 patients at the University of Michigan under IRB approval. We obtained samples at the first clinical signs of acute GVHD prior to treatment and at equivalent time points in patients without GVHD (Table 1). The median duration of follow-up was 420 days with a minimum follow-up of 180 days. Patients with veno-occlusive disease, idiopathic pneumonia syndrome, or septic shock were not included. We measured plasma levels of the 7 proteins by sequential ELISA. Logistic regression models with and without leave-one-out-cross-validation (LOOCV) tested the correlation of the laboratory values with the diagnosis of acute GVHD using area under the receiver-operating-characteristic (ROC) curves (AUC). The training set consisted of 282 randomly selected patients; the validation set included the remaining 142 patients. The final optimal fingerprint of four proteins excluded CRP because of its association with non-specific inflammation and included IL-2R-α, TNFR1, IL-8 and HGF, with AUCs of 0.91 and 0.89 in the training set (without and with LOOCV, respectively) and 0.86 in the validation set. The fingerprint had a strong association with grade of GVHD (p<0.001) and target organ (p=0.002) at onset; interestingly, HGF had the strongest association. Using a predicted probability of acute GVHD of at least 50%, the fingerprint had a 72% sensitivity and 89% specificity. When we categorized the predicted risk of acute GVHD into low (0.00–0.59), moderate (0.60–094) and high (0.95–1.00), the plasma fingerprint predicted long-term survival (Figure 1, p<0.001). We conclude that this plasma protein fingerprint has good sensitivity, high specificity, strong association with initial grade and target organ of acute GVHD, and effectively stratifies patients into three risk groups for GVHD that correlate with long term survival. Figure Figure Table 1: Patients characteristics GVHD- (N=242) GVHD+ (N=182) Age-yr Median (range) 45 (1–69) 49 (1–71) Donor type (%) MRD: 169 (70%) MRD: 105 (58%) URD: 73 (30%) URD: 77 (42%) Conditioning regimen Intensity (%) Full: 182 (75%) Full: 114 (63%) Reduced: 60 (25%) Reduced: 68 (37%) Day after BMT of samples : median (range) 30 (7–104) 29 (5–119) Grade at GVHD Onset (%) Grade 0 Grade 1 Grade 2 Grade 3–4 242 (57%) 48 (12%) 100 (24%) 34 (7%) Organ Target at GVHD Onset (%) n/a Skin Gut Liver Combined 119 (65%) 38 (21%) 7 (4%) 18 (10%)

2016 ◽  
Vol 23 (6) ◽  
pp. 1003-1008 ◽  
Author(s):  
Antonio Macciò ◽  
Paraskevas Kotsonis ◽  
Giacomo Chiappe ◽  
Luca Melis ◽  
Fausto Zamboni ◽  
...  

2017 ◽  
Vol 44 ◽  
pp. 16-21 ◽  
Author(s):  
Michael H. Antoni ◽  
Jamie M. Jacobs ◽  
Laura C. Bouchard ◽  
Suzanne C. Lechner ◽  
Devika R. Jutagir ◽  
...  

Author(s):  
Iaroslav P. Truba ◽  
Ivan V. Dziuryi ◽  
Roman I. Sekelyk ◽  
Oleksandr S. Golovenko

