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  • 1.
    Andersson, Charlotta
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Li, Xingru
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Lorenz, Fryderyk
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Li, Aihong
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Reduction in WT1 Gene Expression During Early Treatment Predicts the Outcome in Patients With Acute Myeloid Leukemia2012In: Diagnostic molecular pathology (Print), ISSN 1052-9551, E-ISSN 1533-4066, Vol. 21, no 4, p. 225-233Article in journal (Refereed)
    Abstract [en]

    Wilms tumor gene 1 (WT1) expression has been suggested as an applicable minimal residual disease marker in acute myeloid leukemia (AML). We evaluated the use of this marker in 43 adult AML patients. Quantitative assessment of WT1 gene transcripts was performed using real-time quantitative-polymerase chain reaction assay. Samples from both the peripheral blood and the bone marrow were analyzed at diagnosis and during follow-up. A strong correlation was observed between WT1 normalized with 2 different control genes (beta-actin and ABL1, P < 0.001). WT1 mRNA level at diagnosis was of no prognostic relevance (P > 0.05). A >= 1-log reduction in WT1 expression in bone marrow samples taken < 1 month after diagnosis significantly correlated with an improved overall survival (P = 0.004) and freedom from relapse (P = 0.010) when beta-actin was used as control gene. Furthermore, a reduction in WT1 expression by >= 2 logs in peripheral blood samples taken at a later time point significantly correlated with a better outcome for overall survival (P = 0.004) and freedom from relapse (P = 0.012). This result was achieved when normalizing against both b-actin and ABL1. These results therefore suggest that WT1 gene expression can provide useful information for minimal residual disease detection in adult AML patients and that combined use of control genes can give more informative results.

  • 2. Cesaro, Simone
    et al.
    Marsh, Judith
    Tridello, Gloria
    Rovò, Alicia
    Maury, Sebastien
    Montante, Barbara
    Masszi, Tamás
    Van Lint, Maria Teresa
    Afanasyev, Boris
    Iriondo Atienza, Arturo
    Bierings, Marc
    Carbone, Cecilia
    Doubek, Michael
    Lanino, Edoardo
    Sarhan, Mahmoud
    Risitano, Antonio
    Steinerova, Katerina
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Pegoraro, Anna
    Passweg, Jakob
    Retrospective survey on the prevalence and outcome of prior autoimmune diseases in patients with aplastic anemia reported to the registry of the European group for blood and marrow transplantation.2010In: Acta Haematologica, ISSN 0001-5792, E-ISSN 1421-9662, Vol. 124, no 1, p. 19-22Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Aplastic anemia (AA) is rarely described after a diagnosis of autoimmune disease (aID). AIMS: To assess the prevalence of prior aID in patients with AA recorded in the registry of the European Group for Blood and Marrow Transplantation (EBMT) and to evaluate treatment and outcome. METHODS: 1,251 AA patients from 18 EBMT centers were assessed. RESULTS: Fifty patients (4%) were eligible: 22 males and 28 females with a median age of 46 years at the diagnosis of aID and of 51 years at the diagnosis of AA. Information on the treatment of AA was available in 49 patients: 38 received only immunosuppressive therapy (IST), 8 patients underwent hematopoietic stem cell transplantation (HSCT) - 6 as first-line therapy and 2 after failure of IST - whilst 3 patients had a spontaneous recovery. After a median follow-up of 3.19 years, 32 patients were alive, including 7 of the 8 patients who underwent HSCT. Only 6 of 32 patients who were alive at the last follow-up were receiving IST for AA. CONCLUSIONS: Most cases of AA following aID benefitted from IST or HSCT if a matched donor was available. Further prospective investigation is needed to assess the effects of IST on the outcome of underlying aID.

  • 3. Hallböök, H
    et al.
    Hägglund, H
    Stockelberg, D
    Nilsson, P-G
    Karlsson, K
    Björkholm, M
    Linderholm, M
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Linder, O
    Smedmyr, B
    Autologous and allogeneic stem cell transplantation in adult ALL: the Swedish Adult ALL Group experience2005In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 35, no 12, p. 1141-1148Article in journal (Refereed)
    Abstract [en]

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

  • 4. Hulegårdh, Erik
    et al.
    Nilsson, Christer
    Lazarevic, Vladimir
    Garelius, Hege
    Antunovic, Petar
    Rangert Derolf, Åsa
    Möllgård, Lars
    Uggla, Bertil
    Wennström, Lovisa
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Swedish Acute Myeloid Leukemia Group.
    Höglund, Martin
    Juliusson, Gunnar
    Stockelberg, Dick
    Lehmann, Sören
    Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: A report from the Swedish Acute Leukemia Registry2015In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 90, no 3, p. 208-214Article in journal (Refereed)
    Abstract [en]

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

  • 5.
    Hultdin, Magnus
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Sundström, Gunnel
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Lundström, Berith
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Samuelsson, Jan
    Birgegård, Gunnar
    Engström Laurent, Anna
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Progression of bone marrow fibrosis in patients with essential thrombocythemia and polycythemia vera during anagrelide treatment.2007In: Med Oncol, ISSN 1357-0560, Vol. 24, no 1, p. 63-70Article in journal (Refereed)
  • 6. Iolascon, Achille
    et al.
    Heimpel, Hermann
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Tamary, Hannah
    Congenital dyserythropoietic anemias: molecular insights and diagnostic approach2013In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 122, no 13, p. 2162-2166Article in journal (Refereed)
    Abstract [en]

    The congenital dyserythropoietic anemias (CDAs) are hereditary disorders characterized by distinct morphologic abnormalities of marrow erythroblasts. The unveiling of the genes mutated in the major CDA subgroups (I-CDAN1 and II-SEC23B) has now been completed with the recent identification of the CDA III gene (KIF23). KIF23 encodes mitotic kinesin-like protein 1, which plays a critical role in cytokinesis, whereas the cellular role of the proteins encoded by CDAN1 and SEC23B is still unknown. CDA variants with mutations in erythroid transcription factor genes (KLF1 and GATA-1) have been recently identified. Molecular diagnosis of CDA is now possible in most patients.

  • 7. Johansson, J-E
    et al.
    Remberger, M
    Lazarevic, Vlj
    Hallböök, H
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kimby, E
    Juliusson, G
    Omar, H
    Hägglund, H
    Allogeneic haematopoietic stem-cell transplantation with reduced intensity conditioning for advanced stage Hodgkin's lymphoma in Sweden: high incidence of post transplant lymphoproliferative disorder.2011In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 46, no 6, p. 870-875Article in journal (Refereed)
    Abstract [en]

    Allogeneic transplantation after reduced intensity conditioning (allo-RIC) is a treatment option for patients with Hodgkin's lymphoma (HL) relapsing after autologous transplantation. In all, 23 adult patients with HL underwent allo-RIC in Sweden between 2000 and 2007. The median number of previous treatment lines was five and 20 patients (87%) were previously autografted. TRM at 100 days and at 1 year was 13 and 22% respectively. Acute GVHD grades II-IV developed in 7 out of 23 patients (30%) and chronic GVHD in 10 out of 20 patients at risk (50%). The OS and EFS at three years was 59 and 27%, respectively. Four patients (17%) developed post transplant lymphoproliferative disease (PTLD) after a median time of 55 days (range 38-95); two of these patients later died. The study confirmed that allo-RIC is feasible, but associated with a substantial relapse rate: only 20% of the patients were still alive 7 years after the transplant. A finding of high incidence of PTLD needs to be confirmed in a larger trial that includes patients with non-HL and CLL.

