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  • 1.
    Amini, R.-M.
    et al.
    Department of Oncology, Regional Oncological Centre, University Hospital of Uppsala, Sweden, Department of Pathology, University of Uppsala, Akademiska sjukhuset, S-751 85 Uppsala, Sweden.
    Glimelius, B.
    Department of Oncology, Regional Oncological Centre, University Hospital of Uppsala, Sweden.
    Gustavsson, A.
    Department of Oncology, Regional Oncological Centre, University Hospital of Lund, Sweden.
    Ekman, T.
    Department of Oncology, Regional Oncological Centre, University Hospital of Göteborg, Sweden.
    Erlanson, M.
    Department of Oncology, Regional Oncological Centre, University Hospital of Umeå, Sweden.
    Haapaniemi, E.
    Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken.
    Enblad, G.
    Department of Oncology, Regional Oncological Centre, University Hospital of Uppsala, Sweden.
    A population-based study of the outcome for patients with first relapse of Hodgkin's lymphoma2002Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 68, nr 4, s. 225-232Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Our aims were to evaluate the response to salvage treatment in relation to initial treatment and to evaluate prognostic factors at the time of relapse in an unselected population of relapsing patients with Hodgkin's lymphoma (HL). Patients and methods: In total, 124 patients younger than 60 yr of age with initial diagnosis of HL in Sweden relapsed between 1985 and 1995. Results: Fifty-eight patients relapsed after initial treatment with radiotherapy (RT) only, 62 after combination chemotherapy (CT), of whom 30 had received additional involved-field RT, and four after a short course of CT followed by extended-field RT. For 37 patients among the 58 relapsers after initial RT treated according to the recommendations of the National guidelines, the 5-yr Hodgkin-specific survival (HLS) was 85%, overall survival (OS) 73% and event-free survival (EFS) 62%, which is not inferior to survival in patients with primarily advanced stages. It was poorer in the 21 patients who initially had received RT only, even though they had been recommended for more extensive treatment. For patients initially treated with a full course (6-8 cycles) of CT the 5-yr HLS was 60%, OS 58% and EFS 22%. Bulky disease and age at diagnosis strongly affected survival in a multivariate analysis. Conclusions: Patients initially treated with RT who relapse have a favourable outcome, provided they have been treated according to the recommendations of the guidelines at the time of diagnosis. Initially bulky disease and, as a consequence, additional RT as part of the initial treatment negatively affect survival at relapse in patients initially treated with a full course of CT.

  • 2. Amini, Rose-Marie
    et al.
    Enblad, Gunilla
    Gustavsson, Anita
    Ekman, Tor
    Erlanson, Martin
    Haapaniemi, Eva
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Glimelius, Bengt
    Treatment outcome in patients younger than 60 years with advanced stages (IIB-IV) of Hodgkin's disease: the Swedish National Health Care Programme experience.2000Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 65, s. 379-389Artikel i tidskrift (Refereegranskat)
  • 3. Baniulis, Danas
    et al.
    Burritt, James B
    Taylor, Ross M
    Dinauer, Mary C
    Heyworth, Paul G
    Parkos, Charles A
    Magnusson, Karl-Eric
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi.
    Jesaitis, Algirdas J
    Monoclonal antibody CL5 recognizes the amino terminal domain of human phagocyte flavocytochrome b558 large subunit, gp91phox2005Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 74, nr 4, s. 337-347Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human phagocyte flavocytochrome b558 (Cytb) is a heterodimeric integral membrane protein that serves as the electron transferase of the β-nicotinamide adenine dinucleotidephosphate, reduced (NADPH)-oxidase, an enzyme complex important in the host defense function of phagocytic cells. In this study, we report the characterization of monoclonal antibody (mAb) CL5 that is specific for the large subunit, gp91phox, of the oxidase protein. This antibody recognizes gp91phox by immunoblot analysis of membrane extracts and samples of the immunopurified gp91phox/p22 phox heterodimer, prepared on anti-p22phox affinity matrices. Phage display analysis confirmed this specificity, indicating that the CL5 epitope contains the region 135-DPYSVALSELGDR of gp91phox. The antibody was used to probe for the presence of gp91phox in membrane preparations from neutrophils of patients with nine genetically distinct forms of X-linked chronic granulomatous disease (CGD). The causative mutations included missense errors as well as nonsense errors that result in premature termination of gp91phox synthesis. Analysis of the CGD samples by immunoblotting indicated that CL5 recognizes only the full-length wild-type and two missense mutations, consistent with the absence of stable short gp91 phox peptide expression in CGD neutrophils. Interestingly, CL5 was also shown to be cross-reactive with cytosolic and membrane-bound gelsolin, identified by purification, mass spectrometry and immunoblot analysis. CL5 probably cross-reacts with the sequence 771-DPLDRAMAEL in the C-terminus of gelsolin. We conclude that mAb CL5 is a useful probe for detection of full length and possibly truncated N-terminal fragments of gp91phox from membranes of Cytb-producing cells. © Blackwell Munksgaard 2005.

  • 4. Baniulis, Danas
    et al.
    Nauseef, William M
    Burritt, James B
    Taylor, Ross M
    Heyworth, Paul G
    Dinauer, Mary C
    Bumelis, Vladas A
    Magnusson, Karl-Eric
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi.
    Jesaitis, Algirdas J
    Unusual polyclonal anti-gp91phox peptide antibody interactions with X-linked chronic granulomatous disease-derived human neutrophils are not from compensatory expression of Nox proteins 1, 3, or 42005Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 74, nr 3, s. 241-249Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To obtain topological information about human phagocyte flavocytochrome b558 (Cytb), rabbit anti-peptide antibodies were raised against synthetic peptides mimicking gp91phox regions: 1-9 (MGN), 30-44 (YRV), 150-159 (ESY), 156-166 (ARK), 247-257 (KIS-1, KIS-2). Following affinity purification on immobilized peptide matrices, all antibodies but not prebleed controls recognized purified detergent-solubilized Cytb by enzyme-linked immunosorbent assay (ELISA). Affinity-purified antibodies recognizing KIS, ARK and ESY but not YRV, MGN or prebleed IgG specifically detected gp91phox in immunoblot analysis. Antibodies recognizing MGN, ESY, ARK and KIS but not YRV or the prebleed IgG fraction labeled intact normal neutrophils. Surprisingly, all antibodies, with the exception of YRV and pre-immune IgG controls, bound both normal and Cytb-negative neutrophils from the obligate heterozygous mother of a patient with X-linked chronic granulomatous disease (X-CGD) and all neutrophils from another patient lacking the gp91phox gene. Further immunochemical examination of membrane fractions derived from nine genetically unrelated patients with X-CGD, using an antibody that recognizes other Nox protein family members, suggests that the unusual reactivity observed does not reflect the compensatory expression of gp91phox homologs Nox1, 3 or 4. These results suggest that an unusual surface reactivity exists on neutrophils derived from X-linked chronic granulomatous disease patients that most likely extends to normal neutrophils as well. The study highlights the need for caution in interpreting the binding of rabbit polyclonal antipeptide antibodies to human neutrophils in general and, in the specific case of antibodies directed against Cytb, the need for Cytb-negative controls.

