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  • 1. Axdorph, Ulla
    et al.
    Stenke, Leif
    Grimfors, Gunnar
    Carneskog, Jan
    Hansen, Jan
    Linder, Olle
    Ljungman, Per
    Löfvenberg, Eva
    Malm, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Simonsson, Bengt
    Turesson, Ingemar
    Vilén, Lars
    Udén, Anne-Marie
    Björkholm, Magnus
    Intensive chemotherapy in patients with chronic myelogenous leukaemia (CML) in accelerated or blastic phase - A report from the Swedish CML Group2002In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 118, no 4, p. 1048-1054Article in journal (Refereed)
    Abstract [en]

    In attempting to restore the chronic phase (CP) of chronic myelogenous leukaemia (CML), the Swedish CML group utilized an intensive chemotherapy protocol for 83 patients (aged 16-79 years) in accelerated (AP, n = 22) or blastic phase (BC, n = 61). Most patients received a combination of mitoxantrone (12 mg/m2/d) and etoposide (100 mg/m2/d) together with cytosine arabinoside (1 g/m2 b.i.d) for 4 d. Overall, 39 patients (47%) achieved a second CP (CP2)/partial remission (PR). Responding patients <65 years were eligible for ablative chemotherapy followed by an allogeneic (SCT) or a double autologous stem cell transplant (ASCT). Seventeen of 34 responders <65 years failed to proceed to transplantation as a result of early disease progression (n = 15) or disease-related complications (n = 2). The remaining 17 patients underwent SCT (n = 9, including four unrelated donor SCT) or ASCT (n = 8). Only one of the eight ASCT patients had a second ASCT, the remaining seven failed because of progression (n = 5) or hypoplasia (n = 2). The median duration of CP2/PR was 6 months (range 1-72 months). Five patients achieved a longer CP2/PR than CP1. The 1 year survival was 70% for SCT/ASCT patients (median survival 21 months), 50% for responding patients overall, but only 7% for non-responders (P < 0.001). Three SCT/ASCT patients are long-term survivors (65+, 66+ and 73+ months). In conclusion, approximately half of the patients achieved a CP2/PR after intensive chemotherapy, with a clear survival advantage for responders vs non-responders. Subsequent SCT/ASCT was feasible for half of the responders (<65 years), and one individual underwent double ASCT. Novel therapeutic options for CML patients in AP/BP are needed.

  • 2.
    Carlsson, Margaretha S.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Department of Biomedicine and Surgery, Hematology. Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences.
    Pharmacokinetics of 2-mercaptopropionylglycine (Tiopronin) in man1993Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    2-Mercaptopropionylglycine (2-MPG, tiopronin) has been used successfully in the treatment of cystinuria despite the lack of knowledge of its pharmacokinetics. Therefore methods based on high-performance liquid chromatography and fluorometric detection were developed for quantitative analysis. The total, non-protein-bound, and free (thiolic) tiopronin were measured in plasma using this method.

    The phannacokinetic disposition of tiopronin in plasma after intravenous administration was best described by a three exponential function. Plasma concentration time-curves of total tiopronin exhibited a rapid distribution phase, a B-phase corresponding to renal excretion, and a long terminal elimination phase. The latter was the result of strong disulphide binding of tiopronin to proteins. The non-protein-bound tiopronin was eliminated faster judging by its early appearance in urine. Mean bioavailability was 63 % in healthy volunteers with great interindividual variability (range 33-91%).

    Multiple dosing studies gave similar pharrnacokinetic parameters as for single dose studies and studies on patients with renal impaitment elucidated the renal clearance of the drug. In vitro studies showed a slow dissolution of the drug dosage form employed. A metabolite, 2-mercaptopropionic acid, was identified and its pharmacokinetics was investigated. The mechanism of action of the drug is discussed based on the results of measuring free tiopronin in plasma.

