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Article: Novel approaches in GVHD therapy.

Svennilson, J

2005 Volume 35 Suppl 1, Page(s) S65–7

Abstract: Severe graft-versus-host disease is a lethal complication to allogeneic haemopoietic stem cell transplantation. This short review gives an overview of novel treatment strategies. Psoralen-enhanced UVA irradiation (PUVA), extracorpoal PUVA, antibodies ... ...

Abstract	Severe graft-versus-host disease is a lethal complication to allogeneic haemopoietic stem cell transplantation. This short review gives an overview of novel treatment strategies. Psoralen-enhanced UVA irradiation (PUVA), extracorpoal PUVA, antibodies against IL-2 and TNF-alpha, thalidomide, octreotide, and mesenchymal stem cells are briefly discussed.
MeSH term(s)	Graft vs Host Disease/therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunosuppressive Agents/therapeutic use ; Mesenchymal Stem Cell Transplantation ; PUVA Therapy
Chemical Substances	Immunosuppressive Agents
Language	English
Publishing date	2005-03
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	632854-4
ISSN	1476-5365 ; 0268-3369 ; 0951-3078
ISSN (online)	1476-5365
ISSN	0268-3369 ; 0951-3078
DOI	10.1038/sj.bmt.1704850
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Article: Is it time to reduce toxicity by non-myeloablative conditioning for allogeneic stem cell transplantation in children?

Svennilson, J / Ringdén, O

Pediatric transplantation

2000 Volume 4, Issue 4, Page(s) 247–251

MeSH term(s)	Child ; Child, Preschool ; Hematopoietic Stem Cell Transplantation/methods ; Humans ; Leukemia/therapy ; Transplantation Conditioning/adverse effects ; Transplantation Conditioning/methods ; Transplantation, Homologous
Language	English
Publishing date	2000-07-07
Publishing country	Denmark
Document type	Comment ; Editorial
ZDB-ID	1390284-2
ISSN	1399-3046 ; 1397-3142
ISSN (online)	1399-3046
ISSN	1397-3142
DOI	10.1034/j.1399-3046.2000.00029.x
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Article: Dopamine in the developing kidney.

Svennilson, J / Aperia, A

The International journal of developmental biology

1999 Volume 43, Issue 5, Page(s) 441–443

Abstract: The adult kidney has a high rate of dopamine (DA) production, metabolism, and signalling. The non-neuronal DA system in the adult kidney is of utmost importance for the regulation of salt metabolism. DA may also act as a transcription factor and may be ... ...

Abstract	The adult kidney has a high rate of dopamine (DA) production, metabolism, and signalling. The non-neuronal DA system in the adult kidney is of utmost importance for the regulation of salt metabolism. DA may also act as a transcription factor and may be of importance for tissue differentiation. In the central nervous system, D1 receptors require the dopamine- and cAMP-regulated phosphoprotein with a molecular weight of 32,000 Dalton (DARPP-32) to mediate their actions. The renal D1 mediates DARPP-32 activation via a cascade involving cAMP and PKA, and protein kinase C (PKC) activation via phospholipase C. Active DARPP-32 has a specific inhibitory effect on protein phosphatase 1 (PP1), leaving, e.g. Na+,K+-ATPase in a phosphorylated, inactive, state. Thus, dopamine acts as a natriuretic hormone in the mature kidney. Here, we discuss the age-dependent distribution and some functional aspects of several parts of the renal dopamine system (dopamine, AADC, COMT, D1 receptor, and DARPP-32) during renal morphogenesis.
MeSH term(s)	Animals ; Dopamine/metabolism ; Dopamine/physiology ; Dopamine and cAMP-Regulated Phosphoprotein 32 ; Kidney/embryology ; Kidney/growth & development ; Kidney/metabolism ; Morphogenesis ; Nerve Tissue Proteins ; Phosphoproteins/metabolism ; Rats
Chemical Substances	Dopamine and cAMP-Regulated Phosphoprotein 32 ; Nerve Tissue Proteins ; Phosphoproteins ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	1999
Publishing country	Spain
Document type	Journal Article ; Review
ZDB-ID	1036070-0
ISSN	1696-3547 ; 0214-6282
ISSN (online)	1696-3547
ISSN	0214-6282
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Article ; Online: Renal, gastrointestinal, and hepatic late effects in survivors of childhood acute myeloid leukemia treated with chemotherapy only--a NOPHO-AML study.