  • 5.
    Birgegard, Gunnar
    et al.
    Uppsala Univ, Sweden.
    Samuelsson, Jan
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Ahlstrand, Erik
    Orebro Univ, Sweden.
    Ejerblad, Elisabeth
    Uppsala Univ, Sweden.
    Enevold, Christian
    Copenhagen Univ Hosp, Denmark.
    Ghanima, Waleed
    Ostfold Hosp, Norway.
    Hasselbalch, Hans
    Zealand Univ Hosp, Denmark.
    Nielsen, Claus H.
    Zealand Univ Hosp, Denmark.
    Knutsen, Havar
    Ulleval Hosp, Norway.
    Pedersen, Ole B.
    Naestved Hosp, Denmark.
    Sorensen, Anders
    Copenhagen Univ Hosp, Denmark; Zealand Univ Hosp, Denmark.
    Andreasson, Bjorn
    NU Hosp Grp, Sweden.
    Inflammatory functional iron deficiency common in myelofibrosis, contributes to anaemia and impairs quality of life. From the Nordic MPN study Group2019Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 102, nr 3, s. 235-240Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives The study investigates the hypothesis that inflammation in myelofibrosis (MF) like in myeloma and lymphoma, may disturb iron distribution and contribute to anaemia. Methods A cross-sectional study of 80 MF and 23 ET patients was performed. Results About 35% of anaemic MF patients had functional iron deficiency (FID) with transferrin saturation amp;lt;20 and normal or elevated S-ferritin (amp;lt;500 mu g/L). In ET, FID was rare. In MF patients with FID, 70.6% were anaemic, vs 29.4% in patients without FID (P = 0.03). Hepcidin was significantly higher in MF patients with anaemia, including transfusion-dependent patients, 50.6 vs 24.4 mu g/L (P = 0.01). There was a significant negative correlation between Hb and inflammatory markers in all MF patients: IL-2, IL-6 and TNF-alpha, (P amp;lt; 0.01-0.03), LD (P = 0.004) and hepcidin (P = 0.03). These correlations were also seen in the subgroup of anaemic MF patients (Table ). Tsat correlated negatively with CRP (P amp;lt; 0.001). Symptom burden was heavier in MF patients with FID, and MPN-SAF quality of life scores correlated with IL-6 and CRP. Conclusions The inflammatory state of MF disturbs iron turnover, FID is common and contributes to anaemia development and impairment of QoL. Anaemic MF patients should be screened for FID.

  • 6.
    Bjerrum, Ole Weis
    et al.
    Rigshosp, Denmark.
    Samuelsson, Jan
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Ghanima, Waleed
    Univ Oslo, Norway; Univ Oslo, Norway.
    Kauppila, Marjut
    Turku Univ Hosp, Finland.
    Andersen, Christen Lykkegaard
    Rigshosp, Denmark; Roskilde Hosp, Denmark.
    Thromboembolism prophylaxis in patients with Philadelphia-negative myeloproliferative neoplasms-Clinical practice among Nordic specialists2018Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 100, nr 5, s. 475-478Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) have higher risks of developing thromboembolisms compared to the general population. International guidelines on the management of MPNs therefore include recommendations concerning thromboembolism prophylaxis. In clinical practice, strict adherence to guidelines may be challenging and dependent on factors such as physician experience, outpatient clinic setting, and access to therapy; however, no data exist on physician adherence or patient compliance to thromboembolism prophylaxis in MPNs. Objectives: The Nordic Myeloproliferative Neoplasm Study Group (NMPN) performed a survey among Nordic hematology specialists with the aim of documenting the implementation of international recommendations in a region of Northern Europe with similar healthcare systems. Results: The study showed that Nordic specialists managed their patients in accordance with international guidelines concerning medical intervention, but to a lesser degree regarding the management of additional cardiovascular risk factors. The survey also drew attention to the common clinical dilemma of combining antiaggregatory agents with vitamin K antagonists (VKA), or novel oral anticoagulants (NOAC), as well as phlebotomy limits in female polycythemia vera patients. Conclusions: The results of this study highlight the importance of considering all risk factors for thrombosis and an optimal collaboration with the primary healthcare sector.

  • 7.
    Eliasson, Pernilla
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för medicinsk cellbiologi.
    Andersson, Patiyan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för medicinsk cellbiologi.
    Willander, Kerstin
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi.
    Linderholm, Mats
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Hematologiska kliniken US.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för medicinsk cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Jönsson, Jan-Ingvar
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för medicinsk cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Letter: Absence of hot spot mutations of the PIK3CA gene in acute myeloid leukaemia2006Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 77, nr 1, s. 86-87Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    [No abstract available]

