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1.
  • Nilsson, Christer, et al. (author)
  • Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting
  • 2019
  • In: Biology of blood and marrow transplantation. - : Elsevier. - 1083-8791 .- 1523-6536. ; 25:9, s. 1770-1778
  • Journal article (peer-reviewed)abstract
    • Secondary AML (s-AML), including AML with an antecedent hematologic disorder (AHD-AML) and therapy-related AML (t-AML), constitutes a large proportion of patients with AML and is considered to confer a dismal prognosis. The role of allogeneic hematopoietic cell transplantation (HCT) in patients with s-AML and the extent to which HCT is performed in these patients has been little studied to date. We used the population-based Swedish AML Registry comprising 3337 intensively treated adult patients over a 17-year period to study the role of HCT within the group of patients with s-AML as well as compared with patients with de novo AML. HCT was performed in 576 patients (22%) with de novo AML, in 74 patients (17%) with AHD-AML, and in 57 patients (20%) with t-AML. At 5 years after diagnosis, there were no survivors among patients with previous myeloproliferative neoplasms who did not undergo HCT, and corresponding survival for patients with antecedent myelodysplastic syndromes and t-AML was and 2% and 4%, respectively. HCT was compared with chemotherapy consolidation in s-AML using 3 models: (1) a 200-day landmark analysis, in which HCT was favorable compared with conventional consolidation (P = .04, log-rank test); (2) a multivariable Cox regression with HCT as a time-dependent variable, in which the hazard ratio for mortality was 0.73 (95% confidence interval, 0.64 to 0.83) for HCT and favored HCT in all subgroups; and (3) a propensity score matching analysis, in which the 5-year overall survival (OS) and relapse-free survival in patients with s-AML in first complete remission (CR1) was 48% and 43%, respectively, for patients undergoing HCT versus 20% and 21%, respectively, for those receiving chemotherapy consolidation (P = .01 and .02, respectively, log-rank test). Our observational data suggest that HCT improves survival and offers the only realistic curative treatment option in patients with s-AML. 
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2.
  • Afram, Gabriel, et al. (author)
  • Higher response rates in patients with severe chronic skin graft-versus-host disease treated with extracorporeal photopheresis
  • 2019
  • In: Central European Journal of Immunology. - : TERMEDIA PUBLISHING HOUSE LTD. - 1426-3912 .- 1644-4124. ; 44:1, s. 84-91
  • Journal article (peer-reviewed)abstract
    • Introduction: Different forms of graft-versus-host disease (GVHD) remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The prognosis for steroid-refractory chronic GVHD (cGVHD) remains poor. Our aim was to evaluate extracorporeal photopheresis (ECP) treatment in cGVHD patients with different organ involvement to detect subgroups of patients with the best response.Material and methods: Thirty-four patients who underwent HSCT and developed moderate (n = 7) or severe (n = 27) steroid-refractory or steroid-dependent cGVHD treated with ECP were included in the analysis. A matched cGVHD control patient group untreated with ECP was collected for comparison.Results: Compared to the control group and the stable/progressive disease (SD/PD) patients, individuals with complete/partial remission have higher overall survival and lower transplant-related mortality. Furthermore, patients with complete and partial remission (CR/PR) had significantly higher levels of albumin and platelets after ECP treatment compared to patients with stable or progressive cGVHD (SD/PD). Corticosteroid treatment and other immunosuppressive agents could successfully be tapered in the CR/PR group compared to the SD/PD patients. In this study patients with skin cGVHD are those with the highest rate of CR/PR after ECP treatment.Conclusions: Our results suggest that ECP treatment is safe and effective for patients with predominantly skin, oral and liver cGVHD.
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3.
  • Afram, Gabriel, et al. (author)
  • Reduced intensity conditioning increases risk of severe cGVHD : identification of risk factors for cGVHD in a multicenter setting
  • 2018
  • In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 35:6
  • Journal article (peer-reviewed)abstract
    • Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Aim is to identify risk factors for the development of cGVHD in a multicenter setting. Patients transplanted between 2000 and 2006 were analyzed (n = 820). Donors were HLA-identical siblings (57%), matched unrelated donors (30%), and HLA-A, B or DR antigen mismatched (13%). Reduced intensity conditioning (RIC) was given to 65% of patients. Overall incidence of cGVHD was 46% for patients surviving more than 100 days after HSCT (n = 747). Older patient age [HR 1.15, p < 0.001], prior acute GVHD [1.30, p = 0.024], and RIC [1.36, p = 0.028] increased overall cGVHD. In addition, RIC [4.85, p < 0.001], prior aGVHD [2.14, p = 0.001] and female donor to male recipient [1.80, p = 0.008] increased the risk of severe cGVHD. ATG had a protective effect for both overall [0.41, p < 0.001] and severe cGVHD [0.20, p < 0.001]. Relapse-free survival (RFS) was impaired in patients with severe cGVHD. RIC, prior aGVHD, and female-to-male donation increase the risk of severe cGVHD. ATG reduces the risk of all grades of cGVHD without hampering RFS. GVHD prophylaxis may be tailored according to the risk profile of patients.
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4.
  • Ali, M. M., et al. (author)
  • Addition of Anti-thymocyte Globulin in Allogeneic Stem Cell Transplantation With Peripheral Stem Cells From Matched Unrelated Donors Improves Graft-Versus-Host Disease and Relapse Free Survival
  • 2021
  • In: Clinical Lymphoma, Myeloma & Leukemia. - : Elsevier. - 2152-2650 .- 2152-2669. ; 21:9, s. 598-605
  • Journal article (peer-reviewed)abstract
    • In 2014 we introduced anti-thymocyte globulin (ATG) to the graft-versus-host disease (GvHD) prophylaxis regimen in allogeneic stem cell transplantation (Allo-HSCT) with peripheral stem cells (PBSC) from matched unrelated donors (MUD). We analysed the outcomes of 415 patients who went through MUD alto-HSCT and received PBSC with or without ATG. We report dramatic reduction of the incidence of chronic GvHD and our study illustrates the benefit of ATG in addition to standard GvHD prophylaxis. Anti-thymocyte globulin (ATG) is commonly used to prevent graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). To evaluate the impact of ATG as part of the GvHD prophylaxis in our institution, we report the outcome of 415 patients with matched unrelated donors (MUD) transplanted for hemato-logical malignancies with or without ATG from 2005 to 2019 at Oslo University Hospital, Norway. The following groups were compared: (1) 154 patients transplanted with peripheral blood stem cells (PBSC) without ATG 2005-2014. (2) 137 patients transplanted with bone marrow stem cells (BMSC) 2005-2019. (3) 124 patients transplanted with PBSC and ATG (PBSC + ATG) 2014-2019. Three years survival was similar in the groups, 61% following allografting with PBSC, 54% with BMSC, and 59% with PBSC + ATG. Acute GvHD grade III-IV was 14%, 14%, and 7%; chronic GvHD was 81%, 32, and 26%; and extensive cGvHD 44%, 15%, and 6% in the corresponding groups. Both acute and chronic GvHD were significantly reduced in the PBSC + ATG-versus the PBSC group (p < 0.05 and p < 0.001 respectively).Transplant-related mortality (TRM) was 33%, 25%, and 17% (p = 0.18). Graft versus host disease and relapse free survival (GRFS) at 3 years was 43 %, 43%, and 64% in the groups. Adding ATG to the GvHD prophylaxis regimen of MUD allo-HSCT with PBSC resulted in a substantial reduction of both acute and chronic GvHD without compromising the disease control, reflected in a superior 3 years GRFS.
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5.
  • Baygan, Arjang, et al. (author)
  • Safety and Side Effects of Using Placenta-Derived Decidual Stromal Cells for Graft-versus-Host Disease and Hemorrhagic Cystitis
  • 2017
  • In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8
  • Journal article (peer-reviewed)abstract
    • Mesenchymal stromal cells (MSCs) are increasingly used in regenerate medicine. Placenta-derived decidual stromal cells (DSCs) are a novel therapy for acute graft-versus-host-disease (GVHD) and hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT). DSCs are more immunosuppressive than MSCs. We assessed adverse events and safety using DSCs among 44 treated patients and 40 controls. The median dose of infused cells was 1.5 (range 0.9–2.9) × 106 DSCs/kg. The patients were given 2 (1–5) doses, with a total of 82 infusions. Monitoring ended 3 months after the last DSC infusion. Three patients had transient reactions during DSC infusion. Laboratory values, hemorrhages, and transfusions were similar in the two groups. The frequency of leukemic relapse (2/2, DSC/controls) and invasive fungal infections (6/6) were the same in the two groups. Causes of death were those seen in HSCT patients: infections (5/3), respiratory failure (1/1), circulatory failure (3/1), thromboembolism (1/0), multiorgan failure (0/1), and GVHD and others (2/7). One-year survival for the DSC patients with GVHD was 67%, which was significantly better than achieved previously at our center. One-year survival was 90% in the DSC-treated HC group. DSC infusions appear safe. Randomized studies are required to prove efficacy.
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6.
