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  • 1.
    Bergfelt, E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Kozlowski, P.
    Univ Orebro, Fac Med & Hlth, Dept Med Sci, Haematol, Orebro, Sweden..
    Ahlberg, L.
    Univ Hosp Linkoping, Dept Haematol, Linkoping, Sweden..
    Bernell, P.
    Karolinska Univ, Karolinska Inst, Dept Med, Div Haematol, Stockholm, Sweden..
    Hulegardh, E.
    Sahlgrens Univ Hosp, Dept Haematol & Coagulat, Gothenburg, Sweden..
    Karbach, H.
    Karlsson, K.
    Univ Hosp Umea, Ctr Canc, Dept Haematol, Umea, Sweden.;Skane Univ Hosp, Dept Haematol, Lund, Sweden..
    Tomaszewska-Toporska, B.
    Skane Univ Hosp, Dept Haematol, Lund, Sweden..
    Astrom, M.
    Univ Orebro, Fac Med & Hlth, Dept Med Sci, Haematol, Orebro, Sweden..
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Relapse Of Acute Lymphoblastic Leukaemia In Older/Elderly Patients - A Swedish Population-Based Study2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, p. 34-35Article in journal (Other academic)
  • 2.
    Bergfelt, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Kozlowski, P.
    Ahlberg, L.
    Hulegardh, E.
    Hägglund, H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Karlsson, K.
    Markuszewska-Kuczymska, A.
    Tomaszewska-Toporska, B.
    Smedmyr, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Astrom, M.
    Amini, Rose Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Minimal Residual Disease in Adults with Philadelphia Negative B-Cell Precursor Acute Lymphoblastic Leukemia a Swedish Population-Based Study2014In: Haematologica (online), ISSN 0390-6078, E-ISSN 1592-8721, Vol. 99, no S1, p. 279-280Article in journal (Other academic)
  • 3.
    Bergfelt, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Kozlowski, P.
    Univ Orebro, Fac Med & Hlth, Dept Med, Haematol Sect, SE-70182 Orebro, Sweden..
    Astrom, M.
    Univ Orebro, Fac Med & Hlth, Dept Med, Haematol Sect, SE-70182 Orebro, Sweden..
    Ahlberg, L.
    Linkoping Univ Hosp, Dept Haematol, S-58185 Linkoping, Sweden..
    Bernell, P.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Div Haematol, Stockholm, Sweden..
    Hulegardh, E.
    Sahlgrens Univ Hosp, Dept Haematol & Coagulat, Gothenburg, Sweden..
    Karbach, H.
    Umea Univ Hosp, Ctr Canc, Dept Haematol, S-90185 Umea, Sweden..
    Karlsson, K.
    Skane Univ Hosp, Dept Haematol, Lund, Sweden..
    Tomaszewska-Toporska, B.
    Skane Univ Hosp, Dept Haematol, Lund, Sweden..
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    PROGNOSIS IN OLDER/ELDERLY PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKAEMIA DIAGNOSED 2005-2012: RESULTS FROM A SWEDISH POPULATION-BASED STUDY2015In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, p. 202-202Article in journal (Other academic)
  • 4.
    Bergfelt, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Kozlowski, Piotr
    Ahlberg, Lucia
    Hulegardh, Erik
    Hagglund, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Karlsson, Karin
    Markuszewska-Kuczymska, Alicja
    Tomaszewska-Toporska, Beata
    Smedmyr, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Astrom, Maria
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Hallböök, Hélene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Satisfactory outcome after intensive chemotherapy with pragmatic use of minimal residual disease (MRD) monitoring in older patients with Philadelphia-negative B cell precursor acute lymphoblastic leukaemia: a Swedish registry-based study2015In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 32, no 4, article id 135Article in journal (Refereed)
    Abstract [en]

    The introduction of minimal residual disease (MRD) monitoring, in the Swedish national guidelines for acute lymphoblastic leukaemia, was evaluated in 35 patients aged 46-79 years (median 61), who were diagnosed from 2007 to 2011 and treated with high-intensity, block-based chemotherapy (ABCDV/VABA induction). Both a high complete remission rate (91 %) and acceptable overall survival (OS) rate (47 %) at 5 years were achieved. MRD by flow cytometry was measured in 73 % of the patients reaching complete remission after the first course, but was omitted by the clinicians for eight patients who were either over 70 years of age or already met conventional high-risk criteria. Factors negatively influencing OS were age over 65 years and WHO status >= 2. MRD < 0.1 % after induction had positive impact on continuous complete remission but not on OS. Only five patients were allocated to allogeneic haematopoietic stem cell transplantation in first remission, mainly due to conventional high risk factors. Thus, use of intensive remission induction therapy is effective in a selection of older patients. In a population for whom the possibilities of treatment escalation are limited, the optimal role of MRD monitoring remains to be determined.

  • 5.
    Enblad, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Karlsson, Hannah
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Gammelgård, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Wenthe, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Lövgren, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Wikstrom, Kristina I.
    Karolinska Univ Hosp Huddinge, VECURA, Stockholm, Sweden.
    Essand, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Savoldo, Barbara
    Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Dotti, Gianpietro
    Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
    Brenner, Malcolm K.
    Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Loskog, Angelica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia2018In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 24, no 24, p. 6185-6194Article in journal (Refereed)
    Abstract [en]

    Purpose: The chimeric antigen receptor (CAR) T-cell therapy has been effective for patients with CD19(+) B-cell malignancies. Most studies have investigated the second-generation CARs with either CD28 or 4-1BB costimulatory domains in the CAR receptor. Here, we describe the first clinical phase I/IIa trial using third-generation CAR T cells targeting CD19 to evaluate safety and efficacy.

    Patients and Methods: Fifteen patients with B-cell lymphoma or leukemia were treated with CAR T cells. The patients with lymphoma received chemotherapy during CAR manufacture and 11 of 15 were given low-dose cyclophosphamide and fludarabine conditioning prior to CAR infusion. Peripheral blood was sampled before and at multiple time points after CAR infusion to evaluate the persistence of CAR T cells and for immune profiling, using quantitative PCR, flow cytometry, and a proteomic array.

    Results: Treatment with third-generation CAR T cells was generally safe with 4 patients requiring hospitalization due to adverse reactions. Six of the 15 patients had initial complete responses [4/11 lymphoma and 2/4 acute lymphoblastic leukemia (ALL)], and 3 of the patients with lymphoma were in remission at 3 months. Two patients are still alive. Best predictor of response was a good immune status prior to CAR infusion with high IL12, DC-Lamp, Fas ligand, and TRAIL. Responding patients had low monocytic myeloid-derived suppressor cells (MDSCs; CD14(+)CD33(+)HLA(-)DR(-)) and low levels of IL6, IL8, NAP3, sPDL1, and sPDL2.

    Conclusions: Third-generation CARs may be efficient in patients with advanced B-cell lymphoproliferative malignancy with only modest toxicity. Immune profiling pre- and posttreatment can be used to find response biomarkers.

