| 1. |
- Björkholm, Magnus, et al.
(författare)
-
Success Story of Targeted Therapy in Chronic Myeloid Leukemia : A Population-Based Study of Patients Diagnosed in Sweden From 1973 to 2008
- 2011
-
Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 29:18, s. 2514-2520
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose Chronic myeloid leukemia (CML) management changed dramatically with the development of imatinib mesylate (IM), the first tyrosine kinase inhibitor targeting the BCR-ABL1 oncoprotein. In Sweden, the drug was approved in November 2001. We report relative survival (RS) of patients with CML diagnosed during a 36-year period. Patients and Methods Using data from the population-based Swedish Cancer Registry and population life tables, we estimated RS for all patients diagnosed with CML from 1973 to 2008 (n = 3,173; 1,796 males and 1,377 females; median age, 62 years). Patients were categorized into five age groups and five calendar periods, the last being 2001 to 2008. Information on use of upfront IM was collected from the Swedish CML registry. Results Relative survival improved with each calendar period, with the greatest improvement between 1994-2000 and 2001-2008. Five-year cumulative relative survival ratios (95% CIs) were 0.21 (0.17 to 0.24) for patients diagnosed 1973-1979, 0.54 (0.50 to 0.58) for 1994-2000, and 0.80 (0.75 to 0.83) for 2001-2008. This improvement was confined to patients younger than 79 years of age. Five-year RSRs for patients diagnosed from 2001 to 2008 were 0.91 (95% CI, 0.85 to 0.94) and 0.25 (95% CI, 0.10 to 0.47) for patients younger than 50 and older than 79 years, respectively. Men had inferior outcome. Upfront overall use of IM increased from 40% (2002) to 84% (2006). Only 18% of patients older than 80 years of age received IM as first-line therapy. Conclusion This large population-based study shows a major improvement in outcome of patients with CML up to 79 years of age diagnosed from 2001 to 2008, mainly caused by an increasing use of IM. The elderly still have poorer outcome, partly because of a limited use of IM.
|
|
| 2. |
|
|
| 3. |
- Derolf, Åsa Rangert
(författare)
-
Predictors of prognosis in acute myeloid leukemia : a clinical and epidemiological study
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- AML is a malignant disorder characterized by clonal expansion of immature myeloid hematopoietic stem cells, myeloblasts, in bone marrow, blood and/or other tissue. Despite advances in treatment the majority of patients eventually die from this aggressive disease. We conducted a study including 9,729 AML patients diagnosed in Sweden 1973-2005 to define survival patterns over time. One-year relative survival ratios (RSRs) improved in all age groups. Improvement in 5-year RSRs was restricted to patients <80 years. The 5-year RSRs in the last calendar period were 0.65, 0.58, 0.36, 0.15, 0.05, and 0.01 for the age groups 0-18, 19-40, 41-60, 61-70, 71-80, and 80+ years, respectively. Intensification of induction and consolidation treatment, an increasing rate of allografted patients, a continuous improvement in supportive care measures, and a more precise risk stratification of patients are probably the most important factors contributing to the improvement. We also assessed the impact of socioeconomic status (SES) on survival in 9,165 patients with AML. Overall, higher white-collar workers had lower mortality compared to other SES groups (p=0.005). In AML patients, a consistently higher overall mortality was observed in blue-collar workers compared to higher white-collar workers in the last three calendar periods (hazard ratio [HR]=1.26; 95% confidence interval (CI) 1.05-1.51; HR=1.23; 1.05-1.45; HR=1.28; 1.04-1.57, respectively). Differences in comorbidities, management, and life-style factors are likely to explain these findings. We determined expression patterns of CD33 and CD15 in leukemic blasts from 129 patients with AML using flow cytometry (FC) and a standard panel of triple antibody combinations. Five patterns, corresponding to the consecutive stages of myeloid differentiation, were identified [I:CD33-/CD15- (n=18), II: CD33+/CD15- (n=43), III: CD33++/CD15 heterogeneous (n=10), IV: CD33+/CD15+ (n=50), V: CD33-/CD15+ (n=8)]. Patients with pattern II had the highest relapse rate and shortest median overall survival (OS; 8 months), but they were also the oldest (median age 72 years) and had a high frequency of unfavorable cytogenetics. Pattern V patients had a short OS (median 14 months) even though they were the youngest (median age 50 years) and had high remission rate. Age (p=0.004), cytogenetics (p=0.011), CD15 expression (p=0.031), and the immunophenotypic classification (p=0.024) were all independent significant predictors for OS. The presence of minimal residual disease (MRD) in AML patients in complete remission (CR) is a predictor of poor prognosis. We determined MRD status by FC in 45 AML patients ≤60 years old in first CR. MRD was determined after induction (MRD1; n=43) and/or at the end of post-remission chemotherapy (MRD2; n=31). Patients with detectable MRD at either time-point who underwent allogeneic or autologous stem cell transplantation (SCT) had significantly better 5-year relapse-free survival than patients not transplanted (MRD1: 83%, 54%, and 8%, respectively, p<0.0001; MRD2: 80%, 53%, and 0%, respectively, p=0.003). We identified 11,039 patients with yeloproliferative neoplasms (MPNs) from the Swedish Cancer Registry and major hematology units. Through record-linkage with the Cancer Registry patients who developed AML (n=271) and myelodysplastic syndromes (MDS; n=21) were identified. For each patient with a subsequent AML/MDS diagnosis (cases) two matched patients without AML/MDS (controls) were identified. After exclusions the final study population consisted of 162 cases (153 AML, 9 MDS) and 242 controls. 25% of patients with AML/MDS development were never exposed to cytotoxic agents. Compared to no hydroxyurea (HU) exposure the odds ratios (with 95% CIs) for 1-499 g, 500-999 g, >1000 g of HU were 1.22 (0.61-2.45), 1.41 (0.58-3.40), and 1.35 (0.55-3.32), respectively for AML/MDS development (not significant). In contrast, MPN patients who received radioactive phosphorus (P32) >1000 MBq and alkylating agents >1 g had a 4.60-fold (2.15-9.85; p<0.0001) and 3.39-fold (1.08-10.59; p=0.036) increased risk of AML/MDS, respectively. Lower exposures to P32 and alkylators were not associated with a significantly increased risk of AML/MDS.
