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  • 1.
    Groevdal, M
    et al.
    Karolinska Institute.
    Kahn, R
    Karolinska Institute.
    Jansson, M
    Karolinska Institute.
    Aggerholm, A
    Aarhus University Hospital.
    Antunovic, Petar
    Linköpings universitet, Institutionen för biomedicin och kirurgi. Linköpings universitet, Hälsouniversitetet.
    Astermark, J
    Malmö University Hospital.
    Bernell, P
    Karolinska University Hospital.
    Engstroem, L
    Rigshosp, Copenhagen.
    Linder, O
    Örebro University Hospital.
    Nilsson, L
    Lund University Hospital.
    Olsson, A
    Sahlgrens University Hospital.
    Skovholm, M
    Aalborg Hospital.
    Tangen, J
    Aalborg Hospital.
    Maintenance treatment with 5-azacitidine for patients with high risk myelodysplastic syndrome (MDS) or acute myeloid leukemia following MDS (MDS-AML) in complete remission (CR) after induction chemotherapy2009Ingår i: in Leukemia Research, vol 33, 2009, Vol. 33, s. S49-S50Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 2.
    Grovdal, M.
    et al.
    Grövdal, M., Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
    Khan, R.
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
    Aggerholm, A.
    Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.
    Antunovic, Petar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi.
    Astermark, J.
    Department for Haematology and Coagulation Disorders, Malmö University Hospital, Malmö, Sweden.
    Bernell, P.
    Division of Haematology, Department of Medicine, Karolinska University Hospital, Solna, Stockholm, Sweden.
    Engstrom, L.-M.
    Engström, L.-M., Medical Clinic, Department of Haematology, University Hospital of Norrland, Umeå, Sweden.
    Kjeldsen, L.
    Department of Haematology, Rigshospitalet, Copenhagen, Denmark.
    Linder, O.
    Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Nilsson, L.
    Haematopoietic Stem Cell Laboratory, Department of Haematology, Lund University Hospital, Lund, Sweden.
    Olsson, A.
    Department of Haematology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Wallvik, J.
    Division of Haematology, Department of Medicine, Sundsvall Hospital, Sundsvall, Sweden.
    Tangen, J.M.
    Department of Haematology, Ullevål University Hospital, Oslo, Norway.
    Oberg, G.
    Öberg, G., Department of Haematology, Uppsala Academic Hospital, Uppsala, Sweden.
    Jacobsen, S.E.
    Haematopoietic Stem Cell Laboratory, Department of Haematology, Lund University Hospital, Lund, Sweden.
    Hokland, P.
    Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.
    Porwit, A.
    Department of Pathology, Radiumhemmet, Karolinska University Hospital, Solna, Stockholm, Sweden.
    Hellstrom-Lindberg, E.
    Hellström-Lindberg, E., Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Huddinge, SE-14186 Stockholm, Sweden.
    Negative effect of DNA hypermethylation on the outcome of intensive chemotherapy in older patients with high-risk myelodysplastic syndromes and acute myeloid leukemia following myelodysplastic syndrome2007Ingår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 13, nr 23, s. 7107-7112Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Promoter hypermethylation of, for example, tumor-suppressor genes, is considered to be an important step in cancerogenesis and a negative risk factor for survival in patients with myelodysplastic syndromes (MDS), however, its role for response to therapy has not been determined. This study was designed to assess the effect of methylation status on the outcome of conventional induction chemotherapy. Experimental Design: Sixty patients with high-risk MDS or acute myeloid leukemia following MDS were treated with standard doses of daunorubicin and 1-ß-D-arabinofuranosylcytosine. Standard prognostic variables and methylation status of the P15ink4b (P15), E-cadherin (CDH), and hypermethylated in cancer1 (HIC) genes were analyzed before treatment. Results: Forty percent of the patients achieved complete remission (CR). CR rate was lower in patients with high WBC counts (P = 0.03) and high CD34 expression on bone marrow cells (P = 0.02).Whereas P15 status alonewas not significantly associatedwith CR rate (P = 0.25), no patient with hypermethylation of all three genes achieved CR (P = 0.03).Moreover, patientswith CDH methylation showed a significantly lower CR rate (P = 0.008), and CDH methylation retained its prognostic value also in the multivariate analysis. Hypermethylation was associated with increased CD34 expression, but not with other known predictive factors for response, such as cytogenetic profile. Conclusions: We show for the first time a significant effect of methylation status on the outcome of conventional chemotherapy in high-risk MDS and acute myelogenous leukemia following MDS. Provided confirmed in an independent study, our results should be used as a basis for therapeutic decision-making in this patient group. © 2007 American Association for Cancer Research.

  • 3.
    Grovdal, Michael
    et al.
    Karolinska Institute.
    Karimi, Mohsen
    Karolinska Institute.