  • Bergkvist, Karin, et al. (author)
  • General health, symptom occurrence, and self-efficacy in adult survivors after allogeneic hematopoietic stem cell transplantation : a cross-sectional comparison between hospital care and home care
  • 2015
  • In: Supportive Care in Cancer. - : Springer Science and Business Media LLC. - 0941-4355 .- 1433-7339. ; 23:5, s. 1273-83
  • Journal article (peer-reviewed)abstract
    • PURPOSE: Earlier studies have shown that home care during the neutropenic phase after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is medically safe, with positive outcomes. However, there have been few results on long-term outcomes after home care. The aims of this study were to compare general health, symptom occurrence, and self-efficacy in adult survivors who received either home care or hospital care during the early neutropenic phase after allo-HSCT and to investigate whether demographic or medical variables were associated with general health or symptom occurrence in this patient population.METHODS: In a cross-sectional survey, 117 patients (hospital care: n = 78; home care: n = 39) rated their general health (SF-36), symptom occurrence (SFID-SCT, HADS), and self-efficacy (GSE) at a median of 5 (1-11) years post-HSCT.RESULTS: No differences were found regarding general health, symptom occurrence, or self-efficacy between groups. The majority of patients in both hospital care (77 %) and home care (78 %) rated their general health as "good" with a median of 14 (0-36) current symptoms. Symptoms of fatigue and sexual problems were among the most common. Poor general health was associated with acute graft-versus-host disease (GVHD), low self-efficacy, and cord blood stem cells. A high symptom occurrence was associated with female gender, acute GVHD, and low self-efficacy.CONCLUSIONS: No long-term differences in general health and symptom occurrence were observed between home care and hospital care. Thus, home care is an alternative treatment method for patients who for various reasons prefer this treatment option. We therefore encourage other centers to offer home care to patients.
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7.
  • Berglund, Sofia, et al. (author)
  • Granulocyte transfusions could benefit patients with severe oral mucositis after allogeneic hematopoietic stem cell transplantation
  • 2019
  • In: Vox Sanguinis. - : Wiley-Blackwell. - 0042-9007 .- 1423-0410. ; 114:7, s. 769-777
  • Journal article (peer-reviewed)abstract
    • Background and objectives Mucositis is a common complication after allogeneic hematopoietic stem cell transplantation (HSCT), and is caused by a combination of conditioning-induced mucosal damage and severe neutropenia. The symptoms include oral and abdominal pain, inability to swallow food and fluids, and severe diarrhoea. Severe mucositis is associated with increased risk of Graft-versus-Host disease and infection. Granulocyte transfusions (GCX) could be a treatment option, and our objective was to study its feasibility and potential benefits. Material and methods This retrospective, single-centre study included 30 patients receiving GCX because of severe oral mucositis after HSCT during 2005-2017. Clinical outcome, response to GCX, change in opiate administration and adverse events were studied. Results Twenty-seven patients received GCX from donors pre-treated with steroids and G-CSF, and three from donors pre-treated with steroids only. Overall response was 83% (24/29 evaluable patients). Fifteen patients reached a complete response. In 14 of 24 responders, a reduction of the administration of opiate pain relief was seen. In eight patients this reduction was >= 50% of the dose. Adverse events (AEs) were reported in 14 cases, and were mild to moderate, and well manageable with symptomatic treatment. No life-threatening or fatal AEs were recorded. Conclusions These results indicate that GCX could be a safe and effective treatment for oral mucositis after HSCT with the potential to reduce the necessity of opiate analgesic treatment in this disorder. No severe AEs were seen in this study, but the risk for severe pulmonary AEs after GCX needs to be considered.
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8.
  • Carreira, Abel Santos, et al. (author)
  • Bloodstream Infections and Outcomes Following Allogeneic Hematopoietic Cell Transplantation : A Single-Center Study
  • 2022
  • In: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 28:1, s. 50.e1-50.e8
  • Journal article (peer-reviewed)abstract
    • This study investigated the single-center incidence and risk factors for bloodstream infections (BSIs) in 651 adults who underwent allogeneic hematopoietic cell transplantation (alloHCT) between 2015 and 2019 and explored the impact of these BSIs on post-transplantation outcomes. Antibiotic prophylaxis with ciprofloxacin was given during the aplastic phase. Overall, the median patient age was 57 years, 79.7% of patients received an alternative donor graft, and 68.7% received post-transplantation cyclophosphamide (PTCy) as part of their graft-versus-host disease (GVHD) prophylaxis. Of the 651 patients, 358 (55.0%) had at least 1 episode of BSI, and the overall mortality rate secondary to this complication was 7.5% (12.6% among those diagnosed with at least 1 episode of BSI). BSI was more often diagnosed during the first 30 days (58.7%), and gram-positive bacteria were the most prevalent microorganisms isolated during the entire post-transplantation follow-up (62%). A high Disease Risk Index (hazard ratio [HR], 1.47; P < .029) and receipt of PTCy-based GVHD prophylaxis (HR, 3.33; P < .001) were identified as risk factors for BSI. Additionally, univariate analysis showed that patients diagnosed with a BSI during post-transplantation follow-up had worse overall survival (HR, 2.48; P < .001) and higher nonrelapse mortality (HR, 2.68; P < .001) than those without BSI. In conclusion, alloHCT recipients with a BSI had a higher risk of mortality compared with those who did not develop BSI. The inclusion of PTCy as part of GVHD prophylaxis was identified as an independent risk factor for BSI during early post-transplantation follow-up. Single-center analyses focused on reporting the incidence and risk factors for BSI highlight the need for active implementation of preemptive strategies to decrease BSI incidence in the alloHCT setting.
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9.
  • Carreira, Abel Santos, et al. (author)
  • Interaction Between High-Dose Intravenous Busulfan and Post-Transplantation Cyclophosphamide on Hemorrhagic Cystitis After Allogeneic Hematopoietic Cell Transplantation
  • 2023
  • In: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 29:9, s. 581.e1-581.e8
  • Journal article (peer-reviewed)abstract
    • This study investigates the incidence and predictors of hemorrhagic cystitis (HC) in 960 adults undergoing allo- hematopoietic stem cell transplantation. Two hundred fifty-two (26.5%) patients received myeloablative conditioning regimens, and 81.4% received high-dose intravenous busulfan (HD Bu). Six hundred ninety-five (72.4%) patients received post-transplantation cyclophosphamide (PTCY)-based prophylaxis, and 91.4% additionally received anti-thymocyte globulin (ATG) and Cyclosporine A (CsA) (PTCY-ATG-CsA). Two hundred twenty-eight (23.8%) patients developed HC. The day 100 cumulative incidences of grades 2-4 and 3-4 HC were 11.1% and 4.9%. BK virus was isolated in 58.3% of urinary samples. Using HD BU myeloablative regimens increased the risk for grade 2-4 HC (hazard ratio [HR] = 1.97, P = .035), and HD BU combined with ATG-PTCY-CsA increased this 4 times (HR = 4.06, P < .001) for grade 2-4 HC compared to patients who received neither of these drugs. A significant correlation was documented between grade II-IV acute graft-versus-host disease and grade 2-4 HC (HR = 2.10, P < .001). Moreover, patients with BK-POS grade 2-4 HC had lower 1-year overall survival (HR = 1.51, P = .009) and higher non-relapse mortality (HR = 2.31, P < .001), and patients with BK-NEG grade 2-4 HC had comparable post-transplantation outcomes. In conclusion, intravenous HD Bu was identified as a predictor for grade 2-4 HC. Moreover, when HD Bu was combined with PTCY-ATG-CsA, the risk increased 4-fold. Based on the results provided by this study, preventing the onset of HC, especially in high-risk patients, is mandatory because its presence significantly increases the risk for mortality.
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10.
  • Cheng, Guang‐Shing, et al. (author)
  • Multicenter evaluation of parametric response mapping as an indicator of bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation
  • 2020
  • In: American Journal of Transplantation. - : Wiley. - 1600-6135 .- 1600-6143. ; 20:8, s. 2198-2205
  • Journal article (peer-reviewed)abstract
    • Parametric response mapping (PRM) is a novel computed tomography (CT) technology that has shown potential for assessment of bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplantation (HCT). The primary aim of this study was to evaluate whether variations in image acquisition under real-world conditions affect the PRM measurements of clinically diagnosed BOS. CT scans were obtained retrospectively from 72 HCT recipients with BOS and graft-versus-host disease from Fred Hutchinson Cancer Research Center, Karolinska Institute, and the University of Michigan. Whole lung volumetric scans were performed at inspiration and expiration using site-specific acquisition and reconstruction protocols. PRM and pulmonary function measurements were assessed. Patients with moderately severe BOS at diagnosis (median forced expiratory volume at 1 second [FEV1] 53.5% predicted) had similar characteristics between sites. Variations in site-specific CT acquisition protocols had a negligible effect on the PRM-derived small airways disease (SAD), that is, BOS measurements. PRM-derived SAD was found to correlate with FEV1% predicted and FEV1/ forced vital capacity (R = −0.236, P = .046; and R = −0.689, P < .0001, respectively), which suggests that elevated levels in the PRM measurements are primarily affected by BOS airflow obstruction and not CT scan acquisition parameters. Based on these results, PRM may be applied broadly for post-HCT diagnosis and monitoring of BOS.
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11.
  • Ek, Mats, et al. (author)
  • Biological degradation of EDTA in pulping effluents at higher pH - a laboratory study
  • 1999
  • Reports (other academic/artistic)abstract
    • The biological degradation of EDTA at different pH, sludge load and sludge age has been investigated in laboratory experiments. The experiments showed that relatively fast degradation of EDTA in the form found in this waste water (from production of TMP) took place at least at pH around 8,5 with moderate COD load and high sludge age. In continuous reactors the degradation of EDTA in a pulp and paper waste water was 2-3 mg EDTA/g SS*day at both pH 7 and 8,5, and at sludge ages from 5 to 21 days. The degradation was dependent on sludge load, and no degradation was seen above 1 g COD/g SS*day. In kinetic experiments with half strength waste water the same degradation rate (1,5-2 mg EDTA/g SS*day) was found at pH 7 and at pH 8,5 with sludge of low age (9 and 5 days SRT). Much faster degradation was found at pH 8,5 with sludge of high age (21 days in the continuous experiment). The mean degradation rate was over 10 mg EDTA/g SS*day from 20 to 5 mg EDTA/l. vmax was determined to be 35 mg EDTA/g SS*day and KM to 31 mg EDTA/l. COD removal was at least as good at pH 8,5 as at pH 7. Sludge properties were best at pH 8,5 and long sludge retention time (giving low sludge load). Both sludge volume index and residual suspended solids after sedimentation were lower than under normal conditions at pH 7. The direct cost for caustic lime would be about 15 SEK per ton of TMP, with a water like the one investigated here. This can vary a lot dependent on starting pH and buffering capacity. Costs for addition of nitrogen source could probably be omitted, but this is normally not more than 1-2 SEK per ton of TMP
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12.
