Publications by authors named "Dick Stockelberg"

27 Publications

  • Page 1 of 1

Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting.

Biol Blood Marrow Transplant 2019 09 6;25(9):1770-1778. Epub 2019 Jun 6.

Division of Hematology, Department of Medicine, Karolinska Institute, Stockholm, Sweden; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Secondary AML (s-AML), including AML with an antecedent hematologic disorder (AHD-AML) and therapy-related AML (t-AML), constitutes a large proportion of patients with AML and is considered to confer a dismal prognosis. The role of allogeneic hematopoietic cell transplantation (HCT) in patients with s-AML and the extent to which HCT is performed in these patients has been little studied to date. We used the population-based Swedish AML Registry comprising 3337 intensively treated adult patients over a 17-year period to study the role of HCT within the group of patients with s-AML as well as compared with patients with de novo AML. HCT was performed in 576 patients (22%) with de novo AML, in 74 patients (17%) with AHD-AML, and in 57 patients (20%) with t-AML. At 5 years after diagnosis, there were no survivors among patients with previous myeloproliferative neoplasms who did not undergo HCT, and corresponding survival for patients with antecedent myelodysplastic syndromes and t-AML was and 2% and 4%, respectively. HCT was compared with chemotherapy consolidation in s-AML using 3 models: (1) a 200-day landmark analysis, in which HCT was favorable compared with conventional consolidation (P = .04, log-rank test); (2) a multivariable Cox regression with HCT as a time-dependent variable, in which the hazard ratio for mortality was 0.73 (95% confidence interval, 0.64 to 0.83) for HCT and favored HCT in all subgroups; and (3) a propensity score matching analysis, in which the 5-year overall survival (OS) and relapse-free survival in patients with s-AML in first complete remission (CR1) was 48% and 43%, respectively, for patients undergoing HCT versus 20% and 21%, respectively, for those receiving chemotherapy consolidation (P = .01 and .02, respectively, log-rank test). Our observational data suggest that HCT improves survival and offers the only realistic curative treatment option in patients with s-AML.
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http://dx.doi.org/10.1016/j.bbmt.2019.05.038DOI Listing
September 2019

Caring Through Web-Based Communication: A Qualitative Evaluation of a Nursing Intervention to Create Holistic Well-Being Among Patients With Hematological Disease.

J Holist Nurs 2018 Sep 22;36(3):218-227. Epub 2016 Sep 22.

Jönköping University, Sweden.

Purpose: To examine how written communication between patients with hematological diseases and a nurse within a web-based communication service can be caring.

Design: The study is based on qualitative deductive content analysis of 109 written messages between 10 patients and a responding nurse. The evaluated nursing intervention is a web-based communication service where patients could request support from a responding nurse during 2 months of use. A structured theoretical matrix based on Swanson's theory of caring including compassion, competence, and upholding trust is used for the analysis.

Findings: Nursing compassion emerges when patients share personal matters and the nurse has an opportunity to explicitly display genuine interest and understanding. Nursing competence is required when patients ask for or are in need of information, advice, and emotional support. The nurse can uphold trust when compassion and competence are exhibited and patients share their innermost feelings.

Conclusions: Web-based communication has the potential to contribute to holistic well-being according to Swanson's theory of caring. The written word lasts, can be read repeatedly, and in connection with writing there is time for reflection. However, the lack of nonverbal cues makes it important that the nurse answers in a fully accurate and explicitly caring way.
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http://dx.doi.org/10.1177/0898010116667343DOI Listing
September 2018

Acute de novo Leukemia in Estonia and Western Sweden 1982-2006: Positive Trend in the Survival of Acute Leukemia over 25 Years.

Acta Haematol 2016 19;136(3):167-73. Epub 2016 Aug 19.