  • 8. Juliusson, G
    et al.
    Billström, R
    Gruber, A
    Hellström-Lindberg, E
    Höglunds, M
    Karlsson, K
    Stockelberg, D
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Attitude towards remission induction for elderly patients with acute myeloid leukemia influences survival.2006In: Leukemia, Vol. 20, no 1, p. 42-7Article in journal (Refereed)
    Abstract [en]

    Combination chemotherapy may induce remission from acute myeloid leukemia (AML), but validated criteria for treatment of elderly are lacking. The remission intention (RI) rate for elderly patients, as reported to the Swedish Leukemia Registry, was known to be different when comparing the six health care regions, but the consequences of different management are unknown. The Leukemia Registry, containing 1672 AML patients diagnosed between 1997 and 2001, with 98% coverage and a median follow-up of 4 years, was completed with data from the compulsory cancer and population registries. Among 506 treated and untreated patients aged 70-79 years with AML (non-APL), there was a direct correlation between the RI rate in each health region (range 36-76%) and the two-year overall survival, with no censored observations (6-21%) (chi-squared for trend=11.3, P<0.001; r2=0.86, P<0.02, nonparametric). A 1-month landmark analysis showed significantly better survival in regions with higher RI rates (P=0.003). Differences could not be explained by demographics, and was found in both de novo and secondary leukemias. The 5-year survival of the overall population aged 70-79 years was similar between the regions. Survival of 70-79-year-old AML patients is better in regions where more elderly patients are judged eligible for remission induction.

  • 9. Juliusson, Gunnar
    et al.
    Antunovic, Petar
    Derolf, Åsa
    Lehmann, Sören
    Möllgård, Lars
    Stockelberg, Dick
    Tidefelt, Ulf
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Höglund, Martin
    Age and acute myeloid leukemia: Real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry.2009In: Blood, ISSN 1528-0020, Vol. 113, no 18, p. 4179-4187Article in journal (Refereed)
    Abstract [en]

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

  • 10. Juliusson, Gunnar
    et al.
    Karlsson, Karin
    Lazarevic, Vladimir Lj
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brune, Mats
    Antunovic, Petar
    Derolf, Asa
    Hägglund, Hans
    Karbach, Holger
    Lehmann, Sören
    Möllgård, Lars
    Stockelberg, Dick
    Hallböök, Helene
    Höglund, Martin
    Hematopoietic stem cell transplantation rates and long-term survival in acute myeloid and lymphoblastic leukemia: Real-World Population-Based Data From the Swedish Acute Leukemia Registry 1997-20062011In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 117, no 18, p. 4238-4246Article in journal (Refereed)
    Abstract [en]

    Background: Allogeneic stem cell transplantation (alloSCT) reduces relapse rates in acute leukemia, but outcome is hampered by toxicity. Population-based data avoid patient selection and may therefore substitute for lack of randomized trials.

    Methods: We evaluated alloSCT rates within the Swedish Acute Leukemia Registry, including 3899 adult patients diagnosed from 1997 through 2006 with a coverage of 98% and a median follow-up of 6.2 years.

    Results:: AlloSCT rates and survival decreased rapidly with age >55 years. The 8-year overall survival (OS) was 65% in patients <30 years and 38% in patients <60 years and was similar for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Among 1073 patients <60 years, alloSCT was performed in 42% and 49% of patients with AML and ALL, respectively. Two-thirds of the alloSCTs were performed in first complete remission, and half used unrelated donors, the same in AML and ALL. Regional differences in management and outcome were found: 60% of AML patients <40 years received alloSCT in all parts of Sweden, but two-thirds of AML patients 40-59 years had alloSCT in one region compared with one-third in other regions (P<.001), with improved 8-year OS among all AML patients in this age cohort (51% vs 30%; P = .005).

    Conclusions: More Swedish AML patients received alloSCT, and long-term survival was better than in recently published large international studies, despite our lack of selection bias. There was no correlation between alloSCT rate and survival in ALL. In adult AML patients <60 years of age, a high alloSCT rate was associated with better long-term survival, but there was no such correlation in ALL.

  • 11. Kristinsson, Sigurdur Y
    et al.
    Björkholm, Magnus
    Andersson, Therese M-L
    Eloranta, Sandra
    Dickman, Paul W
    Goldin, Lynn R
    Blimark, Cecilie
    Mellqvist, Ulf-Henrik
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Turesson, Ingemar
    Landgren, Ola
    Patterns of survival and causes of death following a diagnosis of monoclonal gammopathy of undetermined significance. A population-based study.2009In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 94, no 12, p. 1714-1720Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There are limited data on survival patterns among patients with monoclonal gammopathy of undetermined significance. DESIGN AND METHODS: We compared the survival of 4,259 patients with monoclonal gammopathy of undetermined significance, collected from hematology outpatient units in Sweden, with the survival of the general population by computing relative survival ratios. We also compared causes of death in these patients with those in 16,151 matched controls. RESULTS: One-, 5-, 10-, and 15-year relative survival ratios were 0.98 (95% CI 0.97-0.99), 0.93 (0.91-0.95), 0.82 (0.79-0.84), and 0.70 (0.64-0.76), respectively. Younger age at diagnosis of the gammopathy was associated with a significantly lower excess mortality compared to that in older patients (p<0.001). The excess mortality among patients with gammopathy increased with longer follow-up (p<0.0001). IgM (versus IgG/A) gammopathy was associated with a superior survival (p=0.038). Patients with monoclonal gammopathy of undetermined significance had an increased risk of dying from multiple myeloma (hazards ratio (HR)=553; 95% CI 77-3946), Waldenström's macroglobulinemia (HR=infinity), other lymphoproliferative malignancies (6.5; 2.8-15.1), other hematologic malignancies (22.9; 8.9-58.7), amyloidosis (HR=infinity), bacterial infections (3.4; 1.7-6.7), ischemic heart disease (1.3; 1.1-1.4), other heart disorders (1.5; 1.2-1.8), other hematologic conditions (6.9; 2.7-18), liver (2.1; 1.1-4.2), and renal diseases (3.2; 2.0-4.9). CONCLUSIONS: Our finding of decreased life expectancy in patients with monoclonal gammopathy of undetermined significance, which was most pronounced in the elderly and explained by both malignant transformation and non-malignant causes, is of importance in the understanding and clinical management of this disease. The underlying mechanisms may be causally related to the gammopathy, but may also be explained by underlying disease that led to the detection of the hematologic disease. Our results are of importance since they give a true estimation of survival in patients with monoclonal gammopathy of undetermined significance diagnosed in clinical practice.