  • 6.
    Enblad, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Karlsson, Hannah
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Wenthe, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Wikström, Kristina I.
    Karolinska Hosp, VECURA, Huddinge, Sweden..
    Essand, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Savoldo, Barbara
    Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA..
    Dotti, Gianpietro
    Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA..
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Brenner, Malcolm K.
    Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA..
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Loskog, Angelica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    A Clinical Trial Using Third Generation CD19 Targeting CAR T Cells for Relapsed Lymphoma and Leukemia2016In: Molecular Therapy, ISSN 1525-0016, E-ISSN 1525-0024, Vol. 24, p. S295-S296Article in journal (Other academic)
  • 7.
    Enblad, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Karlsson, Hannah
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Wikström, Kristina
    Karolinska Univ Hosp, VECURA, Stockholm, Sweden..
    Essand, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Savoldo, Barbara
    Baylor Collage Med, Ctr Cell & Gene Therapy, Houston, TX USA..
    Brenner, Malcolm K.
    Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.;Houston Methodist Hosp, Houston, TX USA..
    Dotti, Gianpietro
    Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.;Houston Methodist Hosp, Houston, TX USA..
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Loskog, Angelica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Third Generation CD19-CAR T Cells for Relapsed and Refractory Lymphoma and Leukemia Report from the Swedish Phase I/IIa Trial2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 23Article in journal (Other academic)
  • 8. Frandsen, Thomas Leth
    et al.
    Heyman, Mats
    Abrahamsson, Jonas
    Vettenranta, Kim
    Asberg, Ann
    Vaitkeviciene, Goda
    Pruunsild, Kaie
    Toft, Nina
    Birgens, Henrik
    Hallböök, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Quist-Paulsen, Petter
    Griskevicius, Laimonas
    Helt, Louise
    Hansen, Birgitte Vilsboll
    Schmiegelow, Kjeld
    Complying with the European Clinical Trials directive while surviving the administrative pressure: An alternative approach to toxicity registration in a cancer trial2014In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 50, no 2, p. 251-259Article in journal (Refereed)
    Abstract [en]

    The European Clinical Trials Directive of 2004 has increased the amount of paper work and reduced the number of initiated clinical trials. Particularly multinational trials have been delayed. To meet this challenge we developed a novel, simplified, fast and easy strategy for on-line toxicity registration for patients treated according to the Nordic/Baltic acute lymphoblastic leukaemia protocol, NOPHO ALL 2008, for children and young adults, including three randomisations. We used a risk-assessment based approach, avoiding reporting of expected adverse events and instead concentrating on 20 well-known serious, but rarer events with focus on changes in therapy introduced in the treatment protocol. This toxicity registration strategy was approved by the relevant regulatory authorities in all seven countries involved, as compliant within the EU directive of 2004. The centre compliance to registration was excellent with 98.9% of all patients being registered within 5 weeks from the requested quarterly registration. Currently, four toxicities (thrombosis, fungal infections, pancreatitis and allergic reactions) have been chosen for further detailed exploration due to the cumulative fraction of patients with positive registrations exceeding 5%. This toxicity registration offers real-time toxicity profiles of the total study cohort and provides early warnings of specific toxicities that require further investigation.

  • 9.
    Giebel, Sebastian
    et al.
    Maria Sklodowska Curie Inst Canc Ctr, Gliwice Branch, Gliwice, Poland.
    Marks, David, I
    Univ Hosp Bristol Natl Hlth Serv Fdn Trust, Bristol, Avon, England.
    Boissel, Nicolas
    Hop St Louis, Paris, France.
    Baron, Frederic
    Univ Liege, CHU Sart Tilman, Liege, Belgium.
    Chiaretti, Sabina
    Sapienza Univ, Rome, Italy.
    Ciceri, Fabio
    Ist Sci San Raffaele, Milan, Italy.
    Cornelissen, Jan J.
    Erasmus MC, Univ Med Ctr, Canc Inst, Rotterdam, Netherlands.
    Doubek, Michael
    Univ Hosp, Brno, Czech Republic.
    Esteve, Jordi
    Hosp Clin Barcelona, IDIBAPS, Barcelona, Spain.
    Fielding, Adele
    Univ Coll London Hosp, North London Canc Network, London, England.
    Foa, Robin
    Sapienza Univ, Rome, Italy.
    Gorin, Norbert-Claude
    EBMT Acute Leukemia Working Party Off, Paris, France;Hosp St Antoine, Paris, France.
    Gokbuget, Nicola
    Maria Sklodowska Curie Inst Canc Ctr, Gliwice Branch, Gliwice, Poland;Hop St Louis, Paris, France.
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Hoelzer, Dieter
    Goethe Univ, Univ Hosp, Frankfurt, Germany.
    Paravichnikova, Elena
    Russia Federat Minist Publ Hlth, FGBU Hematol Res Ctr, Moscow, Russia.
    Ribera, Josep-Maria
    ICO Hosp Germans Trias & Pujol, Jose Carreras Res Inst, Badalona, Spain.
    Savani, Bipin
    Vanderbilt Univ, Med Ctr, Nashville, TN USA.
    Rijneveld, Anita W.
    Erasmus MC, Univ Med Ctr, Canc Inst, Rotterdam, Netherlands.
    Schmid, Christoph
    Ludwig Maximilians Univ Munchen, Klinikum Augsburg, Munich, Germany.
    Wartiovaara-Kautto, Ulla
    Helsinki Univ Hosp, Helsinki, Finland.
    Mohty, Mohamad
    Univ Coll London Hosp, North London Canc Network, London, England;EBMT Acute Leukemia Working Party Off, Paris, France.
    Nagler, Arnon
    Univ Coll London Hosp, North London Canc Network, London, England;Cha Sheba Med Ctr, Tel Hashomer, Israel.
    Dombret, Herve
    Hop St Louis, Paris, France.
    Hematopoietic stem cell transplantation for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first remission: a position statement of the European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL) and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)2019In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 54, no 6, p. 798-809Article, review/survey (Refereed)
    Abstract [en]

    Allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission is a standard of care for adult patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) and high risk of relapse. However, the stratification systems vary among study groups. Inadequate response at the level of minimal residual disease is the most commonly accepted factor indicating the need for alloHSCT. In this consensus paper on behalf of the European Working Group for Adult Acute Lymphoblastic Leukemia and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we summarize available evidence and reflect current clinical practice in major European study groups regarding both indications for HSCT and particular aspects of the procedure including the choice of donor, source of stem cells and conditioning. Finally, we propose recommendations for daily clinical practice as well as for planning of prospective trials.

  • 10. Giebel, Sebastian
    et al.
    Thomas, Xavier
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Geissler, Klaus
    Boiron, Jean-Michel
    Huguet, Francoise
    Koller, Elisabeth
    Jaeger, Ulrich
    Smedmyr, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Hellmann, Andrzej
    Holowiecki, Jerzy
    The prophylactic use of granulocyte-colony stimulating factor during remission induction is associated with increased leukaemia-free survival of adults with acute lymphoblastic leukaemia: A joint analysis of five randomised trials on behalf of the EWALL2012In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 48, no 3, p. 360-367Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Granulocyte-colony stimulating factor (G-CSF) is used to prevent febrile neutropenia and support intense chemotherapy. However, its impact on long-term outcome in oncological patients including adults with acute lymphoblastic leukaemia (ALL) has not been determined so far.