    Khan, Rasheed
    Karolinska Institute.
    Aggerholm, Anni
    Aarhus University Hospital.
    Antunovic, Petar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Astermark, Jan
    Malmö University Hospital.
    Bernell, Per
    Malmö University Hospital.
    Engstrom, Lena-Maria
    University Norrland, Umeå.
    Kjeldsen, Lars
    Rigshospital, Copenhagen.
    Linder, Olle
    Örebro University Hospital.
    Nilsson, Lars
    Lund University Hospital.
    Olsson, Anna
    Sahlgrens University Hospital.
    Holm, Mette S.
    Aarhus University Hospital.
    Tangen, Jon M.
    Ullevaal University Hospital.
    Wallvik, Jonas
    Sundsvall Hospital.
    Oberg, Gunnar
    Academy Hospital, Uppsala.
    Hokland, Peter
    Aarhus University Hospital.
    E. Jacobsen, Sten
    Univ Lund Hosp, Haematopoiet Stem Cell Lab, S-22185 Lund, Sweden.
    Porwit, Anna
    Karolinska University Hospital.
    Hellstrom-Lindberg, Eva
    Karolinska Institute.
    Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy2010Ingår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 150, nr 3, s. 293-302Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pgreater thanThis prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction chemotherapy. Sixty patients were enrolled and treated by standard induction chemotherapy. Patients that reached CR started maintenance therapy with subcutaneous azacytidine, 5/28 d until relapse. Promoter-methylation status of CDKN2B (P15 ink4b), CDH1 and HIC1 was examined pre-induction, in CR and 6, 12 and 24 months post CR. Twenty-four (40%) patients achieved CR after induction chemotherapy and 23 started maintenance treatment with azacytidine. Median CR duration was 13 center dot 5 months, greater than 24 months in 17% of the patients, and 18-30 center dot 5 months in the four patients with trisomy 8. CR duration was not associated with CDKN2B methylation status or karyotype. Median overall survival was 20 months. Hypermethylation of CDH1 was significantly associated with low CR rate, early relapse, and short overall survival (P = 0 center dot 003). 5-azacytidine treatment, at a dose of 60 mg/m2 was well tolerated. Grade III-IV thrombocytopenia and neutropenia occurred after 9 center dot 5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients.

  • 4.
    Hulegardh, Erik
    et al.
    Sahlgrens University Hospital, Sweden; Sahlgrens University Hospital, Sweden.
    Nilsson, Christer
    Karolinska University Hospital, Sweden.
    Lazarevic, Vladimir
    Swedish Acute Myeloid Leukemia Grp; Skåne University Hospital, Sweden; Skåne University Hospital, Sweden; Lund University, Sweden.
    Garelius, Hege
    Swedish Acute Myeloid Leukemia Grp; Sahlgrens University Hospital, Sweden; Sahlgrens University Hospital, Sweden.
    Antunovic, Petar
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Swedish Acute Myeloid Leukemia Grp.
    Rangert Derolf, Asa
    Swedish Acute Myeloid Leukemia Grp; Karolinska University Hospital, Sweden; Karolinska University Hospital, Sweden.
    Mollgard, Lars
    Swedish Acute Myeloid Leukemia Grp; Sahlgrens University Hospital, Sweden; Sahlgrens University Hospital, Sweden.
    Uggla, Bertil
    Swedish Acute Myeloid Leukemia Grp; Örebro University Hospital, Sweden.
    Wennstrom, Lovisa
    Swedish Acute Myeloid Leukemia Grp; Sahlgrens University Hospital, Sweden; Sahlgrens University Hospital, Sweden.
    Wahlin, Anders
    Swedish Acute Myeloid Leukemia Grp; Umeå University, Sweden; Norrland University Hospital, Sweden.
    Hoglund, Martin
    Swedish Acute Myeloid Leukemia Grp; Academic Hospital, Sweden; Academic Hospital, Sweden.
    Juliusson, Gunnar
    Skåne University Hospital, Sweden; Skåne University Hospital, Sweden; Lund University, Sweden;Swedish Acute Myeloid Leukemia Grp.
    Stockelberg, Dick
    Swedish Acute Myeloid Leukemia Grp; Sahlgrens University Hospital, Sweden; Sahlgrens University Hospital, Sweden.
    Lehmann, Soren
    Swedish Acute Myeloid Leukemia Grp; Karolinska University Hospital, Sweden.
    Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: A report from the Swedish Acute Leukemia Registry2015Ingår i: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 90, nr 3, s. 208-214Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Patients with secondary acute myeloid leukemia (AML) often escape inclusion in clinical trials and thus, population-based studies are crucial for its accurate characterization. In this first large population-based study on secondary AML, we studied AML with an antecedent hematological disease (AHD-AML) or therapy-related AML (t-AML) in the population-based Swedish Acute Leukemia Registry. The study included 3,363 adult patients of which 2,474 (73.6%) had de novo AML, 630 (18.7%) AHD-AML, and 259 (7.7%) t-AML. Secondary AML differed significantly compared to de novo AML with respect to age, gender, and cytogenetic risk. Complete remission (CR) rates were significantly lower but early death rates similar in secondary AML. In a multivariable analysis, AHD-AML (HR 1.51; 95% CI 1.26-1.79) and t-AML (1.72; 1.38-2.15) were independent risk factors for poor survival. The negative impact of AHD-AML and t-AML on survival was highly age dependent with a considerable impact in younger patients, but without independent prognostic value in the elderly. Although patients with secondary leukemia did poorly with intensive treatment, early death rates and survival were significantly worse with palliative treatment. We conclude that secondary AML in a population-based setting has a striking impact on survival in younger AML patients, whereas it lacks prognostic value among the elderly patients.

  • 5.
    Ingram, W.
    et al.
    Department of Haematological Medicine, Kings College Hospital, London, United Kingdom.
    Lea, N.C.
    Department of Haematological Medicine, Kings College Hospital, London, United Kingdom.
    Cervera, J.
    The Servicio de Hematologia y Hemoterapia, Hospital Universitario La Fe, Valencia, Spain.
    Germing, U.
    Department of Haematology, Oncology and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany.
    Fenaux, P.
    Hematology Department, Hopital Avicenne, Bobigny, France.
    Cassinat, B.
    Hematology Department, Hopital Avicenne, Bobigny, France.
    Kiladjian, J.J.
    Hematology Department, Hopital Avicenne, Bobigny, France.
    Varkonyi, J.
    Third Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
    Antunovic, Petar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi.
    Westwood, N.B.
    Department of Haematological Medicine, Kings College Hospital, London, United Kingdom.
    Arno, M.J.
    Genomics Center, School of Biomedical and Health Sciences, Kings College London, London, United Kingdom.
    Mohamedali, A.
    Department of Haematological Medicine, Kings College Hospital, London, United Kingdom.
    Gaken, J.
    Department of Haematological Medicine, Kings College Hospital, London, United Kingdom.
    Kontou, T.
    Department of Haematological Medicine, Kings College Hospital, London, United Kingdom.
    Czepulkowski, B.H.
    Department of Haematological Medicine, Kings College Hospital, London, United Kingdom.
    Twine, N.A.
    Department of Haematological Medicine, Kings College Hospital, London, United Kingdom.
    Tamaska, J.
    National Health Centre, Semmelweis University, Budapest, Hungary.
    Csomer, J.
    Institute of Pathology and Cancer Research, Semmelweis University, Budapest, Hungary.
    Benedek, S.
    Third Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
    Gattermann, N.
    Department of Haematology, Oncology and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany.
    Zipperer, E.
    Department of Haematology, Oncology and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany.
    Giagounidis, A.
    Department of Oncology and Clinical Immunology, St-Johannes-Hospital, Duisburg, Germany.
    Garcia-Casado, Z.
    The Servicio de Hematologia y Hemoterapia, Hospital Universitario La Fe, Valencia, Spain.
    Sanz, G.
    The Servicio de Hematologia y Hemoterapia, Hospital Universitario La Fe, Valencia, Spain.
    Mufti, G.J.
    Department of Haematological Medicine, Kings College Hospital, London, United Kingdom.
    The JAK2 V617F mutation identifies a subgroup of MDS patients with isolated deletion 5q and a proliferative bone marrow [14]2006Ingår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 20, nr 7, s. 1319-1321Övrigt (Övrigt vetenskapligt)
    Abstract [en]

    [No abstract available]

  • 6.
    Juliusson, G
    et al.
    Lund University.
    Wahlin, A
    Norrland University Hospital.
    Stockelberg, D
    Sahlgrens University Hospital.
    Mollgard, L
    Karolinska University Hospital.
    Brune, M
    Sahlgrens University Hospital.
    Antunovic, Petar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Lehmann, S
    Karolinska University Hospital.
    Tidefelt, U
    Orebro University Hospital.
    Lazarevic, V
    University Lund Hospital.
    Rangert Derolf, A
    Karolinska University Hospital.
    Hoglund, M
    Uppsala Academic Hospital.
    Superior long-term survival with a high rate of allogeneic stem cell transplantation in AML (non-APL) patients below 60 years of age in BONE MARROW TRANSPLANTATION, vol 45, issue , pp S9-S102010Ingår i: BONE MARROW TRANSPLANTATION, Nature Publishing Group , 2010, Vol. 45, s. S9-S10Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 7.
    Juliusson, Gunnar
    et al.
    Lund University Hospital.
    Antunovic, Petar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Derolf, Asa
    Karolinska University Hospital.