  • 3. Gruber, A
    et al.
    Björkholm, M
    Brinch, L
    Evensen, S
    Gustavsson, B
    Hedenus, M
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Lofvenberg, E
    Nesthus, I
    Simonsson, B
    Sjö, M
    Stenke, L
    Tangen, JM
    Tidefelt, U
    Uden, AM
    Paul, C
    Liliemark, J
    A phase I/II study of the MDR modulator Valspodar (PSC 833) combined with daunorubicin and cytarabine in patients with relapsed and primary refractory acute myeloid leukemia2003In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 27, no 4, p. 323-328Article in journal (Refereed)
    Abstract [en]

    The cyclosporine analog Valspodar (PSC 833, Novartis Pharma) is a strong inhibitor of the mdr1 gene product p-glycoprotein (pgp). A phase I/II study was conducted in order to evaluate if addition of Valspodar to treatment with daunorubicin and cytarabine, given to patients with primary refractory or relapsed acute myeloid leukemia, could increase the complete remission rate. Fifty-three patients were treated in cohorts of three to six patients. Twelve patients reached a complete remission in bone marrow, five of whom also normalized their peripheral blood values. Three patients experienced treatment-related deaths from pneumonia, liver failure and cerebral hemorrhage, respectively. It is concluded that Valspodar 10mg/kg per 24h in combination with daunorubicin 45mg/m2 for 3 days and cytarabine 1g/m2 twice daily for 4 days is tolerable in this heavily pre-treated group of patients. Due to the moderate treatment results, the phase II part of the study was ended prematurely. The modulation of only pgp did not give an obvious improvement of the treatment results in this group of patients. ⌐ 2002 Elsevier Science Ltd. All rights reserved.

  • 4.
    Gréen, Henrik
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Lindqvist Appell, Malin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Zackrisson, Anna Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    P-gp and mdr-1 mRNA in leukemic cells fromAML patients during chemotheraphy.2001In: Proceedings of the American Association for Cancer Research,2001, 2001, p. 345-355Conference paper (Refereed)
  • 5. Hallböök, Helene
    et al.
    Simonsson, Bengt
    Ahlgren, Thomas
    Björkholm, Magnus
    Carneskog, Jan
    Grimfors, Gunnar
    Hast, Robert
    Karlsson, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Kimby, Eva
    Lerner, Richard
    Linder, Olle
    Linderholm, Mats
    Löfvenberg, Eva
    Malm, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Nilsson, Per-Gunnar
    Paul, Christer
    Stenke, Leif
    Stockelberg, Dick
    Tidefelt, Ulf
    Turesson, Ingemar
    Uden-Blome, Ann-Marie
    Vilen, Lars
    Wahlin, Anders
    Winquist, Ingemar
    Smedmyr, Bengt
    High-dose cytarabine in upfront therapy for adult patients with acute lymphoblastic leukaemia2002In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 118, p. 748-754Article in journal (Refereed)
  • 6. Itälä, M
    et al.
    Geisler, CH
    Kimby, E
    Juvonen, E
    Tjonnfjord, G
    Karlsson, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Remes, K
    Standard-dose anti-CD20 antibody rituximab has efficacy in chronic lymphocytic leukaemia: Results from a nordic multicentre study2002In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 69, no 3, p. 129-134Article in journal (Refereed)
    Abstract [en]

    Objectives: This prospective multicentre study was conducted to assess the efficacy of the monoclonal anti-CD20 antibody rituximab in patients with chronic lymphocytic leukaemia (CLL). Secondary objectives were defined as the tolerability and feasibility of rituximab in patients with CLL. Methods: Twenty-four heavily pretreated patients with CLL were treated with a standard dose of 375 mg m-2 of rituximab given once weekly for four doses. Results: The overall response rate was 35% and all the responses were partial as defined by the revised NCI criteria. In 17 (85%) of 20 patients with initially measurable peripheral lymph nodes the size of lymph nodes decreased by at least 50%, while an improvement of the bone marrow infiltration was observed only in two (11%) of 18 evaluable patients. The median duration of the overall response was 12.5 wk. Rituximab was relatively well tolerated. Although side-effects were common (75%) they were usually mild or moderate. There was only one grade 3 adverse event and no grade 4 events. Conclusions: Standard-dose rituximab has activity in heavily pretreated patients with CLL, although the response is mainly limited to the lymph nodes and of short duration. Since rituximab has in vitro synergism with chemotherapeutic agents and is well tolerated by CLL patients, it is reasonable to investigate rituximab in combination with other treatments.