The problem of the effectiveness of obstruction at the level of the aortic arch is still a matter of discus-sion in the modern literature. Traditionally, by excision of the coarctation part, in the presence of hypoplasia, the incision is extended to a narrowed area and a modification of the classical end-to-end anastomosis is applied in the form of an elongated or expanded variant. Recently, when proximal part is involved in the pathological process, cardiac surgeons have been more likely to use median sternotomy using other types of plastic surgery, including dilation of the narrowed area with a pericardial patch, or pulmonary artery tissue. Accordingly, the analysis of the results of the use of end-to-end anastomosis in young children with aortic arch hypoplasia, especially in view of long-term survival and the level of reoperation, is an important issue of neonatal cardiac surgery. The aim. To evaluate the effectiveness of the use of an extended end-to-end anastomosis after reconstruction of the aortic arch in children under 1 year of age. Materials and methods. The study material included 348 infants who underwent surgical correction of aortic arch hypoplasia through the method of extended end-to-end anastomosis from 2010 to 2020. The operations were performed at the National Amosov Institute of Cardiovascular Surgery of the NAMS of Ukraine and the Ukrainian Children’s Cardiac Center. The study group included only patients with two-ventricular physiology. There were 233 male patients (67%) and 115 female patients (33%). The mean age was 1.07 (0.20; 2.30) months, the mean weight was 3.89 (3.30; 4.90) kg, the mean body surface area was 0.23 (0.20; 0.28) m2. Diagnosis of aortic arch hypoplasia was based on two-dimensional echocardiography. Results. According to echocardiography, after surgery there was a significant decrease in the pressure gradient in the aortic arch from 48.3 ± 20.3 to 16 ± 6.9 (p<0.05), left ventricular PV increased significantly from 61.6 ± 12% to 66.3 ± 6.4% (p> 0.05). The hospital mortality was 1.7% (n = 6). The causes of mortality were not related to the end-to-end aortic arch technique. The duration of follow-up period ranged from 1 month to 9.3 years. Two deaths occurred in the follow-up period. Thirty-two (9.1%) patients developed aortic arch restenosis in the postoperative period. Balloon dilatation of restenosis was performed in 21 patients. Eleven patients underwent repeated aortic arch repair surgery through the median sternotomy. There were no central nervous system complications in the follow-up period. Conclusions. The use of an extended end-to-end anastomosis in the surgical treatment of aortic arch hypoplasia demon strates low hospital mortality and high long-term survival. Indications for the effective use of this type of reconstruction are hypoplasia of the isthmus and distal aortic arch.


2021 ◽  
pp. 1-6
Author(s):  
Camille Buffet ◽  
Sophie Leboulleux ◽  
Françoise Kraeber-Bodéré ◽  
Caroline Bodet-Milin ◽  
Laure Cabanes ◽  
...  

<b><i>Background:</i></b> Cardiac metastases from thyroid cancers are uncommon with a poor prognosis. There is a lack of long-term follow-up studies. <b><i>Cases:</i></b> We report 2 cases of cardiac metastasis from medullary thyroid cancer (MTC). Both patients presented limited metastatic disease apart from a cardiac metastasis. The initial diagnosis was challenging and was facilitated by functional imaging with an immuno-PET-CT using an anti-CEA bispecific antibody and a <sup>68</sup>Ga-labeled peptide. Both patients were treated with the multitarget kinase inhibitor vandetanib with prolonged stability. The first patient was alive at the last follow-up, 14 years after the diagnosis of cardiac metastasis. The second patient required surgical excision of the cardiac mass because of disease progression under vandetanib. <b><i>Conclusion:</i></b> These cases illustrate long-term survival and effectiveness of clinical management of 2 patients who developed cardiac metastases from MTC, in the current era of personalized medicine with targeted therapy.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2195-2195
Author(s):  
Sung-Eun Lee ◽  
Sung Soo Park ◽  
Young-Woo Jeon ◽  
Jae-Ho Yoon ◽  
Byung Sik Cho ◽  
...  