Department of Internal Medicine/Hematology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

This study focuses on the incidence, treatment, and survival of de novo acute leukemia in a 25-year perspective in western Sweden and Estonia. At the beginning of our study, Estonia was a part of the Eastern bloc with planned economy, but since 1991 it is a member of the European Union and transforming into a market economy. Survival rates have steadily increased in both countries. However, a gap between their survival curves remains. Based on our data, it is difficult to explain the big difference in the 5-year relative survival in favor of western Sweden (55 vs. 22%). In Germany, there was a big difference in overall cancer survival between East and West Germany after the fall of the iron curtain, but today no difference is seen. Differences in survival are probably due to a higher proportion of intense chemotherapy regimens and a higher rate of hematopoietic stem cell transplantations in Sweden. Other important factors might be better supportive care and diagnostics as well as better adjuvant therapy. Better staff training and conditions in wards are also factors that might play an essential role.
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http://dx.doi.org/10.1159/000446525DOI Listing
December 2016

Association between TERT promoter polymorphisms and acute myeloid leukemia risk and prognosis.

Oncotarget 2015 Sep;6(28):25109-20

Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Telomerase reverse transcriptase gene (TERT) promoter mutations are identified in many malignancies but not in hematological malignancies. Here we analyzed TERT and protection of telomeres 1 gene (POT1) mutations, and four different TERT SNVs in 226 acute myeloid leukemia (AML) patients and 806 healthy individuals in a case referent design, where also overall survival was assessed. A significant association for increased risk of AML was found for TERT SNVs, rs2853669 (OR = 2.45, p = 0.00015) and rs2736100 (OR = 1.5, p = 0.03). The overall survival for patients with CC genotype of rs2853669 was significantly shorter compared to those with TT or TC genotypes (p = 0.036 and 0.029 respectively). The influence of TERT rs2853669 CC on survival was confirmed in multivariable Cox regression analysis as an independent risk biomarker in addition to high risk group, higher age and treatment. No hot spot TERT promoter mutations at -228C > T or -250C > T or POT1 mutations could be identified in this AML cohort. We show that rs2853669 CC may be a risk factor for the development of AML that may also be used as a prognostic marker to identify high risk normal karyotype-AML (NK-AML) patients, for treatment guidance.
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http://dx.doi.org/10.18632/oncotarget.4668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694818PMC
September 2015

Acute Myeloid Leukemia in Adolescents and Young Adults Treated in Pediatric and Adult Departments in the Nordic Countries.

Pediatr Blood Cancer 2016 Jan 18;63(1):83-92. Epub 2015 Aug 18.

Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.

Background: Studies on adolescents and young adults with acute lymphoblastic leukemia suggest better results when using pediatric protocols for adult patients, while corresponding data for acute myeloid leukemia (AML) are limited.

Procedure: We investigated disease characteristics and outcome for de novo AML patients 10-30 years old treated in pediatric or adult departments. We included 166 patients 10-18 years of age with AML treated according to the pediatric NOPHO-protocols (1993-2009) compared with 253 patients aged 15-30 years treated in hematology departments (1996-2009) in the Nordic countries.

Results: The incidence of AML was 4.9/million/year for the age group 10-14 years, 6.5 for 15-18 years, and 6.9 for 19-30 years. Acute promyelocytic leukemia (APL) was more frequent in adults and in females of all ages. Pediatric patients with APL had similar overall survival as pediatric patients without APL. Overall survival at 5 years was 60% (52-68%) for pediatric patients compared to 65% (58-70%) for adult patients. Cytogenetics and presenting white blood cell count were the only independent prognostic factors for overall survival. Age was not an independent prognostic factor.

Conclusions: No difference was found in outcome for AML patients age 10-30 years treated according to pediatric as compared to adult protocols.
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http://dx.doi.org/10.1002/pbc.25713DOI Listing
January 2016

Induction with azacytidine followed by allogeneic hematopoietic stem cell transplantation in a Jehovah's Witness with acute monocytic leukemia.

Clin Case Rep 2015 May 13;3(5):287-90. Epub 2015 Feb 13.

Section for Haematology and Coagulation, Department of Medicine, Sahlgrenska University Hospital Gothenburg, Sweden.

We have used a hypomethylating agent instead of conventional chemotherapy to induce remission in a young Jehovah's Witness with acute monocytic leukemia to avoid severe myelosuppression and blood product support. The treatment was consolidated with reduced intensity allogeneic stem cell transplantation. This could be an alternative when transfusions must be avoided.
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http://dx.doi.org/10.1002/ccr3.212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427369PMC
May 2015

Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: a report from the Swedish Acute Leukemia Registry.

Am J Hematol 2015 Mar 16;90(3):208-14. Epub 2015 Jan 16.