Skou, Anne-Sofie / Glosli, Heidi / Jahnukainen, Kirsi / Jarfelt, Marianne / Jónmundsson, Guðmundur K / Malmros-Svennilson, Johan / Nysom, Karsten / Hasle, Henrik

Pediatric blood & cancer

2014 Volume 61, Issue 9, Page(s) 1638–1643

Abstract: Background: We investigated the spectrum, frequency, and risk factors for renal, gastrointestinal, and hepatic late adverse effects in survivors of childhood acute myeloid leukemia (AML) without relapse treated with chemotherapy alone according to three ...

Abstract	Background: We investigated the spectrum, frequency, and risk factors for renal, gastrointestinal, and hepatic late adverse effects in survivors of childhood acute myeloid leukemia (AML) without relapse treated with chemotherapy alone according to three consecutive AML trials by the Nordic Society of Pediatric Hematology and Oncology (NOPHO). Methods: A population-based cohort of children treated for AML according to the NOPHO-AML-84, -88, and -93 trials included 138 eligible survivors of whom 102 (74%) completed a questionnaire and 104 (75%) had a clinical examination and blood sampling performed. Eighty-five of 94 (90%) eligible sibling controls completed a similar questionnaire. Siblings had no clinical examination or blood sampling performed. Results: At a median of 11 years (range 4-25) after diagnosis, renal, gastrointestinal, and hepatic disorders were rare both in survivors of childhood AML and in sibling controls, with no significant differences. Ferritin was elevated in 21 (21%) AML survivors but none had biochemical signs of liver damage. Viral hepatitis was present in three and cholelithiasis in two AML survivors. One adult survivor had hypertension, two had slightly elevated systolic blood pressure, and eight survivors had slightly elevated diastolic blood pressure. These persons all had normal creatinine and cystatin C levels. Marginal abnormalities in potassium, magnesium, calcium, or bicarbonate levels were found in 34 survivors. Conclusion: Survivors of childhood AML treated with chemotherapy only experienced few renal, gastrointestinal, and hepatic late effects.
MeSH term(s)	Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Gastrointestinal Diseases/chemically induced ; Gastrointestinal Diseases/diagnosis ; Gastrointestinal Diseases/mortality ; Humans ; Infant ; Infant, Newborn ; Kidney Diseases/chemically induced ; Kidney Diseases/diagnosis ; Kidney Diseases/mortality ; Leukemia, Myeloid, Acute/drug therapy ; Liver Diseases/diagnosis ; Liver Diseases/etiology ; Liver Diseases/mortality ; Male ; Prognosis ; Survival Rate ; Survivors/statistics & numerical data ; Young Adult
Language	English
Publishing date	2014-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.25069
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Article: Risk factors for moderate-to-severe acute graft-vs.-host disease after allogeneic stem cell transplantation in children.

Svennilson, Johan / Remberger, Mats / Ringdén, Olle

Pediatric transplantation

2003 Volume 7, Issue 2, Page(s) 130–136

Abstract: Severe acute graft-vs.-host disease (aGVHD) remains a major cause of transplantation-related mortality. However, because of a graft-vs.-leukaemia effect, a mild (grade I) aGVHD is desirable. As risk factors predisposing for aGVHD are not necessarily the ... ...