  • 7.
    Juliusson, Gunnar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Celsing, Fredrik
    Turesson, Ingemar
    Lenhoff, Stig
    Adriansson, Magnus
    Malm, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Frequent good partial remissions from thalidomide including best response ever in patients with advanced refractory and relapsed myeloma2000In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 109, no 1, p. 89-96Article in journal (Refereed)
    Abstract [en]

    Twenty-three patients with advanced and heavily pretreated myeloma were treated with thalidomide. Starting dose was 200 mg/d, and 20 patients had dose escalations up to 400 (n = 5), 600 (n = 12) or 800 mg/d (n = 3), usually in divided doses. Nineteen patients were refractory to recent chemotherapy, and four had untreated relapse after prior intensive therapy. Ten out of 23 patients (43%) achieved partial response (PR, nine with refractory and one with relapsed disease), six patients had minor response or stabilization of the disease and four had disease progression. Another three patients died early from advanced myeloma at less than 3 weeks of thalidomide therapy. Of the 10 patients with PR, seven had a better response than after any prior therapy, despite vincristine-doxorubicin-dexamethasone (VAD)-based treatment in all but one and high-dose melphalan with autologous stem cell support in four. Time to achieve PR was rapid in patients receiving thalidomide in divided doses (median 31 d). Responses also included reduced bone marrow plasma cell infiltration and improved general status. Normalized polyclonal gammaglobulin levels were seen in four cases. Six out of 10 patients with PR remained in remission with a median time on treatment of 23 weeks (range 15- 50 weeks). Sedation was common but usually tolerable, and some patients continued full- or part-time work. Four patients had skin problems, three patients had pneumonia, one hypothyrosis, one sinus bradycardia and one minor sensory neuropathy. Thalidomide may induce good partial remissions in advanced refractory myeloma with tolerable toxicity, and should be evaluated in other settings for myeloma patients. Divided thalidomide doses seem to reduce time to achieve remission and may improve response rate.

  • 8.
    Juliusson, Gunnar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Höglund, Martin
    Karlsson, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Löfgren, Christina
    Möllgård, Lars
    Paul, Christer
    Tidefelt, Ulf
    Björkholm, Magnus
    Increased remissions from one course for intermediate-dose cytosine arabinoside and idarubicin in elderly acute myeloid leukaemia when combined with cladribine. A randomized population-based phase II study2003In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 123, no 5, p. 810-818Article in journal (Refereed)
    Abstract [en]

    Cladribine has single-drug activity in acute myeloid leukaemia (AML), and may enhance the formation of the active metabolite (ara-CTP) of cytosine arabinoside (ara-C). To evaluate the feasibility of adding intermittent cladribine to intermediate-dose ara-C (1 g/m2/2 h) b.i.d. for 4 d with idarubicin (CCI), we performed a 2:1 randomized phase II trial in AML patients aged over 60 years. Primary endpoints were time to recovery from cytopenia and need for supportive care following the first course. Sixty-three patients (median 71 years, range 60-84 years) were included, constituting 72% of all eligible patients. Toxicity was limited, with no differences between the treatment arms. The early toxic death rate was 11%. The median time to recovery from neutropenia and thrombocytopenia was 22 and 17 d from the start of course no. 1, respectively, and the requirement for platelet and red cell transfusions was four and eight units respectively. Patients had a median of 8 d with fever over 38░C, and 17 d with intravenous antibiotic treatment. The overall complete remission (CR) rate was 62%, with 51% CR from one course of CCI in comparison with 35% for the two-drug therapy (P = 0.014). The median survival with a 2-year follow-up was 14 months, and the 2-year survival was over 30%, with no differences between the treatment arms. Considering the median age and our population-based approach, the overall results are encouraging.

  • 9.
    Juliusson, Gunnar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Karlsson, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Malm, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    More potent graft-versus-myeloma effect than graft-versus-renal cell cancer effect2002In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 43, no 11, p. 2233-2234Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 10.
    Juliusson, Gunnar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Karlsson, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Malm, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Frödin, U
    Mollen, AS
    Backström, G
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Adjusted conditioning for allogeneic transplantation in a single center setting: Mixed chimerism heralds relapse2003In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 44, no 4, p. 669-679Article in journal (Refereed)
    Abstract [en]