Department of Medicine and Regional Tumor Registry, Sahlgrenska University Hospital, Göteborg, Sweden.

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.
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http://dx.doi.org/10.1002/ajh.23908DOI Listing
March 2015

Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population-based series of acute myeloid leukaemia.

Eur J Haematol 2015 May 3;94(5):419-23. Epub 2014 Oct 3.

Department of Hematology and Coagulation, Skåne University Hospital, Lund, Sweden; Stem Cell Center, Lund University, Lund, Sweden.

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 80 yr 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.
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http://dx.doi.org/10.1111/ejh.12446DOI Listing
May 2015

Impact of ABCB1 single nucleotide polymorphisms 1236C>T and 2677G>T on overall survival in FLT3 wild-type de novo AML patients with normal karyotype.

Br J Haematol 2014 Dec 23;167(5):671-80. Epub 2014 Aug 23.

Clinical Pharmacology, Division of Drug Research, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden.

Drug resistance is a clinically relevant problem in the treatment of acute myeloid leukaemia (AML). We have previously reported a relationship between single nucleotide polymorphisms (SNPs) of ABCB1, encoding the multi-drug transporter P-glycoprotein, and overall survival (OS) in normal karyotype (NK)-AML. Here we extended this material, enabling subgroup analysis based on FLT3 and NPM1 status, to further elucidate the influence of ABCB1 SNPs. De novo NK-AML patients (n = 201) were analysed for 1199G>A, 1236C>T, 2677G>T/A and 3435C>T, and correlations to outcome were investigated. FLT3 wild-type 1236C/C patients have significantly shorter OS compared to patients carrying the variant allele; medians 20 vs. 49 months, respectively, P = 0·017. There was also an inferior outcome in FLT3 wild-type 2677G/G patients compared to patients carrying the variant allele, median OS 20 vs. 35 months, respectively, P = 0·039. This was confirmed in Cox regression analysis. Our results indicate that ABCB1 1236C>T and 2677G>T may be used as prognostic markers to distinguish relatively high risk patients in the intermediate risk FLT3 wild-type group, which may contribute to future individualizing of treatment strategies.
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http://dx.doi.org/10.1111/bjh.13097DOI Listing
December 2014

The meaning of web-based communication for support: from the patients' perspective within a hematological healthcare setting.

Cancer Nurs 2015 Mar-Apr;38(2):145-54

Author Affiliations: School of Health Sciences, Jönköping University (Drs Högberg and Broström); School of Health Sciences, University of Borås (Ms Högberg, and Drs Sandman and Nyström); Section for Hematology and Coagulation, Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden (Dr Stockelberg).

Background: Being critically ill with a hematological disease is a challenge, sometimes causing a need for support in the adjustment to the stressful life situation. By providing Web-based communication for support from a nurse, patients get access to an alternative and untraditional way to communicate their issues.

Objective: The aim was to describe the meaning of using Web-based communication for support from a patient perspective.

Methods: A comprehensive randomized pilot study (n = 30) was conducted, allowing 15 patients in the experimental group to have access to the Web-based communication, to evaluate feasibility. Of these 15 participants, 10 were interviewed, focusing on their experiences. An empirical hermeneutical approach was used and the interpretive analysis focused on the meanings.

Results: Web-based communication for support means a space for patients to have their say, consolidation of a matter, an extended caring relationship, access to individual medical assessment, and an opportunity for emotional processing. The main interpretation indicates that the patient's influence on the communication strengthens according to the asynchronous, faceless, and written communication. The increased, and in some sense constant, access to an individual medical and caring assessment, in turn, implies a feeling of safety.

Conclusion: Web-based communication for support seems to have the potential to enhance patients' participation on their own terms.

Implications For Practice: To achieve the possible advantages of Web-based communication for support, nurses must acquire knowledge about caring writing. It requires respect for the patient and articulated accuracy and attention in the response given.
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http://dx.doi.org/10.1097/NCC.0000000000000145DOI Listing
August 2016

[Pascal turns one--time for the next step].

Authors:
Dick Stockelberg

Lakartidningen 2013 Apr 3-16;110(27-28):1295-6

Sahlgrenska sjukhuset, Göteborg.