    METHODS:

    In the current study follow-up data from individual patients recruited in five multicentre, prospective, randomised trials were pooled to perform a joint analysis. Among 347 adults and adolescents with ALL, 185 were assigned to receive prophylactically G-CSF along with induction chemotherapy while 162 patients were treated without G-CSF support.

    RESULTS:

    With the median follow-up of 5.3years, there was a tendency towards increased 5year probability of the overall survival for the G-CSF arm compared to the controls (32%±4% versus 23%±4%, p=.07), which reached statistical significance in a subgroup of T-ALL (51%±8% versus 29%±9%, p=.01) and among patients aged 21-40years (44%±6% versus 27%±6%, p=.03). The probability of leukaemia-free survival was 38%±4% and 24%±4% (p=.01) while the median remission duration equalled 33 and 17months (p=.007), respectively. In a multivariate analysis the prophylactic use of G-CSF was independently associated with reduced risk of relapse (hazard ratio (HR)=.64, p=.007) and treatment failure (HR=.67, p=.02).

    CONCLUSIONS:

    The prophylactic use of G-CSF during induction of ALL is associated with improved long-term outcome and should be recommended especially in a setting of T-ALL and in 'young adults'. Our analysis provides the first direct evidence coming from prospective trials for the impact of primary G-CSF prophylaxis on disease-free survival of oncological patients.

  • 11. Gustaf, Edgren
    et al.
    Bjorkholm, Magnus
    Bernell, Per
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Dickman, Paul W.
    Survival from Acute Lymphoblastic Leukemia (ALL) in Adult Patients in the United States and Sweden: Evidence of Recent Improvement2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 12.
    Hallböök, Helene
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Barbany, Gisela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Åleskog, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Björnberg, Annelie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Lindhagen, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    In vitro activity of imatinib in cells from patients with adult acute lymphoblastic leukemia2005In: Anti-Cancer Drugs, ISSN 0959-4973, E-ISSN 1473-5741, Vol. 16, no 6, p. 631-634Article in journal (Refereed)
    Abstract [en]

    We evaluated the in vitro activity of imatinib on BCR-ABL-positive and -negative tumor cells from patients with adult acute lymphoblastic leukemia (ALL), and investigated in vitro interactions between imatinib and conventional agents. A non-clonogenic cytotoxicity assay was used to analyze p190 BCR-ABL-positive (n = 4), p210 BCR-ABL-positive (n = 2) and BCR-ABL-negative (n = 9) tumor cells from adult ALL patients. The in vitro cytotoxic effect of imatinib was studied alone, and in combination with the cytotoxic agents cytarabine, prednisolone, vincristine, daunorubicin, asparaginase and mercaptopurine. The BCR-ABL-positive samples were significantly (p < 0.05) more sensitive to imatinib than the BCR-ABL-negative at the concentrations 0.1, 1 and 10 muM. Interestingly, the two p210 samples were somewhat less sensitive to imatinib than the p190 samples. Daunorubicin, prednisolone and cytarabine showed the largest benefit from combination with imatinib compared to the most active single agent. The study confirms that drug sensitivity to imatinib is specific for BCR-ABL-positive samples. The results also suggest that combinations between imatinib and daunorubicin, predisolone or cytarabine may be advantageous for the treatment of Philadelphia-positive ALL.

  • 13.
    Hallböök, Helene
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Hägglund, Hans
    Stockelberg, Dick
    Nilsson, Per-Gunnar
    Karlsson, Karin
    Björkholm, Magnus
    Linderholm, Mats
    Wahlin, Anders
    Linder, Olle
    Smedmyr, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Autologous and allogeneic stem cell transplantation in adult ALL: The Swedish Adult ALL Group experience2005In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 35, no 12, p. 1141-1148Article in journal (Refereed)
    Abstract [en]

    Adult patients with acute lymphoblastic leukaemia (ALL) have been treated according to national protocols in Sweden since 1986. Stem cell transplantation (SCT) has been recommended in first remission for patients with risk factors for relapse, and for standard risk patients only after relapse. In this retrospective study, the results of autologous and allogeneic SCT in these populations were evaluated. In total, 187 patients with a median age of 34 years (17-66 years) underwent SCT. The 5-year disease-free survival (DFS), for all patients, was 26% (Confidence intervals (CI) 20-32%). The 5-year DFS was higher for patients transplanted in first remission 32% (CI 24-40%) compared to 14% (CI 5-23%; P<0.0001) in patients transplanted beyond first remission. No significant differences in DFS (P=0.06) were determined between autologous, related donor and unrelated donor SCT in the whole cohort. A lower relapse rate was counterbalanced by higher treatment-related mortality in patients undergoing allogeneic SCT. In Philadelphia-positive ALL, allogeneic SCT was superior to autologous SCT, with a 5-year DFS of 30% (CI 12-47%) vs 0% (P=0.04). Limited chronic graft-versus-host-disease (GVHD) was associated with an improved DFS of 53% (CI 38-69%) compared to no chronic GVHD of 22% (CI 10-36%; P=0.0008), indicating a clinically important graft-versus-leukaemia effect.

  • 14.
    Hallböök, Helene
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Lidström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Pauksens, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Ciprofloxacin prophylaxis delays initiation of broad-spectrum antibiotic therapy and reduces the overall use of antimicrobial agents during induction therapy for acute leukaemia: A single-centre study2016In: INFECTIOUS DISEASES, ISSN 2374-4235, Vol. 48, no 6, p. 443-448Article in journal (Refereed)
    Abstract [en]

    Background Due to an outbreak of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, the routine use of fluoroquinolone prophylaxis was questioned. As a result, this study was conducted with the aim to evaluate the impact of ciprofloxacin-prophylaxis on the use of broad-spectrum antibioctics and anti-mycotics. Methods A cohort of 139 consecutive patients with acute leukaemia treated with remission-inducing induction chemotherapy between 2004-2012 at the Department of Haematology in Uppsala University Hospital was analysed. Results Fifty-three patients (38%) received broad-spectrum antibiotics at the initiation of chemotherapy and were not eligible for prophylaxis. Of the remaining patients, the initiation of broad-spectrum antibiotics was delayed by 3 days in those receiving ciprofloxacin prophylaxis (n = 47) compared with those receiving no prophylaxis (n = 39). The median duration of systemic antibiotic treatment was 6 days shorter in patients receiving ciprofloxacin prophylaxis (12 vs 18 days; p = 0.0005) and the cumulative (total) median days on systemic antibiotic treatment was shortened by 8 days (15 vs 23 days, p = 0.0008). Piperacillin/tazobactam (p = 0.02), carbapenems (p = 0.05) and empiric broad-spectrum antifungals (p < 0.01) were used significantly less often when ciprofloxacin prophylaxis was given. Conclusions Ciprofloxacin prophylaxis delayed empiric therapy by 3 days and reduced overall antibiotic use in this study. These benefits must be evaluated vs the risks of development of resistant bacterial strains, making fluoroquinolone prophylaxis an open question for debate.