  • 8.
    Hjorth-Hansen, Henrik
    et al.
    St Olavs Hospital, Norway; Norwegian University of Science and Technology NTNU, Norway.
    Stenke, Leif
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Söderlund, Stina
    University of Uppsala Hospital, Sweden.
    Dreimane, Arta
    Linköpings universitet, Institutionen för medicin och hälsa. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US. Linköpings universitet, Medicinska fakulteten.
    Ehrencrona, Hans
    Skåne University Hospital, Sweden.
    Gedde-Dahl, Tobias
    University of Oslo, Norway.
    Tore Gjertsen, Bjorn
    Haukeland Hospital, Norway; University of Bergen, Norway.
    Hoglund, Martin
    University of Uppsala Hospital, Sweden.
    Koskenvesa, Perttu
    University of Helsinki, Finland; University of Helsinki, Finland.
    Lotfi, Kourosh
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
    Majeed, Waleed
    Stavanger University Hospital, Norway.
    Markevarn, Berit
    Umeå University Hospital, Sweden.
    Ohm, Lotta
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Olsson-Stromberg, Ulla
    University of Uppsala Hospital, Sweden.
    Remes, Kari
    Turku University, Finland.
    Suominen, Merja
    Kanta Hame Central Hospital, Finland.
    Simonsson, Bengt
    University of Uppsala Hospital, Sweden.
    Porkka, Kimmo
    University of Helsinki, Finland; University of Helsinki, Finland.
    Mustjoki, Satu
    University of Helsinki, Finland; University of Helsinki, Finland.
    Richter, Johan
    Skåne University Hospital, Sweden.
    Dasatinib induces fast and deep responses in newly diagnosed chronic myeloid leukaemia patients in chronic phase: clinical results from a randomised phase-2 study (NordCML006)2015Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 94, nr 3, s. 243-250Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We randomised 46 newly diagnosed patients with chronic myeloid leukaemia (median age 56) to receive dasatinib 100mg QD or imatinib 400mg QD and report outcome as an intention-to-treat analysis with 36months follow-up. Early cytogenetic and molecular responses were superior in the dasatinib group, with a tendency that imatinib patients caught up with time. For instance, MR3.0 was reached at 3months in 36% vs. 8% (P=0.02), at 12months in 81% vs. 46% (P=0.02) and at 18months in 73% vs. 65% (n.s.) of the patients in the two groups. In contrast, MR4.5 was consistently superior in the dasatinib group at all time points from 6months onwards, reaching 61% vs. 21% (Pless than0.05) at 36months. Sixty-four vs. 71% of the patients in the dasatinib and imatinib arms, respectively, remained on assigned drug. Dasatinib dose was frequently reduced, but with maintained excellent effect. One imatinib patient progressed to blastic phase, but no CML-related deaths occurred. In conclusion, our data compare favourably with those of the dasatinib registration study, DASISION. The fast and deep molecular responses induced by dasatinib compared with imatinib may be exploited to increase the proportion of patients who can achieve a treatment-free remission after treatment discontinuation.

  • 9. Itälä, M
    et al.
    Geisler, CH
    Kimby, E
    Juvonen, E
    Tjonnfjord, G
    Karlsson, Karin
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Hematologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Hematologiska kliniken US.
    Remes, K
    Standard-dose anti-CD20 antibody rituximab has efficacy in chronic lymphocytic leukaemia: Results from a nordic multicentre study2002Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 69, nr 3, s. 129-134Artikel i tidskrift (Refereegranskat)
    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.

  • 10.
    Jakobsen Falk, Ingrid
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet.
    Willander, Kerstin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Chaireti, Roza
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Närsjukvården i centrala Östergötland, Medicinska akutkliniken. Karolinska University Hospital, Sweden.
    Lund, Johan
    Huddinge University Hospital, Sweden.
    Nahi, Hareth
    Huddinge University Hospital, Sweden.
    Hermanson, Monica
    Uppsala University, Sweden.
    Green, Henrik
    National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Lotfi, Kourosh
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    TP53 mutations and MDM2(SNP309) identify subgroups of AML patients with impaired outcome2015Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 94, nr 4, s. 355-362Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundTP53 is commonly mutated in several cancers and confers treatment resistance and poor prognosis. Altered expression of mouse double minute 2 (MDM2), a negative regulator of p53, may also attenuate normal p53 signaling, thereby enhancing tumor transformation and resistance to apoptosis. The single nucleotide polymorphism (SNP) 309 has been reported to increase MDM2 expression and impair normal p53 response. Experimental designWe investigated the frequency and impact of TP53 mutations (TP53mut) and MDM2(SNP309) on treatment outcome and overall survival (OS) in 189 Swedish acute myeloid leukemia patients. The genetic analyses were performed using SSCA and direct sequencing (for mutations in exon 5-8 of TP53) and Pyrosequencing (for the MDM2(SNP309)). ResultsWe found a high frequency (22%) of TP53mut in patients with cytogenetic aberrations, with association to high-risk cytogenetics (Pless than0.001). TP53mut patients had lower response rates (22% compared with 76% CR in TP53 wild-type (wt) patients, Pless than0.001) and reduced OS (2 and 16months, respectively, Pless than0.001). In TP53wt patients with high or intermediate risk cytogenetic aberrations, the MDM2(SNP309) conferred an impaired outcome, with patients carrying the alternative G-allele having shorter OS compared with T/T patients (median 9 vs. 50months, P=0.020). ConclusionsOur results show that TP53mut analysis and MDM2(SNP309) genotyping may be useful tools for prognostication, risk stratification, and selection of patients most likely to benefit from new drugs targeting the p53 signaling pathway.

  • 11.
    Järemo, Petter
    Department of Clinical Chemistry, Örebro Medical Center Hospital, Örebro, Sweden.
    Computerised method for recording platelet density distribution1995Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 54, nr 5, s. 304-309Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In the present study a computerized apparatus was employed for scanning light transmission variations along test tubes containing density-separated platelets. The device consists of a stepping motor, a stationary halogen lamp and a photopotentiometer connected to a personal computer. Anticoagulated whole blood was layered on a preformed continuous Percoll gradient having a density span from 1090 kg/l (bottom) to 1040 kg/l (top). After centrifugation at 3400g for 1.5 hours, high-density cells (i.e. erythrocytes) pass through to the bottom of the test tube and the lighter platelets remain in the gradient. The test tube is moved by the computer between the halogen lamp and the photopotentiometer. Transmission variations along the gradient were recorded and registered in the computer. Density markers beads were used as an internal standard and platelet peak density was determined. After perforating the test tube the gradient was divided into 45 aliquots. In all fractions determination of platelet counts and mean platelet volume was carried out. In addition, in the aliquots having a platelet count > 20 × 1012/l the ratio β-thromboglobulin per platelet was also determined. The platelet distribution in the gradient was illustrated graphically. A good agreement was found when comparing platelet distributions in the gradients and light transmission variations along the test tubes.

  • 12.
    Kozlowski, Piotr
    et al.
    Örebro University Hospital, Sweden .
    Astrom, Maria
    Örebro University Hospital, Sweden .
    Ahlberg, Lucia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Bernell, Per
    Karolinska University Hospital, Sweden .
    Hulegardh, Erik
    Sahlgrenska University, Sweden .
    Hagglund, Hans
    Karolinska University Hospital, Sweden .
    Karlsson, Karin
    Skåne University Hospital, Sweden .
    Markuszewska-Kuczymska, Alicja
    University Hospital, Sweden .
    Tomaszewska-Toporska, Beata
    Skåne University Hospital, Sweden .
    Smedmyr, Bengt
    Uppsala University, Sweden .
    Amini, Rose-Marie
    Uppsala University, Sweden .
    Hallbook, Helene
    Uppsala University, Sweden .
    High relapse rate of T cell acute lymphoblastic leukemia in adults treated with Hyper-CVAD chemotherapy in Sweden2014Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 92, nr 5, s. 377-381Artikel i tidskrift (Refereegranskat)
    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 greater than= 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.