    Lehmann, Soren
    Karolinska University Hospital.
    Mollgard, Lars
    Karolinska University Hospital.
    Stockelberg, Dick
    Sahlgrens University Hospital.
    Tidefelt, Ulf
    Örebro University Hospital.
    Wahlin, Anders
    Norrland University Hospital.
    Hoglund , Martin
    Acad Hospital, Uppsala.
    Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry2009Ingår i: BLOOD, ISSN 0006-4971 , Vol. 113, nr 18, s. 4179-4187Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Acute myeloid leukemia (AML) is most common in the elderly, and most elderly are thought to be unfit for intensive treatment because of the risk of fatal toxicity. The Swedish Acute Leukemia Registry covers 98% of all patients with AML (non-acute promyelocytic leukemia) diagnosed in 1997 to 2005 (n = 2767), with a median follow-up of 5 years, and reports eligibility for intensive therapy, performance status (PS), complete remission rates, and survival. Outcomes were strongly age and PS dependent. Early death rates were always lower with intensive therapy than with palliation only. Long-term survivors were found among elderly given intensive treatment despite poor initial PS. Total survival of elderly AML patients was better in the geographic regions where most of them were given standard intensive therapy. This analysis provides unique real world data from a large, complete, and unselected AML population, both treated and untreated, and gives background to treatment decisions for the elderly. Standard intensive treatment improves early death rates and long-term survival compared with palliation. Most AML patients up to 80 years of age should be considered fit for intensive therapy, and new therapies must be compared with standard induction.

  • 8.
    Juliusson, Gunnar
    et al.
    Lund University.
    Karlsson, Karin
    Skåne University Hospital.
    Lj Lazarevic, Vladimir
    Skåne University Hospital.
    Wahlin, Anders
    Umeå University.
    Brune, Mats
    Sahlgrens University Hospital.
    Antunovic, Petar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi.
    Derolf, Asa
    Karolinska University Hospital.
    Hagglund, Hans
    Karolinska University Hospital.
    Karbach, Holger
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Lehmann, Soren
    Karolinska University Hospital.
    Mollgard, Lars
    Karolinska University Hospital.
    Stockelberg, Dick
    Sahlgrens University Hospital.
    Hallbook, Helene
    Academic Hospital, Uppsala.
    Hoglund, Martin
    Academic Hospital, Uppsala.
    Hematopoietic Stem Cell Transplantation Rates and Long-Term Survival in Acute Myeloid and Lymphoblastic Leukemia Real-World Population-Based Data From the Swedish Acute Leukemia Registry 1997-20062011Ingår i: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 117, nr 18, s. 4238-4246Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Allogeneic stem cell transplantation (alloSCT) reduces relapse rates in acute leukemia, but outcome is hampered by toxicity. Population-based data avoid patient selection and may therefore substitute for lack of randomized trials. METHODS: We evaluated alloSCT rates within the Swedish Acute Leukemia Registry, including 3899 adult patients diagnosed from 1997 through 2006 with a coverage of 98% and a median follow-up of 6.2 years. RESULTS: AlloSCT rates and survival decreased rapidly with age andgt;55 years. The 8-year overall survival (OS) was 65% in patients andlt;30 years and 38% in patients andlt;60 years and was similar for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Among 1073 patients andlt;60 years, alloSCT was performed in 42% and 49% of patients with AML and ALL, respectively. Two-thirds of the alloSCTs were performed in first complete remission, and half used unrelated donors, the same in AML and ALL. Regional differences in management and outcome were found: 60% of AML patients andlt;40 years received alloSCT in all parts of Sweden, but two-thirds of AML patients 40-59 years had alloSCT in one region compared with one-third in other regions (Pandlt;.001), with improved 8-year OS among all AML patients in this age cohort (51% vs 30%; P = .005). CONCLUSIONS: More Swedish AML patients received alloSCT, and long-term survival was better than in recently published large international studies, despite our lack of selection bias. There was no correlation between alloSCT rate and survival in ALL. In adult AML patients andlt;60 years of age, a high alloSCT rate was associated with better long-term survival, but there was no such correlation in ALL.

  • 9.
    Juliusson, Gunnar
    et al.
    Lund Stem Cell Centre.
    Mollgard, Lars
    Karolinska University.
    Lehmann, Soren
    Karolinska Institute.
    Tidefelt, Ulf
    Örebro Med Centre Hospital.
    Stockelberg, Dick
    Sahlgrenska University Hospital.
    Brune, Mats L
    Sahlgrens University Hospital.
    Lazarevic, Vladimir
    Lund University Hospital.
    Antunovic, Petar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi.
    Wahlin, Anders
    Umeå University Hospital.
    Hoglund, Martin
    Uppsala University Hospital.