  • Ek, Mats, et al. (author)
  • Kompostering av förorenad sand
  • 1999
  • Reports (other academic/artistic)abstract
    • Till en ren och homogen sand sattes 3-metylbensoesyra, p-kresol, m-xylenol, karbazol och fluoranten, vardera till en halt kring 100 mg/kg fuktig sand. Föreningarna valdes för att de ofta förekommer i mark förorenad med kreosot och petroleumprodukter. Den förorenade sanden ympades med slam från ett kommunalt avloppsreningsverk och fördelades på 10 olika tunnor för komposteringsförsök. Fukthalt (33-59% av fältkapacitet), temperatur (25-35°C) och till-sats av extra substrat och närsalter varierades i ett faktorförsök. Prover togs ut från sanden under nedbrytningsförloppet, och utgående luft från tunnorna analyserades också. Som jämförelse behandlades samma förorenade sand i slurryform, med och utan en inhibitor för biologisk aktivitet. De mest svårlösliga föreningarna, karbazol och fluoranten, blev så ojämnt fördelade i sanden att det inte gick att säga något om deras eventuella nedbrytning. Av de övriga föreningarna avlägsnades i de flesta fall 60-100% under 16 veckors försök. Både hastigheten och sluthalten påverkades av fukthalt och temperatur, däremot hade extra tillsats av substrat och närsalter ingen inverkan. Fukthalt och temperatur påverkade förhållandet mellan avgång till luft och biologisk (kemisk) omvandling. De kemiska analyserna kompletterades med biologiska test med växter och maskar. Den hämmande effekten av den ursprungliga förorenade sanden och ett par behandlade prover var ungefär den som man kunde vänta sig från tidigare försök med rena substanser. I de fall den toxiska effekten var större än den förväntade, kan skillnaden bero på synergistiska effekter eller på toxiska metaboliter
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13.
  • El-Serafi, Ibrahim, et al. (author)
  • Reduced Risk of Sinusoidal Obstruction Syndrome of the Liver after Busulfan-Cyclophosphamide Conditioning Prior to Allogeneic Hematopoietic Stem Cell Transplantation
  • 2020
  • In: Clinical and Translational Science. - : Wiley. - 1752-8054 .- 1752-8062. ; 13:2, s. 293-300
  • Journal article (peer-reviewed)abstract
    • The aim of this study is to evaluate the incidence of sinusoidal obstruction syndrome (SOS) of the liver and the clinical outcome after hematopoietic stem cell transplantation (HSCT) based on several modifications in our protocols. We retrospectively investigated 372 patients undergoing myeloablative conditioning with oral busulfan (Bu) and cyclophosphamide before allogeneic HSCT during 1990-2015. Patients' supportive care was changed in order to reduce the regimen-related toxicities. Norethisterone use was terminated in 1998, therapeutic drug monitoring of Bu was initiated in 2000, and the use of liver supportive drugs, such as ursodeoxycholic acid and N-acetyl-L-cysteine, were started in 2002 and 2009, respectively. In total, 26 patients (7.0%) developed SOS at a median of 19 days after transplantation. Of these 26 patients, 20 died at a median of 119 days after HSCT and 102 days after the diagnosis of SOS. The incidence of SOS decreased over time in accordance with the improvements in supportive care. The highest incidence of SOS was during 1995-1999 (16.2%) compared with 2.3% during 2010-2015. Overall survival for patients with SOS was 62%, 46%, and 27% at 100 days, 1 year, and 5 years after HSCT, respectively, compared with 92%, 77%, and 66% for those who did not develop SOS (P < 0.001). In conclusion, the incidence of SOS and related deaths were significantly decreased over the last years. Our institution pursues massive preventative and personalized measures for SOS. This strategy may also be applicable in other conditioning protocols in order to reduce the incidence of SOS and, hence, improve the clinical outcome.
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14.
  • El-Serafi, Ibrahim, et al. (author)
  • The effect of N-acetyl-l-cysteine (NAC) on liver toxicity and clinical outcome after hematopoietic stem cell transplantation
  • 2018
  • In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
  • Journal article (peer-reviewed)abstract
    • Busulphan (Bu) is a myeloablative drug used for conditioning prior to hematopoietic stem cell transplantation. Bu is predominantly metabolized through glutathione conjugation, a reaction that consumes the hepatic glutathione. N-acetyl-l-cysteine (NAC) is a glutathione precursor used in the treatment of acetaminophen hepatotoxicity. NAC does not interfere with the busulphan myeloablative effect. We investigated the effect of NAC concomitant treatment during busulphan conditioning on the liver enzymes as well as the clinical outcome. Prophylactic NAC treatment was given to 54 patients upon the start of busulphan conditioning. These patients were compared with 54 historical matched controls who did not receive NAC treatment. In patients treated with NAC, aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were significantly (P amp;lt; 0.05) decreased after conditioning compared to their start values. Within the NAC-group, liver enzymes were normalized in those patients (30%) who had significantly high start values. No significant decrease in enzyme levels was observed in the control group. Furthermore, NAC affected neither Bu kinetics nor clinical outcome (sinusoidal obstruction syndrome incidence, graft-versus-host disease and/or graft failure). In conclusion: NAC is a potential prophylactic treatment for hepatotoxicity during busulphan conditioning. NAC therapy did not alter busulphan kinetics or affect clinical outcome.
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15.
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16.
  • Garcia‐Horton, Alejandro, et al. (author)
  • Patient age and donor HLA matching can stratify allogeneic hematopoietic cell transplantation patients into prognostic groups
  • 2022
  • In: European Journal of Haematology. - England : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 109:6, s. 672-679
  • Journal article (peer-reviewed)abstract
    • Background: Mixed results surround the accuracy of commonly used prognostic risk scores to predict overall survival (OS) and non-relapse mortality (NRM) in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. We hypothesize that a simple prognostic score performs better than conventional scoring systems.Patients and methods: OS risk factors, HCT-CI, age-HCT-CI, and augmented-HCT-CI were studied in 299 patients who underwent allo-HCT for myeloid and lymphoid malignancies. A scoring system was developed based on results and validated in a different cohort of 455 patients.Results: Two-year OS was 51% (95% confidence interval (CI) 0.45–0.56); 2-year NRM was 34% (95% CI 0.29–0.39). HCT-CI and associated scores were grouped into 0–2 and ≥3. Age and HLA mismatch status were the only risk factors to affect OS in multivariate analysis (p = 0.02 and 0.05, respectively). HCT-CI and associated scores were not informative for OS prediction. The weighted scoring system assigned 0 to 2 points for age < 50, 50–64, or ≥65, respectively, and 0–1 points for no HLA mismatch versus any mismatch (except HLA-DQ). Distinct 2-year OS (62%, 53%, and 38% [p = <0.001]) and NRM (24%, 34%, and 43% [p = 0.02]) groups were characterized. The scoring system was validated in a second independent cohort with similar results on OS and NRM (p < 0.001).Conclusions: A simple scoring system based on recipient's age and mismatch status accurately predict OS and NRM in two distinct cohorts of allo-HCT patients. Its simplicity makes it a helpful tool to aid clinicians and patients in clinical decision-making.
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17.
  • Garming-Legert, Karin, et al. (author)
  • Oral mucositis after tacrolimus/sirolimus or cyclosporine/methotrexate as graft-versus-host disease prophylaxis
  • 2020
  • In: Oral Diseases. - : John Wiley & Sons. - 1354-523X .- 1601-0825. ; 27:5, s. 1217-1225
  • Journal article (peer-reviewed)abstract
    • Objectives: To determine whether treatment with tacrolimus plus sirolimus (Tac/Sir) as a prophylaxis for graft-versus-host disease worsens severe oral mucositis and delays healing compared to cyclosporine plus methotrexate (CsA/Mtx) following haematopoietic stem cell transplantation.Subjects and methods: The study comprised 141 patients: 73 randomized to receive Tac/Sir and 68 to receive CsA/Mtx. The oral mucositis assessment scale and toxicity grading according to WHO were used to assess the severity, peak and duration of oral mucositis from the day -3 to day 24 post-transplant.Results: Eighty-seven patients developed oral mucositis in the first 24 days post-transplant. No significant difference in oral mucositis severity between the Tac/Sir and CsA/Mtx groups was observed. The peak oral mucositis score occurred on day 10 in both groups. Although oral mucositis scores had returned to baseline in the CsA/Mtx group on day 24 post-transplant, no significant difference compared with the Tac/Sir group was found.Conclusions: The introduction of tacrolimus/sirolimus as a graft-versus-host disease prophylaxis in haematopoietic stem cell transplantation increased neither the incidence nor severity of oral mucositis compared with cyclosporine/methotrexate. Furthermore, oral mucositis healing was not prolonged and followed the same time pattern as cyclosporine/methotrexate.
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18.