  • 12. Kristinsson, Sigurdur Y
    et al.
    Björkholm, Magnus
    Goldin, Lynn R
    Blimark, Cecilie
    Mellqvist, Ulf-Henrik
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Turesson, Ingemar
    Landgren, Ola
    Patterns of hematologic malignancies and solid tumors among 37,838 first-degree relatives of 13,896 patients with multiple myeloma in Sweden.2009In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 125, no 9, p. 2147-2150Article in journal (Refereed)
    Abstract [en]

    There are emerging data to suggest a role for genetic factors in the pathogenesis of multiple myeloma (MM). Based on small numbers, certain solid tumors have been reported to occur more frequently among blood relatives of patients with MM. Using population-based data, we assessed risks for hematologic malignancies, monoclonal gammopathy of undetermined significance (MGUS), and solid tumors among first-degree relatives of patients with MM. We included 13,896 patients with MM and 54,365 matched controls. Also we identified first-degree relatives of patients with MM (n = 37,838) and controls (n = 151,068). Using a marginal survival model, we estimated relative risks (RRs) and 95% confidence intervals (CIs) for hematologic and solid tumors among family members of patients with MM and controls as measures of familial aggregation. Compared with relatives of controls, relatives of patients with MM had an increased risk of developing MM (RR = 2.1; 95% CI 1.6-2.9), MGUS (2.1; 1.5-3.1), acute lymphoblastic leukemia (ALL) (2.1; 1.0-4.2), any solid tumor (1.1; 1.0-1.1) and bladder cancer (1.3; 1.0-1.5). No significantly increased risk was found for other hematologic or solid malignancies. Our findings support a role for a shared susceptibility (genetic, environmental or both) that predisposes to MM, MGUS, ALL and bladder cancer.

  • 13. Kristinsson, Sigurdur Y
    et al.
    Pfeiffer, Ruth M
    Björkholm, Magnus
    Goldin, Lynn R
    Schulman, Sam
    Blimark, Cecilie
    Mellqvist, Ulf-Henrik
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Turesson, Ingemar
    Landgren, Ola
    Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma: a population-based study2010In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 115, no 24, p. 4991-4998Article in journal (Refereed)
    Abstract [en]

    Patients with multiple myeloma (MM) have an increased risk of venous thrombosis. Interestingly, excess risk of venous thromboembolism has been observed among patients with monoclonal gammopathy of undetermined significance (MGUS). Using population-based data from Sweden, we assessed the risks of venous and arterial thrombosis in 18,627 MM and 5326 MGUS patients diagnosed from 1958 to 2006, compared with 70,991 and 20,161 matched controls, respectively. At 1, 5, and 10 years after MM diagnosis, there was an increased risk of venous thrombosis: hazard ratios (95% confidence intervals) were 7.5 (6.4-8.9), 4.6 (4.1-5.1), and 4.1 (3.8-4.5), respectively. The corresponding results for arterial thrombosis were 1.9 (1.8-2.1), 1.5 (1.4-1.6), and 1.5 (1.4-1.5). At 1, 5, and 10 years after MGUS diagnosis, hazard ratios were 3.4 (2.5-4.6), 2.1 (1.7-2.5), and 2.1 (1.8-2.4) for venous thrombosis. The corresponding risks for arterial thrombosis were 1.7 (1.5-1.9), 1.3 (1.2-1.4), and 1.3 (1.3-1.4). IgG/IgA (but not IgM) MGUS patients had increased risks for venous and arterial thrombosis. Risks for thrombosis did not vary by M-protein concentration (> 10.0 g/L or < 10.0 g/L) at diagnosis. MGUS patients with (vs without) thrombosis had no excess risk of MM or Waldenström macroglobulinemia. Our findings are of relevance for future studies and for improvement of thrombosis prophylaxis strategies.

  • 14. Kristinsson, Sigurdur Y
    et al.
    Tang, Min
    Pfeiffer, Ruth M
    Björkholm, Magnus
    Blimark, Cecilie
    Mellqvist, Ulf-Henrik
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Turesson, Ingemar
    Landgren, Ola
    Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study2010In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 116, no 15, p. 2651-2655Article in journal (Refereed)
    Abstract [en]

    Patients with multiple myeloma (MM) have an increased risk of fractures. On the basis of small numbers, patients with monoclonal gammopathy of undetermined significance (MGUS) have been reported to have an increased fracture risk. Using population-based data from Sweden, we assessed the risks of fractures in 5326 MGUS patients diagnosed from 1958 to 2006, compared with 20 161 matched controls. MGUS patients had an increased risk of any fracture at 5 (hazard ratio [HR] = 1.74; 95% confidence interval [CI], 1.58-1.92) and 10 (HR = 1.61; 95% CI, 1.49-1.74) years. The risk was significantly higher for axial (skull, vertebral/pelvis, and sternum/costae) compared with distal (arm and leg) fractures (P < .001). On the basis of 10 years of follow-up, there was an increased risk of vertebral/pelvic (HR = 2.37; 95% CI, 2.02-2.78), sternal/costae (HR = 1.93; 95% CI, 1.5-2.48), arm (HR = 1.23; 95% CI, 1.06-1.43), leg (HR = 1.40; 95% CI, 1.26-1.56), and other/multiple fractures (HR = 4.25; 95% CI, 3.29-5.51). Risks for fractures did not differ by isotype or M protein concentration at diagnosis. MGUS patients with (versus without) fractures had no excess risk of MM or Waldenström macroglobulinemia. Our results suggest that bone alterations are present in early myelomagenesis. Our findings may have implications for the development of better prophylaxis for bone disease in MGUS, and they provide novel clues on pathogenesis of MM bone disease.

  • 15. Kristinsson, Sigurdur Y
    et al.
    Tang, Min
    Pfeiffer, Ruth M
    Björkholm, Magnus
    Goldin, Lynn R
    Blimark, Cecilie
    Mellqvist, Ulf-Henrik
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Turesson, Ingemar
    Landgren, Ola
    Monoclonal gammopathy of undetermined significance and risk of infections: a population-based study.2012In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 97, no 6, p. 854-858Article in journal (Refereed)
    Abstract [en]

    No comprehensive evaluation has been conducted to assess the risk of viral and bacterial infections among patients with monoclonal gammopathy of undetermined significance. Using population-based data from Sweden, we estimated risk of infections among 5,326 MGUS patients compared to 20,161 matched controls. Patients with monoclonal gammopathy of undetermined significance had a 2-fold increased risk (P<0.05) of developing any infection at 5 and 10 years of follow-up. More specifically, patients with monoclonal gammopathy of undetermined significance had an increased risk (P<0.05) of bacterial infections (pneumonia, osteomyelitis, septicemia, pyelonephritis, cellulitis, endocarditis, and meningitis), and viral infections (influenza and herpes zoster). Patients with monoclonal gammopathy of undetermined significance with M-protein concentrations >2.5 g/dL at diagnosis had highest risks of infections; however, the risk was also increased (P<0.05) among those with concentrations <0.5 g/dL. Patients with monoclonal gammopathy of undetermined significance who developed infections had no excess risk of developing multiple myeloma. Our findings provide novel clues for the mechanisms behind infections in patients with plasma cell dyscrasias, and may have clinical implications.