  • 13.
    Kozlowski, Piotr
    et al.
    Örebro University, Sweden.
    Lennmyr, Emma
    Uppsala University, Sweden.
    Ahlberg, Lucia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Bernell, Per
    Karolinska Institute, Sweden.
    Hulegardh, Erik
    Sahlgrens University Hospital, Sweden.
    Karbach, Holger
    University Hospital Umeå, Sweden.
    Karlsson, Karin
    Skåne University Hospital, Sweden.
    Tomaszewska-Toporska, Beata
    Skåne University Hospital, Sweden.
    Åström, Maria
    Örebro University, Sweden.
    Hallbook, Helene
    Uppsala University, Sweden.
    Age but not Philadelphia positivity impairs outcome in older/elderly patients with acute lymphoblastic leukemia in Sweden2017Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 99, nr 2, s. 141-149Artikel i tidskrift (Refereegranskat)
    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.

  • 14.
    Kuchinskaya, E
    et al.
    Karolinska Institutet.
    Heyman, M
    Karolinska Institutet.
    Grandér, D
    Karolinska Institutet.
    Linderholm, Mats
    Karolinska Institutet.
    Söderhäll, S
    Karolinska Institutet.
    Zaritskey, A
    Saint-Petersburg I. Pavlov State Medical University, Russia .
    Nordgren, A
    Karolinska Institutet.
    Porwit-MacDonald, A
    Karolinska Institutet.
    Zueva, E
    Saint-Petersburg I. Pavlov State Medical University.
    Pawitan, Y
    Karolinska Institutet.
    Corcoran, M
    Karolinska Institutet.
    Nordenskjöld, M
    Karolinska Institutet.
    Blennow, E
    Karolinska Institutet.
    Children and adults with acute lymphoblastic leukaemia have similar gene expression profiles2005Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 74, nr 6, s. 466-480Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To compare the gene expression pattern in children and adults with acute lymphoblastic leukaemia (ALL) in order to improve our understanding of the difference in disease biology and prognosis. Methods: The gene expression profiles in diagnostic samples from 29 children and 15 adults with ALL were analysed using the oligonucleotide chip Hu95ver2a, produced by Affymetrix. Results: Unsupervised hierarchical cluster analysis revealed that, in spite of differences in outcome, patients clustered irrespective of age, first by T-cell or B-precursor immunophenotype, and second by cytogenetic changes within the B-precursor group. The expression pattern analysis allowed the reclassification of some samples into the proper cytogenetic group. We also showed that separate clustering of samples with the BCR/ABL translocation could be explained by different breakpoint regions in the BCR. No significant difference in gene expression was observed between samples with and without CDKN2A deletion within the B-precursor group. Analysis of different age groups revealed a similarity in expression profiles when infants with the MLL translocation and adults over 40 yr of age were compared irrespective of karyotype. Conclusions: In spite of the difference in clinical outcome, the gene expression pattern in children and adults with ALL is very similar and is primarily dependent on immunophenotype and cytogenetic aberrations. However, when age groups are compared, the expression patterns of infants and adults over 40 show a remarkable similarity.

  • 15.
    Landberg, Niklas
    et al.
    Lund University, Sweden.
    Dreimane, Arta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Rissler, Marianne
    Lund University, Sweden.
    Billstrom, Rolf
    Central Hospital Skovde, Sweden.
    Agerstam, Helena
    Lund University, Sweden.
    Primary cells in BCR/FGFR1-positive 8p11 myeloproliferative syndrome are sensitive to dovitinib, ponatinib, and dasatinib2017Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 99, nr 5, s. 442-448Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ObjectivesTranslocations involving the fibroblast growth factor receptor 1 (FGFR1) gene are associated with the 8p11 myeloproliferative syndrome (EMS), a rare neoplasm that following a usually short chronic phase progresses into acute myeloid or lymphoid leukemia. The treatment commonly involves chemotherapy and, if possible, allogeneic stem cell transplantation which is the only therapeutic option for long-term survival. Given the aggressive course of EMS, we here evaluated tyrosine kinase inhibitors as treatment options to delay disease progression. MethodsWe described a new case of EMS and used chromosome analyses, PCR, and sequencing to investigate the underlying genetic aberrations. The sensitivity to several tyrosine kinase inhibitors was tested in vitro on the EMS cell line KG1 and on primary cells from the newly diagnosed EMS patient. ResultsA translocation involving chromosomes 8 and 22 was detected, and a BCR/FGFR1 fusion gene was confirmed and characterized by sequencing. KG1 cells and primary EMS cells displayed distinct sensitivity to dovitinib, ponatinib, and dasatinib as compared to normal bone marrow control cells. ConclusionsThese results suggest that treatment with tyrosine kinase inhibitors may be beneficial for patients with EMS during the search for a suitable stem cell donor and for those not eligible for transplantation.