Abstract	Severe acute graft-vs.-host disease (aGVHD) remains a major cause of transplantation-related mortality. However, because of a graft-vs.-leukaemia effect, a mild (grade I) aGVHD is desirable. As risk factors predisposing for aGVHD are not necessarily the same in children and adults, we have performed a retrospective analysis of risk factors (RFs) for grade II-IV aGVHD in 258 paediatric patients undergoing allogeneic stem cell transplantation at our centre. Thirty-two potential RFs were assessed with univariate analysis in logistic regression. Eleven factors were selected for further evaluation in stepwise elimination multivariate analysis. Three independent RFs were found: (1) donor other than human lekocyte antigen (HLA)-identical sibling [odds ratio (OR) 6.1, p < 0.001); (2) single drug [cyclosporine A (CsA) or methotrexate (Mtx)] graft-vs.-host disease (GVHD) prophylaxis (OR 7.0, p < 0.001); and (3) ABO disparity of any kind (OR 2.4, p = 0.02). The RFs were additive: moderate-to-severe aGVHD was seen in none of the patients without any RFs; in 16% with one RF; in 32% with two RFs and in 67% with all three RFs present. Single drug GVHD prophylaxis (CsA or Mtx), any kind of ABO mismatch, and non-sibling donors are RFs for grade II-IV acute GVHD in paediatric SCT. We encourage the use of combination GVHD prophylaxis in children. ABO mismatch should be considered when choosing between otherwise equally suitable donors.
MeSH term(s)	Acute Disease ; Adolescent ; Child ; Child, Preschool ; Female ; Graft vs Host Disease/etiology ; Graft vs Host Disease/prevention & control ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunosuppression/methods ; Infant ; Infant, Newborn ; Logistic Models ; Male ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Transplantation, Homologous
Language	English
Publishing date	2003-02-05
Publishing country	Denmark
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1390284-2
ISSN	1399-3046 ; 1397-3142
ISSN (online)	1399-3046
ISSN	1397-3142
DOI	10.1034/j.1399-3046.2003.00030.x
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Article ; Online: A reduced intensity conditioning protocol associated with excellent survival in patients with myelofibrosis.

George, B / Kerridge, I / Gottlieb, D / Huang, G / Hertzberg, M / Svennilson, J / Bradstock, K

Bone marrow transplantation

2008 Volume 42, Issue 8, Page(s) 567–568

MeSH term(s)	Adult ; Female ; Humans ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; Primary Myelofibrosis/genetics ; Primary Myelofibrosis/therapy ; Remission Induction ; Transplantation Conditioning/methods ; Transplantation, Homologous
Language	English
Publishing date	2008-10
Publishing country	England
Document type	Letter
ZDB-ID	632854-4
ISSN	1476-5365 ; 0268-3369 ; 0951-3078
ISSN (online)	1476-5365
ISSN	0268-3369 ; 0951-3078
DOI	10.1038/bmt.2008.219
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Zs.A 2168: Show issues

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Article: Age-dependent expression of protein phosphatase 2A in the developing rat kidney.

Svennilson, J / Sandberg-Nordqvist, A / Aperia, A

Pediatric nephrology (Berlin, Germany)

1999 Volume 13, Issue 9, Page(s) 800–805

Abstract: Several lines of evidence suggest that the serine/threonine protein phosphatase (PP)2A is of vital importance for cell cycle regulation, cell differentiation, and signal transduction. This prompted us to study the expression of the mRNA for PP2A ... ...

Abstract	Several lines of evidence suggest that the serine/threonine protein phosphatase (PP)2A is of vital importance for cell cycle regulation, cell differentiation, and signal transduction. This prompted us to study the expression of the mRNA for PP2A catalytic isoforms alpha and beta in the developing rat kidney using in situ hybridization histochemistry. The expression patterns of the two isoforms were strikingly similar. Both were ubiquitously expressed in early metanephric kidneys. Later in gestation they were expressed in the nephrogenic zone. Strong expression was observed on postnatal day (PN) 10. This was followed by a downregulation at PN20, i.e., when nephrogenesis is completed. The expression in the adult kidney was very weak and mainly confined to the medulla. In a phosphatase activity assay, PP2A accounted for 78% of the total serine/threonine phosphatase activity in embryonic day 15 rat kidneys. PP1 was the main contributor to the remaining activity. In conclusion, PP2A is the major serine/threonine phosphatase in fetal kidneys. The age-dependent expression pattern supports the concept that this enzyme is of particular importance during renal morphogenesis and development.
MeSH term(s)	Aging ; Animals ; Animals, Newborn ; Embryonic and Fetal Development ; Enzyme Inhibitors/pharmacology ; Gene Expression Regulation, Developmental ; In Situ Hybridization ; Kidney/embryology ; Kidney/enzymology ; Okadaic Acid/pharmacology ; Phosphoprotein Phosphatases/biosynthesis ; Phosphorylation ; Protein Phosphatase 2 ; Rats ; Rats, Sprague-Dawley ; Time Factors
Chemical Substances	Enzyme Inhibitors ; Okadaic Acid (1W21G5Q4N2) ; Phosphoprotein Phosphatases (EC 3.1.3.16) ; Protein Phosphatase 2 (EC 3.1.3.16)
Language	English
Publishing date	1999-11
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s004670050704
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Article ; Online: Quality of health in survivors of childhood acute myeloid leukemia treated with chemotherapy only: a NOPHO-AML study.