  • 16. Landgren, Ola
    et al.
    Kristinsson, Sigurdur Y
    Goldin, Lynn R
    Caporaso, Neil E
    Blimark, Cecilie
    Mellqvist, Ulf-Henrik
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Björkholm, Magnus
    Turesson, Ingemar
    Risk of plasma cell and lymphoproliferative disorders among 14621 first-degree relatives of 4458 patients with monoclonal gammopathy of undetermined significance in Sweden.2009In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 114, no 4, p. 791-795Article in journal (Refereed)
    Abstract [en]

    Familial clustering of the precursor condition, monoclonal gammopathy of undetermined significance (MGUS) has been observed in case reports and in smaller studies. Using population-based data from Sweden, we identified 4458 MGUS patients, 17505 population-based controls, and first-degree relatives of patients (n = 14621) and controls (n = 58387) with the aim to assess risk of MGUS and lymphoproliferative malignancies among first-degree relatives of MGUS patients. Compared with relatives of controls, relatives of MGUS patients had increased risk of MGUS (relative risk [RR] = 2.8; 1.4-5.6), multiple myeloma (MM; RR = 2.9; 1.9-4.3), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM; RR = 4.0; 1.5-11), and chronic lymphocytic leukemia (CLL; RR = 2.0; 1.2-2.3). Relatives of patients with IgG/IgA MGUS had a 4.0-fold (1.7-9.2), 2.9-fold (1.7-4.9), and 20-fold (2.3-170) elevated risk of developing MGUS, MM, and LPL/WM, respectively. Relatives of IgM MGUS patients had 5.0-fold (1.1-23) increased CLL risk and nonsignificant excess MM and LPL/WM risks. The results were very similar when we assessed risk by type of first-degree relative, age at MGUS (above/below 65 years), or sex. Risk of non-Hodgkin lymphoma or Hodgkin lymphoma was not increased among MGUS relatives. Among first-degree relatives of a nationwide MGUS cohort, we found elevated risks of MGUS, MM, LPL/WM, and CLL, supporting a role for germline susceptibility genes, shared environmental influences, or an interaction between both.

  • 17. Lanza, Francesco
    et al.
    Campioni, Diana C.
    Hellmann, Andrzej
    Milone, Giuseppe
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Walewski, Jan
    Spedini, Pierangelo
    Fiamenghi, Cristina
    Cuneo, Antonio
    Knopinska, Wanda
    Swierkowska-Czeneszew, Monica
    Petriz, Jordi
    Fruehauf, Stefan
    Farge, Dominique
    Mohty, Mohamad
    Passweg, Jacob
    Ruuto, Tapani
    Madrigal, Alejandro
    Johnsen, Hans E.
    Individual Quality Assessment of Autografting by Probability Estimation for Clinical Endpoints: A Prospective Validation Study from the European Group for Blood and Marrow Transplantation2013In: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 19, no 12, p. 1670-1676Article, review/survey (Refereed)
    Abstract [en]

    The aim of supportive autografting is to reduce the side effects from stem cell transplantation and avoid procedure-related health disadvantages for patients at the lowest possible cost and resource expenditure. Economic evaluation of health care is becoming increasingly important. We report clinical and laboratory data collected from 397 consecutive adult patients (173 non-Hodgkin lymphoma, 30 Hodgkin lymphoma, 160 multiple myeloma, 7 autoimmune diseases, and 28 acute leukemia) who underwent their first autologous peripheral blood stem cell transplantation (PBSCT). We considered primary endpoints evaluating health economic efficacy (eg, antibiotic administration, transfusion of blood components, and time in hospital), secondary endpoints evaluating toxicity (in accordance with Common Toxicity Criteria), and tertiary endpoints evaluating safety (le, the risk of regimen-related death or disease progression within the first year after PBSCT). A time-dependent grading of efficacy is proposed with day 21 for multiple myeloma and day 25 for the other disease categories (depending on the length of the conditioning regimen) as the acceptable maximum time in hospital, which together with antibiotics, antifungal, or transfusion therapy delineates four groups: favorable (<= 7 days on antibiotics and no transfusions; <= 21 [25] days in hospital), intermediate (from 7 to 10 days on antibiotics and <3 transfusions, <= 21 to 25 days in hospital or >= 7 days on antibiotics and no transfusions; from 21 to 30 days [25 to 34] in hospital), unfavorable (>7 days on antibiotics, >3 but <6 transfusions; >30/34 days in hospital after transplantation), and very unfavorable (>10 days on antibiotics, >6 transfusions; >30 to 34 days in hospital). The multivariate analysis showed that (1) PBSC harvests of >= 4 x 10(6)/kg CD34 + cells in 1 apheresis procedure were associated with a favorable outcome in all patient categories except acute myelogenous leukemia and acute lymphoblastic leukemia (P = .001), (2) >= 5 x 10(6)/kg CD34 + cells infused predicted better transplantation outcome in all patient categories (P < .0001) except acute myelogenous leukemia and acute lymphoblastic leukemia, (3) 1 or 2 aphereses (P = .001) predicted good outcome, (4) toxicity increased with higher graft volume reinfused (>500 mL) (P = .002), and (5) patients with a central venous catheter during both collection and infusion of PBSC had a more favorable outcome post-PBSCT than peripheral access (P = .007). The type of mobilization regimen did not affect the outcome of auto-PBSCT. The present study identified predictive variables, which may be useful in future individual pretransplantation probability evaluations with the goal to improve supportive care. (C) 2013 American Society for Blood and Marrow Transplantation.

  • 18. Lazarevic, V.
    et al.
    Horstedt, A-S
    Johansson, B.
    Antunovic, P.
    Billstrom, R.
    Derolf, A.
    Hulegardh, E.
    Lehmann, S.
    Mollgard, L.
    Nilsson, C.
    Peterson, S.
    Stockelberg, D.
    Uggla, B.
    Wennstrom, L.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hoglund, M.
    Juliusson, G.
    Incidence and prognostic significance of karyotypic subgroups in older patients with acute myeloid leukemia: the Swedish population-based experience2014In: Blood Cancer Journal, ISSN 2044-5385, E-ISSN 2044-5385, Vol. 4, p. e188-Article in journal (Refereed)
    Abstract [en]

    The Swedish population-based acute myeloid leukemia registry contains data from 3251 patients (excluding acute promyelocytic leukemia) diagnosed between 1997 and 2006. Informative cytogenetic data from 1893 patients were retrospectively added, including 1054 patients aged between 60 and 79 years. Clonal abnormalities were found in 57% of the informative karyotypes. Karyotypic patterns differed by age: t(8; 21), inv(16) and t(11q23) were more common in younger patients, whereas loss of 5q, 7q and 17p, monosomal karyotype (MK) and complex karyotypes were more common in older patients. Loss of 5q, 7q and 17p often occurred together within MK. Patients with >= 5 chromosome abnormalities had worse overall survival than those with fewer abnormalities or normal karyotype in all age groups. Loss of 5q, 7q and/or 17p had, in contrast to MK, a further negative impact on survival. Multivariable Cox regression analyses on risk factors in patients <80 years with cytogenetic abnormalities and intensive treatment revealed that age and performance status had the most significant impact on survival (both P<0.001), followed by sex (P = 0.0135) and a karyotype including - 7/del(7q) (P = 0.048).