  • 16.
    Lazarevic, Vladimir
    et al.
    Skåne University Hospital, Sweden; Lund University, Sweden.
    Horstedt, Ann-Sofi
    Skåne University Hospital, Sweden.
    Johansson, Bertil
    University of and Regional Labs Regional Skåne, Sweden; Lund University, Sweden.
    Antunovic, Petar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US. Linköpings universitet, Hälsouniversitetet.
    Billstrom, Rolf
    Central Hospital Skovde, Sweden.
    Derolf, Asa
    Karolinska University Hospital, Sweden; Karolinska University Hospital, Sweden.
    Lehmann, Soeren
    Karolinska University Hospital, Sweden; Karolinska University Hospital, Sweden.
    Moellgard, Lars
    Sahlgrens University Hospital, Sweden.
    Peterson, Stefan
    Skåne University Hospital, Sweden.
    Stockelberg, Dick
    Sahlgrens University Hospital, Sweden.
    Uggla, Bertil
    Örebro University Hospital, Sweden.
    Vennstroem, Lovisa
    Sahlgrens University Hospital, Sweden.
    Wahlin, Anders
    Umeå University, Sweden.
    Hoeglund, Martin
    Academic Hospital, Sweden.
    Juliusson, Gunnar
    Skåne University Hospital, Sweden; Lund University, Sweden; Academic Hospital, Sweden.
    Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population-based series of acute myeloid leukaemia2015Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 94, nr 5, s. 419-423Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 17.
    Lennmyr, Emma
    et al.
    Uppsala Univ, Sweden.
    Karlsson, Karin
    Skane Univ Hosp, Sweden.
    Ahlberg, Lucia
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Garelius, Hege
    Sahlgrens Univ Hosp, Sweden.
    Hulegardh, Erik
    Sahlgrens Univ Hosp, Sweden.
    Izarra, Antonio S.
    Univ Hosp Umea, Sweden.
    Joelsson, Joel
    Karolinska Inst, Sweden.
    Kozlowski, Piotr
    Orebro Univ, Sweden.
    Moicean, Andreea
    Cent Hosp Skovde, Sweden.
    Tomaszewska-Toporska, Beata
    Skane Univ Hosp, Sweden.
    Lubking, Anna
    Skane Univ Hosp, Sweden.
    Hallbook, Helene
    Uppsala Univ, Sweden.
    Survival in adult acute lymphoblastic leukaemia (ALL): A report from the Swedish ALL Registry2019Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 103, nr 2, s. 88-98Artikel i tidskrift (Refereegranskat)
    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 amp;gt;65 years from 7% (95% CI 2.6-11) to 11% (95% CI 5.9-16) (P amp;lt; 0.05). Men with Ph-neg B-ALL 46-65 years had inferior OS compared with women (P amp;lt; 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.

  • 18.
    Lj Lazarevic, Vladimir
    et al.
    Skåne University Hospital, Sweden; Lund University, Sweden.
    Rosso, Aldana
    Skåne University Hospital, Sweden; Lund University, Sweden.
    Juliusson, Gunnar
    Skåne University Hospital, Sweden; Lund University, Sweden.
    Antunovic, Petar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Rangert Derolf, Åsa
    Karolinska University Hospital, Sweden.
    Deneberg, Stefan
    Karolinska University Hospital, Sweden.
    Mollgård, Lars
    Sahlgrens University Hospital, Sweden.
    Uggla, Bertil
    Örebro University Hospital, Sweden.
    Wennstrom, Lovisa
    Sahlgrens University Hospital, Sweden.
    Wahlin, Anders
    Umeå University, Sweden.
    Höglund, Martin
    Academic Hospital, Sweden.
    Lehmann, Sören
    Academic Hospital, Sweden.
    Johansson, Bertil
    University of and Regional Labs Regional Skåne, Sweden; Lund University, Sweden.
    Incidence and prognostic significance of isolated trisomies in adult acute myeloid leukemia: A population-based study from the Swedish AML registry2017Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 98, nr 5, s. 493-500Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives and MethodsTo ascertain the incidence/clinical implications of isolated autosomal trisomies in adult acute myeloid leukemia (AML), all such cases were retrieved from the Swedish AML Registry. ResultsOf the 3179 cytogenetically informative AMLs diagnosed January 1997-May 2015, 246 (7.7%) had isolated trisomies. The frequency increased by age (2.4% at age 18-60years vs. 23% at amp;gt;60years; Pamp;lt;.0001); the median age was 69years. The five most common were +8 (4.0%), +13 (0.9%), +11 (0.8%), +21 (0.7%), and +4 (0.5%). Age and gender, types of AML and treatment, and complete remission and early death rates did not differ between the single trisomy and the intermediate risk (IR) groups or among cases with isolated gains of chromosomes 4, 8, 11, 13, or 21. The overall survival (OS) was similar in the single trisomy (median 1.6years) and IR groups (1.7years; P=.251). The OS differed among the most frequent isolated trisomies; the median OS was 2.5years for +4, 1.9years for +21, 1.5years for +8, 1.1years for +11, and 0.8years for +13 (P=.013). ConclusionAML with single trisomies, with the exception of +13, should be grouped as IR.

  • 19.
    Molin, D.
    et al.
    Department of Oncology, Uppsala, Sweden, Dept. Oncol., Radiol.,/Clin. I., Rudbeck Laboratory, University Hospital, SE-751 85 Uppsala, Sweden.
    Enblad, G.
    Department of Oncology, Uppsala, Sweden.
    Gustavsson, A.
    Department of Oncology, Lund, Sweden.
    Ekman, T.
    Department of Oncology, Gothenburg, Sweden.
    Erlanson, M.
    Department of Oncology, Umeå, Sweden.
    Haapaniemi, E.
    Glimelius, B.
    Department of Oncology, Uppsala, Sweden.
    Early and intermediate stage Hodgkin's lymphoma - Report from the Swedish National Care Programme2003Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 70, nr 3, s. 172-180Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In Sweden a National Care Programme provides treatment principles for Hodgkin's lymphoma (HL) since 1985, for early and intermediate stages often less extensive than international recommendations. The purpose is to evaluate long-term results of these principles. A total of 308 patients (167 men and 141 women), 17-59 yr old (median 31), diagnosed during 1985-92, pathological stage (PS) I-III1A and I-IIB and clinical stage (CS) I-IIA, mean follow-up 8.8 yr, were studied. Staging laparotomy was recommended in CS IIA. Recommended treatment was mantle or mini-mantle radiotherapy (RT) alone in CS IA, and PS I-IIA and subtotal nodal irradiation in PS III1A if the disease was not bulky. Patients in PS I-IIA and III1A with bulky disease, and PS I-IIB received one cycle of mechlorethamine, vincristine, prednisone, procarbazine/doxorubicin, bleomycin, vinblastine, lacarbazine (MOPP/ABVD) before irradiation. The remaining patients received three to four cycles of MOPP/ABVD with RT to bulky disease. Relapse-free (RFS), Hodgkin specific (HLS), and overall survival (OS) at 10 yr were 74%, 92% and 85%. In the individual stages, RFS ranged from 53% (PSIII1A) to 90% (PS IA). RFS (P = 0.006), HLS, and OS were significantly better in patients treated with chemotherapy compared with those treated with RT alone, especially in patients with bulky disease (P = 0.0005). The international prognostic score did not provide any prognostic information. The OS rates are in agreement with results from international centres during that time. The recommended treatment was sufficient to produce the desired results of <20-30% recurrences, except in PS III1A. Most relapses could be salvaged. Patients with risk factors treated with one MOPP/ABVD and RT had an excellent outcome, superior to those without risk factors treated with RT alone. These results favour the trend to treat early and intermediate stages with a short course of chemotherapy followed by limited RT.