  • Gerbitz, Armin, et al. (author)
  • Prevention of CMV/EBV reactivation by double-specific T cells in patients after allogeneic stem cell transplantation : results from the randomized phase I/IIa MULTIVIR-01 study
  • 2023
  • In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
  • Journal article (peer-reviewed)abstract
    • IntroductionAllogeneic stem cell transplantation is used to cure hematologic malignancies or deficiencies of the hematopoietic system. It is associated with severe immunodeficiency of the host early after transplant and therefore early reactivation of latent herpesviruses such as CMV and EBV within the first 100 days are frequent. Small studies and case series indicated that application of herpes virus specific T cells can control and prevent disease in this patient population.MethodsWe report the results of a randomized controlled multi centre phase I/IIa study (MULTIVIR-01) using a newly developed T cell product with specificity for CMV and EBV derived from the allogeneic stem cell grafts used for transplantation. The study aimed at prevention and preemptive treatment of both viruses in patients after allogeneic stem cell transplantation targeting first infusion on day +30. Primary endpoints were acute transfusion reaction and acute-graft versus-host-disease after infusion of activated T cells.ResultsThirty-three patients were screened and 9 patients were treated with a total of 25 doses of the T cell product. We show that central manufacturing can be achieved successfully under study conditions and the product can be applied without major side effects. Overall survival, transplant related mortality, cumulative incidence of graft versus host disease and number of severe adverse events were not different between treatment and control groups. Expansion of CMV/EBV specific T cells was observed in a fraction of patients, but overall there was no difference in virus reactivation.DiscussionOur study results indicate peptide stimulated epitope specific T cells derived from stem cell grafts can be administered safely for prevention and preemptive treatment of reactivation without evidence for induction of acute graft versus host disease.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT02227641.
  •  
19.
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20.
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21.
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22.
  • Lim, Yeong Jer, et al. (author)
  • COVID‐19 outcomes in haematopoietic cell transplant recipients : A systematic review and meta‐analysis
  • 2022
  • In: eJHaem. - USA : John Wiley & Sons. - 2688-6146. ; 3:3, s. 862-872
  • Journal article (peer-reviewed)abstract
    • Up-to-date information on coronavirus disease 2019 (COVID-19) outcomes and risk factors in haematopoietic cell transplantation (HCT) recipients is required to inform on decisions about cancer treatment and COVID-19 mitigation strategies. We performed a meta-analysis to address this knowledge gap. All studies with at least five patients who reported COVID-19-related deaths in HCT recipients were included. The primary outcome was COVID-19-related death. Secondary outcomes were COVID-19-related mechanical ventilation (MV) and intensive care unit (ITU) admission. The cumulative COVID-19-related death rate among HCT recipients was 21% (95% confidence interval [CI] 18%–24%), while MV and ITU admission rates were 14% (95% CI 11%–17%) and 18% (95% CI 14%–22%), respectively. Subgroup analysis showed higher death rates in patients who developed COVID-19 within 12 months of HCT (risk ratio [RR] 1.82, 95% CI 1.09–3.03), within 6 months of receiving immunosuppressant drugs (RR 2.11, 95% CI 1.38–3.20) or in the context of active graft-versus-host disease (RR 2.38, 95% CI 1.10–5.16). Our findings support the idea that HCT should remain an integral part of cancer treatment during the COVID-19 pandemic but also highlight the need to prioritise preventative measures in those patients who are at increased risk of adverse COVID-19 outcomes.
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23.
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24.
  • Machaczka, Maciej, et al. (author)
  • Allogeneic hematopoietic stem cell transplant with reduced-intensity conditioning for chronic lymphocytic leukemia in Sweden: does donor T-cell engraftment 3 months after transplant predict survival?
  • 2012
  • In: Leukemia and Lymphoma. - : Informa Healthcare. - 1042-8194 .- 1029-2403. ; 53:9, s. 1699-1705
  • Journal article (peer-reviewed)abstract
    • Thirty-eight adult patients with chronic lymphocytic leukemia (CLL) underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplant (allo-SCT) in Sweden between 1999 and 2007. The cumulative incidences of acute graft-versus-host disease (GVHD) grades II-IV and chronic GVHD were 29% and 47%, respectively. Rates of non-relapse mortality, progression-free survival (PFS) and overall survival (OS) were 18%, 47% and 74% at 1 year, and 21%, 25% and 45% at 5 years, respectively. T-cell chimerism after transplant was measured in 31 out of 34 patients (91%) surviving beyond day + 100. Seventeen patients achieved andgt; 90% donor T-cell engraftment at 3 months after allo-SCT and, compared with the 12 patients with andlt;= 90% donor T-cell engraftment, they showed favorable PFS at 1 year (82% vs. 33%, p = 0.002) and better long-term PFS and OS (p = 0.002 and 0.046, respectively). Donor T-cell engraftment of andgt; 90% at 3 months after RIC allo-SCT for CLL seems to predict favorable short-term and long-term outcome.
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25.
  • Machaczka, Maciej, et al. (author)
  • Allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning for chronic lymphocytic leukemia in Sweden : Does donor T-cell engraftment 3 months after transplantation predict survival?
  • 2012
  • In: Leukemia and Lymphoma. - London : Informa Healthcare. - 1042-8194 .- 1029-2403. ; 53:9, s. 1699-1705
  • Journal article (peer-reviewed)abstract
    • Thirty-eight adult patients with chronic lymphocytic leukemia (CLL) underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) in Sweden between 1999 and 2007. The cumulative incidences of acute GVHD grades II-IV and chronic GVHD were 29% and 48%, respectively. Rates of non-relapse mortality, progression-free survival (PFS) and overall survival (OS) were 18%, 47% and 74% at 1 year, and 21%, 25% and 45% at 5 years, respectively. T-cell chimerism after transplantation was measured in 31 out of 34 patients (91%) surviving beyond day +100. Seventeen patients achieved >90% donor T-cell engraftment at 3 months after allo-SCT and, compared with the 12 patients with ≤90% donor T-cell engraftment, they showed favorable PFS at 1 year (82% vs. 33%, P=0.002), and better long-term PFS and OS (P=0.002 and 0.05 respectively). Donor T-cell engraftment of >90% at 3 months after RIC allo-SCT for CLL seems to predict favorable short-term and long-term outcome.
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26.
  • Machaczka, Maciej, et al. (author)
  • High incidence of chronic graft-versus-host disease after myeloablative allogeneic stem cell transplantation for chronic lymphocytic leukemia in Sweden : graft-versus-leukemia effect protects against relapse
  • 2013
  • In: Medical Oncology. - : Springer Science and Business Media LLC. - 1559-131X .- 1357-0560. ; 30:4, s. 762-762
  • Journal article (peer-reviewed)abstract
    • Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment option for eligible patients with chronic lymphocytic leukemia (CLL). However, it is known that cure of CLL is only possible if a graft-versus-leukemia effect is present. Between 1994 and 2007, 48 adults underwent allo-SCT for poor-risk CLL in Sweden. Of these, ten (21%) patients aged 24-53 years (median: 46 years) received myeloablative conditioning (MAC), based on TBI and cyclophosphamide. All MAC patients had refractory, poorly controlled CLL before allo-SCT (partial remission in 9/10 patients and progressive disease in one). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II-IV was 30%. Nine patients developed chronic GVHD; extensive in four. Rates of nonrelapse mortality at 1, 3 and 10 years were 0, 10 and 20%, respectively. Two patients relapsed 36 and 53 months after transplantation. Six patients were still alive after a median follow-up time of 11.5 years (range 5.9-13.7). The probabilities of relapse-free and overall survival from 1, 3 and 5 years after transplantation were 100, 90 and 70%, and 100, 90 and 80%, respectively. Nevertheless, our analysis of long-term outcome after MAC allo-SCT for CLL suggests that younger patients with poorly controlled CLL may benefit from MAC allo-SCT.
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27.
  • Magalhaes, Isabelle, et al. (author)
  • Mesothelin Expression in Patients with High-Grade Serous Ovarian Cancer Does Not Predict Clinical Outcome But Correlates with CD11c+ Expression in Tumor
  • 2020
  • In: Advances in Therapy. - : Springer. - 0741-238X .- 1865-8652. ; 37:12, s. 5023-5031
  • Journal article (peer-reviewed)abstract
    • Introduction: Mesothelin (MSLN) is overexpressed in several tumors including ovarian cancer and is the target of current trials. There is limited and conflicting data on MSLN prognostic impact in ovarian cancer.Methods: We performed a retrospective study on patients with high-grade serous ovarian cancer, analyzing MSLN expression by immunohistochemistry and examining the correlation of its expression to overall and progression-free survival. Correlations of expression of MSLN, CD8, and macrophage markers in different tumor compartments were also investigated.Results: Positive MSLN expression was detected in 55.1% of primary tumors and 51.5% of the metastases. MSLN expression was not correlated with survival. We observed a significant positive correlation (r = 0.34, p = 0.01) between MSLN expression in the metastatic site and CD11c expression in total tumor area and perivascular area in the primary tumor.Conclusion: Our results show that MSLN expression does not correlate with clinical outcome. The impact of the correlation between MSLN and CD11c+ cells on immunotherapy outcome should be further explored.
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28.
  • Novitzky-Basso, Igor, et al. (author)
  • Population-based real-world registry study to evaluate clinical outcomes of chronic graft-versus-host disease
  • 2023
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 21:3
  • Journal article (peer-reviewed)abstract
    • Introduction: Chronic graft-versus-host disease (cGVHD) is a serious immune-mediated complication after allogeneic haematopoietic stem cell transplantation (HSCT), but in patients with malignancy, cGVHD development is associated with superior survival. Lack of reliable biomarkers and clinical underreporting means there is insufficient understanding of cGVHD clinical outcomes and balance between cGVHD treatment and maintaining beneficial graft-versus-tumour effects.Methods: We performed a Swedish population-wide registry study following patients who underwent allogeneic HSCT 2006-2015. cGVHD status was retrospectively classified using a real-world method based on the timing and extent of systemic immunosuppressive treatment.Results: cGVHD incidence among patients surviving >= 6 months post-HSCT (n = 1246) was 71.9%, significantly higher than previously reported. 5-year overall survival in patients surviving >= 6 months post-HSCT was 67.7%, 63.3%, and 65.3%, in non-, mild, and moderate-severe cGVHD, respectively. Non-cGVHD patients had a mortality risk almost five-fold higher compared to moderate-severe cGVHD patients 12-months post-HSCT. Moderate-severe cGVHD patients had greater healthcare utilization compared with mild and non cGVHD patients.Conclusion: cGVHD incidence was high among HSCT survivors. Non-cGVHD patients had higher mortality during the first 6 months of follow-up; however, moderate-severe cGVHD patients had more comorbidities and healthcare utilization. This study highlights the urgent need for new treatments and real-time methods to monitor effective immunosuppression after HSCT.