  • 19.
    Lazarevic, Vladimir
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Andersson, Charlotte
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Golovleva, Irina
    Chromosome aberrations including der(6)t(2;6)(p15;p21.3) and der(22)t(3;22)(p21;p11) in the evolution of essential thrombocythemia to myelofibrosis with myeloid metaplasia.2006In: Cancer Genet Cytogenet, ISSN 0165-4608, Vol. 165, no 1, p. 87-9Article in journal (Refereed)
  • 20.
    Lazarevic, Vladimir
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Golovleva, Irina
    Nygren, Ida
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Induction chemotherapy and post-remission imatinib therapy for de Novo BCR-ABL-positive AML.2006In: Am J Hematol, ISSN 0361-8609, Vol. 81, no 6, p. 470-1Article in journal (Refereed)
  • 21.
    Lazarevic, Vladimir
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Hägg, Erik
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Hiccups and severe hyponatremia associated with high-dose cyclophosphamide in conditioning regimen for allogeneic stem cell transplantation.2007In: Am J Hematol, ISSN 0361-8609, Vol. 82, no 1, p. 88-Article in journal (Refereed)
  • 22.
    Lazarevic, Vladimir
    et al.
    Lund, Sweden.
    Hörstedt, Ann-Sofi
    Lund, Sweden.
    Johansson, Bertil
    Lund, Sweden.
    Antunovic, Petar
    Linköping, Sweden.
    Billström, Rolf
    Skövde, Sweden.
    Derolf, Åsa
    Stockholm and Huddinge, Sweden.
    Lehmann, Sören
    Stockholm and Huddinge, Sweden.
    Möllgård, Lars
    Göteborg, Sweden.
    Peterson, Stefan
    Lund, Sweden.
    Stockelberg, Dick
    Göteborg, Sweden.
    Uggla, Bertil
    Örebro, Sweden.
    Vennström, Lovisa
    Göteborg, Sweden.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Höglund, Martin
    Uppsala, Sweden.
    Juliusson, Gunnar
    Lund, Sweden.
    Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population-based series of acute myeloid leukaemia2015In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 94, no 5, p. 419-423Article in journal (Refereed)
    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 (P<0.001). 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.

  • 23. Lazarevic, Vladimir L J
    et al.
    Hägglund, Hans
    Remberger, Mats
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hallböök, Helene
    Juliusson, Gunnar
    Kimby, Eva
    Malm, Claes
    Omar, Hamdy
    Johansson, Jan-Erik
    Long-term survival following allogeneic or syngeneic stem cell transplant for follicular lymphoma in Sweden2011In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 52, no 1, p. 69-71Article in journal (Refereed)
  • 24.
    Lazarevic, Vladimir Lj
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Liljeholm, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Forsberg, Karin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Fludarabine, cyclophosphamide and rituximab (FCR) induced pulmonary hypertension in Waldenstrom macroglobulinemia.2008In: Leukemia & lymphoma, ISSN 1029-2403, Vol. 49, no 6, p. 1209-1211Article in journal (Refereed)
  • 25. Lazarevic, Vladimir Lj
    et al.
    Remberger, Mats
    Hägglund, Hans
    Hallböök, Helene
    Juliusson, Gunnar
    Kimby, Eva
    Malm, Claes
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Omar, Hamdy
    Johansson, Jan-Erik
    Myeloablative allogeneic stem cell transplantation for lymphoblastic lymphoma in Sweden: a retrospective study.2011In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 86, no 8, p. 709-710Article in journal (Refereed)
  • 26. Lazarevic, Vladimir
    et al.
    Remberger, Mats
    Hägglund, Hans
    Juliusson, Gunnar
    Omar, Hamdy
    Halböök, Helene
    Kimby, Eva
    Malm, Claes
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Jan-Erik
    Long-term survival after allogeneic stem cell transplantation for relapsed large B cell lymphomas: a retrospective study2012In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 53, no 3, p. 503-505Article in journal (Refereed)
  • 27.
    Lazarevic, Vladimir
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Conditioning with fludarabine alone and allogeneic transplantation as a successful rescue therapy for persistent, severe iatrogenic aplasia after relapse of acute myeloid leukemia.2007In: Bone Marrow Transplant, ISSN 0268-3369, Vol. 39, no 1, p. 53-4Article in journal (Refereed)
  • 28.
    Lazarevic, Vladimir
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Hultdin, Magnus
    Zhan, Fenguang
    Shaughnessy, John
    Chronic lymphocytic leukemia with osteolytic Richter's syndrome mimicking myeloma bone disease shows no over-expression of DKK1.2006In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 47, no 9, p. 1987-8Article in journal (Refereed)
  • 29. Lehmann, Soren
    et al.
    Lazarevic, Vladimir
    Hörstedt, Ann-Sofi
    Hulegårdh, Erik
    Nilsson, Christer
    Antunovic, Petar
    Derolf, Åsa Rangert
    Möllgård, Lars
    Uggla, Bertil
    Vennström, Lovisa
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Höglund, Martin
    Stockelberg, Dick
    Juliusson, Gunnar
    Poor Outcome in Secondary Acute Myeloid Leukemia (AML): A First Report From the Population-Based Swedish Acute Leukemia Registry2012In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 120, no 21Article in journal (Other academic)
  • 30. Lehmann, Sören
    et al.
    Ravn, S
    Carlsson, L
    Antunovic, P
    Deneberg, S
    Möllgård, L
    Rangert Derolf, Å
    Stockelberg, D
    Tidefelt, U
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wennström, L
    Högberg, M
    Juliusson, G
    Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry2011In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 25, no 7, p. 1128-1134Article in journal (Refereed)
    Abstract [en]

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

  • 31.
    Liljeholm, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Irvine, Andrew F
    Vikberg, Ann-Louise
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Norberg, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Month, Stacy
    Sandström, Herbert
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Mishima, Masanori
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Congenital dyserythropoietic anemia type III (CDA III) is caused by a mutation in kinesin family member, KIF23.2013In: Blood, ISSN 0006-4971, E-ISSN 1528-0020Article in journal (Refereed)
    Abstract [en]

    Haplotype analysis and targeted next-generation resequencing allowed us to identify a mutation in the KIF23 gene and to show its association with an autosomal dominant form of congenital dyserythropoietic anemia type III (CDA III). The region at 15q23 where CDA III was mapped in a large Swedish family was targeted by array-based sequence capture in a female diagnosed with CDA III and her healthy sister. Prioritization of all detected sequence changes revealed 10 variants unique for the CDA III patient. Among those variants, a novel mutation c.2747C>G (p.P916R) was found in KIF23, which encodes mitotic kinesin-like protein 1 (MKLP1). This variant segregates with CDA III in the Swedish and American families but was not found in 356 control individuals. RNA expression of the 2 known splice isoforms of KIF23 as well as a novel one lacking the exons 17 and 18 was detected in a broad range of human tissues. RNA interference-based knock-down and rescue experiments demonstrated that the p.P916R mutation causes cytokinesis failure in HeLa cells, consistent with appearance of large multinucleated erythroblasts in CDA III patients. We conclude that CDA III is caused by a mutation in KIF23/MKLP1, a conserved mitotic kinesin crucial for cytokinesis.