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December 2013

Decreased survival in normal karyotype AML with single-nucleotide polymorphisms in genes encoding the AraC metabolizing enzymes cytidine deaminase and 5'-nucleotidase.

Am J Hematol 2013 Dec 9;88(12):1001-6. Epub 2013 Sep 9.

Clinical Pharmacology, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden.

De novo acute myeloid leukemia with normal karyotype (NK-AML) comprises a large group of patients with no common cytogenetic alterations and with a large variation in treatment response. Single-nucleotide polymorphisms (SNPs) in genes related to the metabolism of the nucleoside analogue AraC, the backbone in AML treatment, might affect drug sensitivity and treatment outcome. Therefore, SNPs may serve as prognostic biomarkers aiding clinicians in individualized treatment decisions, with the aim of improving patient outcomes. We analyzed polymorphisms in genes encoding cytidine deaminase (CDA 79A>C rs2072671 and -451C>T rs532545), 5'-nucleotidase (cN-II 7A>G rs10883841), and deoxycytidine kinase (DCK 3'UTR 948T>C rs4643786) in 205 de novo NK-AML patients. In FLT3-internal tandem duplication (ITD)-positive patients, the CDA 79C/C and -451T/T genotypes were associated with shorter overall survival compared to other genotypes (5 vs. 24 months, P < 0.001 and 5 vs. 23 months, P = 0.015, respectively), and this was most pronounced in FLT3-ITD-positive/NPM1-positive patients. We observed altered in vitro sensitivity to topoisomerase inhibitory drugs, but not to nucleoside analogues, and a decrease in global DNA methylation in cells carrying both CDA variant alleles. A shorter survival was also observed for the cN-II variant allele, but only in FLT3-ITD-negative patients (25 vs. 31 months, P = 0.075). Our results indicate that polymorphisms in genes related to nucleoside analog drug metabolism may serve as prognostic markers in de novo NK-AML.
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http://dx.doi.org/10.1002/ajh.23549DOI Listing
December 2013

Sequential population-based studies over 25 years on the incidence and survival of acute de novo leukemias in Estonia and in a well-defined region of western Sweden during 1982-2006: a survey of patients aged ≥65 years.

Med Oncol 2013 Mar 9;30(1):487. Epub 2013 Feb 9.

Clinic of Hematology and Oncology, Tartu University Clinic, Tartu, Estonia.

Estonia regained independence in 1991 after five decades of occupation by the Soviet Union. The present population-based survey was carried out over five consecutive 5-year study periods (1982-2006) on the incidence and survival of de novo acute leukemia patients aged ≥65 years at diagnosis in Estonia and in a well-defined area in western Sweden. During the study period of retrospective work (1982-1996), the first 10 years were carried out while Estonia was still under the mentorship of the Soviet Union. Over these years, Estonian hematologists did not have access to therapeutic measures readily available to Swedish hematologists, and the results for survival for western Swedish patients with acute myeloid leukemia (AML) far exceeded those of their Estonian counterparts. However, the results for acute lymphoblastic leukemia were equally dismal in the two countries. Subsequent prospective population-based studies were carried out during the years 1997-2006. A gradual improvement as to long-term relative survival of the Estonian AML patients was observed. When studying 2002-2006, no difference as regards relative survival at 5 years was anymore present between the two countries. Over the first 20 years of our population-based studies, it was repeatedly observed that the age-standardized incidence rate particularly for de novo AML was considerably higher for the western Swedish as compared to the Estonian cohorts. During the last 5-year study period (2002-2006), no such difference between the two countries was present, indicating that some true changes in the reporting procedure in Estonia had occurred.
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http://dx.doi.org/10.1007/s12032-013-0487-xDOI Listing
March 2013

The incidence and survival of acute de novo leukemias in Estonia and in a well-defined region of western Sweden during 1997-2001: a survey of patients aged 16-64 years.

Acta Haematol 2011 13;126(3):176-85. Epub 2011 Aug 13.

Department of Internal Medicine/Hematology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

Background: In a recent retrospective study, we investigated the incidence and survival of de novo acute leukemia (AL) patients aged 16-64 years over three 5-year periods (1982-1996) in Estonia and in the Western Swedish Health Care Region. The incidence rates were similar in the two countries, but the survival data were highly different. Thus, relative survival at 5 years for de novo AL patients in Estonia was virtually negligible, whereas the corresponding figures for the Swedish patients increased from 20.3 to 38.9% during the study period.