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29.
  • Novitzky‐Basso, Igor, et al. (author)
  • Anti‐thymocyte Globulin and Post‐Transplant Cyclophosphamide do not abrogate the inferior outcome risk conferred by human leukocyte antigen‐A and ‐B mismatched donors
  • 2022
  • In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 108:4, s. 288-297
  • Journal article (peer-reviewed)abstract
    • In donor selection for allogeneic stem cell transplant, several factors are considered for potential impact on transplant outcome. Previous publications suggested single HLA-mismatched unrelated donors (MMUD) may be equivalent to 10/10 matched unrelated donors (MUDs). We retrospectively examined factors affecting outcome in a single-center study using ATG followed by post-transplant cyclophosphamide, termed ATG-PTCy, GvHD prophylaxis. Fifty-two patients who received grafts from MMUD and 188 patients transplanted from MUD between January 2015 and December 2019, at Princess Margaret Cancer Centre, Canada, were enrolled. All patients received reduced-intensity conditioning. Overall survival for 9/10 recipients at 2 years was significantly worse, 37.2% versus 68.5% for 10/10 MUDs, p < .001, as were NRM at 1 year 39.5% versus 11.7%, p < .001, and GRFS at 2 years 29.8% versus 58.8%, p < .001, respectively, potentially due to higher incidence of infections including CMV. By multivariable analysis, factors correlating with survival negatively were DRI, and MMUD, whereas for NRM MMUD and increasing age were unfavorable. For GRFS significant unfavorable factors included donor age ≤32 years, female donor to male recipient, DRI high-very high and MMUD. These data suggest that MMUD, primarily HLA-A and HLA-B MMUD, confer significantly inferior outcome despite use of ATG-PTCy. Further development of novel conditioning regimens and GvHD prophylaxis is needed to mitigate these risks.
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30.
  • Novitzky‐Basso, Igor, et al. (author)
  • Anti‐thymocyte globulin and post‐transplant cyclophosphamide predisposes to inferior outcome when using cryopreserved stem cell grafts
  • 2021
  • In: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 108:1, s. 61-72
  • Journal article (peer-reviewed)abstract
    • During 2020, the concurrent novel COVID-19 pandemic lead to widespread cryopreservation of allogeneic hematopoietic cell transplant grafts based on National Marrow Donor Program and European Society of Blood and Marrow Transplantation recommendations, in order to secure grafts before the start of conditioning chemotherapy. We sought to examine the impact of this change in practice on patient outcomes. We analyzed the outcomes of 483 patients who received hematopoietic stem cell transplantation (HSCT) between August 2017 and August 2020, at Princess Margaret Cancer Centre, Canada, in the retrospective study, comparing the outcomes between those who received cryopreserved or fresh peripheral blood stem cell grafts. Overall compared with those who received fresh grafts (n = 348), patients who received cryopreserved grafts (n = 135) had reduced survival and GRFS, reduced incidence of chronic graft-versus-host disease (GvHD), delay in neutrophil engraftment, and higher graft failure (GF), with no significant difference in relapse incidence or acute GvHD. However, recipients of cryopreserved matched-related donor HSCT showed significantly worse OS, NRM, GRFS compared with fresh grafts. Multivariable analysis of the entire cohort showed significant impact of cryopreservation on OS, relapse, cGvHD, GF, and GRFS. We conclude that cryopreservation was associated with inferior outcomes post-HSCT, possibly due to the combination of ATG and post-transplant cyclophosphamide impacting differential tolerance to cryopreservation on components of the stem cell graft; further studies are warranted to elucidate mechanisms for this observation.
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31.
  • Pang, Ian, et al. (author)
  • Letermovir prophylaxis for cytomegalovirus reactivation in allogeneic hematopoietic cell transplant recipients : Single center Canadian data
  • 2024
  • In: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 112:2, s. 301-309
  • Journal article (peer-reviewed)abstract
    • Background: Cytomegalovirus (CMV) is associated with morbidity and mortality following allogeneic hematopoietic cell transplantation (alloHCT). Letermovir is a novel antiviral agent that prevents CMV reactivation in alloHCT patients, with limited data regarding influence on post-alloHCT outcomes.Methods: We retrospectively examined 273 alloHCT recipients, 158 in the non-letermovir cohort (NLC), and 115 in the cohort using letermovir prophylaxis (LC). Patients that received letermovir were CMV-seropositive and met criteria for high risk of CMV reactivation.Results: Median start of letermovir was 21 days post-alloHCT, median duration of prophylaxis was 86 days. Letermovir prophylaxis demonstrated a statistically significant reduction in first CMV reactivation (at 200 days post 63.9% in the NLC vs. 35.7% in the LC; p < .001). On univariate analysis at 1 year, overall survival (OS) for NLC was 79.6% and 79.5% for LC (p = .54). Non relapse mortality (NRM) at 1 year for NLC was 12% and 12.3% for LC (p = .69). Cumulative incidence of relapse (CIR) at 1 year was 13.9% for NLC versus 17.1 for the LC (p = .27). On multivariable analysis, there was no significant difference between the two cohorts for OS, NRM, and CIR.Conclusions: Letermovir prophylaxis started at day +21 post-alloHCT reduced CMV reactivation, with no impact on posttransplant outcomes.
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32.
  • Pereira, Mariana Pinto, et al. (author)
  • Choosing Between Older Matched Sibling Donor and Younger Matched Unrelated Donor in Allogeneic Hematopoietic Cell Transplantation : Comparison of Clinical Outcomes in Acute Myeloid Leukemia and Myelodysplastic Syndrome
  • 2023
  • In: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 29:11
  • Journal article (peer-reviewed)abstract
    • The choice between an older matched sibling donor (MSD) and a younger matched unrelated donor (MUD) in allogeneic hematopoietic cell transplantation (HCT) remains a subject of ongoing debate. In this single-center retrospective study of 377 patients who received peripheral blood stem cell (PBSC) transplants for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), we compared outcomes of 85 patients who received grafts from MSDs age >60 years and 292 patients who received grafts from MUDs age <30 years. Compared to recipients of MSD transplants, recipients of MUD transplants were younger and more likely to receive dual T cell depletion (TCD), a higher CD34(+) cell dose, and a fresh graft. Recipients of MSD transplants were maintained on immunosuppressive therapy longer than those who received MUD grafts. We found no differences in overall survival, relapse-free survival, graft-versus-host disease (GVHD)-free and relapse-free survival, nonrelapse mortality, relapse, engraftment, graft failure, and acute GVHD between recipients of MSD grafts and recipients of MUD grafts. We report a higher 30-day incidence, but not 1-year incidence, of bloodstream infections among recipients of MUD transplants compared to subjects who received their grafts from a MSD. The incidence of moderate-severe chronic GVHD was higher in MSD graft recipients compared with MUD graft recipients in univariate analysis, but not in multivariate analysis. Although this difference could reflect the greater use of dual TCD, known to be associated with very low rates of chronic GVHD in MUD transplant recipients, the incidence of moderate-severe chronic GVHD was no different between MSD and MUD transplant recipients following propensity score matching, suggesting that other variables could be responsible. Taken together, our data suggest that in patients with AML or MDS who receive PBSC transplants, such factors as convenience, ease of access, and costs should be considered when selecting an older MSD over a younger MUD.
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33.
  • Pérez-Simón, Jose A, et al. (author)
  • Evaluation of prognostic factors among patients with chronic graft-versus-host disease
  • 2012
  • In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 97:8, s. 1187-1195
  • Journal article (peer-reviewed)abstract
    • BACKGROUND:Chronic graft-versus-host disease (cGVHD) is a major complication after allogeneic stem cell transplantation with an adverse effect on both mortality and morbidity. In 2005, the National Institute of Health proposed new criteria for diagnosis and classification of chronic graft-versus-host disease for clinical trials. New sub-categories were recognized such as late onset acute graft-versus-host disease and overlap syndrome.DESIGN AND METHODS:We evaluated the prognostic impact of the new sub-categories as well as the clinical scoring system proposed by the National Institute of Health in a retrospective, multicenter study of 820 patients undergoing allogeneic stem cell transplantation between 2000 and 2006 at 3 different institutions. Patients were retrospectively categorized according to the National Institute of Health criteria from patients' medical histories.RESULTS:As far as the new sub-categories are concerned, in univariate analysis diagnosis of overlap syndrome adversely affected the outcome. Also, the number of organs involved for a cut-off value of 4 significantly influenced both cGVHD related mortality and survival. In multivariate analysis, in addition to NIH score, platelet count and performance score at the time of cGVHD diagnosis, plus gut involvement, significantly influenced outcome. These 3 variables allowed us to develop a simple score system which identifies 4 subgroups of patients with 84%, 64%, 43% and 0% overall survival at five years after cGVHD diagnosis (score 0: HR=15.96 (95% CI: 6.85-37.17), P<0.001; score 1: HR=5.47 (95% CI: 2.6-11.5), P<0.001; score 2: HR=2.8 (95% CI: 1.32-5.93), P=0.007).CONCLUSIONS:In summary, we have identified a powerful and simple tool to discriminate different subgroups of patients in terms of chronic graft-versus-host disease related mortality and survival.
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34.
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35.
