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  • 1.
    Arvidson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kildal, Morten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Linde, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Toxic epidermal necrolysis and hemolytic uremic syndrome after allogeneic stem-cell transplantation2007In: Pediatric Transplantation, ISSN 1397-3142, E-ISSN 1399-3046, Vol. 11, no 6, p. 689-693Article in journal (Refereed)
    Abstract [en]

    TEN and HUS are challenging complications with excessive mortality after HSCT. We report the development of these two conditions in combination in a nine-yr-old boy after HSCT from an unrelated donor. TEN with skin detachment of more than 90% of body surface area developed after initial treatment for GvHD. Within a few days of admission to the burns unit, the patient developed severe hemolysis, hypertension, thrombocytopenia, and acute renal failure consistent with HUS, apparently caused by CSA. The management included intensive care in a burns unit, accelerated drug removal using plasmapheresis, and a dedicated multi-disciplinary team approach to balance immunosuppression and infections management in a situation with extensive skin detachment. The patient survived and recovered renal function but requires continued treatment for severe GvHD. Suspecting and identifying causative drugs together with meticulous supportive care in the burns unit is essential in the management of these patients and long-term survival is possible.

  • 2.
    Frisk, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Arvidson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Risk factors for cardiovascular disease are increased in young adults treated with stem cell transplantation during childhood2012In: Pediatric Transplantation, ISSN 1397-3142, E-ISSN 1399-3046, Vol. 16, no 4, p. 385-391Article in journal (Refereed)
    Abstract [en]

    We measured risk factors for CVD in 18 patients at a median of 18.2 yr after SCT and in sex and age-matched controls. Three patients (17%), but none of the controls, met the criteria for the MetS (p = 0.25). In the patients, we found higher levels of triglycerides (0.94 vs. 0.62 mm, p = 0.019), total cholesterol (5.1 vs. 4.0 mm, p = 0.017), LDL (3.4 vs. 2.6 mm, p = 0.019), apolipoprotein B (1.04 vs. 0.74 g/L, p = 0.004), apolipoprotein B/A1 ratio (0.7 vs. 0.5, p = 0.026), and lower levels of adiponectin (4.9 vs. 7.5 mg/L, p = 0.008) than in the controls. The patients had a lower GHmax (9 vs. 20.7 mU/L, p = 0.002). GHmax was significantly correlated inversely with triglycerides (r = -0.64, p = 0.008), total cholesterol (r = -0.61, p = 0.011), apolipoprotein B (r = -0.60, p = 0.014), and apolipoprotein B/A1 ratio (r = -0.66, p = 0.005). We recorded a significantly thicker carotid intima layer among the patients than among matched controls (0.15 vs. 0.13 mm, p = 0.034). The level of adiponectin correlated inversely with carotid intima thickness (r = -0.55, p = 0.023). After SCT in childhood, long-term survivors may be at risk of developing premature CVD.

  • 3.
    Frisk, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Arvidson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Normal long-term parathyroid function after autologous bone marrow transplantation in children2007In: Pediatric Transplantation, ISSN 1397-3142, E-ISSN 1399-3046, Vol. 11, no 2, p. 205-208Article in journal (Refereed)
    Abstract [en]

    Parathyroid function was recently reported to be affected in more than one-third of pediatric BMT patients conditioned without irradiation. Our aim was to describe parathyroid function in children with malignant hematological disease after autologous BMT with and without TBI. PTH, albumin-corrected serum calcium, and serum phosphate were analyzed in 35 children followed for six months to nine yr after BMT. Twelve patients were conditioned with chemotherapy alone, and 23 patients received TBI as well. In the TBI group, 11 patients had previously received additional CRT. We found normal levels of PTH in children post-BMT, with the exception of four patients (11%) who showed transient PTH elevation during the first year of follow-up, There was no difference between those who had received irradiation and those who had not. Serum calcium was unchanged after BMT. An age-corrected quotient of serum phosphate decreased slightly. Renal function which was normal before BMT decreased slightly in both groups after BMT, but was within the normal range. Parathyroid function was found to be normal during the time frame of this study, irrespective of whether irradiation had been given.