Aim: To prospectively compare the results for incidence and outcome of de novo AL between the two countries during 1997-2001.

Results: Incidence rates for de novo AL were lower in Estonia than in western Sweden but not significantly so. However, the survival for de novo AL patients in Estonia had improved considerably, with the relative survival at 5 years being 16.4%; such improvement was particularly seen in acute myeloid leukemia patients. For the Swedish patients, no change in survival was recorded.

Conclusion: In Estonia, a remarkable improvement in outcome for young de novo AL patients was seen after 1996. Nevertheless, relative survival for the Estonian patients had still not reached the levels found in the Swedish cohort.
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http://dx.doi.org/10.1159/000329526DOI Listing
November 2011

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 1997-2006.

Cancer 2011 Sep 8;117(18):4238-46. Epub 2011 Mar 8.

Department of Hematology and Regional Tumor Registry, Skåne University Hospital and Lund University, Lund, Sweden.

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.
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http://dx.doi.org/10.1002/cncr.26033DOI Listing
September 2011

The incidence and survival of acute de novo leukemias in Estonia and in a well-defined region of western Sweden during 1997-2001: a survey of patients aged >or=65 years.

Cancer Epidemiol 2010 Feb 13;34(1):24-8. Epub 2010 Jan 13.

Department of Hematology, North Estonian Regional Hospital, Tallinn, Estonia.

Background: In a recently published retrospective population-based study over three 5-year periods (1982-1996) we investigated the outcome for de novo acute leukemia (AL) patients aged >or=65 years at diagnosis in Estonia (a country that had been occupied by the Soviet Union over 5 decades) and in the so-called Western Swedish Health Care Region. The age-standardized yearly incidence rates regarding the total number of de novo AL was 5.3/100000 inhabitant for Estonia and 8.0 for Sweden, this difference being statistically significant merely as regards acute myeloid leukemia (AML). The relative survival for the total cohort of de novo AL as well as for de novo AML was significantly longer (p<0.001) for Swedish as compared to Estonian patients.

Methods: In view of the miserable outcome for the Estonian patients we decided to prospectively compare the results for incidence and outcome of de novo AL between the two countries.

Results: The present report covers the first 5-year period comprising 1997-2001 and deals only with patients aged >or=65 years at diagnosis. The age-adjusted annual incidence rates for de novo AML were lower in Estonia (6.4/100000) than in Sweden (9.2/100000) but not significantly so. The present results also show that the outcome for the Estonian AML patients had improved considerably over the study period; thus, at no time point, i.e., at 1, 3 and 5 years did relative survival between the two countries differ significantly.

Conclusion: Yet, as compared to the Swedish cohort relative survival for the Estonian patients did still not reach an acceptable level.
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http://dx.doi.org/10.1016/j.canep.2009.12.004DOI Listing
February 2010

Health-related quality of life in patients undergoing allogeneic stem cell transplantation after reduced intensity conditioning versus myeloablative conditioning.

Cancer Nurs 2009 Jul-Aug;32(4):325-34

Section of Hematology and Coagulation, Sahlgrenska University Hospital, Vita stråket 12, Göteborg 413 45, Sweden.

The aim of this prospective study was to describe health-related quality of life (HRQOL) in patients during the first year after stem cell transplantation (SCT) who were undergoing reduced intensive conditioning (RIC) compared with patients undergoing myeloablative conditioning (MAC). Fifty-seven patients (25 for MAC and 32 for RIC) were enrolled in the study. HRQOL was assessed at 6 occasions during the first year after SCT using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and the 19-item treatment-specific module High-Dose Chemotherapy. Both groups reported most symptoms and worst functioning 1 month after SCT, but there were substantial differences. The MAC group deteriorated considerably in 20 symptom scales compared with 8 in the RIC group (score differences <10; P values ranged from .001 to .05). Dry mouth, sore mouth, appetite loss, and change of taste were among the most frequent symptoms in both groups. Thereafter, the functioning improved and the symptom scores decreased and returned to baseline in both groups, except dry mouth, which remained a worse problem for the MAC group. Overall, the RIC group regained health and QOL faster than the MAC group did. However, there were no significant differences in global QOL between the groups 1 year after SCT.
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http://dx.doi.org/10.1097/NCC.0b013e31819b5c81DOI Listing
October 2009

Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry.