  • 15. Hulegardh, E.
    et al.
    Hägglund, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Ahlberg, L.
    Karlsson, K.
    Karbach, H.
    Markuszewska, A.
    Persson, Inger
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    Astrom, M.
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Outcome after HSCT in Philadelphia chromosome positive acute lymphoblastic leukemia in Sweden: a population-based study2014In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 31, no 8, p. 66-Article in journal (Refereed)
    Abstract [en]

    Even in the tyrosine kinase inhibitor era, allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as standard care for adult Philadelphia (Ph) positive acute lymphoblastic leukemia (ALL). In this retrospective national study, we have reviewed the outcome after HSCT in Sweden for adult Ph-positive ALL between 2000 and 2009. In total, 51 patients with median age 42 (range 20-66) years underwent HSCT. Mainly allogeneic HSCT was performed (24 related donor, 24 unrelated donor and one cord blood), and only two patients were treated with an autologous HSCT. The 5-year OS was 51 (37-64) %. The probabilities of morphological relapse and non-relapse mortality (NRM) at 5 years were 36 (23-49) and 18 (9-29) %, respectively. For the allogeneic transplanted, the 5-year OS was for patients <40 years 70 (50-90) % and for patients >= 40 years 34 (16-52) %, p = 0.002. The 5-year probability of NRM was for patients <40 years 10 (2-28) % compared to 25 (11-42) % for patients >= 40 years (p = 0.04). Patients with chronic graft-versus-host disease (GVHD) had a 5-year morphological relapse probability of 20 (6-40) % compared to 59 (35-77) % for patients without chronic GVHD (p = 0.03). Age >= 40 years and the absence of chronic GVHD were confirmed as independent negative prognostic factors for relapse and non-relapse mortality in a multivariate analysis although the impact of chronic GVHD was significant only in the older age cohort.

  • 16.
    Kinch, Amelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Arvidson, Johan
    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.
    Sällström, K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Bondeson, Kåre
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Pauksen, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Epstein-Barr virus-related disease after allogeneic HSCT and use of pre-emptive rituximab: Clinical Features And Outcome2017In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 52, no Supplement: 1, p. S88-S88Article in journal (Other academic)
  • 17.
    Kinch, Amelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Arvidson, Johan
    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.
    Sällström, Kalle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Bondeson, Kåre
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
    Pauksen, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Long-term outcome of Epstein-Barr virus DNAemia and PTLD with the use of preemptive rituximab following allogeneic HSCT2018In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 59, no 5, p. 1172-1179Article in journal (Refereed)
    Abstract [en]

    We studied retrospectively the outcome of Epstein-Barr virus (EBV)-related disease with EBV monitoring and preemptive rituximab to prevent post-transplant lymphoproliferative disorder (PTLD) in 319 consecutive allogeneic stem cell transplantations 2004-2012. Patients who received anti-thymocyte globulin (ATG) or alemtuzumab were regarded as high-risk for PTLD (n = 214). EBV DNAemia ≥1000 copies/mL plasma was observed in 50 (23%) of the high-risk patients. Thirty-three of the high-risk (15%) and one of the low-risk (1%) patients received rituximab, in combination with reduction of immunosuppression (n = 24) or chemotherapy (n = 4). Although rituximab was initiated only 5 d after first EBV load ≥1000 copies/mL, 85% of the rituximab-treated patients developed symptoms (lymphadenopathy 50%, fever 76%, and encephalitis/meningitis 12%). Response-rate to EBV treatment was 88%. Overall survival at 1- and 5-year was 71 and 52% for rituximab-treated patients, which was not inferior to all other patients post-transplant. In conclusion, rituximab therapy for EBV DNAemia does not affect long-term survival negatively.

  • 18. Kozlowski, Piotr
    et al.
    Astrom, Maria
    Ahlberg, Lucia
    Bernell, Per
    Hulegardh, Erik
    Hägglund, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Karlsson, Karin
    Markuszewska-Kuczymska, Alicja
    Tomaszewska-Toporska, Beata
    Smedmyr, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    High relapse rate of T cell acute lymphoblastic leukemia in adults treated with Hyper-CVAD chemotherapy in Sweden2014In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 92, no 5, p. 377-381Article in journal (Refereed)
    Abstract [en]

    Background Hyper-CVAD is widely used to treat acute lymphoblastic leukemia (ALL) and aggressive lymphomas. This multicenter, population-based study assessed the efficacy of Hyper-CVAD as first-line therapy in patients with T-cell ALL (T-ALL). Patients and methods Between October 2002 and September 2006, 24 patients were diagnosed with T-ALL in Sweden; 19 were eligible for treatment with the protocol. Results The median age was 32yr (range 18-72yr). Complete remission (CR) was obtained in 17 of 19 (89%) patients, and the treatment was relatively well tolerated. Allogeneic stem cell transplantation (SCT) was recommended in high-risk disease and was performed in four patients upfront. Two- and 5-yr leukemia-free survivals (LFS) in 17 patients with CR achievement were identical, at 29% (95% confidence interval [CI]: 8-51). Two- and 5-yr overall survival (OS) in whole cohort was 63% (95% CI: 42-85) and 47% (95% CI: 26-69), respectively. The 5-yr LFS for 15 patients who did not receive allogeneic SCT upfront were 20% (95% CI: 0-40), although 14 of 15 completed the protocol (eight cycles). Relapse occurred in 2 of 4 upfront-transplanted patients and in 12 of 15 patients treated with chemotherapy alone, six of whom received allogeneic SCT in CR2. Age >= 35yr influenced OS negatively in univariate analysis (HR 5.1, 95% CI: 1.55-16.7). Conclusions Hyper-CVAD treatment resulted in a high CR rate and appeared safe, but it showed poor efficacy at preventing relapse. Therefore, this treatment is no longer recommended for adults with T-ALL in Sweden.

  • 19. Kozlowski, Piotr
    et al.
    Astrom, Maria
    Ahlberg, Lucia
    Bernell, Per
    Hulegardh, Erik
    Hägglund, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Karlsson, Karin
    Markuszewska-Kuczymska, Alicja
    Tomaszewska-Toporska, Beata
    Smedmyr, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    High curability via intensive reinduction chemotherapy and stem cell transplantation in young adults with relapsed acute lymphoblastic leukemia in Sweden 2003-20072012In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 97, no 9, p. 1414-1421Article in journal (Refereed)
    Abstract [en]

    Background A minority of patients with adult acute lymphoblastic leukemia who relapse are rescued. The aim of this population-based study was to assess the results of reinduction treatment and allogeneic stem cell transplantation in patients in second complete remission.

    Design and Methods Between 2003-2007, 76 adults (<66 years) with relapsed acute lymphoblastic leukemia (Burkitt's leukemia excluded) were prospectively reported to The Swedish Adult Acute Leukemia Registry and later evaluated.

    Results Reinduction with: (i) mitoxantrone, etoposide, and cytarabine (MEA); (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor (FLAG-Asp); and (iii) cytarabine, betamethasone, cyclophosphamide, daunorubicin, and vincristine (ABCDV) resulted in complete remission in 6/9 (67%), 10/16 (63%) and 9/21 (43%) of the patients, respectively. Allogeneic stem cell transplantation was performed during second complete remission in 29 patients. Multivariate analysis regarding overall survival after relapse revealed that age over 35 years at diagnosis and relapse within 18 months were negative prognostic factors. Overall survival rates at 3 and 5 years were 22% (95% CI: 13-32) and 15% (95% CI: 7-24). Of 19 patients less than 35 years at diagnosis who underwent allogeneic stem cell transplantation in second remission, ten (53%) are still alive at a median of 5.5 years (range, 4.2-8.3) after relapse, whereas all patients over 35 years old at diagnosis have died.