  • Prem, Shruti, et al. (author)
  • Relationship between certain HLA alleles and the risk of cytomegalovirus reactivation following allogeneic hematopoietic stem cell transplantation
  • 2022
  • In: Transplant Infectious Disease. - : John Wiley & Sons. - 1398-2273 .- 1399-3062. ; 24:4
  • Journal article (peer-reviewed)abstract
    • Introduction: Evidence is emerging to support an association between certain human leukocyte antigen (HLA) alleles and the risk of cytomegalovirus (CMV) reactivation following allogeneic hematopoietic stem cell transplant (allo-HSCT). The primary aim of this study was to identify HLA alleles associated with resistance or susceptibility to CMV reactivation. Methods: We studied 586 adults who underwent al lo-HSCT for high-risk hematological malignancies. High-resolution HLA typing data were available for recipients and donors. HLA class I and II alleles observed at a frequency of >5% in our population were included in the analysis. A CMV viremia level of more than 200 IU/ml on weekly monitoring was considered to be indicative of CMV reactivation. Results: The median follow-up time in surviving patients was 21 months (range 4-74 months). The cumulative incidence of CMV reactivation at 6 months in the entire cohort was 55% (95% confidence interval [CI] 50.8%-59.2%). Mismatched donors, increasing recipient age, occurrence of acute graft versus host disease and recipient CMV seropositivity were associated with an increased risk of CMV reactivation. HLA B*07:02 (hazard ratio 0.59, 95% CI 0.40-0.83) was associated with a decreased risk of CMV reactivation. Patients who developed CMV reactivation had a lower incidence of relapse, higher transplant-related mortality (TRM) and lower overall survival (OS) than those without CMV reactivation. There was an adverse correlation of OS and TRM with increasing numbers of CMV reactivations. Conclusion: We observed that HLA B*07:02 was associated with a decreased risk of CMV reactivation. CMV reactivation was associated with lower relapse post-transplant, but this did not translate into a survival benefit due to higher TRM.
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36.
  • Queralt Salas, Maria, et al. (author)
  • High incidence but low mortality of EBV-reactivation and PTLD after alloHCT using ATG and PTCy for GVHD prophylaxis
  • 2020
  • In: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 61:13, s. 3198-3208
  • Journal article (peer-reviewed)abstract
    • We explore risk factors and impacts of post-transplant EBV-Reactivation (EBV-R) and PTLD in 270 patients that underwent RIC alloHCT using ATG-PTCy and cyclosporine for GVHD prophylaxis. Twenty-five (12%) patients had probable (n = 7) or proven (n = 18) PTLD. Patients were managed with reduction of immunosuppression and 22 with weekly rituximab (375 mg/m2 IV). ORR was 84%; 8 (32%) recipients died, and one-year OS and NRM of patients with PTLD was 59.7% and 37%, respectively. One hundred seventy-two (63.7%) recipients had EBV-R. One-year OS and RFS of patients with EBV-R were 68.2% and 60.6%, and of EBV-Negative patients were 62.1% and 50.1%, respectively. High incidence but low mortality of EBV-R and PTLD was documented. EBV-R induced a protective effect on RFS in multivariable analysis (HR 0.91, p = .011). Therefore, EBV-R may have a protective effect on RFS in this setting. Further research is necessary to evaluate the interplay of EBV-R, immune reconstitution, and post-transplant outcomes.
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37.
  • Remberger, Mats (author)
  • Cytokine production in allogeneic haematopoietic stem-cell transplantation patients
  • 1999
  • Doctoral thesis (other academic/artistic)abstract
    • Severe immunological complications may occur after haematopoietic stem-cell transplantation (HSCT). These include acute graft-versus-host disease (GVHD), veno-occlusive disease of the liver (VOD) and severe infections. Since cytokines control the behaviour of all cells involved in the immune system, it has been proposed that dysregulation of the cytokine network may be involved in these complications. We determined the serum levels of cytokines during pretransplant conditioning and during various complications. We found increased serum levels of TNF-[alpha] during conditioning in patients who later developed moderate to severe acute GVHD. Furthermore, high levels of TNF-[alpha] were associated with a lowered risk of relapse among patients with malignant disease. Diagnoses like CML and MDS were also associated with higher levels of TNF-[alpha] Another feared complication is VOID, with an incidence of 10% - 70% and a mortality rate of 30%-50%. The initiating factor appears to be endothelial injury caused by chemotherapy or chemo-radiotherapy. We found increased levels of soluble IL-2 receptors (slL-2R) during VOID. This indicates an activation of the immune system during such a complication since IL-6 and IFN-[gamma] had also increased. We likewise found extremely high levels of IL-8 during severe VOD. This is probably a marker of the extent of tissue damage. Such findings may be used as diagnostic tools and prognostic markers of VOID. A non-invasive diagnostic tool is valuable since biopsy may cause haemorrhage because the patients are often refractory to platelet transfusions during VOID. The highest levels of IL-10 occurred early during acute GVHD, with decreasing levels when GVHD persisted. Since IL-10 is an inhibitor of inflammatory reactions, this may represent an inadequate attempt by the immune system to reverse an inflammatory state. In an analysis of the serum levels of various cytokines in sibling HSCT recipients, we found a correlation between IVIG treatment and decreased serum levels of i) sIL-2R, IL-3, IL-4 and GM-CSF in patients with no complications, ii) IL-1ra in patients with acute GVHD and iii) IL-10 in those with CMV infection. Using an unrelated donor, anti-T-cell antibodies was added to the conditioning regimen to reduce the risk of rejection and GVHD. We compared the outcome using three antibodies. The highest incidence of acute GVHD II-IV occurred in patients treated with OKT-3. Marked increase in the release of inflammatory cytokines like IL-2, IFN-[gamma], TNF-[alpha] and GM-CSF were found after OKT-3 treatment. This may explain why the incidence of GVHD was increased in this group, since patients with high levels of TNF-[alpha] run a greater risk of developing GVHD. The lowest incidence of GVHD was found after treatment with Thymoglobuline. This antibody was also the most effective in depleting T-cells. In patients with CML relapses occurred only in those treated with Thymoglobuline. Conclusion: Dysregulation of cytokines is involved in the induction and effector phase of complications like acute GVHD and VOD after HSCT. This dysregulation is initiated during pre-transplant conditioning. Modulation of cytokines may be used for prevention or treatment of such complications. Cytokine analysis are also useful diagnostic tools.
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38.
  • Remberger, Mats, et al. (author)
  • Improved survival after allogeneic hematopoietic stem cell transplantation in recent years : A single-center study
  • 2011
  • In: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 17:11, s. 1688-1697
  • Journal article (peer-reviewed)abstract
    • We analyzed the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) over the past 2 decades. Between 1992 and 2009, 953 patients were treated with HSCT, mainly for a hematologic malignancy. They were divided according to 4 different time periods of treatment: 1992 to 1995, 1996 to 2000, 2001 to 2005, and 2006 to 2009. Over the years, many factors have changed considerably regarding patient age, diagnosis, disease stage, type of donor, stem cell source, genomic HLA typing, cell dose, type of conditioning, treatment of infections, use of granulocyte-colony stimulating factor (G-CSF), use of mesenchymal stem cells, use of cytotoxic T cells, and home care. When we compared the last period (2006-2009) with earlier periods, we found slower neutrophil engraftment, a higher incidence of acute graft-versus-host disease (aGVHD) of grades II-IV, and less chronic GVHD (cGHVD). The incidence of relapse was unchanged over the 4 periods (22%-25%). Overall survival (OS) and transplant-related mortality (TRM) improved significantly in the more recent periods, with the best results during the last period (2006-2009) and a 100-day TRM of 5.5%. This improvement was also apparent in a multivariate analysis. When correcting for differences between the 4 groups, the hazard ratio for mortality in the last period was 0.59 (95% confidence interval [CI]: 0.44-0.79; P < .001) and for TRM it was 0.63 (CI: 0.43-0.92; P = .02). This study shows that the combined efforts to improve outcome after HSCT have been very effective. Even though we now treat older patients with more advanced disease and use more alternative HLA nonidentical donors, OS and TRM have improved. The problem of relapse still has to be remedied. Thus, several different developments together have resulted in significantly lower TRM and improved survival after HSCT over the last few years.
  •  
39.
  • Remberger, Mats, et al. (author)
  • Second allogeneic hematopoietic stem cell transplantation : a treatment for graft failure
  • 2011
  • In: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 25:1, s. E68-E76
  • Journal article (peer-reviewed)abstract
    • We evaluated the results in 20 recent patients treated with a second hematopoietic stem cell transplantation (HSCT) after graft failure (GF). There were 10 children <18 yr of age. Ten patients had a non-malignant disease, and the other 10 had a malignant disease. In most of the transplantations, fludarabine-based reduced intensity conditioning (RIC) was given. Bone marrow was given to 11 patients, peripheral blood system cell (PBSC) in seven and cord blood to two patients. For the second transplantation (n = 20), a new donor was used in nine cases, while the initial donor was used in 11 transplants. Eight patients (40%) suffered from a second GF. Five of these patients were treated with a third HSCT. The probability of survival was 65% one yr and 60% three yr after the second HSCT. No difference in survival was found between patients transplanted with a new donor (56%) compared to those using the original donor (64%). The three-yr survival was 70% for children compared to 50% for adults (p = ns). Patients with a non-malignant disorder showed a three-yr survival of 90% compared to 20% in patients with a malignant disease (p = 0.005). We concluded that re-transplantation using RIC is a valid option for GF, especially in patients with non-malignant disorders.
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40.