|
|
| 4. |
- Juliusson, Gunnar, et al.
(författare)
-
Age and acute myeloid leukemia : real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry
- 2009
-
Ingår i: Blood. - Washington D.C. : American Society of Haematology. - 0006-4971 .- 1528-0020. ; 113:18, s. 4179-4187
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Lj Lazarevic, Vladimir, et al.
(författare)
-
Incidence and prognostic significance of isolated trisomies in adult acute myeloid leukemia : A population-based study from the Swedish AML registry
- 2017
-
Ingår i: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 98:5, s. 493-500
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES AND METHODS: To ascertain the incidence/clinical implications of isolated autosomal trisomies in adult acute myeloid leukemia (AML), all such cases were retrieved from the Swedish AML Registry.RESULTS: Of the 3179 cytogenetically informative AMLs diagnosed January 1997-May 2015, 246 (7.7%) had isolated trisomies. The frequency increased by age (2.4% at age 18-60 years vs. 23% at >60 years; P<.0001); the median age was 69 years. The five most common were +8 (4.0%), +13 (0.9%), +11 (0.8%), +21 (0.7%), and +4 (0.5%). Age and gender, types of AML and treatment, and complete remission and early death rates did not differ between the single trisomy and the intermediate risk (IR) groups or among cases with isolated gains of chromosomes 4, 8, 11, 13, or 21. The overall survival (OS) was similar in the single trisomy (median 1.6 years) and IR groups (1.7 years; P=.251). The OS differed among the most frequent isolated trisomies; the median OS was 2.5 years for +4, 1.9 years for +21, 1.5 years for +8, 1.1 years for +11, and 0.8 years for +13 (P=.013).CONCLUSION: AML with single trisomies, with the exception of +13, should be grouped as IR.
|
|
| 9. |
- Orsmark-Pietras, Christina, et al.
(författare)
-
Clinical and genomic characterization of patients diagnosed with the provisional entity acute myeloid leukemia with BCR-ABL1, a Swedish population-based study
- 2021
-
Ingår i: Genes, Chromosomes and Cancer. - : Wiley-Liss Inc.. - 1045-2257 .- 1098-2264. ; 60:6, s. 426-433
-
Tidskriftsartikel (refereegranskat)abstract
- Acute myeloid leukemia (AML) with t(9;22)(q34;q11), also known as AML with BCR-ABL1, is a rare, provisional entity in the WHO 2016 classification and is considered a high-risk disease according to the European LeukemiaNet 2017 risk stratification. We here present a retrospective, population-based study of this disease entity from the Swedish Acute Leukemia Registry. By strict clinical inclusion criteria we aimed to identify genetic markers further distinguishing AML with t(9;22) as a separate entity. Twenty-five patients were identified and next-generation sequencing using a 54-gene panel was performed in 21 cases. Interestingly, no mutations were found in NPM1, FLT3, or DNMT3A, three frequently mutated genes in AML. Instead, RUNX1 was the most commonly mutated gene, with aberrations present in 38% of the cases compared to around 10% in de novo AML. Additional mutations were identified in genes involved in RNA splicing (SRSF2, SF3B1) and chromatin regulation (ASXL1, STAG2, BCOR, BCORL1). Less frequently, mutations were found in IDH2, NRAS, TET2, and TP53. The mutational landscape exhibited a similar pattern as recently described in patients with chronic myeloid leukemia (CML) in myeloid blast crisis (BC). Despite the concomitant presence of BCR-ABL1 and RUNX1 mutations in our cohort, both features of high-risk AML, the RUNX1-mutated cases showed a superior overall survival compared to RUNX1 wildtype cases. Our results suggest that the molecular characteristics of AML with t(9;22)/BCR-ABL1 and CML in myeloid BC are similar and do not support a distinction of the two disease entities based on their underlying molecular alterations.
|
|
| 10. |
|
|