    The role of mixed chimerism on subsequent relapse was prospectively evaluated in an allotransplant program. Sixty-six patients with median age of 54 and mainly high-risk hematologic disease and/or solid tumors had individually adjusted non-myeloablative conditioning. Thirty-nine donors were siblings and 27 unrelated. Frequent chimerism analyses supported immune manipulation including donor lymphocyte infusions. The need for transfusions, iv fluids, and antibiotics, and weight loss was less than in a control cohort. Most patients had immediate full and consistent donor chimerism, one-third required immune manipulation. Eight of ten evaluable CML patients were BCR/ABL-negative at days 14-58 post-transplant. Mixed chimerism frequently preceded relapse, and the relapse rate was 38% in 26 patients with mixed chimerism vs. 11% among 35 with consistent full donor chimerism (p = 0.015). The current transplant- and disease-related mortality were 11 and 9%, respectively, among 35 non-high-risk patients, and 35 and 10% for 29 high-risk patients with hematologic malignancy. With a median follow-up of 15 months the 2-year overall survival is 73% for non-high-risk, and 46% for high-risk patients. Adjusted conditioning reduces early toxicity and resource requirements without impairing tumor control, probably due to a rapid establishment of the graft-versus-cancer effect. Mixed chimerism heralded relapse, and tumor-related mortality is not greater with adjusted than with conventional conditioning.

  • 11.
    Karlsson, Karin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Strömberg, Mats
    Liliemark, Jan
    Delannoy, André
    Johnson, S A N
    Porwit, Anja
    Kimby, Eva
    Lärfars, Gerd
    Cristiansen, Ilse
    Nilsson, Göran
    Celsing, Fredrik
    Sundström, Gunnel
    Luthman, Mikaela
    Tidefelt, Ulf
    Wallvik, Jonas
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Oral cladribine for B-cell chronic lymphocytic leukaemia: Report of a phase II trial with a 3-d, 3-weekly schedule in untreated and pretreated patients, and a long-term follow-up of 126 previously untreated patients2002In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 116, no 3, p. 538-548Article in journal (Refereed)
    Abstract [en]

    A phase II study was undertaken to evaluate the efficacy and toxicity of a new schedule of cladribine administration (10 mg/m2 orally daily for 3 d every 3 weeks) in 107 patients with B-cell chronic lymphocytic leukaemia (CLL). To minimize toxicity, treatment withdrawal criteria were defined. The results of the 63 previously untreated patients were retrospectively compared with 63 from an earlier study using a 5-d monthly schedule. The compiled data were analysed for prognostic factors for survival. No significant difference regarding response were seen in the two cohorts of the 126 previously untreated patients. The complete response (CR), nodular partial response (nPR) and partial response (PR) rates were 15%, 21% and 41%. Quality of response had no impact on survival. The 3- and 5-year overall survival for previously untreated patients was 73% and 58%, respectively, with a median follow-up of 54 months. Pretreatment haemoglobin < 11.0 g/dl and elevated beta-2-microglobulin had a negative influence on survival. Major infections occurred in 21% of patients in the 3-d study compared with 35% in the 5-d study. The overall response (OR) and CR rates in the 40 previously treated patients were 34% and 5% respectively. Median overall survival was 24 months and median progression-free survival for responding patients was 14 months. Cladribine used as a single agent is an effective treatment with an acceptable safety profile for pretreated and untreated B-CLL. The achievement of complete remission was not a prerequisite for long-term survival.

  • 12. Lenhoff, Stig
    et al.
    Hjorth, Martin
    Holmberg, Erik
    Turesson, Ingemar
    Westin, Jan
    Lanng Nielsen, Johan
    Wislöff, Finn
    Brinch, Lorentz
    Carlson, Kristina
    Carlsson, Margaretha
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Dahl, Inger-Marie
    Gimsing, Peter
    Hippe, Erik
    Johnsen, Hans
    Lamvik, Jon
    Löfvenberg, Eva
    Nesthus, Ingerid
    Rödjer, Stig
    Impact on survival of high-dose therapy with autologous stem cell support in patients younger than 60 years with newly diagnosed multiple myeloma: a population-based study.2000In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 95Article in journal (Refereed)
  • 13. Panagopoulos, Ioannis
    et al.
    Fioretos, Thoas
    Isaksson, Margareth
    Mitelman, Felix
    Johansson, Bertil
    Theorin, Niklas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    RT-PCR analysis of acute myeloid leukemia with t(8,16)(p11,p13): Identification of a novel MOZ/CBP transcript and absence of CBP/MOZ expression [1]2002In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 35, no 4, p. 372-374Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 14.
    Söderholm, Johan D
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Malm, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Long-term endoscopic remission of Crohn disease after autologous stem cell transplantation for acute myeloid leukaemia2002In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 37, no 5, p. 613-616Article in journal (Refereed)
    Abstract [en]