  • Remberger, Mats, Professor, 1955-, et al. (author)
  • Superior Graft-versus-Host Disease-Free Relapse-Free Survival in Matched Unrelated Donor Hematopoietic Stem Cell Transplantation with Anti-Thymocyte Globulin (ATG) Compared to Matched Related Donor without ATG
  • 2021
  • In: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 27:7, s. 621.e1-621.e3
  • Journal article (peer-reviewed)abstract
    • The use of anti-T cell globulin (ATG) in allogeneic stem cell transplantation with matched unrelated donors (MUDs) is considered standard of care in many transplant centers, as these patients are at higher risk of developing acute and chronic graft-versus-host disease (GVHD). Several publications have reported reduced incidence of chronic GVHD compared to matched related donors (MRDs). This may support the idea of introducing ATG in prospective clinical trials, also in MRDs, in an effort to reduce the long-term complications with moderate and severe GVHD. We retrospectively analyzed 169 patients, in whom ATG was given to patients who underwent transplantation with MUDs (n = 124) and not MRDs (n = 45). The incidence acute GVHD II to IV and III to IV was significantly lower in the MUD group compared to the MRD group (28.2% versus 51.3% and 8.1% versus 24.7%). Extensive chronic GVHD incidence was 5% versus 40%. Our results further support the rationale for examining the efficacy of ATG in MRDs in prospective randomized trials.
  •  
41.
  • Remberger, Mats, et al. (author)
  • The CD34+ Cell Dose Matters in Hematopoietic Stem Cell Transplantation with Peripheral Blood Stem Cells from Sibling Donors
  • 2020
  • In: Clinical Hematology International. - : Springer Science and Business Media LLC. - 2590-0048. ; 2:2, s. 74-81
  • Journal article (peer-reviewed)abstract
    • The effect of CD34+ cell dose in allogeneic hematopoietic stem cell transplantation (HSCT) on overall survival (OS) and incidence of acute and chronic graft-versus-host disease (GvHD) has not been established and few studies have been performed. Our single center analysis included 189 patients with hematological malignancies who received peripheral blood stem cell (PBSC) grafts from sibling donors. Myeloablative conditioning was used in 88 cases and 101 received reduced intensity conditioning. The median CD34+ cell dose was 5.6 × 106/kg (0.6–17.0). In the multivariate analysis, a CD34 cell dose of 6–7 × 106/kg was associated with better OS and lower transplant-related mortality (TRM), while a dose of <5 × 106/kg led to increased relapse and reduced chronic GVHD (cGVHD). A high CD34 cell-dose (>6.5 × 106/kg) correlated with less acute GVHD (aGVHD) II–IV. We conclude that the CD34 cell dose has an impact on the outcome of HSCT from sibling donor PBSCs.
  •  
42.
  • Ringdén, Olle, et al. (author)
  • Cytokine levels following allogeneic hematopoietic cell transplantation : a match-pair analysis of home care versus hospital care
  • 2021
  • In: International Journal of Hematology. - : Springer Nature. - 0925-5710 .- 1865-3774. ; 113:5, s. 712-722
  • Journal article (peer-reviewed)abstract
    • Following allogeneic hematopoietic cell transplantation (HCT), patients living near the hospital were treated at home instead of in isolation in the hospital. We analyzed cytokines using Luminex assays for the first 3 weeks after HCT and compared patients treated at home (n = 42) with matched patients isolated in the hospital (n = 37). In the multivariate analysis, patients treated at home had decreased GM-CSF, IFN-γ (p < 0.01), IL-13, IL-5 (p < 0.05), and IL-2 (p < 0.07). Bloodstream infections, anti-thymocyte globulin, G-CSF treatment, immunosuppression, reduced-intensity conditioning (RIC), related vs. unrelated donors, and graft source affected various cytokine levels. When patients with RIC were analyzed separately, home care patients had reduced G-CSF (p = 0.04) and increased vascular endothelial growth factor (VEGF, p = 0.001) at 3 weeks compared with hospital care patients. Patients with low GM-CSF (p < 0.036) and low IFNγ (p = 0.07) had improved survival. Acute GVHD grades III–IV was seen in 7% and 16% of home care and hospital care patients, respectively. One-year transplantation-related mortality was 7% and 16% and survival at 5 years was 69% and 57% in the two groups, respectively. To conclude, patients treated in the hospital showed varying increased levels of GM-CSF, IFN-γ, IL-13, G-CSF, IL-5, and IL-2 and decreased VEGF, which may contribute to acute GVHD.
  •  
43.
  • Ringden, Olle, et al. (author)
  • The Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Inherited Diseases Is Influenced by HLA Match, Year of Transplantation, and Immunized Female Donor
  • 2019
  • In: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337 .- 1534-6080. ; 103:6, s. 1247-1252
  • Journal article (peer-reviewed)abstract
    • Background For many inborn errors of metabolism (IEM), allogeneic hematopoietic stem cell transplantation (HSCT) is the only cure.Methods We report the outcome in 160 patients with inherited diseases, who were treated with HSCT in 3 decades. Median age was 3 years (range 0.1-63). Grafts were from matched related donors (MRDs, 56), matched unrelated donors (MUDs, 66), or HLA-mismatched donors (38).Results Graft failure (GF) occurred in 26 patients (16%), severe acute graft-versus-host disease (GVHD) in 9 (6%), and chronic GVHD in 23 (12%). Ten-year survival was 64% before the year 2000 and 86% after that (P = 0.01). Ten-year survival for MRD grafts was 90%, as opposed to 79% for MUD grafts and 56% for HLA-mismatched grafts (P = 0.03). In multivariate analysis, GF was associated with having an HLA-mismatched donor (P < 0.05) or MUD (P = 0.015) and with reduced-intensity conditioning (P < 0.01). Death was associated with year of transplant (P = 0.015), having an HLA-mismatched donor (P < 0.001), and being a male recipient from an immune female donor (P = 0.05).Conclusions The outcome after HSCT for IEM depends on HLA match, year and immune female donor.
  •  
44.
  • Ringdén, Olle, et al. (author)
  • Transplantation of Autologous and Allogeneic Bone Marrow With Liver From A Cadaveric Donor for Primary Liver Cancer1
  • 2000
  • In: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337 .- 1534-6080. ; 69:10, s. 2043-2048
  • Journal article (other academic/artistic)abstract
    • BackgroundIn histocompatibility mismatched experimental animals, a combination of T-cell-depleted autologous and allogeneic marrow may induce mixed chimerism and tolerance. Patients with large primary liver tumors have a poor outcome. We investigated whether it were possible to induce mixed chimerism and obtain an antitumor effect in a patient with a large primary liver cancer after combined liver and bone marrow transplantation (BMT).MethodsA 46-year-old female with a primary non resectable liver cancer received a liver transplant from a cadaveric donor. Subsequently, she was conditioned with 4×2 Gy of total lymphoid irradiation, 120 mg/kg cyclophosphamide, and 7.5 Gy total body irradiation. Twelve days after liver transplantation, she received T-cell-depleted autologous : cadaveric 5/6 antigen HLA-mismatched marrow in a proportion of CD34+ cells of 0.5 : 3.0×106/kg. Chimerism status was determined with polymerase chain reaction amplification of variable number tandem repeats from DNA obtained from CD3+, CD19+, and CD45+ magnetic-bead-separated cells.ResultsThe early posttransplant period was uneventful; liver function was normal and the hematopoietic engraftment of donor and recipient origin was prompt. [alpha]-fetoprotein levels dropped from 440 to 35 µg/l. One month after marrow transplantation, donor T-cells decreased markedly. Monoclonal antibody OKT-3 and 105/kg donor T-cells were given. One month later, the patient developed diarrhea and abdominal pain. A colonoscopy showed moderate gastrointestinal acute graft-versus-host disease and a Cryptosporidium infection. Three months after BMT, she became a complete donor chimera. Chimera cells showed little, if any, reactivity in mixed lymphocyte cultures to recipient and donor cells, but reacted to third party. Five months after BMT, she developed progressive Aspergillus fumigatus pneumonia and died. No tumor was found at the autopsy.ConclusionWe obtained mixed donor-recipient hematopoietic chimerism without severe acute graft-versus-host-disease, after combined T-cell depleted autologous and allogeneic BMT and a transplantation of a liver from an HLA-mismatched cadaveric donor. Additional donor T-cells enhanced donor bone marrow engraftment, but rejected the autograft. On the basis of this first attempt, further clinical studies are warranted.
  •  
45.
  • Ruutu, Tapani, et al. (author)
  • Improved survival with ursodeoxycholic acid prophylaxis in allogeneic stem cell transplantation : long-term follow-up of a randomized study
  • 2014
  • In: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 20:1, s. 135-138
  • Journal article (peer-reviewed)abstract
    • We report the long-term results of a prospective randomized study on the use of ursodeoxycholic acid (UDCA) for prevention of hepatic complications after allogeneic stem cell transplantation. Two hundred forty-two patients, 232 with malignant disease, were randomized to receive (n = 123) or not to receive (n = 119) UDCA from the beginning of the conditioning until 90 days post-transplantation. The results were reported after 1-year follow-up. UDCA administration reduced significantly the proportion of patients developing high serum bilirubin levels as well as the incidence of severe acute graft-versus-host disease (GVHD), liver GVHD, and intestinal GVHD. In the UDCA prophylaxis group, nonrelapse mortality (NRM) was lower and overall survival better than in the control group. After a 10-year follow-up, the difference in the survival and NRM in favor of the UDCA-treated group, seen at 1 year, was maintained (survival 48% versus 38%, P = .037; NRM 28% versus 41%, P = .01). A landmark analysis in patients surviving at 1 year post-transplantation showed no significant differences between the study groups in the long-term follow-up in chronic GVHD, relapse rate, NRM, disease-free survival, or overall survival. These long-term results continue to support the useful role of UDCA in the prevention of transplant-related complications in allogeneic transplantation.
  •  
46.