Blood 2009 Apr 13;113(18):4179-87. Epub 2008 Nov 13.

Department of Hematology and Regional Tumor Registry, Lund University Hospital, Lund, Sweden.

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.
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http://dx.doi.org/10.1182/blood-2008-07-172007DOI Listing
April 2009

[Specialist associations' mission: equal and good cancer care for all].

Lakartidningen 2008 Jan 30-Feb 5;105(5):306-7

Universitetssjukhuset i Linköping.

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April 2008

Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia.

N Engl J Med 2007 Jan;356(4):348-59

University of Cologne, Cologne, Germany.

Background: Patients with neutropenia resulting from chemotherapy for acute myelogenous leukemia or the myelodysplastic syndrome are at high risk for difficult-to-treat and often fatal invasive fungal infections.

Methods: In this randomized, multicenter study involving evaluators who were unaware of treatment assignments, we compared the efficacy and safety of posaconazole with those of fluconazole or itraconazole as prophylaxis for patients with prolonged neutropenia. Patients received prophylaxis with each cycle of chemotherapy until recovery from neutropenia and complete remission, until occurrence of an invasive fungal infection, or for up to 12 weeks, whichever came first. We compared the incidence of proven or probable invasive fungal infections during treatment (the primary end point) between the posaconazole and fluconazole or itraconazole groups; death from any cause and time to death were secondary end points.

Results: A total of 304 patients were randomly assigned to receive posaconazole, and 298 patients were randomly assigned to receive fluconazole (240) or itraconazole (58). Proven or probable invasive fungal infections were reported in 7 patients (2%) in the posaconazole group and 25 patients (8%) in the fluconazole or itraconazole group (absolute reduction in the posaconazole group, -6%; 95% confidence interval, -9.7 to -2.5%; P<0.001), fulfilling statistical criteria for superiority. Significantly fewer patients in the posaconazole group had invasive aspergillosis (2 [1%] vs. 20 [7%], P<0.001). Survival was significantly longer among recipients of posaconazole than among recipients of fluconazole or itraconazole (P=0.04). Serious adverse events possibly or probably related to treatment were reported by 19 patients (6%) in the posaconazole group and 6 patients (2%) in the fluconazole or itraconazole group (P=0.01). The most common treatment-related adverse events in both groups were gastrointestinal tract disturbances.

Conclusions: In patients undergoing chemotherapy for acute myelogenous leukemia or the myelodysplastic syndrome, posaconazole prevented invasive fungal infections more effectively than did either fluconazole or itraconazole and improved overall survival. There were more serious adverse events possibly or probably related to treatment in the posaconazole group. (ClinicalTrials.gov number, NCT00044486 [ClinicalTrials.gov].).
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http://dx.doi.org/10.1056/NEJMoa061094DOI Listing
January 2007

Changes in expression of apoptosis-related genes are linked to the molecular response to imatinib treatment in chronic-phase chronic myeloid leukemia patients.

Acta Haematol 2007 9;117(2):83-90. Epub 2006 Nov 9.

Department of Internal Medicine/Haematology, Sahlgrenska University Hospital, Gothenburg, Sweden.

Most patients with a chronic phase of chronic myeloid leukemia (CML) treated with imatinib mesylate achieve a cytogenetic remission, but in the majority, residual disease is detectable by RT-PCR. The mechanisms by which residual leukemic cells survive imatinib treatment are unresolved. However, induction of apoptosis in leukemic stem cells and immunotherapy are currently under investigation. We studied the mRNA expression of apoptosis-related genes in peripheral blood mononuclear cells from chronic-phase CML patients before imatinib treatment. It was found that their BCL2 and BAD expression was significantly different compared to the normal controls, and a lower BAD expression was associated with a better molecular response to imatinib treatment at 12 months.
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http://dx.doi.org/10.1159/000096858DOI Listing
March 2007

Not all imatinib resistance in CML are BCR-ABL kinase domain mutations.

Ann Hematol 2006 Dec 28;85(12):841-7. Epub 2006 Sep 28.