    Proportion of Adult AML Patient Population Receiving Allogeneic Stem Cell Transplantation and Long-Term Outcome: Real World Data From the Swedish National Acute Leukemia Registry. in BLOOD, vol 114, issue 22, pp 903-9032009Ingår i: BLOOD, American Society of Hematology , 2009, Vol. 114, nr 22, s. 903-903Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 10.
    Lazarevic, V.
    et al.
    Skåne University Hospital, Sweden Lund University, Sweden .
    Horstedt, A-S
    Skåne University Hospital, Sweden .
    Johansson, B.
    University of and Regional Labs Regional Skåne, Sweden Lund University, Sweden .
    Antunovic, Petar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Billstrom, R.
    Central Hospital Skovde, Sweden .
    Derolf, A.
    Karolinska University Hospital, Sweden Karolinska University Hospital, Sweden .
    Hulegardh, E.
    Sahlgrens University Hospital, Sweden .
    Lehmann, S.
    Karolinska University Hospital, Sweden Karolinska University Hospital, Sweden .
    Mollgard, L.
    Sahlgrens University Hospital, Sweden .
    Nilsson, C.
    Karolinska University Hospital, Sweden Karolinska University Hospital, Sweden .
    Peterson, S.
    Skåne University Hospital, Sweden .
    Stockelberg, D.
    Sahlgrens University Hospital, Sweden .
    Uggla, B.
    Örebro University Hospital, Sweden .
    Wennstrom, L.
    Sahlgrens University Hospital, Sweden .
    Wahlin, A.
    Umeå University, Sweden .
    Hoglund, M.
    Academic Hospital, Sweden .
    Juliusson, G.
    Skåne University Hospital, Sweden Lund University, Sweden .
    Incidence and prognostic significance of karyotypic subgroups in older patients with acute myeloid leukemia: the Swedish population-based experience2014Ingår i: Blood Cancer Journal, ISSN 2044-5385, E-ISSN 2044-5385, Vol. 4, nr e188Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Swedish population-based acute myeloid leukemia registry contains data from 3251 patients (excluding acute promyelocytic leukemia) diagnosed between 1997 and 2006. Informative cytogenetic data from 1893 patients were retrospectively added, including 1054 patients aged between 60 and 79 years. Clonal abnormalities were found in 57% of the informative karyotypes. Karyotypic patterns differed by age: t(8; 21), inv(16) and t(11q23) were more common in younger patients, whereas loss of 5q, 7q and 17p, monosomal karyotype (MK) and complex karyotypes were more common in older patients. Loss of 5q, 7q and 17p often occurred together within MK. Patients with greater than= 5 chromosome abnormalities had worse overall survival than those with fewer abnormalities or normal karyotype in all age groups. Loss of 5q, 7q and/or 17p had, in contrast to MK, a further negative impact on survival. Multivariable Cox regression analyses on risk factors in patients less than80 years with cytogenetic abnormalities and intensive treatment revealed that age and performance status had the most significant impact on survival (both Pless than0.001), followed by sex (P = 0.0135) and a karyotype including - 7/del(7q) (P = 0.048).

  • 11.
    Lazarevic, Vladimir
    et al.
    Skåne University Hospital, Sweden; Lund University, Sweden.
    Horstedt, Ann-Sofi
    Skåne University Hospital, Sweden.
    Johansson, Bertil
    University of and Regional Labs Regional Skåne, Sweden; Lund University, Sweden.
    Antunovic, Petar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US. Linköpings universitet, Hälsouniversitetet.
    Billstrom, Rolf
    Central Hospital Skovde, Sweden.
    Derolf, Asa
    Karolinska University Hospital, Sweden; Karolinska University Hospital, Sweden.
    Lehmann, Soeren
    Karolinska University Hospital, Sweden; Karolinska University Hospital, Sweden.
    Moellgard, Lars
    Sahlgrens University Hospital, Sweden.
    Peterson, Stefan
    Skåne University Hospital, Sweden.
    Stockelberg, Dick
    Sahlgrens University Hospital, Sweden.
    Uggla, Bertil
    Örebro University Hospital, Sweden.
    Vennstroem, Lovisa
    Sahlgrens University Hospital, Sweden.
    Wahlin, Anders
    Umeå University, Sweden.
    Hoeglund, Martin
    Academic Hospital, Sweden.
    Juliusson, Gunnar
    Skåne University Hospital, Sweden; Lund University, Sweden; Academic Hospital, Sweden.
    Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population-based series of acute myeloid leukaemia2015Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 94, nr 5, s. 419-423Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Unsuccessful cytogenetics (UC) in patients with acute myeloid leukaemia (AML) treated on different SWOG trials was recently reported to be associated with increased age and dismal outcome. To ascertain whether this holds true also in unselected patients with AML, we retrieved all cytogenetic reports in cases from the population-based Swedish AML Registry. Between 1997 and 2006, 1737 patients below 80yr of age without myelosarcoma or acute promyelocytic leukaemia received intensive treatment. The frequencies of UC and unperformed cytogenetics (UPC) were 2.1% and 20%, respectively. The early death rates differed between the cytogenetic subgroups (P=0.006) with the highest rates in patients with UC (14%) and UPC (12%) followed by high-risk (HR) AML, intermediate risk (IR) and standard risk (SR) cases successfully karyotyped (8.6%, 5.9%, and 5.8%, respectively). The complete remission rate was lower in UC and UPC and HR compared with the other risk groups (Pless than0.001). The overall five-year survival rates were 25% for UC and 22% for UPC, whereas the corresponding frequencies for SR, IR and HR AML patients without UC and UPC were 64%, 31% and 15%, respectively. In conclusion, lack of cytogenetic data translates into a poor prognosis.

  • 12.
    Lazarevic, Vladimir
    et al.
    Skåne University Hospital, Sweden; Lund University, Sweden.
    Rosso, Aldana
    Skåne University Hospital, Sweden.
    Juliusson, Gunnar
    Skåne University Hospital, Sweden; Lund University, Sweden.
    Antunovic, Petar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US. Linköpings universitet, Medicinska fakulteten.
    Rangert-Derolf, Asa
    Karolinska University Hospital, Sweden.
    Lehmann, Soren
    Karolinska University Hospital, Sweden.
    Mollgard, Lars
    Sahlgrens University Hospital, Sweden.
    Uggla, Bertil
    Örebro University Hospital, Sweden.
    Wennstrom, Lovisa
    Sahlgrens University Hospital, Sweden.
    Wahlin, Anders
    Umeå University, Sweden.
    Hoglund, Martin
    Academic Hospital, Sweden.
    Johansson, Bertil
    University of and Regional Labs Regional Skåne, Sweden; Lund University, Sweden.
    Prognostic significance of high hyperdiploid and triploid/tetraploid adult acute myeloid leukemia2015Ingår i: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 90, nr 9, s. 800-805Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To ascertain the clinical implications of high hyperdiploid (HH; 49-65 chromosomes) and triploid/tetraploid (TT; greater than65 chromosomes) adult acute myeloid leukemia (AML), all such cases were retrieved from the Swedish AML Registry. Of the 3,654 cytogenetically informative cases diagnosed between January 1997 and May 2014, 68 (1.9%) were HH (n=50)/TT (n=18). Patients with HH/TT were older than those with intermediate risk (IR) AML (median 71 years vs. 67 years; P=0.042) and less often had de novo AML (63% vs. 79%; P=0.004); no such differences were observed between HH/TT and complex karyotype (CK) AML. The overall survival (OS) was similar between patients with HH/TT and CK AML (median 0.9 years vs. 0.6 years; P=0.082), whereas OS was significantly longer (median 1.6 years; P=0.028) for IR AML. The OS was shorter for cases with HH than with TT (median 0.6 years vs. 1.4 years; P=0.032) and for HH/TT AMLs with adverse abnormalities (median 0.8 years vs. 1.1 years; P=0.044). In conclusion, HH/TT AML is associated with a poor outcome, but chromosome numbers greater than65 and absence of adverse aberrations seem to translate into a more favorable prognosis. Thus, HH/TT AMLs are clinically heterogeneous and should not automatically be grouped as high risk.Am. J. Hematol. 90:800-805, 2015. (c) 2015 Wiley Periodicals, Inc.

  • 13.
    Lehmann, S.
    et al.
    Karolinska University Hospital.
    Ravn, A.
    Karolinska University Hospital.
    Carlsson, L.
    Karolinska University Hospital.
    Antunovic, Petar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi.
    Deneberg, S.
    Karolinska University Hospital.
    Mollgard, L.
    Karolinska University Hospital.
    Rangert Derolf, A.
    Karolinska University Hospital.
    Stockelberg, D.
    Sahlgrens University Hospital.
    Tidefelt, U.
    Orebro University Hospital.
    Wahlin, A.
    Umea University.
    Wennstrom, L.
    Sahlgrens University Hospital.
    Hoglund, M.
    Acad Hospital, Uppsala.
    Juliusson, G.
    Skane University Hospital.
    Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry2011Ingår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 25, nr 7, s. 1128-1134Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Our knowledge about acute promyelocytic leukemia (APL) patients is mainly based on data from clinical trials, whereas population-based information is scarce. We studied APL patients diagnosed between 1997 and 2006 in the population-based Swedish Adult Acute Leukemia Registry. Of a total of 3897 acute leukemia cases, 3205 (82%) had non-APL acute myeloid leukemia (AML) and 105 (2.7%) had APL. The incidence of APL was 0.145 per 100 000 inhabitants per year. The median age at the time of diagnosis was 54 years; 62% were female and 38% male. Among younger APL patients, female sex predominated (89% of patients less than 40 years). Of the 105 APL patients, 30 (29%) died within 30 days (that is, early death (ED)) (median 4 days) and 28 (26%) within 14 days from diagnosis. In all, 41% of the EDs were due to hemorrhage; 35% of ED patients never received all-trans-retinoic acid treatment. ED rates increased with age but more clearly with poor performance status. ED was also associated with high white blood cells, lactate dehydro-genase, creatinine, C-reactive protein and low platelet count. Of non-ED patients, 97% achieved complete remission of which 16% subsequently relapsed. In total, 62% are still alive at 6.4 years median follow-up. We conclude that ED rates remain very high in an unselected APL population.

  • 14.
    Nilsson-Ehle, Herman
    et al.
    Sahlgrens University Hospital.
    Birgegard, Gunnar
    University Uppsala Hospital.
    Samuelsson, Jan
    Stockholm S Hospital.
    Antunovic, Petar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi.
    Astermark, Jan
    University Hospital MAS.
    Garelius, Hege
    Sahlgrens University Hospital.
    Engstrom, Lena M
    Umea University Hospital.
    Kjeldsen, Lars
    Rigshospital.
    Nilsson, Lars
    Lund University Hospital.
    Olsson, Anna
    Sahlgrens University Hospital.
    Skov-Holm, Mette
    Aarhus University Hospital.
    Wallvik, Jonas
    Sundsvall Hospital.
    Gulbrandsen, Nina
    Ullevaal University Hospital.
    Hellstrom-Lindberg, Eva
    Karolinska University Hospital Huddinge.
    Quality of life, physical function and MRI T2*in elderly low-risk MDS patients treated to a haemoglobin level of andgt;= 120 g/L with darbepoetin alfa +/- filgrastim or erythrocyte transfusions2011Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 87, nr 3, s. 244-252Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Anaemia in low-risk myelodysplastic syndromes (MDS) is associated with reduced quality of life (QoL). Response to treatment with erythropoietin +/- granulocyte colony-stimulating factor (G-CSF) is associated with improved QoL, but whether transfusion therapy with higher haemoglobin (Hb) target levels has similar effects is unknown. The objective for this prospective phase II Nordic multicentre trial was to assess QoL, response rate and physical function in elderly anaemic MDS patients treated to a target Hb level of andgt; 120 g /L. Methods: Thirty-six elderly patients with low-and intermediate-1 risk MDS received darbepoetin (DA) 300 mu g/wk, with the addition of G-CSF if no response. If the Hb target was reached at 16 wk, treatment was maintained until week 26. Remaining patients were transfused to reach the target level for at least 8 wk. Results: Twenty-seven patients completed the study. Response rate to DA +/- G-CSF was 67% in evaluable patients and 56% according to intention to treat. Eighteen patients reached the target Hb level according to protocol. QoL scores for fatigue, dyspnoea, constipation, and physical, role and social functioning improved significantly during study, with similar results for transfused and untransfused patients. Maintaining Hb andgt; 120 g /L did not confer a higher transfusion rate, once the target was reached. In two of fourteen patients, magnetic resonance imaging T2* indicated cardiac iron overload, however, without association with ferritin levels. Conclusions: In elderly anaemic MDS patients, an increment in haemoglobin is associated with improved QoL, whether induced by growth factor treatment or transfusion therapy.

  • 15.
    Schober, Sebastian J
    et al.
    Department of Pediatrics and Childrens Cancer Research Center, TUM School of Medicine, Technical University of Munich, Kinderklinik München Schwabing, 80804 Munich, Germany.
    von Luettichau, Irene
    Department of Pediatrics and Childrens Cancer Research Center, TUM School of Medicine, Technical University of Munich, Kinderklinik München Schwabing, 80804 Munich, Germany.
    Wawer, Angela
    Department of Pediatrics and Childrens Cancer Research Center, TUM School of Medicine, Technical University of Munich, Kinderklinik München Schwabing, 80804 Munich, Germany.
    Steinhauser, Maximilian
    Department of Pediatrics and Childrens Cancer Research Center, TUM School of Medicine, Technical University of Munich, Kinderklinik München Schwabing, 80804 Munich, Germany.
    Salat, Christoph
    Medical Center for Hematology and Oncology Munich MVZ, 80639 Munich, Germany.
    Schwinger, Wolfgang
    Department of Pediatrics, Medical University of Graz, A-8036 Graz, Austria.
    Ussowicz, Marek
    Department of Pediatric Oncology, Hematology and Bone Marrow Transplantation, Wroclaw Medical University, 50-368 Wroclaw, Poland.
    Antunovic, Petar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Regionalt Cancercentrum.