  • 20.
    Nagler, Arnon
    et al.
    Chaim Sheba Medical Centre, Israel .
    Labopin, Myriam
    UPMC University of Paris, France .
    Shimoni, Avichai
    Chaim Sheba Medical Centre, Israel .
    Mufti, Ghulam J
    Kings Coll London, England .
    Cornelissen, Jan J
    Erasmus Medical Centre Daniel den Hoed, Netherlands .
    Blaise, Didier
    Institute J Paoli I Calmettes, France .
    Janssen, Jeroen J W M
    Vrije University of Amsterdam, Netherlands .
    Milpied, Noel
    CHU Bordeaux, France .
    Vindelov, Lars
    Rigshosp, Denmark .
    Petersen, Eefke
    University of Medical Centre, Netherlands .
    Gribben, John
    St Bartholomews and Royal London Hospital, England .
    Bacigalupo, Andrea
    Osped San Martino Genova, Italy .
    Malm, Claes
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Niederwieser, Dietger
    University Hospital Leipzig, Germany .
    Socie, Gerard J
    Hop St Louis, France .
    Arnold, Renate
    Charite, Germany .
    Brown, Paul
    St James Hospital, Ireland .
    Goker, Hakan
    Hacettepe University, Turkey .
    Rocha, Vanderson
    CHU Nantes, France .
    Mohty, Mohamad
    EBMT ALWP, France University of Paris 07, France .
    Mobilized peripheral blood stem cells compared with bone marrow from HLA-identical siblings for reduced-intensity conditioning transplantation in acute myeloid leukemia in complete remission: a retrospective analysis from the Acute Leukemia Working Party of EBMT2012Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 89, nr 3, s. 206-213Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Reduced-intensity conditioning (RIC)-alloSCT is increasingly used for acute myelogenous leukemia. Limited data are available for the comparison of peripheral blood stem cells with bone marrow for RIC-alloSCT. We used the European Group for Blood and Marrow Transplantation (EBMT) ALWP data to compare the outcome of mobilized peripheral blood stem cells (PBSC) (n = 1430) vs. bone marrow (BM) (n = 107) for acute myelogenous leukemia (AML) patients with complete remission that underwent RIC-alloSCT from compatible sibling donors. The leukemia features, the disease status, and the time from diagnosis were similar between the two groups. Engraftment was achieved in 99% and 93% in the PBSC and BM groups, respectively (P andlt; 0.0001). The day of engraftment was significantly earlier for the PBSC vs. the BM group, 15 (159) and 19 (569), respectively (P andlt; 0.001). Acute GVHD, severe GVHD (grade IIIIV) and chronic GVHD did not differ between the groups. leukemia-free survival (LFS), relapse, and non-relapsed mortality (NRM) were 51 +/- 2%, 32 +/- 1%, and 17 +/- 1% vs. 50 +/- 6%, 38 +/- 6%, and 12 +/- 3% for the PBSC and BM groups, respectively. Our results indicate faster engraftment, but no difference in GVHD, LFS, relapse, and NRM when comparing PBSC to BM grafts from sibling donors following RIC conditioning. This is the first study comparing PBSC to BM grafts in the RIC setting, analyzing a homogeneous population of patients with AML in remission. Whether PBSC should be preferred for advanced phases of the disease, where the outcome is dominated by relapse incidences, needs further investigation.

  • 21.
    Nahi, Hareth
    et al.
    Karolinska Institute, Sweden.
    Genell, Anna
    Regional Cancer Centre West, Sweden.
    Walinder, Goran
    Karolinska Institute, Sweden.
    Uttervall, Katarina
    Karolinska Institute, Sweden.
    Juliusson, Gunnar
    Lund University, Sweden.
    Karin, Forsberg
    Umeå University Hospital, Sweden.
    Hansson, Markus
    Lund University, Sweden.
    Svensson, Ronald
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Linder, Olle
    Örebro University Hospital, Sweden.
    Carlson, Kristina
    Uppsala University Hospital, Sweden.
    Bjorkstrand, Bo
    Karolinska Institute, Sweden.
    Kristinsson, Sigurdur Y.
    Karolinska Institute, Sweden.
    Henrik Mellqvist, Ulf
    South Elvsborg Hospital, Sweden.
    Blimark, Cecilie
    Sahlgrens University Hospital, Sweden.
    Turesson, Ingemar
    Skåne University Hospital, Sweden.
    Incidence, characteristics, and outcome of solitary plasmacytoma and plasma cell leukemia. Population-based data from the Swedish Myeloma Register2017Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 99, nr 3, s. 216-222Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Solitary plasmacytoma (SP) and plasma cell leukemia (PCL) are uncommon (3-6%) types of plasma cell disease. The risk of progression to symptomatic multiple myeloma (MM) is probably important for the outcome of SP. PCL is rare and has a dismal outcome. In this study, we report on incidence and survival in PCL/SP, and progression to MM in SP, using the prospective observational Swedish Multiple Myeloma Register designed to document all newly diagnosed plasma cell diseases in Sweden since 2008. Both solitary bone plasmacytoma (SBP) (n=124) and extramedullary plasmacytoma (EMP) (n=67) have better overall survival (OS) than MM (n=3549). Progression to MM was higher in SBP than in EMP (35% and 7% at 2years, respectively), but this did not translate into better survival in EMP. In spite of treatment developments, the OS of primary PCL is still dismal (median of 11months, 0% at 5years). Hence, there is a great need for diagnostic and treatment guidelines as well as prospective studies addressing the role for alternative treatment options, such as allogeneic stem cell transplantation and monoclonal antibodies in the treatment of PCL.