Molgaard-Hansen, Lene / Glosli, Heidi / Jahnukainen, Kirsi / Jarfelt, Marianne / Jónmundsson, Guðmundur K / Malmros-Svennilson, Johan / Nysom, Karsten / Hasle, Henrik

Pediatric blood & cancer

2011 Volume 57, Issue 7, Page(s) 1222–1229

Abstract: Background: More than 60% of children with acute myeloid leukemia (AML) become long-term survivors, and approximately 50% are cured with chemotherapy only. Limited data exist about their long-term morbidity and social outcomes. The aim of the study was ... ...

Abstract	Background: More than 60% of children with acute myeloid leukemia (AML) become long-term survivors, and approximately 50% are cured with chemotherapy only. Limited data exist about their long-term morbidity and social outcomes. The aim of the study was to compare the self-reported use of health care services, health experience, social outcomes, and lifestyle behavior of AML survivors with that of their sibling controls. Methods: This population-based study included 138 children treated for AML according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO)-AML-84, -88, and -93 trials, and alive by June 30, 2007. Patients treated with hematopoietic stem cell transplantation (HSCT) or relapse were not included. Altogether, 102 (74%) survivors and 91% of their siblings completed a questionnaire. Results: The median follow-up was 11 (range 4-25) years after diagnosis. AML survivors had no increased rate of hospitalization compared with sibling controls, but were more often receiving prescription drugs, especially for asthma (23% vs. 9%, P = 0.03). Self-reported health experience was excellent or very good in 77% and comparable with that of siblings. Educational achievement, employment, and marital status were comparable in the two groups. Among surviving AML patients, 23% were current smokers and 24% of their siblings were current smokers. Conclusions: The self-reported health of children treated on NOPHO-AML protocols without HSCT was good, and their use of health care services was limited. Reported health and social outcomes were comparable to those of their siblings. Many survivors were smoking which may increase the risk of late effects.
MeSH term(s)	Adolescent ; Adult ; Age of Onset ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Health Status ; Humans ; Infant ; Infant, Newborn ; Leukemia, Myeloid, Acute/complications ; Leukemia, Myeloid, Acute/drug therapy ; Male ; Quality of Life ; Surveys and Questionnaires ; Survivors/statistics & numerical data ; Young Adult
Language	English
Publishing date	2011-12-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.22931
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Article ; Online: Single versus double unrelated umbilical cord blood units for allogeneic transplantation in adults with advanced haematological malignancies: a retrospective comparison of outcomes.

Bradstock, K / Hertzberg, M / Kerridge, I / Svennilson, J / George, B / McGurgan, M / Huang, G / Antonenas, V / Gottlieb, D

Internal medicine journal

2009 Volume 39, Issue 11, Page(s) 744–751

Abstract: Background: Unrelated umbilical cord blood has emerged as an alternative stem cell source for allogeneic transplantation for patients with haematological malignancies, but in adults is limited by the low number of stem cells present in banked cord blood ...