    Conclusions Allogeneic stem cell transplantation remains the treatment of choice for young adults with relapsed acute lymphoblastic leukemia. Both (i) mitoxantrone, etoposide, and cytarabine and (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor seem effective as reinduction treatments and should be further evaluated. New salvage strategies are needed, especially for patients over 35 years old at diagnosis.

  • 20.
    Kozlowski, Piotr
    et al.
    Orebro Univ, Sch Med Sci, Dept Med, Orebro, Sweden..
    Lennmyr, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Ahlberg, Lucia
    Univ Hosp Linkoping, Dept Hematol, Linkoping, Sweden..
    Bernell, Per
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Div Hematol, Stockholm, Sweden..
    Hulegårdh, Erik
    Sahlgrens Univ Hosp, Dept Hematol & Coagulat, Gothenburg, Sweden..
    Karbach, Holger
    Univ Hosp Umea, Ctr Canc, Dept Hematol, Umea, Sweden..
    Karlsson, Karin
    Skane Univ Hosp, Dept Hematol & Oncol, Lund, Sweden..
    Tomaszewska-Toporska, Beata
    Skane Univ Hosp, Dept Hematol & Oncol, Lund, Sweden..
    Åström, Maria
    Orebro Univ, Sch Med Sci, Dept Med, Orebro, Sweden..
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Age but not Philadelphia positivity impairs outcome in older/elderly patients with acute lymphoblastic leukemia in Sweden2017In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 99, no 2, p. 141-149Article in journal (Refereed)
    Abstract [en]

    ObjectivesOlder/elderly patients with acute lymphoblastic leukemia (ALL) are poorly represented in clinical trials. MethodsUsing Swedish national leukemia registries, we investigated disease/patient characteristics, treatment choices, outcome, and the impact of an age-adapted protocol (introduced in 2009) in this population-based study of patients aged 55-85years, diagnosed with ALL 2005-2012. ResultsOf 174 patients, 82% had B-phenotype, 11% Burkitt leukemia (excluded), and 7% T-phenotype. Philadelphia chromosome positivity (Ph+) occurred in 35%. Of the 155 B- and T-ALL patients, 80% were treated with intensive protocols, and 20% with a palliative approach. Higher age and WHO performance status 2 influenced the choice of palliation. Intensive, palliative, and both approaches resulted in complete remission rate 83/16/70% and 3-year overall survival (OS) 32/3/26%. The age-adapted protocol did not improve outcome. With intensive treatment, platelet count 35x10(9)/L and age 75years were adverse prognostic factors for OS, Ph+ was not. Male sex was an adverse prognostic factor in the 55-64 year age-group. ConclusionsWe report a high frequency of Ph+ in older/elderly patients, with no evidence of poorer outcome compared to Ph-negative disease. Overall prognosis for elderly patients with ALL remains dismal, despite the use of age-adapted treatment.

  • 21.
    Larfors, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Parental Age, Family Size, and Offspring's Risk of Childhood and Adult Acute Leukemia2012In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 21, no 7, p. 1185-1190Article in journal (Refereed)
    Abstract [en]

    Background: An association between childhood acute leukemia and advanced parental age was observed more than 50 years ago, and the association has been repeated in several, but not all, subsequent studies. In contrast to the many studies addressing childhood leukemia, few have included adult patients.

    Methods: In this register-based case control study, we examined the association between parental age and incidence of acute leukemia in 2,660 childhood cases and 4,412 adult cases of acute leukemia, compared with 28,288 age-matched controls selected from a population-based register. Relative risks were estimated with conditional logistic regression.

    Results: We found a small increased risk of childhood acute lymphoblastic leukemia with increasing paternal age (adjusted OR, 1.05 per 5-year increase in age). Risk estimates were similar for childhood acute myeloid leukemia (AML), whereas no association was found with adult leukemia. Meanwhile, we observed a decreased risk of adult AML with increasing number of siblings, both older and younger.

    Conclusions: The results support the idea of a prenatal etiology of leukemia but indicate that parental age effects are limited to childhood cases. Impact: This is the first large study on parental age and leukemia risk, which includes adult cases. The finding on family size and risk of adult AM L needs to be validated in future studies.

  • 22. Lazarevic, Vladimir
    et al.
    Remberger, Mats
    Hägglund, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Juliusson, Gunnar
    Omar, Hamdy
    Halböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Kimby, Eva
    Malm, Claes
    Wahlin, Anders
    Johansson, Jan-Erik
    Long-term survival after allogeneic stem cell transplant for relapsed large B cell lymphomas: a retrospective study2012In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 53, no 3, p. 503-505Article in journal (Refereed)
  • 23.
    Lennmyr, Emma Bergfelt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Kozlowski, Piotr
    Orebro Univ, Sch Med Sci, Dept Med, Orebro, Sweden.
    Ahlberg, Lucia
    Univ Hosp Linkoping, Dept Hematol, Linkoping, Sweden.
    Bernell, Per
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Div Hematol, Stockholm, Sweden.
    Hulegardh, Erik
    Sahlgrens Univ Hosp, Dept Hematol & Coagulat, Gothenburg, Sweden.
    Izarra, Antonio Santamaria
    Univ Hosp Umea, Canc Ctr, Dept Hematol, Umea, Sweden.
    Karlsson, Karin
    Skane Univ Hosp, Dept Hematol & Oncol, Lund, Sweden.
    Tomaszewska-Toporska, Beata
    Skane Univ Hosp, Dept Hematol & Oncol, Lund, Sweden.
    Astrom, Maria
    Orebro Univ, Sch Med Sci, Dept Med, Orebro, Sweden.
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Real-world data on first relapse of acute lymphoblastic leukemia in patients > 55 years2018In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 59, no 10, p. 2470-2473Article in journal (Other academic)
  • 24.
    Lennmyr, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Karlsson, Karin
    Abrahamsson, Marie
    Ebrahim, Feresthe
    Lübking, Anna
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Juliusson, Gunnar
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Introducing Patient Reported Outcome in the Acute Leukemia Quality Registries in SwedenManuscript (preprint) (Other academic)
  • 25.
    Lennmyr, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Karlsson, Karin
    Skane Univ Hosp, Dept Haematol Oncol & Radiophys, Lund, Sweden.
    Ahlberg, Lucia
    Univ Hosp Linkoping, Dept Haematol, Linkoping, Sweden.
    Garelius, Hege
    Sahlgrens Univ Hosp, Sect Haematol & Coagulat, Dept Med, Gothenburg, Sweden.
    Hulegardh, Erik
    Sahlgrens Univ Hosp, Sect Haematol & Coagulat, Dept Med, Gothenburg, Sweden.
    Izarra, Antonio S.
    Univ Hosp Umea, Ctr Canc, Dept Haematol, Umea, Sweden.
    Joelsson, Joel
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Div Haematol, Stockholm, Sweden.
    Kozlowski, Piotr
    Orebro Univ, Sch Med Sci, Dept Med, Orebro, Sweden.
    Moicean, Andreea
    Cent Hosp Skovde, Dept Med, Skovde, Sweden.
    Tomaszewska-Toporska, Beata
    Skane Univ Hosp, Dept Haematol Oncol & Radiophys, Lund, Sweden.
    Lubking, Anna
    Skane Univ Hosp, Dept Haematol Oncol & Radiophys, Lund, Sweden.
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Survival in adult acute lymphoblastic leukaemia (ALL): A report from the Swedish ALL Registry2019In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 103, no 2, p. 88-98Article in journal (Refereed)
    Abstract [en]

    Objectives: As new, effective therapies emerge for acute lymphoblastic leukaemia (ALL), the results of clinical trials need to relate to standard of care.