  • 22.
    Nilsson-Ehle, Herman
    et al.
    Sahlgrens University Hospital.
    Birgegard, Gunnar
    University Uppsala Hospital.
    Samuelsson, Jan
    Stockholm S Hospital.
    Antunovic, Petar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi.
    Astermark, Jan
    University Hospital MAS.
    Garelius, Hege
    Sahlgrens University Hospital.
    Engstrom, Lena M
    Umea University Hospital.
    Kjeldsen, Lars
    Rigshospital.
    Nilsson, Lars
    Lund University Hospital.
    Olsson, Anna
    Sahlgrens University Hospital.
    Skov-Holm, Mette
    Aarhus University Hospital.
    Wallvik, Jonas
    Sundsvall Hospital.
    Gulbrandsen, Nina
    Ullevaal University Hospital.
    Hellstrom-Lindberg, Eva
    Karolinska University Hospital Huddinge.
    Quality of life, physical function and MRI T2*in elderly low-risk MDS patients treated to a haemoglobin level of andgt;= 120 g/L with darbepoetin alfa +/- filgrastim or erythrocyte transfusions2011Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 87, nr 3, s. 244-252Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 23.
    Söderlund, Stina
    et al.
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Dahlen, Torsten
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Sandin, Fredrik
    Regional Cancer Centre Uppsala Örebro, Sweden.
    Olsson-Stromberg, Ulla
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Creignou, Maria
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Dreimane, Arta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US. Linköpings universitet, Medicinska fakulteten.
    Lubking, Anna
    Skåne University Hospital, Sweden.
    Markevarn, Berit
    Umeå University Hospital, Sweden.
    Sjalander, Anders
    Umeå University, Sweden.
    Wadenvik, Hans
    Sahlgrens University Hospital, Sweden.
    Stenke, Leif
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Richter, Johan
    Skåne University Hospital, Sweden.
    Hoglund, Martin
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Advanced phase chronic myeloid leukaemia (CML) in the tyrosine kinase inhibitor era - a report from the Swedish CML register2017Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 98, nr 1, s. 57-66Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: The primary goal in management of chronic phase (CP) chronic myeloid leukaemia (CML) is to prevent disease progression to accelerated phase (AP) or blast crisis (BC). We have evaluated progression rates in a decentralised healthcare setting and characterised patients progressing to AP/BC on TKI treatment. Methods: Using data from the Swedish CML register, we identified CP-CML patients diagnosed 2007-2011 who progressed to AP/BC within 2 yrs from diagnosis (n = 18) as well as patients diagnosed in advanced phase during 2007-2012 (n = 36) from a total of 544 newly diagnosed CML cases. We evaluated baseline characteristics, progression rates, outcome and adherence to guidelines for monitoring and treatment. Results: The cumulative progression rate at 2 yrs was 4.3%. All 18 progression cases had been treated with imatinib, and six progressed within 6 months. High-risk EUTOS score was associated to a higher risk of progression. Insufficient cytogenetic and/or molecular monitoring was found in 33%. Median survival after transformation during TKI treatment was 1.4 yrs. In those presenting with BC and AP, median survival was 1.6 yrs and not reached, respectively. Conclusion: In this population-based setting, progression rates appear comparable to that reported from clinical trials, with similar dismal patient outcome. Improved adherence to CML guidelines may minimise the risk of disease progression.

  • 24.
    Terpos, Evangelos
    et al.
    Univ Athens, Greece.
    Katodritou, Eirini
    Theagen Canc Ctr, Greece.
    de la Rubia, Javier
    Univ Catolica Valencia, Spain.
    Hungria, Vania
    Theagen Canc Ctr, Greece; Ctr Estudos Hemoctr Santa Casa Sao Paolo, Brazil.
    Hulin, Cyrille
    CHU Bordeaux, France.
    Roussou, Maria
    Univ Athens, Greece.
    Delforge, Michel
    Univ Hosp Leuven, Belgium.
    Bries, Greet
    AZ Turnhout, Belgium.
    Stoppa, Anne-Marie
    Inst Paoli Calmettes, France.
    Aagesen, Jesper
    Ryhov Cty Hosp, Sweden.
    Sargin, Deniz
    Istanbul Univ, Turkey.
    Belch, Andrew
    Cross Canc Inst, Canada.
    Ahlberg, Lucia
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Diels, Joris
    Janssen Res and Dev, Belgium.
    Olie, Robert A.
    Janssen Cilag AG, Switzerland.
    Robinson, Don Jr.
    Janssen Global Serv, NJ USA.
    Spencer, Mike
    Janssen Cilag UK, England.
    Potamianou, Anna
    Janssen Cilag Pharmaceut SACI, Greece.
    van de Velde, Helgi
    Janssen Res and Dev, Belgium; Millennium Pharmaceut Inc, MA USA.
    Dimopoulos, Meletios A.
    Univ Athens, Greece.
    Bortezomib-based therapy for relapsed/refractory multiple myeloma in real-world medical practice2018Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 101, nr 4, s. 556-565Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The efficacy and safety of bortezomib-based therapy for relapsed/refractory multiple myeloma (RRMM) in clinical trials may differ from the oncology practice experience. The electronic VELCADE (R) OBservational Study was designed to prospectively evaluate bortezomib for multiple myeloma (MM) in real-world medical practice. Method: Patients scheduled to receive intravenous bortezomib for MM were eligible. The primary objective was to evaluate clinical outcomes, including response, time to response, time to next therapy, treatment-free interval, progression-free survival (PFS), and overall survival (OS). Secondary objectives included safety and healthcare resource utilization. Results: In total, 873 patients with a median of two therapy lines prior to initiating bortezomib were included. The overall response rate (amp;gt;= partial response) was 69%, including 37% complete response/near-complete response. Median time to response was 1.8 months, median time to next therapy was 9.7 months, and median treatment-free interval was 7.9 months. After 22.6 months median follow-up, median PFS was 12.0 months and median OS was 36.1 months. The most common adverse events (AEs) were neuropathy not otherwise specified (19%), diarrhea NOS, and thrombocytopenia (each 17%); 230 (26%) patients discontinued bortezomib due to AEs. Of 689 (79%) patients without baseline peripheral neuropathy (PN), the rate of new-onset any-grade PN increased to 51% (12% grade 3/4) by cycle 8. Overall, 244 (28%) patients were hospitalized, 372 (43%) attended an outpatient visit, and 341 (39%) underwent a diagnostic/therapeutic procedure during bortezomib treatment. Conclusion: These prospective real-world data demonstrate the effectiveness and safety of bortezomib-based therapy for RRMM and confirm high response rates and long OS for this population.