  • 32.
    Lindqvist, Ebba K.
    et al.
    Department of Medicine, Division of Hematology, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden.
    Goldin, Lynn R.
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, United States.
    Landgren, Ola
    Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, United States.
    Blimark, Cecilie
    Department of Medicine, Section of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Mellqvist, Ulf-Henrik
    Department of Medicine, Section of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Turesson, Ingemar
    Department of Hematology, Skane University Hospital, Malmo, Sweden.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Björkholm, Magnus
    Department of Medicine, Division of Hematology, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden.
    Kristinsson, Sigurdur Y.
    Department of Medicine, Division of Hematology, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden.
    Personal and family history of immune-related conditions increase the risk of plasma cell disorders: a population-based study2011In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 118, no 24, p. 6284-6291Article in journal (Refereed)
    Abstract [en]

    The associations between immune-related conditions and multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) have previously been investigated with inconsistent results. In a large population-based study, we identified 19 112 patients with MM, 5403 patients with MGUS, 96 617 matched control subjects, and 262 931 first-degree relatives. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for the association of MM and MGUS with immune-related conditions by use of logistic regression. A personal history of all infections combined was associated with a significantly increased risk of MM (OR = 1.2; 95% CI, 1.1-1.3), and a personal history of all conditions in the categories infections (OR = 1.6; 95% CI, 1.5-1.7), inflammatory conditions (OR = 1.4; 95% CI, 1.2-1.5), and autoimmune diseases (OR = 2.1; 95% CI, 1.9-2.4) was associated with a significantly increased risk of MGUS. Several specific immune-related conditions elevated the risk of MM and/or MGUS. A family history of autoimmune disease was associated with a significantly increased risk of MGUS (OR = 1.1; 95% CI, 1.00-1.2), but not MM. Our findings suggest that immune-related conditions and/or their treatment are of importance in the etiology of MGUS and possibly MM. The association of both personal and family history of autoimmune disease with MGUS indicates the potential for shared susceptibility for these conditions. (Blood. 2011; 118(24): 6284-6291)

  • 33. Machaczka, Maciej
    et al.
    Johansson, Jan-Erik
    Remberger, Mats
    Hallböök, Helene
    Malm, Claes
    Lazarevic, Vladimir Lj
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Omar, Hamdy
    Juliusson, Gunnar
    Kimby, Eva
    Hägglund, Hans
    Allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning for chronic lymphocytic leukemia in Sweden: Does donor T-cell engraftment 3 months after transplantation predict survival?2012In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 53, no 9, p. 1699-1705Article in journal (Refereed)
    Abstract [en]

    Thirty-eight adult patients with chronic lymphocytic leukemia (CLL) underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) in Sweden between 1999 and 2007. The cumulative incidences of acute GVHD grades II-IV and chronic GVHD were 29% and 48%, respectively. Rates of non-relapse mortality, progression-free survival (PFS) and overall survival (OS) were 18%, 47% and 74% at 1 year, and 21%, 25% and 45% at 5 years, respectively. T-cell chimerism after transplantation was measured in 31 out of 34 patients (91%) surviving beyond day +100. Seventeen patients achieved >90% donor T-cell engraftment at 3 months after allo-SCT and, compared with the 12 patients with ≤90% donor T-cell engraftment, they showed favorable PFS at 1 year (82% vs. 33%, P=0.002), and better long-term PFS and OS (P=0.002 and 0.05 respectively). Donor T-cell engraftment of >90% at 3 months after RIC allo-SCT for CLL seems to predict favorable short-term and long-term outcome.

  • 34.
    Mei, Ya-Fang
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Segerman, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Lindman, Kristina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Hörnsten, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Human hematopoietic (CD34+) stem cells possess high-affinity receptors for adenovirus type 11p2004In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 328, no 2, p. 198-207Article in journal (Refereed)
    Abstract [en]

    Gene transfer into human hematopoietic stem cells using Ad5 is inefficient due to lack of the primary receptor CAR and the secondary receptors alphavbeta3 integrin and alphavbeta5 integrin, and due to the high seroprevalence of Ad5 antibodies in most adults, resulting in diminished gene transduction. In the present study, we screened six species (species A-F) of adenovirus, displaying different tropisms for interaction with CD34+ cells, at the level of virus attachment and expression. Virus particles were biotinylated and their binding capacity was determined by FACS analysis using streptavidin-FITC. Ad11p, Ad35, and Ad3 (species B) showed high binding affinity, while Ad7, Ad11a (species B), and Ad37 (species D) displayed intermediate affinity. Virions of Ad4 (species E), Ad5 (species C), Ad31 (species A), and Ad41 (species F) hardly bound to hematopoietic progenitor cells. Using a double-labeling system, we demonstrated that adenoviruses bind to quiescent CD34+ cells. Ad11p virions showed the highest affinity among the adenoviruses detected. We further confirmed that virus fiber-specific receptors were present on the hematopoietic progenitor cell surface, because both recombinant fiber of Ad11p and specific antiserum against rfiber could block virus attachment. The ability of the adenoviruses to infect hematopoietic cells was studied by immunofluorescence staining. The adenoviruses from species B and Ad37 showed higher infectivity than Ad31, Ad5, Ad4, and Ad41. Among the studied species B adenoviruses, Ad11p manifested a superior infectivity. Thus, we have confirmed that these cells have high-affinity receptors for species B:2 human adenovirus, Ad11p, and this virus may be used as candidate vector to target therapeutic genes to hematopoietic stem cells.

  • 35.
    Nylander, Elisabet
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Dermatology and Venerology.
    Wahlin, Ylva-Britt
    Umeå University, Faculty of Medicine, Odontology, Oral and Maxillofacial Radiology.
    Lundskog, B
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Genital graft-versus-host disease in a male following allogeneic stem cell transplantation2007In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 87, no 4, p. 367-368Article in journal (Refereed)
  • 36. Olsson-Strömberg, Ulla
    et al.
    Simonsson, Bengt
    Ahlgren, Tomas
    Björkholm, Magnus
    Carlsson, Karin
    Gahrton, Gösta
    Hast, Robert
    Löfvenberg, Eva
    Linder, Olle
    Ljungman, Per
    Malm, Claes
    Paul, Christer
    Rodjer, Stig
    Turesson, Ingemar
    Uden, Ann-Mari
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Killander, Andreas
    Wadman, Bengt
    Westin, Jan
    Vikrot, Olle
    Zettervall, Olle
    Öberg, Gunnar
    Comparison of busulphan, hydroxyurea and allogeneic bone marrow transplantation (BMT) in chronic myeloid leukaemia: BMT prolongs survival.2004In: Hematol J, ISSN 1466-4860, Vol. 5, no 6, p. 462-6Article in journal (Refereed)
  • 37. Passweg, J R
    et al.
    Rabusin, M
    Musso, M
    Beguin, Y
    Cesaro, S
    Ehninger, G
    Espigado, I
    Iriondo, A
    Jost, L
    Koza, V
    Lenhoff, S
    Lisukov, I
    Locatelli, F
    Marmont, A
    Philippe, P
    Pilatrino, C
    Quartier, P
    Stary, J
    Veys, P
    Vormoor, J
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Zintl, F
    Bocelli-Tyndall, C
    Tyndall, A
    Gratwohl, A
    Haematopoetic stem cell transplantation for refractory autoimmune cytopenia.2004In: Br J Haematol, ISSN 0007-1048, Vol. 125, no 6, p. 749-55Article in journal (Refereed)
  • 38. Simonsson, Bengt
    et al.
    Öberg, Gunnar
    Björeman, Mats
    Björkholm, Magnus
    Carneskog, Jan
    Karlsson, Karin
    Gahrton, Gösta
    Grimfors, Gunnar
    Hast, Robert
    Karle, Hans
    Linder, Olle
    Ljungman, Per
    Nielsen, Johan L
    Nilsson, Jonas
    Löfvenberg, Eva
    Malm, Claes
    Olsson, Karin
    Olsson-Strömberg, Ulla
    Paul, Christer
    Stenke, Leif
    Stentoft, Jesper
    Turesson, Ingemar
    Udén, Ann-Marie
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Vilén, Lars
    Weis-Bjerrum, Ole
    Intensive treatment and stem cell transplantation in chronic myelogenous leukemia: long-term follow-up2005In: Acta Haematologica, ISSN 0001-5792, E-ISSN 1421-9662, Vol. 113, no 3, p. 155-162Article in journal (Refereed)
    Abstract [en]