  • 4.
    Gustafsson, Britt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology. Karolinska Inst, Dept Clin Intervent & Technol CLINTEC, Stockholm, Sweden.;Childrens Univ Hosp, Dept Womens & Childrens Hlth, Pediat Oncol, Uppsala, Sweden..
    Frisk, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology. Childrens Univ Hosp, Dept Womens & Childrens Hlth, Pediat Oncol, Uppsala, Sweden.
    Szakos, Attilla
    Karolinska Univ Hosp, Dept Pathol & Cytol, Stockholm, Sweden..
    Sadeghi, Behnam
    Karolinska Inst, Dept Lab Med, Div Therapeut Immunol, Stockholm, Sweden..
    Ringden, Olle
    Karolinska Inst, Dept Lab Med, Div Therapeut Immunol, Stockholm, Sweden..
    Frost, B M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology. Childrens Univ Hosp, Dept Womens & Childrens Hlth, Pediat Oncol, Uppsala, Sweden.
    Successful treatment with placenta-derived decidual stromal cells in a pediatric patient with life-threatening acute gastrointestinal graft-versus-host disease2017In: Pediatric Transplantation, ISSN 1397-3142, E-ISSN 1399-3046, Vol. 21, no 5, article id e12990Article in journal (Refereed)
    Abstract [en]

    Severe aGvHD is a life-threatening complication after allogeneic HSCT. The GI tract is considered to play a key role in aGvHD, where the disease process can start and is one of the major target organs. Here, we present a case of a one-year-old child with a life-threatening GI-aGvHD stage IV, post-HSCT, resistant to steroids and MMF for 4 weeks. He was successfully treated with placenta-derived DSC.

  • 5.
    Lindahl Norberg, Annika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care. Karolinska Institutet.
    Mellgren, Karin
    Winiarski, Jacek
    Forinder, Ulla
    Relationship between problems related to child late effects and parent burnout after pediatric hematopoietic stem cell transplantation2014In: Pediatric Transplantation, ISSN 1397-3142, E-ISSN 1399-3046, Vol. 18, no 3, p. 302-309Article in journal (Refereed)
    Abstract [en]

    A few studies have indicated that parents' reactions to a child's serious disease may entail long-term stress for the parents. However, further knowledge of its consequences is valuable. The aim of the study was to investigate the occurrence of burnout in a Swedish national sample of parents of children who had undergone HSCT and survived. Burnout (Shirom-Melamed Burnout Questionnaire) and estimations of the child's health status (Lansky/Karnofsky estimations and study-specific questions) were self-reported by 159 mothers and 123 fathers. In addition, physicians made estimations of the child's health status (Lansky/Karnofsky estimations). Nonparametric tests revealed that burnout symptoms occurred more often among fathers of children who had undergone transplantation within the last five yr compared to fathers of children with no history of serious disease (34.4% vs. 19.9%). Burnout among mothers and fathers was associated with the child's number and severity of health impairments up to five yr after the child underwent HSCT (Spearman's rho for mothers 0.26-0.36 and for fathers 0.36-0.61). In conclusion, chronic stress in parents after a child's HSCT seems to abate eventually. However, parents should be monitored and offered adequate support when needed. Moreover, the situation of fathers in the often mother-dominated pediatric setting should receive more attention in research as well as in the clinic.