    A favourable course of Crohn disease has been observed after allogeneic bone marrow transplantation, and there is now mounting evidence that autologous stem cell may be an effective treatment for severe autoimmune diseases. Here, we present the first long-term endoscopic follow-up of a patient with Crohn disease undergoing autologous stem cell transplantation for haematological disease. A 54-year-old woman developed Crohn disease and was submitted to ileocaecal resection. Four months after surgery, the patient contracted acute myeloid leukaemia. She was initially treated with chemotherapy, and subsequently underwent autologous stem cell transplantation. Following transplantation, the patient has remained in clinical remission regarding both diseases, without anti-inflammatory medication. She has undergone ileo-colonoscopy with normal findings at 1, 2, 3 and 5 years after transplantation. This case suggests that autologous stem cell transplantation can change not only the clinical course, but also the natural history of intestinal inflammation in Crohn disease. This has pathophysiological as well as therapeutic implications.

  • 15. Tidefelt, U
    et al.
    Liliemark, J
    Gruber, A
    Sundman-Engberg, B
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Stenke, L
    Elmhorn-Rosenborg, A
    Möllgård, L
    Lehman, S
    Xu, D
    Covelli, A
    Gustavsson, B
    Paul, C
    Liliemark, E
    P-glycoprotein inhibitor valspodar (PSC 833) increases the intracellular concentrations of Deunorubicin in vivo in patients with P-glycoprotein-positive acute myeloid leukemia.2000In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 18, p. 1837-1844Article in journal (Refereed)
  • 16. Tobin, G
    et al.
    Thunberg, U
    Johnson, A
    Eriksson, I
    Soderberg, O
    Karlsson, Karin
    Linköping University, Department of Biomedicine and Surgery, Hematology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology.
    Merup, M
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Vilpo, J
    Enblad, G
    Sundstrom, C
    Roos, G
    Rosenquist, R
    Chronic lymphocytic leukemias utilizing the V(H)3-21 gene display highly restricted V(lambda)2-14 gene use and homologous CDR3s: implicating recognition of a common antigen epitope2003In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 101, no 12, p. 4952-4957Article in journal (Refereed)
    Abstract [en]

    The immunoglobulin variable heavy chain (IgV(H)) gene mutation status is an important prognostic factor in chronic lymphocytic leukemia (CLL), since cases with mutated V-H genes show significantly longer survival than unmutated cases. Recently, we reported a preferential use of the V(H)3-21 gene in mutated CLL and showed that mutated V(H)3-21 cases had an inferior overall survival compared with other mutated CLL. In order to further characterize this subset, we performed VH gene analysis in 265 CLL cases and identified 31 V(H)3-21 cases (11.7%), 21 cases had mutated and 10 cases unmutated VH genes. Regardless Of VH gene mutation status, a poor overall survival was found in the VH3-21 cases with a median survival of 83 months. These survival data confirm that V(H)3-21 cases do not fit into the general prognostic grouping of mutated and unmutated CLL. A large fraction Of V(H)3-21 cases also demonstrated unique features with shorter lengths of the third complementarity determining region (CDR3) and CDR3s with highly homologous amino acid sequences. Furthermore, the V(H)3-21 cases showed a striking dominance of X light chain expression, and analysis of the Iglambda gene rearrangements revealed highly restricted use of the Vlambda2-14/J(lambda)3 genes in the majority of cases. Taken together, our new findings strengthen the suggestion that V(H)3-21-using cases comprise a new CLL entity, irrespective Of VH gene mutation status, and implicate that a common antigen epitope, perhaps of pathogenic significance, is recognized by the highly homologous V(H)3-21/V(lambda)2-14 Ig molecules expressed in individual tumors. (Blood. 2003,101:4952-4957).

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