    Methods: We used the population-based Swedish ALL Registry to evaluate characteristics, treatment and long-term outcome in 933 patients with diagnosis between 1997 and 2015.

    Results: The median age was 53 years. The frequency of Philadelphia (Ph)-positive leukaemia was 34% of examined B-ALL with a peak incidence at 50-59 years. Five-year overall survival (OS) improved between 1997-2006 and 2007-2015; in patients 18-45 years from 50% (95% CI 43-57) to 65% (95% CI 58-72), 46-65 years from 25% (95% CI 18-32) to 46% (95% CI 37-55) and >65 years from 7% (95% CI 2.6-11) to 11% (95% CI 5.9-16) (P < 0.05). Men with Ph-neg B-ALL 46-65 years had inferior OS compared with women (P < 0.01). Standardised mortality ratio was 5.7 (95% CI 5.0-6.3) for patients who survived 5 years from diagnosis. In multivariable analysis, Ph-positive disease was not associated with impaired prognosis but with lower risk of death in 2007-2015.

    Conclusions: In a population-based cohort, OS has improved in adult ALL, especially for Ph-positive disease but for middle-aged men with Ph-negative B-ALL outcome was poor. Cure without late toxicity or relapse is still desired.

  • 26. Machaczka, Maciej
    et al.
    Johansson, Jan-Erik
    Remberger, Mats
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Lazarevic, Vladimir Lj
    Wahlin, Björn Engelbrekt
    Omar, Hamdy
    Wahlin, Anders
    Juliusson, Gunnar
    Kimby, Eva
    Hägglund, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    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 relapse2013In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 30, no 4, p. 762-Article in journal (Refereed)
    Abstract [en]

    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.

  • 27. Machaczka, Maciej
    et al.
    Johansson, Jan-Erik
    Remberger, Mats
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Malm, Claes
    Lazarevic, Vladimir Lj
    Wahlin, Anders
    Omar, Hamdy
    Juliusson, Gunnar
    Kimby, Eva
    Hägglund, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    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?2012In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 53, no 9, p. 1699-1705Article in journal (Refereed)
    Abstract [en]

    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 > 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 0.046, 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.

  • 28.
    Mogensen, Signe Sloth
    et al.
    Rigshosp, Univ Hosp, Juliane Marie Ctr, Dept Pediat & Adolescent Med, JMC 5704,Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
    Harila-Saari, Arja
    Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Stockholm, Sweden.
    Makitie, Outi
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden;Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden.
    Myrberg, Ida Hed
    Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Stockholm, Sweden.
    Niinimaki, Riitta
    Oulu Univ Hosp, Dept Children & Adolescents, Oulu, Finland;Univ Oulu, PEDEGO Res Unit, Oulu, Finland.
    Vestli, Anne
    Oslo Univ Hosp, Div Pediat & Adolescent Med, Dept Pediat Oncol & Hematol, Oslo, Norway.
    Hafsteinsdottir, Solveig
    Landspitali Univ Hosp, Childrens Hosp, Reykjavik, Iceland.
    Griskevicius, Laimonas
    Vilnius Univ, Fac Med, Vilnius, Lithuania;Vilnius Univ Hosp Santariskiu Klinikos, Transfus Med Ctr, Vilnius, Lithuania;Vilnius Univ Hosp Santariskiu Klinikos, Dept Hematol, Oncol, Vilnius, Lithuania.
    Saks, Kadri
    Tallinn Childrens Hosp, Dept Hematol Oncol, Tallinn, Estonia.
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
    Retpen, Jens
    Univ Hosp Herlev Gentofte, Dept Orthoped Surg, Copenhagen, Denmark.
    Helt, Louise Rold
    Rigshosp, Univ Hosp, Juliane Marie Ctr, Dept Pediat & Adolescent Med, JMC 5704,Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
    Toft, Nina
    Rigshosp, Univ Hosp, Dept Hematol, Copenhagen, Denmark.
    Schmiegelow, Kjeld
    Univ Copenhagen, Fac Med, Inst Clin Med, Copenhagen, Denmark;Rigshosp, Univ Hosp, Juliane Marie Ctr, Dept Pediat & Adolescent Med, JMC 5704,Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
    Frandsen, Thomas Leth
    Rigshosp, Univ Hosp, Juliane Marie Ctr, Dept Pediat & Adolescent Med, JMC 5704,Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
    Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia2018In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 65, no 10, article id e27300Article in journal (Refereed)
    Abstract [en]

    Background: Treatment-related osteonecrosis (ON) is a serious complication of treatment of acute lymphoblastic leukemia (ALL).

    Procedure: This study included 1,489 patients with ALL, aged 1-45years, treated according to the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol, using alternate-week dexamethasone during delayed intensification, with prospective registration of symptomatic ON. We aimed at comparing risk factors, timing, and clinical characteristics of ON in children and young adults.

    Results: ON was diagnosed in 67 patients, yielding a 5-year cumulative incidence of 6.3%, but 28% in female adolescents. Median age at ALL diagnosis was 12.1years and 14.9years for females and males, respectively. At ON diagnosis, 59 patients had bone pain (91%) and 30 (46%) had multiple-joint involvement. The median interval between ALL and ON diagnosis was significantly shorter in children aged 1.0-9.9years (0.7years [range: 0.2-2.1]) compared with adolescents (1.8years [range: 0.3-3.7, P<0.001]) and adults (2.1years [range: 0.4-5.3, P=0.001]). Female sex was a risk factor in adolescent patients (hazard ratio [HR]=2.1, 95% confidence interval [CI]: 1.1-4.2) but not in children aged 1.1-9.9years (HR=2.4, 95% CI: 0.9-6.2, P=0.08) or adults aged 19-45years (HR=1.1, 95% CI: 0.3-4.0). Age above 10years at ALL diagnosis (odds ratio [OR]=3.7, P=0.026) and multiple joints affected at ON diagnosis (OR=3.4, P=0.027) were risk factors for developing severe ON.

    Conclusion: We provide a detailed phenotype of patients with ALL with symptomatic ON, including description of risk factors and timing of ON across age groups. This awareness is essential in exploring measures to prevent development of ON.