  • 6.
    Malenicka, S.
    et al.
    Karolinska Inst, Karolinska Univ Hosp Huddinge, Astrid Lindgren Childrens Hosp, Dept Pediat Gastroenterol Hepatol & Nutr,CLINTEC, Stockholm, Sweden..
    Ericzon, B. -G
    Jorgensen, M. H.
    Rigshosp, Dept Pediat & Adolescent Med, Copenhagen, Denmark..
    Isoniemi, H.
    Univ Helsinki, Dept Transplantat Surg, Cent Hosp, Helsinki, Finland..
    Karlsen, T. H.
    Oslo Univ Hosp, Dept Gastroenterol, Rikshosp, Oslo, Norway..
    Krantz, M.
    Queen Silvia Childrens Hosp, Dept Pediat Gastroenterol Hepatol & Nutr, Gothenburg, Sweden..
    Naeser, V.
    Rigshosp, Fac Med, Copenhagen, Denmark..
    Olausson, M.
    Sahlgrens Univ Hosp, Dept Transplantat Surg, Gothenburg, Sweden..
    Rasmussen, A.
    Rigshosp, Dept Transplantat Surg, Copenhagen, Denmark..
    Rönnholm, K.
    Univ Helsinki, Cent Hosp, Dept Pediat Nephrol, Helsinki, Finland..
    Sanengen, T.
    Oslo Univ Hosp, Dept Pediat Gastroenterol, Rikshosp, Oslo, Norway..
    Scholz, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery. Univ Uppsala Hosp, Dept Transplantat Surg, Uppsala, Sweden..
    Fischler, B.
    Karolinska Inst, Karolinska Univ Hosp Huddinge, Astrid Lindgren Childrens Hosp, Dept Pediat Gastroenterol Hepatol & Nutr,CLINTEC, Stockholm, Sweden..
    Nemeth, A.
    Karolinska Inst, Karolinska Univ Hosp Huddinge, Astrid Lindgren Childrens Hosp, Dept Pediat Gastroenterol Hepatol & Nutr,CLINTEC, Stockholm, Sweden..
    Impaired intention-to-treat survival after listing for liver transplantation in children with biliary atresia compared to other chronic liver diseases: 20 years' experience from the Nordic countries2017In: Pediatric Transplantation, ISSN 1397-3142, E-ISSN 1399-3046, Vol. 21, no 2, article id e12851Article in journal (Refereed)
    Abstract [en]

    Biliary atresia (BA) is the most common indication for LT in children. We investigated whether this diagnosis per se, compared to other chronic liver diseases (OCLD), had an influence on patient survival. Data from 421 Scandinavian children, 194 with BA and 227 with OCLD, listed for LT between 1990 and 2010 were analyzed. The intention-to-treat survival and influencing risk factors were studied. Patients with BA had higher risk of death after listing than patients with OCLD. The youngest (< 1 year) and smallest (< 10 kg) children with the highest bilirubin (> 510 mu mol/L), highest INR (> 1.6), and highest PELD score (> 20) listed during 1990s had the worst outcome. Given the same PELD score, patients with BA had higher risk of death than patients with OCLD. For adolescents, low weight/BMI was the only prognostic marker. Impaired intention-to-treat survival in patients with BA was mainly explained by more advanced liver disease in younger ages and higher proportion of young children in the BA group rather than diagnosis per se. PELD score predicted death, but seemed to underestimate the severity of liver disease in patients with BA. Poor nutritional status and severe cholestasis had negative impact on survival, supporting the "sickest children first" allocation policy and correction of malnutrition before surgery.

  • 7.
    Mellgren, Karin
    et al.
    Univ Gothenburg, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden..
    Arvidson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Toporski, Jacek
    Skane Univ Hosp, Dept Pediat, Sect Pediat Oncol Hematol, Lund, Sweden..
    Winiarski, Jacek
    Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Chimerism analysis in clinical practice and its relevance for the detection of graft rejection and malignant relapse in pediatric hematopoietic stem cell transplant patients2015In: Pediatric Transplantation, ISSN 1397-3142, E-ISSN 1399-3046, Vol. 19, no 7, p. 758-766Article in journal (Refereed)
    Abstract [en]

    Chimerism and clinical outcome data from 244 hematopoietic stem cell transplants in 218 children were retrospectively analyzed to assess their relevance for the detection of graft rejection and malignant relapse. Patients transplanted for a non-malignant disease had significantly higher proportions of residual recipient T cells in peripheral blood at one, three, and sixmonths compared with patients transplanted for malignant disease. Recipient T-cell levels were below 50% at onemonth after transplantation in most patients (129 of 152 transplants). Graft rejection occurred more frequently in the group of patients with high levels of recipient cells at onemonth (10 graft rejections in the 23 patients with recipient T cells >50% at onemonth as compared to seven graft rejections occurred in 129 patients with recipient T cells <50% (p<0.001). Multilineage chimerism data in 87 children with leukemia at one, three, and sixmonths after transplantation were not correlated with subsequent relapse of malignant disease. In conclusion, early analysis of lineage-specific chimerism in peripheral blood can be used to identify patients who are at high risk of graft rejection. However, the efficacy of early chimerism analysis for predicting leukemia relapse was limited.