Department of Internal Medicine/Haematology, Sahlgrenska University Hospital, Gothenburg, 413 45, Sweden.

Point mutations within the ABL kinase domain of the BCR-ABL gene are associated with clinical resistance to imatinib mesylate in chronic myeloid leukemia (CML). To obtain more information about the association between BCR-ABL mutations and type of imatinib resistance, we studied 30 early chronic phase (CP) CML patients, commencing imatinib therapy, using a conventional sequencing technique. Seven patients treated in late CP and three patients treated in the accelerated phase were included for comparison. Blood samples were collected before and every third month during imatinib therapy. Mutations were not seen in any blood sample collected before start of therapy. During imatinib treatment, 2 of the 30 early CP patients acquired point mutations and both of them had other signs of imatinib resistance. None of the five early CP patients with a complete hematologic response (HR), but no cytogenetic response at 12 months, displayed any missense mutation. Likewise, none of 12 early CP patients with detectable BCR-ABL transcripts but in complete hematologic and cytogenetic remission at 12 months displayed any mutation. We conclude that screening early CP patients for BCR-ABL mutations before start of imatinib therapy is not cost-effective. BCR-ABL kinase domain mutations do not appear to explain cytogenetic or molecular (detectable BCR-ABL transcripts by polymerase chain reaction) disease persistence in patients otherwise in stable disease. However, in patients with signs of expanding disease burden, a search for BCR-ABL mutations is warranted.
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http://dx.doi.org/10.1007/s00277-006-0171-8DOI Listing
December 2006

Serial monitoring of BCR-ABL transcripts in chronic myelogenous leukemia (CML) treated with imatinib mesylate.

Med Oncol 2004 ;21(4):349-58

Department of Internal Medicine, Haematology section, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden.

Survival among chronic myelogenous leukemia (CML) patients can be linked to the reduction in leukemic cell burden. Treatment with imatinib mesylate results in a high frequency of complete cytogenetic response, which can be further stratified using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). We have serially monitored peripheral blood and bone marrow BCR-ABL transcripts using qRT-PCR in CML patients commencing imatinib therapy, and compared the results with bone marrow cytogenetics. Seventeen patients (aged 25-74 yr) with Philadelphia chromosome positive CML in first chronic phase were treated with imatinib targeting a dose of 400 mg/d. The median follow up is 30 mo (range 9-33 mo). Every third month the product of the BCR-ABL fusion gene was evaluated in both blood and bone marrow specimens by real-time RT-PCR using the TaqMan probe system. In 113 simultaneously obtained blood and bone marrow samples, the BCR-ABL transcript values agreed well with cytogenetic data. Blood and bone marrow specimens gave comparable values for BCR-ABL transcripts. Before start of imatinib therapy there was a considerable variation in BCR-ABL transcripts among the patients, ranging approximately one log (base 10). Similarly, patients with a complete cytogenetic response following imatinib therapy had variable BCR-ABL transcript levels, ranging at least three logs (base 10). The major decline in BCR-ABL transcripts occurred within 6 mo after start of imatinib therapy. The decline in BCR-ABL transcripts, following imatinib therapy, appears to level off at 12-15 mo. Two late responders were identified with a still decreasing level in BCR-ABL transcripts after 24 mo of treatment. It is concluded that BCR-ABL mRNA quantification in peripheral blood is suitable for routine monitoring of the response to treatment and long-term disease status in CML, especially in patients who have achieved a complete cytogenetic response. A plateau in BCR-ABL transcripts seems to have been reached after 12-15 mo of imatinib treatment; however, some "late responders" are seen.
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http://dx.doi.org/10.1385/MO:21:4:349DOI Listing
March 2005

The incidence and survival of acute de novo leukaemias in Estonia and in a well defined region of Western Sweden during 1982-1996: a survey of patients aged 16-64 years.

Leuk Lymphoma 2004 May;45(5):915-21

Haematology and Coagulation Section, Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.