    In the present study we combined interferon (IFN) and hydroxyurea (HU) treatment, intensive chemotherapy and autologous stem cell transplantation (SCT) in newly diagnosed chronic myelogenous leukemia patients aged below 56 years, not eligible for allogeneic SCT. Patients who had an HLA-identical sibling donor and no contraindication went for an allogeneic SCT (related donor, RD). After diagnosis, patients not allotransplanted received HU and IFN to keep WBC and platelet counts low. After 6 months patients with Ph-positive cells still present in the bone marrow received 1–3 courses of intensive chemotherapy. Those who became Ph-negative after IFN + HU or after 1–3 chemotherapy courses underwent autologous SCT. Some patients with poor cytogenetic response were allotransplanted with an unrelated donor (URD). IFN + HU reduced the percentage of Ph-positive metaphases in 56% of patients, and 1 patient became Ph-negative. After one or two intensive cytotherapies 86 and 88% had a Ph reduction, and 34 and 40% became Ph-negative, respectively. In patients receiving a third intensive chemotherapy 92% achieved a Ph reduction and 8% became Ph-negative. The median survival after auto-SCT (n = 46) was 7.5 years. The chance of remaining Ph-negative for up to 10 years after autologous SCT was around 20%. The overall survival for allo-SCT RD (n = 91) and URD (n = 28) was almost the same, i.e. ≈60% at 10 years. The median survival for all 251 patients registered was 8 years (historical controls 3.5 years). The role of the treatment schedule presented in the imatinib era is discussed.

  • 39. Stenberg, Anna
    et al.
    Malinovsky, Dmitry
    Ohlander, Björn
    Andrén, Henrik
    Forsling, Willis
    Engström, Lena-Maria
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Engström, Emma
    Rodushkin, Ilia
    Baxter, Douglas C
    Measurement of iron and zinc isotopes in human whole blood: preliminary application to the study of HFE genotypes.2005In: J Trace Elem Med Biol, ISSN 0946-672X, Vol. 19, no 1, p. 55-60Article in journal (Refereed)
  • 40.
    Sundström, Gunnel
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Dahl, Inger Marie S
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Lundström, Berit
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Engström Laurent, Anna
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Bone marrow hyaluronan distribution in patients with acute myeloid leukemia.2005In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 22, no 1, p. 71-78Article in journal (Refereed)
    Abstract [en]

    The present study investigated potential age-related changes in human muscle spindles with respect to the intrafusal fiber-type content and myosin heavy chain (MyHC) composition in biceps brachii muscle. The total number of intrafusal fibers per spindle decreased significantly with aging, due to a significant reduction in the number of nuclear chain fibers. Nuclear chain fibers in old spindles were short and some showed novel expression of MyHC α-cardiac. The expression of MyHC α-cardiac in bag1 and bag2 fibers was greatly decreased in the A region. The expression of slow MyHC was increased in nuclear bag1 fibers and that of fetal MyHC decreased in bag2 fibers whereas the patterns of distribution of the remaing MyHC isoforms were generelly not affected by aging. We conclude that aging appears to have an important impact on muscle spindle composition. These changes in muscle spindle phenotype may reflect an age-related deterioration in sensory and motor innervation and are likely to have an impact in motor control in the elderly.

  • 41. Ulla, Olsson-Strömberg
    et al.
    Höglund, M
    Björkholm, M
    Braide, I
    Carlson, K
    Gahrton, G
    Grimfors, G
    Hast, R
    Lerner, R
    Linder, O
    Ljungman, P
    Löfvenberg, E
    Malm, C
    Nilsson, PG
    Paul, C
    Rödjer, S
    Stenke, L
    Tidefeldt, U
    Turesson, I
    Uden, AM
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Vilen, L
    Winqvist, I
    Zettervall, O
    Oberg, G
    Simonsson, B
    Successful mobilization of Ph-negative blood stem cells with intensive chemotherapy + G-CSF in patients with chronic myelogenous leukemia in first chronic phase.2006In: Leuk Lymphoma, Vol. 47, no 9, p. 1768-73Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to investigate the feasibility of mobilizing Philadelphia chromosome negative (Ph-) blood stem cells (BSC) with intensive chemotherapy and lenograstim (G-CSF) in patients with CML in first chronic phase (CP1). During 1994-1999 12 centers included 37 patients <56 years. All patients received 6 months' IFN, stopping at median 36 (1-290) days prior to the mobilization chemotherapy. All received one cycle of daunorubicin 50 mg/m2 and 1 hour infusion on days 1-3, and cytarabine (ara-C) 200 mg/m2 24 hours' i.v. infusion on days 1-7 (DA) followed by G-CSF 526 microg s.c. once daily from day 8 after the start of chemotherapy. Leukaphereses were initiated when the number of CD 34+ cells was >5/microl blood. Patients mobilizing poorly could receive a 4-day cycle of chemotherapy with mitoxantrone 12 mg/m2/day and 1 hour i.v infusion, etoposide 100 mg/m2/day and 1 hour i.v. infusion and ara-C 1 g/m2/twice a day with 2 hours' i.v infusion (MEA) or a second DA, followed by G-CSF 526 microg s.c once daily from day 8 after the start of chemotherapy. Twenty-seven patients received one cycle of chemotherapy and G-CSF, whereas 10 were mobilized twice. Twenty-three patients (62%) were successfully (MNC >3.5 x 10(8)/kg, CFU-GM >1.0 x 10(4)/kg, CD34+ cells >2.0 x 10(6)/kg and no Ph+ cells in the apheresis product) [n = 16] or partially successfully (as defined above but 1-34% Ph+ cells in the apheresis product) [n = 7] mobilized. There was no mortality during the mobilization procedure. Twenty-one/23 patients subsequently underwent auto-SCT. The time with PMN <0.5 x 10(9)/l was 10 (range 7-49) and with platelets <20 x 10(9)/l was also 10 (2-173) days. There was no transplant related mortality. The estimated 5-year overall survival after auto-SCT was 68% (95% CI 47 - 90%), with a median follow-up time of 5.2 years.We conclude that in a significant proportion of patients with CML in CP 1, intensive chemotherapy combined with G-CSF mobilizes Ph- BSC sufficient for use in auto-SCT.