Abstract Background: Although recently, Eculizumab, humanized monoclonal antibody directed against complement component C5, has used increasingly for the patients with hemolytic paroxysmal nocturnal hemoglobinuria (PNH), allogeneic stem cell transplantation (allo-SCT) can be curative treatment option especially for PNH patients with combined aplastic anemia (AA). The aim of the present study was to evaluate long-term outcome of allo-SCT in patients with AA/PNH. In addition, patients with classic PNH who underwent allo-SCT in the pre-eculizumab era were also evaluated. Methods: Total of 33 patients with PNH clones underwent allogeneic SCT at our institution between Jan 1998 and Jan 2016. Among them, seven patients had classic PNH and 26 patients with cytopenia had AA/PNH (with bone marrow evidence of a concomitant AA). Results: There were 21 male and 12 female patients with a median age of 34 years (range, 13-56 years). Pre-transplant GPI-AP deficient neutrophils and erythrocytes were 5.6% (0-92) and 21% (0-98.5), respectively. Median white blood cell, absolute neutrophil count, hemoglobin, and platelet at transplant were 2.4×109/L, 0.8×109/L, 7.7 g/dL, and 27×109/L, respectively. Median LDH level was 727 U/L (232-7721 U/L) and 19 (58%) patients had LDH ≥1.5x upper limit of normal. Classic PNH (n=7) and AA/PNH [SAA (n=15), VSAA (n=9), or non-SAA (n=2)] received SCT from HLA-matched sibling (MSD, n=24), unrelated (URD, n=7), or haplo-identical donor (Haplo-SCT, n=2). Since 2003, the conditioning regimen for MSD-SCT was changed from Busulfex (12.8 mg/kg) + cyclophosphamide (CY, 120 mg/kg) to fludarabine (180 mg/m2) + CY (100 mg/kg) + rATG (10 mg/kg). The conditioning regimen for URD-SCT and Haplo-SCT were TBI (800 cGy) + CY (100-120 mg/kg) ± rATG (2.5 mg/kg) and TBI 600cGy + Fludarabine (150 mg/m2) + rATG (5 mg/kg), respectively. After a median follow-up of 57 months (range 6.0-151.3), the 5-year estimated OS rates were 87.9 ± 5.7%. Four patients died of treatment-related mortality (TRM), including acute GVHD (n=1), pneumonia (n = 2), and cerebral hemorrhage (n=1), respectively. Except one patient with early TRM, 32 patients engrafted. Two patients who experienced delayed graft-failure received second transplant and recovered. The cumulative incidence of acute GVHD (≥grade II) and chronic GVHD was 27.3 ± 7.9% and 18.7 ± 7.0%, respectively. Among 25 patients with available follow-up data, PNH clone disappeared at median 3.0 months (range 0.7-45.5) after SCT and reemerging of PNH clones was observed in two patients; one patient showed re-appearance of 2.6% GPI-negative neutrophils at 12 months without PNH symptoms, but disappeared again at 21 months. Another patient suffered from labile graft and received a booster with peripheral blood stem cells. Conclusion: This study showed that long-term transplant outcome in patients with AA/PNH were comparable to that of allogeneic SCT in SAA (the 3-year estimated OS rates were 92.7 and 89 % for MSD-SCT and URD-SCT, respectively) at our institution (ASH Annual Meeting Abstracts 2012;120:4151). Reduced-intensity conditioning regimen was sufficient for the eradication of PNH clone in allogeneic SCT. Therefore, application of allogeneic SCT should be considered in PNH patients with AA in case of availability of well matched donor. Disclosures No relevant conflicts of interest to declare.


2018 ◽  
Vol 268 ◽  
pp. 100-105 ◽  
Author(s):  
Anwar Baban ◽  
Nicoletta Cantarutti ◽  
Rachele Adorisio ◽  
Roberta Lombardi ◽  
Giulio Calcagni ◽  
...  

2020 ◽  
pp. 096914132092303
Author(s):  
Eugenio Paci ◽  
Donella Puliti ◽  
Francesca Maria Carozzi ◽  
Laura Carrozzi ◽  
Fabio Falaschi ◽  
...  

Objectives Overdiagnosis in low-dose computed tomography randomized screening trials varies from 0 to 67%. The National Lung Screening Trial (extended follow-up) and ITALUNG (Italian Lung Cancer Screening Trial) have reported cumulative incidence estimates at long-term follow-up showing low or no overdiagnosis. The Danish Lung Cancer Screening Trial attributed the high overdiagnosis estimate to a likely selection for risk of the active arm. Here, we applied a method already used in benefit and overdiagnosis assessments to compute the long-term survival rates in the ITALUNG arms in order to confirm incidence-excess method assessment. Methods Subjects in the active arm were invited for four screening rounds, while controls were in usual care. Follow-up was extended to 11.3 years. Kaplan-Meyer 5- and 10-year survivals of “resected and early” (stage I or II and resected) and “unresected or late” (stage III or IV or not resected or unclassified) lung cancer cases were compared between arms. Results The updated ITALUNG control arm cumulative incidence rate was lower than in the active arm, but this was not statistically significant (RR: 0.89; 95% CI: 0.67–1.18). A compensatory drop of late cases was observed after baseline screening. The proportion of “resected and early” cases was 38% and 19%, in the active and control arms, respectively. The 10-year survival rates were 64% and 60% in the active and control arms, respectively ( p = 0.689). The five-year survival rates for “unresected or late” cases were 10% and 7% in the active and control arms, respectively ( p = 0.679). Conclusions This long-term survival analysis, by prognostic categories, concluded against the long-term risk of overdiagnosis and contributed to revealing how screening works.


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