    Castagna, Luca
    Department of Oncology and Hematology, IRCCS Humanitas Cancer Center, Humanitas University, 20089, Milan, Italy.
    Kolb, Hans-Jochem
    Department of Pediatrics and Childrens Cancer Research Center, TUM School of Medicine, Technical University of Munich, Kinderklinik München Schwabing, 80804 Munich, Germany.
    Burdach, Stefan E G
    Department of Pediatrics and Childrens Cancer Research Center, TUM School of Medicine, Technical University of Munich, Kinderklinik München Schwabing, 80804 Munich, Germany; CCC München-Comprehensive Cancer Center, DKTK German Cancer Consortium Munich, 80336 Munich, Germany.
    Thiel, Uwe
    Department of Pediatrics and Childrens Cancer Research Center, TUM School of Medicine, Technical University of Munich, Kinderklinik München Schwabing, 80804 Munich, Germany.
    Donor lymphocyte infusions in adolescents and young adults for control of advanced pediatric sarcoma2018Ingår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 9, nr 32, s. 22741-22748Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusions (DLI) may induce a graft-versus-tumor effect in pediatric sarcoma patients. Here, we describe general feasibility, toxicity and efficacy of DLI after allo-SCT.

  • 16.
    Thiel, U
    et al.
    Technical University of Munich, Germany .
    Koscielniak, E
    Klinikum Stuttgart, Germany .
    Blaeschke, F
    Technical University of Munich, Germany .
    Grunewald, T G P.
    Technical University of Munich, Germany .
    Badoglio, M
    Hop St Antoine, France .
    Diaz, M A.
    Hospital Infantil University of Nino Jesus, Spain .
    Paillard, C
    CHU Clermont Ferrand, France .
    Prete, A
    Osped S Orsola Malpighi, Italy .
    Ussowicz, M
    Wroclaw Medical University, Poland .
    Lang, P
    University of Childrens Hospital, Germany .
    Fagioli, F
    Regina Margherita Childrens Hospital, Italy .
    Lutz, P
    Hop Hautepierre, France .
    Ehninger, G
    University Hospital Carl Gustav Carus, Germany .
    Schneider, P
    Rouen University Hospital, France .
    Santucci, A
    University of Perugia, Italy .
    Bader, P
    Goethe University of Frankfurt, Germany .
    Gruhn, B
    Jena University Hospital, Germany .
    Faraci, M
    G Gaslini Childrens Research Institute, Italy .
    Antunovic, Petar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Styczynski, J
    Coll Medical UMK, Poland .
    Krueger, W H.
    Ernst Moritz Arndt University of Greifswald, Germany .
    Castagna, L
    Ist Clin Humanitas, Italy .
    Rohrlich, P
    University of Franche Comte, France .
    Ouachee-Chardin, M
    Hop Robert Debre, France .
    Salmon, A
    CHU Nancy Brabois, France .
    Peters, C
    St Anna Childrens Hospital, Austria .
    Bregni, M
    Osped Circolo, Italy .
    Burdach, S
    Technical University of Munich, Germany .
    Allogeneic stem cell transplantation for patients with advanced rhabdomyosarcoma: a retrospective assessment2013Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 109, nr 10, s. 2523-2532Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Allogeneic haematopoietic stem cell transplantation (allo-SCT) may provide donor cytotoxic T cell-/NK cell-mediated disease control in patients with rhabdomyosarcoma (RMS). However, little is known about the prevalence of graft-vs-RMS effects and only a few case experiences have been reported. less thanbrgreater than less thanbrgreater thanMethods: We evaluated allo-SCT outcomes of 30 European Group for Blood and Marrow Transplantation (EBMT)-registered patients with advanced RMS regarding toxicity, progression-free survival (PFS) and overall survival (OS) after allo-SCT. Twenty patients were conditioned with reduced intensity and ten with high-dose chemotherapy. Twenty-three patients were transplanted with HLA-matched and seven with HLA-mismatched grafts. Three patients additionally received donor lymphocyte infusions (DLIs). Median follow-up was 9 months. less thanbrgreater than less thanbrgreater thanResults: Three-year OS was 20% (s. e.+/- 8%) with a median survival time of 12 months. Cumulative risk of progression was 67% (s. e.+/- 10%) and 11% (s. e.+/- 6%) for death of complications. Thirteen patients developed acute graft-vs-host disease (GvHD) and five developed chronic GvHD. Eighteen patients died of disease and four of complications. Eight patients survived in complete remission (CR) (median: 44 months). No patients with residual disease before allo-SCT were converted to CR. less thanbrgreater than less thanbrgreater thanConclusion: The use of allo-SCT in patients with advanced RMS is currently experimental. In a subset of patients, it may constitute a valuable approach for consolidating CR, but this needs to be validated in prospective trials.

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