  • Röttorp, Jonas, et al. (author)
  • DIKA. Driftstörningar i kommunala avloppsreningsverk - en studie av syreöverföring, ytaktiva ämnen, slamegenskaper och styrmöjligheter 1996-1998
  • 1999
  • Reports (other academic/artistic)abstract
    • Under de senaste 5-10 åren har driftstörningarna ökat i många kommunala avloppsreningsverk. Det har främst varit problem med syresättning, slammets sedimenteringsegenskaper och skumning, med ökade utsläpp som följd. Det här projektet startade med teorin att en del av problemen hade samband med den ökade användningen av biologiskt lätt nedbrytbara tensider. En viktig del i projektet var också att testa möjligheterna till övervakning och styrning av verken med multivariata metoder. En mycket stor mängd data har samlats in från fem reningsverk (Borlänge, Gävle, Haparanda, Karlstad och Örebro). Prover har tagits varannan timme under särskilda intensivprovtagningsdygn. Förutom de vanliga variablerna har då också halten av tensider och fettsyror analyserats, liksom syreöverföringen. Dessutom har verken varje vecka sammanställt en mängd driftdata inklusive mikrobiell och fysikalisk karakterisering av bioslammet. Projektet har visat att: * Tensider och fettsyror i avloppsvattnet stör syreöverföringen. * Problemen kan minskas genom att minska slambelastningen (höja slamhalten), och/eller genom att adsorbera en del av inkommande fettsyror på överskottsslammet. * Mikroskopering av bioslammet och mätningar av dess separationsegenskaper ger värdefulla upplysningar om processens tillstånd. *Det finns möjligheter att övervaka, och styra, processen i realtid med hjälp av några extra givare och multivariata modeller. Ett exempel är modellering av halten totalfosfor i inkommande vatten, som kan beräknas utifrån andra variabler.
  •  
47.
  • Sadeghi, Behnam, et al. (author)
  • Long-Term Follow-Up of a Pilot Study Using Placenta-Derived Decidua Stromal Cells for Severe Acute Graft-versus-Host Disease
  • 2019
  • In: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 54, s. 300-300
  • Journal article (peer-reviewed)abstract
    • There is a need for effective therapy with few side effects for severe acute graft-versus-host disease (GVHD). The placenta protects the fetus from the mother's haploidentical immune system during pregnancy. We found that maternal stromal cells from the fetal membrane, so-called decidua stromal cells (DSCs), are more immunosuppressive than other sources of stromal cells. We prospectively treated 21 patients (median age, 49 years; range, 1.6 to 72 years) for grade II-IV acute GVHD. All 21 patients had biopsy-proven gastrointestinal GVHD. The majority of patients were either steroid-refractory or had progressive GVHD, 11 patients after >7 days or with progression after 3 days, and 10 were refractory to steroids after >3 days. We used an improved protocol in which DSCs were thawed and infused in a buffer with 5% human albumin. DSCs were given at a median dose of 1.2 (range, 0.9 to 2.9) x 10(6) cells/kg body weight with a median of 2 (range, 1 to 6) doses, given 1 week apart. The median viability of thawed DSCs was 93% (range, 69% to 100%), and the median cell passage number was 4 (range, 2 to 4). Complete resolution of GVHD was seen in 11 patients, with a partial response in the other 10. The cumulative incidence of chronic GVHD was 52%. GVHD was mild in 6 patients, moderate in 4 patients, and severe in 1 patient based on National Institutes of Health chronic GVHD severity scoring. Nine patients died, including 3 from relapse and 1 each from acute GVHD and septicemia, Zygomycetes infection, liver insufficiency, cerebral hemorrhage, multiple organ failure, and chronic GVHD with obstructive bronchiolitis. Four-year transplantation-related mortality was 28.6%, and overall survival was 57%. Survival was similar (P= .33) to that for all 293 patients who underwent allogeneic hematopoietic cell transplantation during the same period (2012 to 2015), with 66% overall survival. DSC infusion is a novel therapy for acute GVHD grade II-IV, and a randomized trial is currently underway.
  •  
48.
  • Salas, Maria Queralt, et al. (author)
  • Improving Safety and Outcomes After Allogeneic Hematopoietic Cell Transplantation : A Single-Center Experience
  • 2022
  • In: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 28:5
  • Journal article (peer-reviewed)abstract
    • The implementation of dual T-cell depletion comprising 4.5 mg/kg of antithymocyte globulin (ATG), post-transplantation cyclophosphamide, and cyclosporine A for reduced-intensity allogeneic hematopoietic cell transplantation (HCT) independent of donor source in 2015 significantly improved graft-versus-host disease (GVHD) control at our Institution. Further advances were made between 2017 to 2020 in supportive care of allogeneic HCT recipients and were the subject of this study, with 651 adults included. Transplant outcomes were compared between patients who underwent transplantation during Period 1 (2017-2018) and Period 2 (2019-2020). Main changes implemented during the study period were reduction of ATG dose from 4.5 to 2 mg/kg in matched unrelated donor transplants, abandoning of dual T-cell depletion in matched related donor transplants, combining dual T-cell depletion with myeloablative conditioning for selected patients, and reduction of the target therapeutic cyclosporine level from 200 to 400 ng/L to 150 to 250 ng/L. Other improvements included addition of ursodiol until day 100, implementation of a double responsible physician model, and personalized patient supportive care plan focused on activity and calorie intake. The reduction in intensity of GVHD prophylaxis provided comparable acute GVHD and moderate-severe chronic GVHD between both time periods. Altogether the described improvements in transplant methodology and supportive care showed that compared to Period 1, patients transplanted in Period 2 had superior 1-year overall survival, relapse-free survival, and non-relapsemortality and showed a trend toward better GVHD- and relapse-free survival, without an increase in relapse risk. This study reports the results of outcomes-directed improvements in transplantation design, GVHD prophylaxis, and supportive care, highlighting how transplantation outcomes can be improved through careful modifications in response to meticulously monitored outcomes. (C) 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.
  •  
49.
  • Schain, Frida, et al. (author)
  • Real-world clinical characterization, healthcare resource utilization and productivity loss in chronic graft versus host patients exposed to extracorporeal photopheresis in Sweden
  • 2023
  • In: Transfusion and apheresis science. - : Elsevier BV. - 1473-0502 .- 1878-1683. ; 62:3
  • Journal article (peer-reviewed)abstract
    • Background:Extracorporeal photopheresis (ECP) is frequently used to treat moderate-severe chronic graft versus host disease (cGVHD), however limited data exists describing ECP treatment effects on healthcare and societal costs. We aimed to characterize clinical and health economic outcomes and productivity loss in cGVHD patients exposed to ECP.Methods:We identified 2708 patients aged ≥ 18 years with a record of allogeneic hematopoietic stem cell transplantation (HSCT) in the Swedish Patient Register between 2006 and 2020. Patients exposed to ECP from 3-months post HSCT (index) were included (n= 183). Data was linked to the Prescribed Drug Register, the Cause of Death Register, and the Longitudinal Integrated Database for Health Insurance and Labor Market Studies (LISA).Results:The median patient age at index was 51 years (IQR1–3; 38–61). In the 3-month period before ECP initiation compared to 9–12 months post-ECP, the cumulative three-month dose per patient decreased prednisolone/prednisone (1,381 mg vs. 658 mg, p < 0.001) and cyclosporin (12,242 mg vs. 3,501 mg, p < 0.001). Infection incidence also decreased over the same period (79.2% vs 59.1%, p < 0.001). Time spent in healthcare decreased from 68.9% to 22.1% from the first and fifth follow-up year respectively, and corresponding annual healthcare cost reduced from €27,719 to €1,981. Among patients < 66 years of age, sickness-related workplace absence decreased from 73.2% to 31.9% between the first and fifth follow-up year, with median annual productivity loss decreasing from €20,358 to €7,211 per patient.Conclusions:ECP was associated with reduced use of corticosteroids, immunosuppressive agents, and fewer infections. Furthermore, cost and healthcare utilization decreased over time.
  •  
50.
  • Schain, Frida, et al. (author)
  • Real-world study of direct medical and indirect costs and time spent in healthcare in patients with chronic graft versus host disease
  • 2021
  • In: European Journal of Health Economics. - : Springer Nature. - 1618-7598 .- 1618-7601. ; 22:1, s. 169-180
  • Journal article (peer-reviewed)abstract
    • Chronic graft versus host disease (cGVHD) is a debilitating and costly complication following haemopoietic stem cell transplantation (HSCT). This study describes the economic burden associated with cGVHD. Direct costs associated with specialised healthcare utilisation (inpatient admissions and outpatient visits), as well as indirect costs associated with sickness absence-associated productivity loss were estimated in patients who underwent allogeneic HSCT in Sweden between 2006 and 2015, linking population-based health and economic registers. To capture the period of chronic GVHD, patients were included who survived > 182 days post-HSCT (start of follow-up), and cGVHD was classified based on patient treatment records to correct for any diagnosis underreporting. Patients were classified as 'non-cGVHD' if they received no immunosuppressive treatment, 'mild cGVHD' if they received only systemic corticosteroid treatment or immunosuppressive treatment, or 'moderate-severe cGVHD' if they received extracorporeal photopheresis (ECP) only, corticosteroid treatment and immunosuppressive treatment, or systemic corticosteroid treatment and ECP treatments. Patients with moderate-severe cGVHD spent more time in healthcare, had higher healthcare resource costs and higher sickness absence-related productivity loss compared to patients with non- or mild cGVHD. The cumulative total costs during the first 3 years of follow-up were EUR 14,887,599, EUR 20,544,056, and EUR 47,811,835 for non-, mild, and moderate-severe groups, respectively. The long-term costs incurred with cGVHD following HSCT continue to be very high and significantly impacted by cGVHD severity. This study adds real-world health resource and economic insight relevant for policy-makers and healthcare providers when considering the clinical challenge of balancing immunosuppression to reduce cGVHD.
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