  • 8. Rubin, Johanna
    et al.
    Frost, Britt-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Arvidson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wide, Katarina
    Gustafsson-Jernberg, Åsa
    Gustafsson, Britt
    Intrathecal chemoprophylaxis after HSCT in children2008In: Pediatric Transplantation, ISSN 1397-3142, E-ISSN 1399-3046, Vol. 12, no 8, p. 889-895Article in journal (Refereed)
    Abstract [en]

    At present, the literature on the efficacy and risks of i.t. chemotherapy to children after HSCT is scarce. Current practices to reduce the risk of leukemic relapse in the CNS after HSCT differ between centers of transplantation. We compared 74 patients (56 ALL/18 AML), who received i.t. therapy post-HSCT with 46 patients (36 ALL/10 AML) who did not receive post-HSCT i.t. therapy. The patients were transplanted at the University Children's Hospital, Uppsala or the Karolinska University Hospital, Huddinge, two Swedish transplantation units with different routines concerning i.t. therapy after HSCT. The primary end-point was the number of isolated CNS relapses. Secondary end-points were other types of relapse, death, and neurological complications. There was no statistically significant difference in the incidence of CNS relapses between the groups (p > 0.05). I.t. therapy did not reduce the overall incidence of isolated CNS relapse or mortality. Our study did not demonstrate a protective effect of i.t. therapy indicating that post-HSCT i.t. therapy may only be of limited use in the treatment of acute childhood leukemia. We conclude that with the risks present, i.t. therapy should be carefully evaluated, and only considered in high-risk cases.

  • 9.
    Svenberg, Petter
    et al.
    Oncology/Coagulation Section, Karolinska University Hospital, Stockholm, Sweden.
    Remberger, Mats
    Department of Oncology/Pathology, Karolinska Institute, Stockholm, Sweden.
    Uzunel, Mehmet
    Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
    Mattsson, Jonas
    Department of Oncology/Pathology, Karolinska Institute, Stockholm, Sweden.
    Gustafsson, Britt
    Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, Sweden.
    Fjaertoft, Gustav
    Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, Sweden.
    Sundin, Mikael
    Division of Pediatrics, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden.
    Winiarski, Jacek
    Division of Pediatrics, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden.
    Ringdén, Olle
    Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
    Improved overall survival for pediatric patients undergoing allogeneic hematopoietic stem cell transplantation - A comparison of the last two decades.2016In: Pediatric Transplantation, ISSN 1397-3142, E-ISSN 1399-3046, Vol. 20, no 5, p. 667-74Article in journal (Refereed)
    Abstract [en]

    Pediatric protocols for allogeneic hematopoietic SCT have been altered during the last two decades. To compare the outcomes in children (<18 yr old), who underwent SCT at our center during 1992-2002 (P1) and 2003-2013 (P2). We retrospectively analyzed 188 patients in P1 and 201 patients in P2. The most significant protocol changes during P2 compared with P1 were a decrease in MAC protocols, particularly those containing TBI, an increase in RIC protocols, and altered GvHD prophylaxis. In addition, P2 had more patients with nonmalignant diagnoses (p = 0.002), more mismatched (MM) donors (p = 0.01), and more umbilical CB grafts (p = 0.03). Mesenchymal or DSCs were used for severe acute GvHD during P2. Three-yr OS in P1 was 58%, and in P2, it was 78% (p < 0.001). Improved OS was seen in both malignant disorders (51% vs. 68%; p = 0.05) and nonmalignant disorders (77% vs. 87%; p = 0.04). Multivariate analysis showed that SCT during P2 was associated with reduced mortality (HR = 0.57; p = 0.005), reduced TRM (HR = 0.57; p = 0.03), unchanged relapse rate, similar rate of GF, less chronic GvHD (HR = 0.49; p = 0.01), and more acute GvHD (HR = 1.77, p = 0.007). During recent years, OS has improved at our center, possibly reflecting the introduction of less toxic conditioning regimens and a number of other methodological developments in SCT.

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