  • 42.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Accumulating evidence for a role of p53 in multiple drug resistant acute myeloid leukemia.2008In: Leukemia & lymphoma, ISSN 1029-2403, Vol. 49, no 3, p. 383-384Article in journal (Refereed)
  • 43.
    Wahlin, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Billström, Rolf
    Björ, Ove
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ahlgren, Tomas
    Hedenus, Michael
    Höglund, Martin
    Lindmark, Anders
    Markevärn, Berit
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Bo
    Sallerfors, Bengt
    Brune, Mats
    Results of risk-adapted therapy in acute myeloid leukaemia. A long-term population-based follow-up study2009In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 83, no 2, p. 99-107Article in journal (Refereed)
    Abstract [en]

    In 1997-2003, a protocol for treatment of acute myeloid leukaemia (AML) (except promyelocytic leukaemia) was activated in four Swedish health care regions covering 50% of the national population. Based on cytogenetics and clinical findings, patients aged 18-60 yr were assigned to one of three risk groups. In this report we account for the long-term clinical outcome of enrolled patients. Patients received idarubicin and cytarabine in standard doses as induction therapy and consolidation courses included high-dose cytarabine. Allogeneic stem cell transplantation (allo-SCT) from an human leucocyte antigen-identical sibling was recommended in standard and poor-risk patients, whereas unrelated donor transplant was reserved for poor-risk patients. Autologous (auto-SCT) was optional for standard or poor risk patients not eligible for allo-SCT. Two hundred seventy-nine patients with de novo or secondary (9%) AML, median age 51 (18-60) yr, corresponding to 77% of all patients in the population, were included. Twenty (7%) patients were assigned to the good risk group, whereas 150 (54%) and 109 patients (39%) were assigned to standard- and poor-risk groups, respectively. Induction failures accounted for 55 patients; 16 early deaths eight of whom had white blood cell (WBC) >100 at diagnosis, and 39 refractory disease. Thus, complete remission (CR) rate was 80%. At study closure, the median follow-up time of living patients was 90 months. Median survival time from diagnosis in the whole group was 27 months and 4-yr overall survival (OS) rate was 44%. In good, standard, and poor risk groups, 4-yr OS rates were 60, 57 and 24%, respectively. Median relapse-free survival (RFS) time in CR1 was 25 months and RFS at 4 yr was 44%. Four-year RFS rates were significantly (P < 0.001) different between the three risk groups; 64% in good risk, 51% in standard risk and 27% in poor risk patients. One hundred-ten transplantations were performed in CR1; 74 allo-SCT (50 sibling, 24 unrelated donor), and 36 auto-SCT. Non-relapse mortality was 16% for allo-SCT patients. Outcome after relapse was poor with median time to death 163 d and 4-yr survival rate 17%. Three conclusions were: (i) these data reflect treatment results in a minimally selected population-based cohort of adult AML patients <60 yr old; (ii) a risk-adapted therapy aiming at early allogeneic SCT in patients with a high risk of relapse is hampered by induction deaths, refractory disease, and early relapses; and (iii) high WBC count at diagnosis is confirmed as a strong risk factor for early death but not for relapse.

  • 44.
    Wahlin, Anders
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Eriksson, Marie
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Hultdin, Magnus
    Relation between harvest success and outcome after autologous peripheral blood stem cell transplantation in multiple myeloma.2004In: Eur J Haematol, ISSN 0902-4441, Vol. 73, no 4, p. 263-8Article in journal (Refereed)
  • 45.
    Wahlin, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lorenz, Fryderyk
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Fredriksson, Maritha
    Department of Hematology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Remberger, Mats
    Centre of Allogeneic Stem Cell Transplantation at Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Wahlin, Björn E
    Department of Hematology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Hägglund, Hans
    Department of Hematology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Hyperferritinemia is associated with low incidence of graft versus host disease, high relapse rate, and impaired survival in patients with blood disorders receiving allogeneic hematopoietic stem cell grafts.2011In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 28, no 2, p. 552-558Article in journal (Refereed)
    Abstract [en]

    High pre-transplantation serum ferritin levels have been reported to be associated with impaired survival post-transplantation in patients with acute myeloid leukemia or myelodysplastic syndrome. We performed a retrospective study of 309 patients who underwent allogeneic hematopoietic stem cell transplantation at two transplantation centers. The aim was to determine the effect of pre-transplantation hyperferritinemia on survival, graft versus host disease, and relapse. In both univariate and multivariate analysis, elevated ferritin levels were significantly associated with shorter overall and relapse-free survival times and increased relapse rate, but lower risk of chronic graft versus host disease. Elevated ferritin levels were not associated with non-relapse mortality. We hypothesize that ferritin may exert an immunosuppressive effect, reducing graft versus host disease and graft versus leukemia effects, resulting in increased risk of relapse and impaired survival.

  • 46.
    Wahlin, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Markevärn, Berit
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Golovleva, I
    Nilsson, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Prognostic significance of risk group stratification in elderly patients with acute myeloid leukaemia.2001In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 115, no 1, p. 25-33Article in journal (Refereed)
    Abstract [en]

    Prognostic factors were studied in a series of 211 acute myeloid leukaemia (AML) patients over 60 years of age, treated at a single centre. The patients were allocated into three risk groups based on cytogenetics, occurrence of antecedent haematological disorder and leucocyte count. Only 3% had low-risk features, 39% had intermediate- and 58% had adverse-risk features. Complete remission (CR) was achieved in 43% of all patients. In multivariate analyses, the number of cycles needed to achieve CR and the risk group were significantly associated with the duration of CR. Median survival time for the entire cohort of patients was only 107 d. Advanced age, low induction treatment intensity, treatment during earlier years and adverse-risk group were associated with shorter overall survival times. Risk group classification may help selection of elderly patients with a good chance of benefiting from intensive treatment to actually receive such treatment, while sparing others with a low probability of survival benefit from toxic treatment. Low intensity induction treatment reduces the chance of obtaining complete remission, produces inferior survival times and should consequently be avoided when the aim is to obtain complete remission. In elderly AML patients, introducing age and re-evaluation of intermediate and good prognosis patients regarding response to induction treatment may improve the risk group classification.

  • 47.
    Wahlin, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Markevärn, Berit
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Nilsson, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Improved outcome in adult acute myeloid leukemia is almost entirely restricted to young patients and associated with stem cell transplantation2002In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 68, no 1, p. 54-63Article in journal (Refereed)
    Abstract [en]

    Prognostic factors were studied in a series of 318 patients with acute myeloid leukemia (AML), 17-90 yr old, treated at a single centre during 1982-98, and representing 79% of the total number of cases registered in the area during this period. Risk group stratification based on cytogenetics, occurrence of antecedent hematological disorder, and leukocyte count could be performed in 93%. Five percent were allocated to the favourable risk group, 40% to standard risk, and 55% to adverse risk. Complete remission (CR) was attained in 52%. The CR rate was higher in the favourable (80%) and standard risk groups (69%) than in the adverse risk group (37%). The CR rate increased from 44% in the 1980s to 60% in the 1990s. The 5-yr survival rate for all patients was only 12%. Low age, promyelocytic leukaemia, treatment in the 1990s, high induction treatment intensity, and non-adverse risk group were favourably associated with survival. The median survival time increased from 115 to 349 d between the 1980s and the 1990s, but the 5-yr survival rate was only 11% for patients over 55 yr of age even in the last decade. For the younger patients, the 5-yr overall survival rate increased from 9% to 35% in the last decade. The median time in first remission was 365 d. Age below 56 yr, allogeneic and autologous transplants, and non-adverse risk group were associated with prolonged response duration. The duration of response among all patients increased from 250 d in the 1980s to 451 d in the 1990s, but event-free survival time did not improve significantly in patients above 55 yr of age. Among patients below 56 yr of age, overall survival and event-free survival were significantly better for those who received allogeneic or autologous transplants in first remission than for those who were treated with chemotherapy only. Overall survival times did not improve from the 1980s to the 1990s among those patients below 56 yr who were treated with chemotherapy only in first remission, in spite of the use of transplants in second remission.

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