  • 25.
    Vaht, Krista
    et al.
    Sahlgrens Univ Hosp, Sweden; Gothenburg Univ, Sweden.
    Goransson, Magnus
    Sahlgrens Univ Hosp, Sweden.
    Carlson, Kristina
    Uppsala Univ Hosp, Sweden.
    Isaksson, Cecilia
    Univ Hosp, Sweden.
    Lenhoff, Stig
    Lund Univ, Sweden.
    Sandstedt, Anna
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US. Linköpings universitet, Medicinska fakulteten.
    Uggla, Bertil
    Orebro Univ, Sweden.
    Winiarski, Jacek
    Karolinska Inst, Sweden; CLINTEC, Sweden.
    Ljungman, Per
    Karolinska Inst, Sweden.
    Brune, Mats
    Sahlgrens Univ Hosp, Sweden; Gothenburg Univ, Sweden.
    Andersson, Per-Ola
    Gothenburg Univ, Sweden; Sodra Alvsborg Hosp Boras, Sweden.
    Low response rate to ATG-based immunosuppressive therapy in very severe aplastic anaemia A Swedish nationwide cohort study2018Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 100, nr 6, s. 613-620Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ObjectivesAntithymocyte globulin (ATG)-based immunosuppression remains a cornerstone in aplastic anaemia (AA) treatment. However, most ATG studies are not population-based and knowledge about real-world results concerning response and outcome could offer important information for treating physicians. MethodsWe have recently performed a nationwide retrospective cohort study on all AA patients diagnosed in Sweden in 2000-2011 and now present treatment and outcome data on patients receiving first-line ATG. In total, 158 patients showed a 47.0% response rate which was similar in all age groups (range 41.5%-51.7%) with no difference regarding ATG formulation. The response was significantly associated with severity gradeespecially at time of treatment initiation: very severe (VSAA) 22.7%; severe (SAA) 54.5% (Pamp;lt;.001); and non-severe 88.5% (Pamp;lt;.001). A logistic regression-based predictive model indicated that VSAA patients with an absolute reticulocyte count amp;lt;25x10(9)/L had only a 19% probability of response. In a multivariable analysis, age and VSAA at the time of treatment were the independent factors for inferior survival. ConclusionsReal-world VSAA patients respond poorly to ATG which indicates the need for a different treatment approach. Our findings suggest that age alone should not be a discriminating factor for administering ATG treatment.

  • 26.
    Walsh, S.H.
    et al.
    Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Grabowski, P.
    Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
    Berglund, M.
    Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden.
    Thunberg, U.
    Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden.
    Thorselius, M.
    Thorsélius, M., Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Tobin, G.
    Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Aleskog, A.
    Åleskog, A., Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Karlsson, Katarina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Omvårdnad.
    Sundstrom, C.
    Sundström, C., Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Laurell, A.
    Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden.
    Enblad, G.
    Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden.
    Rosenquist, R.
    Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Roos, G.
    Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden, Department of Medical Biosciences, Umeå University, SE-90187 Umeå, Sweden.
    Telomere length and correlation with histopathogenesis in B-cell leukemias/lymphomas2007Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 78, nr 4, s. 283-289Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Telomere length was recently reported to correlate with cellular origin of B-cell malignancies in relation to the germinal center (GC). In this report, we measured telomere length by quantitative-PCR in 223 B-cell lymphomas/leukemias and correlated results with immunoglobulin (Ig) mutation status and immunostainings for GC/non-GC subtypes of diffuse large B-cell lymphoma (DLBCL). Shortest telomeres were found in Ig-unmutated chronic lymphocytic leukemia (CLL) [median telomere to single copy gene value (T/S) 0.33], differing significantly to Ig-mutated CLL (0.63). Contrary to this, mantle cell lymphomas (MCLs) exhibited similar telomere lengths regardless of Ig mutation status (0.47). Telomere length differed significantly between GC-like (0.73) and non-GC-like DLBCLs (0.43), and follicular lymphomas (FLs) had shorter telomeres (0.53) than GC-DLBCL. Hairy cell leukemias, which display Ig gene intraclonal heterogeneity, had longer telomeres (0.62) than FLs and non-GC-DLBCL, but shorter than GC-DLBCL. We conclude that although DLBCL and CLL subsets can be clearly distinguished, telomere length reflects many parameters and may not simply correlate with GC-related origin. © 2007 The Authors.

  • 27.
    Willander, Kerstin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Hematologiska kliniken US.
    Ungerbäck, Jonas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Karlsson, Karin
    Department of Hematology, Lund University Hospital, Lund, Sweden.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Linderholm, Mats
    Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Hematologiska kliniken US.
    MDM2 SNP309 promoter polymorphism, an independent prognostic factor in chronic lymphocytic leukemia2010Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 85, nr 3, s. 251-256Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The single nucleotide polymorphism SNP309 with a change from T to G in the promoter region of the MDM2 gene is shown to increase the MDM2 protein levels and attenuate the p53 levels and associates with disease progression in several tumors. OBJECTIVE: In this study, the role of the polymorphism was investigated with regard to the clinical outcome in B-cell chronic lymphocytic leukemia (B-CLL). PATIENTS: A total of 210 patients with B-CLL were followed for up to 19 yr. RESULTS: The overall survival (OS) of patients with at least one G-allele was significantly shorter when compared with those with two T-alleles (P = 0.024) with a more pronounced difference in patients below the median age. Age at onset of B-CLL was similar irrespective of MDM2 status. The presence of a G-allele in combination with TP53 mutations or unmutated IgVH gene status resulted in an additive risk of death. CONCLUSION: In this report, with a high proportion of B-CLL patients with an advanced Binet stage and with an unmutated IgVH gene, MDM2 SNP309 was found to be independently associated with OS. The survival difference was more pronounced in younger patients.

  • 28. Wisloff, F
    et al.
    Gulbrandsen, N
    Hjorth, Maria
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik.
    Lenhoff, S
    Fayers, P
    Quality of life may be affected more by disease parameters and response to therapy than by haemoglobin changes2005Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 75, nr 4, s. 293-298Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Earlier studies showing a negative impact of anaemia on quality of life (QOL) lack adequate adjustment for confounding factors such as disease stage and tumour response. We examined the impact of haemoglobin concentration on QOL scores of 745 multiple myeloma patients followed from diagnosis, adjusting for objective disease parameters. Data from two Nordic studies with the EORTC QLQ-C30 questionnaire were analysed using linear regression analysis. Haemoglobin was independently related only to fatigue at baseline (P = 0.001) and at 12 months (P = 0.010). In multivariate analysis, extent of skeletal disease was at least as strong a predictor for fatigue at diagnosis as haemoglobin and was also related to other important QOL scores such as physical functioning, role functioning, global QOL and pain (P < 0.001). At 12 months' follow-up, response to therapy was related to physical functioning (P < 0.001) and pain (P = 0.001). In conclusion, haemoglobin and extent of skeletal disease were both predictors for fatigue in patients with newly diagnosed multiple myeloma, but extent Of skeletal disease was also associated with other important QOL scores. During follow-up, response to therapy emerged as an important predictor variable. When examining the effect of haemoglobin on QOL, it is essential to adjust for disease parameters and response to therapy in order not to overestimate the impact of haemoglobin on QOL. Our findings imply that uncontrolled studies on the effect of erythropoietin (EPO) in cancer patients may be making exaggerated claims for the effect of EPO on QOL.

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