In the present work the incidence and survival of acute de novo leukaemias in two neighbouring countries, were studied retrospectively over three 5-year periods, 1982-1996. The aim was to compare the above variables, particularly with respect to political/socio-economic and environmental factors, in a well defined area of Sweden, the so-called Western Swedish Health Care Region, with Estonia. Population-wise the Western Swedish Region and Estonia are very similar; area-wise they are also well comparable. The present report covers only patients diagnosed between the ages of 16-64 years. The number of acute de novo leukaemias in the two regions was quite similar (Western Sweden n = 282 and Estonia n = 237). The age standardized incidence rate regarding total acute de novo leukaemias was slightly lower in Estonia than in Western Sweden (1.49/100,000 inhabitants/year for Estonia and 1.76 for Sweden, respectively), the difference being not statistically significant. However, the survival data for the two countries were highly different (P < 0.001). Thus, the relative survival for the total group of patients aged 16-64 years in Estonia at 1 year was 20.7% and at 5 years 3.6%, respectively. The corresponding figures for the Swedish patients were considerably higher, 65.2 and 29.4%, respectively. Further, the 5 year survival significantly (P < 0.05) increased for the Swedish patients over the 3 consecutive 5-year periods. No such improvement was recorded for the Estonian patients.
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http://dx.doi.org/10.1080/10428190310001623865DOI Listing
May 2004

[CPP (Cost Per Patient) is functioning well in the everyday care. The myeloma care program in Vastra Gotaland--an illustrative example].

Lakartidningen 2003 Oct;100(42):3316-8

Sektionen för hematologi och koagulation, medicinkliniken, Sahlgrenska Universitetssjukhuset, Göteborg.

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October 2003

Is monosomy 5 an uncommon aberration? Fluorescence in situ hybridization reveals translocations and deletions in myelodysplastic syndromes or acute myelocytic leukemia.

Cancer Genet Cytogenet 2003 Apr;142(2):107-14

Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.

Acquired loss of material from chromosome 5 in bone marrow cells is common in myelodysplastic syndromes (MDS) and acute myelocytic leukemia (AML). In this study, we have applied fluorescence in situ hybridization (FISH) analyses with probes for the three regions 5p15.2, 5q31, 5q33-q34, and whole chromosome 5 painting probes (WCP 5) to investigate what further information could be gained regarding the cytogenetic abnormalities of chromosome 5 in 35 patients with MDS or AML. With FISH, a del(5q) was found in all patients except for two. Translocations of material from chromosome 5 were found in 10 patients. Among 16 patients with clones of monosomy 5 seen by cytogenetics, 14 had deletions or translocations. Different breakpoints on chromosome 5 were observed. In conclusion, the extended FISH analyses yielded additional information about chromosome 5 abnormalities in 60% of the patients. Of interest is the finding of a high proportion of translocations and that monosomy 5 occurs less often than is generally believed.
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http://dx.doi.org/10.1016/s0165-4608(02)00836-1DOI Listing
April 2003

High-dose cytarabine in upfront therapy for adult patients with acute lymphoblastic leukaemia.

Br J Haematol 2002 Sep;118(3):748-54

The Swedish Adult ALL Group, Uppsala University Hospital, Sweden.

In this national study, we have evaluated a new intensive chemotherapy protocol for adult patients with untreated acute lymphoblastic leukaemia (ALL). One hundred and fifty-three patients with median age 42 years received induction therapy with high-dose cytarabine (Ara-C), cyclophosphamide, daunorubicin, vincristine and betamethasone. A high complete remission (CR) rate (90%) was achieved in patients < 60 years compared with 70% in patients > 60 years (P = 0.004). The estimated 3 year overall survival for all patients was 29% (CI 21-36%) and the estimated continuous complete remission (CCR) at 3 years for the patients achieving CR according to the protocol was 36% (CI 27-45%). A favourable pretreatment characteristic was pre-B phenotype, especially for patients < 40 years without any high-risk factor, with an estimated CCR at 3 years of 62% (CI 41-82%). Stem cell transplantation (SCT) as post-remission therapy, mainly for high-risk patients, gave an estimated 3 year disease free survival (DFS) after SCT of 39% (CI 24-54%). No significant differences in DFS could be found between autologous, related or unrelated donor transplantation. We conclude that this intensive protocol resulted in a high CR rate combined with acceptable side-effects and a favourable CCR for patients with pre-B ALL.
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http://dx.doi.org/10.1046/j.1365-2141.2002.03685.xDOI Listing
September 2002