Abstract	Background: Unrelated umbilical cord blood has emerged as an alternative stem cell source for allogeneic transplantation for patients with haematological malignancies, but in adults is limited by the low number of stem cells present in banked cord blood units. We report our experience with double cord blood transplants for adult patients. The aim of the study was to compare the outcomes of double unrelated cord blood transplants in adults with poor prognosis haematological diseases with single cord blood transplants. Methods: Eleven patients, median age 27 years and median weight 69 kg, received transplants of two partially matched unrelated cord blood units after myeloablative conditioning therapy. Results: Neutrophil recovery to 0.5 x 10(9)/L was seen by median day 32 (18-53), and platelet recovery to 50 x 10(9)/L by day 91 (56-381). These results were not significantly different from those reported in patients receiving single cord blood transplants. Acute graft-versus-host disease of grades II-IV was seen in four patients, but no chronic graft-versus-host disease occurred. Transplant-related complications were responsible for the deaths of five patients in the first 3 months post-transplant, whereas two patients died of relapse of their haematological malignancy. Four patients survive, disease free, 17-33 months post-transplant. Conclusion: Transplantation using two partially matched unrelated cord blood units did not appear to result in improvements either in engraftment or survival, as compared with a previous cohort of patients receiving single cord blood units. Further strategies appear to be needed to reduce the duration of severe neutropenia and reduce the high transplant-related mortality in these patients.
MeSH term(s)	Adolescent ; Adult ; Cord Blood Stem Cell Transplantation/methods ; Female ; Fetal Blood/transplantation ; Graft Survival ; Hematologic Neoplasms/mortality ; Hematologic Neoplasms/surgery ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate/trends ; Transplantation, Homologous ; Treatment Outcome ; Young Adult
Language	English
Publishing date	2009-11
Publishing country	Australia
Document type	Comparative Study ; Journal Article
ZDB-ID	2045436-3
ISSN	1445-5994 ; 1444-0903
ISSN (online)	1445-5994
ISSN	1444-0903
DOI	10.1111/j.1445-5994.2008.01825.x
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Article: Protein kinase C in the developing kidney: isoform expression and effects of ceramide and PKC inhibitors.

Serlachius, E / Svennilson, J / Schalling, M / Aperia, A

Kidney international

1997 Volume 52, Issue 4, Page(s) 901–910

Abstract: Protein kinase C (PKC) is a serine/threonine kinase recognized as a key enzyme in signal transduction mechanisms in various biological processes. During development, PKC is involved in the regulation of growth and differentiation. In mature tissue PKC is ...

Abstract	Protein kinase C (PKC) is a serine/threonine kinase recognized as a key enzyme in signal transduction mechanisms in various biological processes. During development, PKC is involved in the regulation of growth and differentiation. In mature tissue PKC is important for homeostatic functions. We studied PKC with regard to expression and effects on differentiation, growth and apoptosis in the developing kidney. Using in situ hybridization, we demonstrate age-dependent expression of PKC alpha, PKC delta, PKC zeta and PKC lambda during fetal and postnatal kidney development. The endogenous sphingolipid product ceramide, as well as specific PKC inhibitors, disturbed nephron formation and induced apoptosis in organ cultures of E13 kidneys. In primary cell cultures of proximal tubule cells, ceramide and the specific PKC inhibitors induced apoptosis. In conclusion, PKC alpha, PKC delta, PKC zeta and PKC lambda are expressed in an age-dependent pattern during kidney development. Inhibition of PKC disturbs nephron formation, inhibits growth and induces apoptosis in the developing kidney. The findings suggest that PKC plays an important role in regulating normal kidney growth and differentiation.
MeSH term(s)	Animals ; Animals, Newborn/growth & development ; Animals, Newborn/metabolism ; Ceramides/pharmacology ; Embryonic and Fetal Development ; Enzyme Inhibitors/pharmacology ; Fetus/metabolism ; Fetus/physiology ; In Situ Hybridization ; Isoenzymes/metabolism ; Kidney/embryology ; Kidney/growth & development ; Kidney/metabolism ; Protein Kinase C/antagonists & inhibitors ; Protein Kinase C/metabolism ; Rats/embryology ; Rats/growth & development ; Rats, Sprague-Dawley
Chemical Substances	Ceramides ; Enzyme Inhibitors ; Isoenzymes ; Protein Kinase C (EC 2.7.11.13)
Language	English
Publishing date	1997-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1038/ki.1997.411
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