  • 29.
    Rank, Cecilie Utke
    et al.
    Univ Copenhagen, Rigshosp, Pediat Oncol Res Lab, Copenhagen, Denmark;Univ Copenhagen, Rigshosp, Dept Hematol, Copenhagen, Denmark.
    Toft, Nina
    Univ Copenhagen, Rigshosp, Dept Hematol, Copenhagen, Denmark.
    Tuckuviene, Ruta
    Aalborg Univ Hosp, Dept Pediat, Aalborg, Denmark.
    Grell, Kathrine
    Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Sect Biostat, Copenhagen, Denmark.
    Nielsen, Ove Juul
    Univ Copenhagen, Rigshosp, Dept Hematol, Copenhagen, Denmark.
    Frandsen, Thomas Leth
    Univ Copenhagen, Rigshosp, Dept Pediat & Adolescent Med, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
    Marquart, Hanne Vibeke Hansen
    Univ Copenhagen, Rigshosp, Dept Clin Immunol, Copenhagen, Denmark.
    Albertsen, Birgitte Klug
    Aarhus Univ Hosp, Dept Pediat, Aarhus, Denmark.
    Tedgard, Ulf
    Lund Univ Hosp, Dept Pediat & Coagulat Disorders, Malmo, Sweden.
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Ruud, Ellen
    Oslo Univ Hosp, Rikshosp, Dept Paediat Med, Oslo, Norway.
    Jarvis, Kirsten Brunsvig
    Oslo Univ Hosp, Rikshosp, Dept Paediat Med, Oslo, Norway.
    Quist-Paulsen, Petter
    Trondheim Reg & Univ Hosp, St Olavs Hosp, Dept Hematol, Trondheim, Norway.
    Huttunen, Pasi
    Helsinki Univ Hosp, Childrens Hosp, Dept Pediat Hematol Oncol & Stem Cell Transplanta, Helsinki, Finland.
    Wartiovaara-Kautto, Ulla
    Helsinki Univ Hosp, Ctr Comprehens Canc, Dept Hematol, Helsinki, Finland;Univ Helsinki, Helsinki, Finland.
    Jonsson, Olafur Gisli
    Univ Hosp, Landspitali, Childrens Hosp, Reykjavik, Iceland.
    Trakymiene, Sonata Saulyte
    Vilnius Univ Hosp Santaros Klin, Childrens Hosp, Ctr Pediat Oncol & Hematol, Vilnius, Lithuania.
    Griskevicius, Laimonas
    Vilnius Univ Hosp Santaros Klin, Dept Hematol Oncol & Transfus Med Ctr, Vilnius, Lithuania;Vilnius Univ, Vilnius, Lithuania.
    Saks, Kadri
    Tallinn Childrens Hosp, Dept Oncohematol, Tallinn, Estonia.
    Punab, Mari
    Tartu Univ Hosp, Dept Hematol & Oncol, Tartu, Estonia.
    Schmiegelow, Kjeld
    Univ Copenhagen, Rigshosp, Pediat Oncol Res Lab, Copenhagen, Denmark;Univ Copenhagen, Rigshosp, Dept Pediat & Adolescent Med, Blegdamsvej 9, DK-2100 Copenhagen, Denmark;Univ Copenhagen, Fac Med, Inst Clin Med, Copenhagen, Denmark.
    Thromboembolism in acute lymphoblastic leukemia: results of NOPHO ALL2008 protocol treatment in patients aged 1 to 45 years2018In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 131, no 22, p. 2475-2484Article in journal (Refereed)
    Abstract [en]

    Thromboembolism frequently occurs during acute lymphoblastic leukemia (ALL) therapy. We prospectively registered thromboembolic events during the treatment of 1772 consecutive Nordic/Baltic patients with ALL aged 1 to 45 years who were treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol (July 2008-April 2017). The 2.5-year cumulative incidence of thromboembolism (N = 137) was 7.9% (95% confidence interval [CI], 6.6-9.1); it was higher in patients aged at least 10 years (P < .0001). Adjusted hazard ratios (HRas) were associated with greater age (range, 10.0-17.9 years: HRa, 4.9 [95% CI, 3.1-7.8; P < .0001]; 18.0-45.9 years: HRa, 6.06 [95% CI, 3.65-10.1; P < .0001]) and mediastinal mass at ALL diagnosis (HRa, 2.1; 95% CI, 1.0-4.3; P = .04). In a multiple absolute risk regression model addressing 3 thromboembolism risk factors, age at least 10 years had the largest absolute risk ratio (RRage, 4.7 [95% CI, 3.1-7.1]; RRenlarged (lymph nodes), 2.0 [95% CI, 1.2-3.1]; RRmediastinal mass, 1.6 [95% CI, 1.0-2.6]). Patients aged 18.0 to 45.9 years had an increased hazard of pulmonary embolism (HRa, 11.6; 95% CI, 4.02-33.7; P < .0001), and patients aged 10.0 to 17.9 years had an increased hazard of cerebral sinus venous thrombosis (HRa, 3.3; 95% CI, 1.5-7.3; P = .003) compared with children younger than 10.0 years. Asparaginase was truncated in 38/128 patients with thromboembolism, whereas thromboembolism diagnosis was unassociated with increased hazard of relapse (P = .6). Five deaths were attributable to thromboembolism, and patients younger than 18.0 years with thromboembolism had increased hazard of dying compared with same-aged patients without thromboembolism (both P <= .01). In conclusion, patients aged at least 10 years could be candidates for preemptive antithrombotic prophylaxis. However, the predictive value of age 10 years or older, enlarged lymph nodes, and mediastinal mass remain to be validated in another cohort.

  • 30.
    Toft, N.
    et al.
    Herlev Univ Hosp, Dept Hematol, Herlev, Denmark.;Rigshosp, Univ Hosp, Dept Hematol, Copenhagen, Denmark..
    Birgens, H.
    Herlev Univ Hosp, Dept Hematol, Herlev, Denmark..
    Abrahamsson, J.
    Queen Silvias Childrens Hosp, Dept Clin Sci, Gothenburg, Sweden..
    Griskevicius, L.
    Vilnius Univ Hosp, Santariskiu Klin, Hematol Oncol & Transfus Med Ctr, Vilnius, Lithuania..
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Heyman, M.
    Karolinska Inst, Karolinska Univ Hosp, Astrid Lindgrens Childrens Hosp, Childhood Canc Res Unit, Stockholm, Sweden..
    Klausen, T. W.
    Herlev Univ Hosp, Dept Hematol, Herlev, Denmark..
    Jonsson, O. G.
    Landspitali Univ Hosp, Childrens Hosp, Reykjavk, Iceland..
    Palk, K.
    North Estonia Med Ctr, Dept Hematol, Tallinn, Estonia..
    Pruunsild, K.
    Tallinn Childrens Hosp, Tallinn, Estonia..
    Quist-Paulsen, P.
    Trondheim Reg & Univ Hosp, St Olavs Hosp, Dept Hematol, Trondheim, Norway..
    Vaitkeviciene, G.
    Vilnius Univ Hosp, Santariskiu Klin, Childrens Hosp, Ctr Pediat Oncol & Hematol, Vilnius, Lithuania..
    Vettenranta, K.
    Univ Helsinki, Cent Hosp, Hosp Children & Adolescents, Div Hematol Oncol & Stem Cell Transplantat, Helsinki, Finland..
    Asberg, A.
    Trondheim Reg & Univ Hosp, St Olavs Hosp, Dept Pediat, Trondheim, Norway..
    Frandsen, T. Leth
    Rigshosp, Dept Pediat & Adolescent Med, Copenhagen, Denmark..
    Marquart, H. V.
    Rigshosp, Univ Hosp, Sect 7631, Dept Clin Immunol, Copenhagen, Denmark..
    Madsen, H. O.
    Rigshosp, Univ Hosp, Sect 7631, Dept Clin Immunol, Copenhagen, Denmark..
    Noren-Nystrom, U.
    Umea Univ, Dept Clin Sci, Pediat, Umea, Sweden..
    Schmiegelow, K.
    Univ Copenhagen, Rigshosp, Dept Pediat & Adolescent Med, Copenhagen, Denmark.;Univ Copenhagen, Fac Med, Inst Clin Med, Copenhagen, Denmark..
    Adults And Children (1-45 Years) With Ph-Negative All Have Almost Identical Outcome In Risk-Stratified Analysis Of Nopho All20082016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, p. 35-35Article in journal (Other academic)
  • 31. Toft, N
    et al.
    Birgens, H
    Abrahamsson, J
    Griškevičius, L
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Heyman, M
    Klausen, T W
    Jónsson, Ó G
    Palk, K
    Pruunsild, K
    Quist-Paulsen, P
    Vaitkeviciene, G
    Vettenranta, K
    Åsberg, A
    Frandsen, T L
    Marquart, H V
    Madsen, H O
    Norén-Nyström, U
    Schmiegelow, K
    Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia.2018In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 32, p. 606-615Article in journal (Refereed)
    Abstract [en]

    Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients were of age 1-9 years (A), 266 were 10-17 years (B) and 221 were 18-45 years (C). Sixteen patients (three adults) died during induction. All others achieved remission after induction or 1-3 intensive blocks. Subsequently, 45 patients (12 adults) died, 122 patients relapsed (32 adults) with a median time to relapse of 1.6 years and 13 (no adult) developed a second malignancy. Median follow-up time was 4.6 years. Among the three age groups, older patients more often had higher risk ALL due to T-ALL (32%/25%/9%, P<0.001), KMT2A rearrangements (6%/5%/3%, P<0.001) and higher day 29 residual leukemia for B-lineage (P<0.001), but not T-ALL (P = 0.53). Event-free survival rates (pEFS(5y)) were 89 +/- 1% (A), 80 +/- 3% (B) and 74 +/- 4% (C) with significant differences only for non-high risk groups. Except for thrombosis, pancreatitis and osteonecrosis, the risk of 19 specified toxicities was not enhanced by age above 10 years. In conclusion, a pediatric-based protocol is tolerable and effective for young adults, despite their increased frequency of higher risk features.

  • 32. Toft, Nina
    et al.
    Birgens, Henrik
    Abrahamsson, Jonas
    Bernell, Per
    Griškevičius, Laimonas
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Heyman, Mats
    Holm, Mette Skov
    Hulegårdh, Erik
    Klausen, Tobias Wirenfeldt
    Marquart, Hanne V
    Jónsson, Olafur Gísli
    Nielsen, Ove Juul
    Quist-Paulsen, Petter
    Taskinen, Mervi
    Vaitkeviciene, Goda
    Vettenranta, Kim
    Asberg, Ann
    Schmiegelow, Kjeld
    Risk group assignment differs for children and adults 1-45 years with acute lymphoblastic leukemia treated by the NOPHO ALL-2008 protocol2013In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 90, no 5, p. 404-412Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The prognosis of acute lymphoblastic leukemia is poorer in adults than in children. Studies have indicated that young adults benefit from pediatric treatment, although no upper age limit has been defined.

    DESIGN AND METHODS:

    We analyzed 749 patients aged 1-45 years treated by the NOPHO ALL-2008 protocol. Minimal residual disease (MRD) on days 29 and 79, immunophenotype, white blood cell count (WBC), and cytogenetics were used to stratify patients to standard, intermediate, or high risk treatment with or without hematopoietic stem cell transplantation.

    RESULTS:

    Adults aged 18-45 had significantly lower WBCs at diagnosis compared to children aged 1-9 and 10-17 years, but significantly more adults were stratified to high-risk chemotherapy (8%, 14%, 17%; p < 0.0001) or high risk chemotherapy with transplantation (4%, 13%, 19%; p < 0.0001). This age dependent skewing of risk grouping reflected more T-ALL (11%, 27%, 33%, p < 0.0001), poorer MRD response day 29 (MRD < 0.1%: 75%, 61%, 52%; p < 0.0001), and more MLL gene rearrangements (3%, 3%, 10%; p = 0.005) in older patients.

    CONCLUSIONS:

    Even if identical diagnostics, treatment, and risk stratification are implemented, more adults will be stratified to high risk therapy, which should be considered when comparing pediatric and adult outcomes.

  • 33. Toft, Nina
    et al.
    Birgens, Henrik
    Abrahamsson, Jonas
    Griškevičius, Laimonas
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Heyman, Mats
    Klausen, Tobias Wirenfeldt
    Jónsson, Ólafur Gísli
    Palk, Katrin
    Pruunsild, Kaie
    Quist-Paulsen, Petter
    Vaitkeviciene, Goda
    Vettenranta, Kim
    Asberg, Ann
    Helt, Louise Rold
    Frandsen, Thomas
    Schmiegelow, Kjeld
    Toxicity profile and treatment delays in NOPHO ALL2008-comparing adults and children with Philadelphia chromosome-negative acute lymphoblastic leukemia2016In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 96, no 2, p. 160-169Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Cure rates improve when adolescents and young adults with acute lymphoblastic leukemia (ALL) are treated according to pediatric protocols. Assumed risks of toxicities and associated delays in treatment have played a role in setting upper age limits. The aim of this study was to examine the toxicity profile and treatment delays in NOPHO ALL2008 comparing children and adults.

    METHODS: We collected information on 19 treatment-related toxicities, systematically captured at 3-month intervals throughout therapy, and time intervals between 12 consecutive treatment phases for 1076 patients aged 1-45 yrs treated according to the Nordic/Baltic ALL2008 protocol.

    RESULTS: No adults died during induction. The duration of induction therapy and postinduction treatment phases did not differ between children and adults, except for patients 18-45 yrs being significantly delayed during two of nine high-risk blocks (median number of days for patients 1-9, 10-17, and 18-45 yrs; the glucocorticosteroid/antimetabolite-based block B1: 24, 26, and 29 d, respectively, P = 0.001, and Block 5 (in most cases also a B block): 29, 29, and 37 d, respectively, P = 0.02). A higher incidence of thrombosis with increasing age was found; highest odds ratio 5.4 (95% CI: (2.6;11.0)) for patients 15-17 yrs compared with children 1-9 yrs (P < 0.0001). Risk of avascular osteonecrosis was related to age with the highest OR for patients 10-14 yrs (OR = 10.4 (95% CI: (4.4;24.9)), P < 0.0001).

    CONCLUSION: Adults followed and tolerated the NOPHO ALL2008 protocol virtually as well as children, although thrombosis and avascular osteonecrosis was most common among adolescents.

1 - 33 of 33
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