Socioeconomic Differences in Patient Survival Are Increasing for Acute Myeloid Leukemia and Multiple Myeloma in Sweden

2009 ◽  
Vol 27 (12) ◽  
pp. 2073-2080 ◽  
Author(s):  
Sigurdur Yngvi Kristinsson ◽  
Åsa Rangert Derolf ◽  
Gustaf Edgren ◽  
Paul W. Dickman ◽  
Magnus Björkholm
Keyword(s):  
Multiple Myeloma ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
White Collar ◽  
Blue Collar ◽  
Lower Mortality ◽  
Blue Collar Workers ◽  
White Collar Workers ◽  
The Impact ◽  
Acute Myeloid

Purpose An association between socioeconomic status (SES) and survival in acute myeloid leukemia (AML) and multiple myeloma (MM) has not been established in developed countries. We assessed the impact of SES on survival in two large population-based cohorts of AML and MM patients diagnosed in Sweden 1973 to 2005. Patients and Methods The relative risk of death (all cause and cause specific) in relation to SES was estimated using Cox's proportional hazards regression. We also conducted analyses stratified by calendar periods (1973 to 1979, 1980 to 1989, 1990 to 1999, and 2000 to 2005). Results We identified a total of 9,165 and 14,744 patients with AML and MM, respectively. Overall, higher white-collar workers had a lower mortality than other SES groups for both AML (P = .005) and MM (P < .005). In AML patients, a consistently higher overall mortality was observed in blue-collar workers compared with higher white-collar workers in the last three periods (hazard ratio [HR], 1.26; 95% CI, 1.05 to 1.51; HR, 1.23; 95% CI, 1.05 to 1.45; HR, 1.28; 95% CI, 1.04 to 1.57, respectively). In MM, no difference was observed in the first two calendar periods. However, in 1990 to 1999, self-employed (HR, 1.18; 95% CI, 1.02 to 1.37), blue-collar workers (HR, 1.18; 95% CI, 1.04 to 1.32), and retired (HR, 1.45; 95% CI, 1.16 to 1.80) had a higher mortality compared to higher white-collar workers. In 2000 to 2005, blue-collar workers had a higher mortality (HR, 1.31; 95% CI, 1.07 to 1.60) compared with higher white-collar workers. Conclusion SES was significantly associated with survival in both AML and MM. Most conspicuously, a lower mortality was observed among the highest SES group during more recent calendar periods. Differences in management, comorbidity, and lifestyle, are likely factors to explain these findings.

High Socioeconomic Status (SES) Is Associated with Superior Survival in Patients with Acute Myeloid Leukemia (AML) and Multiple Myeloma (MM). A Population-Based Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1485-1485
Author(s):  
Sigurdur Y. Kristinsson ◽  
Asa R. Derolf ◽  
Paul W. Dickman ◽  
Gustaf Edgren ◽  
Magnus Bjorkholm
Keyword(s):  
White Collar ◽  
Population Based ◽  
Blue Collar ◽  
Lower Mortality ◽  
Calendar Period ◽  
White Collar Worker ◽  
Blue Collar Workers ◽  
The Third ◽  
White Collar Workers ◽  
The Impact

Abstract Introduction The association between SES and survival in MM and AML has not been studied in detail and the limited results are inconclusive. In the present study the impact of SES on survival was analyzed in a large population-based cohort of MM and AML patients. Patients and Methods From the Swedish Cancer Register we identified all individuals diagnosed with MM and AML between 1973 and 2003. We used type of occupation, combined into seven groups (blue-collar worker, farmer, lower white-collar worker, higher white-collar worker, self-employed, retired, and unknown), from the Swedish National Census Databases as a proxy for SES. The relative risk of death (any cause) in relation to type of occupation and calendar period was estimated using Cox’s proportional hazards regression adjusted for age, sex, calendar period and area of residence. We also conducted analyses stratified by calendar period (1973–1979, 1980–1989, 1990–1999, and 2000–2003). Results A total of 14,200 and 8,831 patients were diagnosed with MM and AML, respectively. The median age at diagnosis was 71.8 years in patients with MM and 69.1 years in AML. The SES distribution was similar between the two diseases. The majority of patients were blue-collar (38.0; 39.5%) and white-collar workers (36.4; 37%), with lower white-collar workers dominating the latter group. Women had a significantly lower mortality than men both among MM (p&lt;0.001) and AML (p&lt;0.05) patients. The mortality among patients diagnosed in more recent calendar periods was lower than among patients diagnosed earlier (p&lt;0.001) Overall, higher white-collar workers had a significantly lower mortality compared to blue-collar workers for both MM (p&lt;0.001) and AML (p&lt;0.001). No significant differences were found between the other SES groups. In MM, analyses stratified by calendar period revealed that the mortality did not differ between the SES groups in the first two calendar periods, but in the third calendar period, 1990–1999, both higher and lower white-collar workers had a significantly lower mortality compared to blue collar workers, hazard ratios (HR) 0.85 (95% CI, 0.75–0.96) and 0.91 (95% CI 0.85–0.98), respectively. In the fourth period the mortality followed the same pattern as in the third period with lower mortality among both higher [HR 0.66 (95% CI, 0.50–0.88)] and lower [HR 0.82 (95% CI, 0.69–0.96)] white-collar workers. In AML patients no difference in mortality in relation to SES was found during the first calendar period. During the last three periods, however, a lower mortality was observed in higher white-collar workers compared to blue-collar workers, HR: 0.79 (0.66–0.95), 0.79 (0.67–0.93) and 0.74 (0.57–0.96) in the periods 1980–1989, 1990–1999 and 2000–2003, respectively. Conclusion SES, here defined as occupational profession, was significantly associated with prognosis in both MM and AML. Most conspicuously, a lower mortality was recorded in white-collar workers during more recent calendar periods. Differences in time to diagnosis (lead-time bias) and treatment strategies may be important factors contributing to this finding. Future studies may identify the relative impact of these and potentially other factors.

AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations

Blood ◽  
2009 ◽  
Vol 114 (26) ◽  
pp. 5352-5361 ◽  
Author(s):  
Jih-Luh Tang ◽  
Hsin-An Hou ◽  
Chien-Yuan Chen ◽  
Chieh-Yu Liu ◽  
Wen-Chien Chou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Remission Rate ◽  
Adult Patients ◽  
Poor Prognostic Factor ◽  
The Impact ◽  
Runx1 Mutation ◽  
Acute Myeloid

AbstractSomatic mutation of the AML1/RUNX1(RUNX1) gene is seen in acute myeloid leukemia (AML) M0 subtype and in AML transformed from myelodysplastic syndrome, but the impact of this gene mutation on survival in AML patients remains unclear. In this study, we sought to determine the clinical implications of RUNX1 mutations in 470 adult patients with de novo non-M3 AML. Sixty-three distinct RUNX1 mutations were identified in 62 persons (13.2%); 32 were in N-terminal and 31, C-terminal. The RUNX1 mutation was closely associated with male sex, older age, lower lactic dehydrogenase value, French-American-British M0/M1 subtypes, and expression of HLA-DR and CD34, but inversely correlated with CD33, CD15, CD19, and CD56 expression. Furthermore, the mutation was positively associated with MLL/PTD but negatively associated with CEBPA and NPM1 mutations. AML patients with RUNX1 mutations had a significantly lower complete remission rate and shorter disease-free and overall survival than those without the mutation. Multivariate analysis demonstrated that RUNX1 mutation was an independent poor prognostic factor for overall survival. Sequential analysis in 133 patients revealed that none acquired novel RUNX1 mutations during clinical courses. Our findings provide evidence that RUNX1 mutations are associated with distinct biologic and clinical characteristics and poor prognosis in patients with de novo AML.

scholarly journals Actin cytoskeleton deregulation confers midostaurin resistance in FLT3-mutant acute myeloid leukemia

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Andoni Garitano-Trojaola ◽  
Ana Sancho ◽  
Ralph Götz ◽  
Patrick Eiring ◽  
Susanne Walz ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Actin Cytoskeleton ◽  
Myeloid Leukemia ◽  
Actin Polymerization ◽  
Cell Stiffness ◽  
Adhesion Forces ◽  
Frequent Mutations ◽  
New Perspective ◽  
The Impact ◽  
Acute Myeloid

AbstractThe presence of FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) is one of the most frequent mutations in acute myeloid leukemia (AML) and is associated with an unfavorable prognosis. FLT3 inhibitors, such as midostaurin, are used clinically but fail to entirely eradicate FLT3-ITD + AML. This study introduces a new perspective and highlights the impact of RAC1-dependent actin cytoskeleton remodeling on resistance to midostaurin in AML. RAC1 hyperactivation leads resistance via hyperphosphorylation of the positive regulator of actin polymerization N-WASP and antiapoptotic BCL-2. RAC1/N-WASP, through ARP2/3 complex activation, increases the number of actin filaments, cell stiffness and adhesion forces to mesenchymal stromal cells (MSCs) being identified as a biomarker of resistance. Midostaurin resistance can be overcome by a combination of midostaruin, the BCL-2 inhibitor venetoclax and the RAC1 inhibitor Eht1864 in midostaurin-resistant AML cell lines and primary samples, providing the first evidence of a potential new treatment approach to eradicate FLT3-ITD + AML.

Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients

Blood ◽  
2011 ◽  
Vol 118 (5) ◽  
pp. 1402-1412 ◽  
Author(s):  
Ahmet H. Elmaagacli ◽  
Nina K. Steckel ◽  
Michael Koldehoff ◽  
Yael Hegerfeldt ◽  
Rudolf Trenschel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Human Cytomegalovirus ◽  
Myeloid Leukemia ◽  
Homogeneous Population ◽  
Relapse Risk ◽  
Pp65 Antigenemia ◽  
Hcmv Replication ◽  
The Impact ◽  
Early Human ◽  
Acute Myeloid

Abstract The impact of early human cytomegalovirus (HCMV) replication on leukemic recurrence was evaluated in 266 consecutive adult (median age, 47 years; range, 18-73 years) acute myeloid leukemia patients, who underwent allogeneic stem cell transplantation (alloSCT) from 10 of 10 high-resolution human leukocyte Ag-identical unrelated (n = 148) or sibling (n = 118) donors. A total of 63% of patients (n = 167) were at risk for HCMV reactivation by patient and donor pretransplantation HCMV serostatus. In 77 patients, first HCMV replication as detected by pp65-antigenemia assay developed at a median of 46 days (range, 25-108 days) after alloSCT. Taking all relevant competing risk factors into account, the cumulative incidence of hematologic relapse at 10 years after alloSCT was 42% (95% confidence interval [CI], 35%-51%) in patients without opposed to 9% (95% CI, 4%-19%) in patients with early pp65-antigenemia (P < .0001). A substantial and independent reduction of the relapse risk associated with early HCMV replication was confirmed by multivariate analysis using time-dependent covariate functions for grades II to IV acute and chronic graft-versus-host disease, and pp65-antigenemia (hazard ratio = 0.2; 95% CI, 0.1-0.4, P < .0001). This is the first report that demonstrates an independent and substantial reduction of the leukemic relapse risk after early replicative HCMV infection in a homogeneous population of adult acute myeloid leukemia patients.

New Strategies for the Treatment of Acute Myeloid Leukemia Including Antibodies and Other Novel Agents

Hematology ◽  
2005 ◽  
Vol 2005 (1) ◽  
pp. 143-150 ◽  
Author(s):  
Martin S. Tallman
Keyword(s):  
Older Adults ◽  
Acute Myeloid Leukemia ◽  
Multidrug Resistance ◽  
Myeloid Leukemia ◽  
Cytotoxic Agents ◽  
High Dose ◽  
Farnesyltransferase Inhibitors ◽  
Younger Adults ◽  
The Impact ◽  
Acute Myeloid

Abstract The prognosis for younger adults (≤ 55–60 years) with acute myeloid leukemia (AML) has improved during the last four decades. However, there has been little progress in the treatment of older adults. This disappointing observation is important because the median age of patients with AML is about 70 years. Approximately 60%–80% of younger adults with AML achieve complete remission (CR) with the cytotoxic agents cytarabine and an anthracycline such as daunorubicin or idarubicin or the anthracenedione mitoxantrone. However, only 30%–40% of such patients are alive and disease-free at 5 years. Among older adults, CR is achieved in 40%–55%, but there are very few long-term survivors. Many studies have evaluated the impact of alternative doses and schedules, as well as additional cytotoxic drugs, on the prognosis for this group of patients. The outcome has not improved substantially beyond that achieved with conventional doses of an anthracycline and cytarabine followed by high-dose cytarabine consolidation. Several factors identified at diagnosis can predict outcome. The most important of these is the karyotype of the leukemic cells. Another critical factor is the presence of transmembrane transporter proteins, which confer multidrug resistance and mutations in or overexpression of specific genes such as WT1, C/EBPα, BAX, and BCL-2/BAX ratio, BAALC, EVI1, KIT and FLT3. The development of specific agents directed at gene mutations, signal transduction pathways and unique cell surface antigens provide the foundation for new therapeutic strategies. Such agents include the immunoconjugate gemtuzumab ozogamicin, multidrug resistance inhibitors, farnesyltransferase inhibitors, histone deacetylase and proteosome inhibitors, antiangiogenesis agents, FLT3 inhibitors, apoptosis inhibitors, and nucleoside analogs. All of these agents can potentially address the heterogeneous abnormalities in AML and significantly improve the outcome for patients.

scholarly journals Stable Isotope Labeling Highlights Enhanced Fatty Acid and Lipid Metabolism in Human Acute Myeloid Leukemia

2018 ◽  
Vol 19 (11) ◽  
pp. 3325 ◽  
Author(s):  
Lucille Stuani ◽  
Fabien Riols ◽  
Pierre Millard ◽  
Marie Sabatier ◽  
Aurélie Batut ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Acute Myeloid Leukemia ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Myeloid Leukemia ◽  
Metabolic Reprogramming ◽  
Frequent Relapses ◽  
The Impact ◽  
Mutant Cells ◽  
Acute Myeloid

Background: In Acute Myeloid Leukemia (AML), a complete response to chemotherapy is usually obtained after conventional chemotherapy but overall patient survival is poor due to highly frequent relapses. As opposed to chronic myeloid leukemia, B lymphoma or multiple myeloma, AML is one of the rare malignant hemopathies the therapy of which has not significantly improved during the past 30 years despite intense research efforts. One promising approach is to determine metabolic dependencies in AML cells. Moreover, two key metabolic enzymes, isocitrate dehydrogenases (IDH1/2), are mutated in more than 15% of AML patient, reinforcing the interest in studying metabolic reprogramming, in particular in this subgroup of patients. Methods: Using a multi-omics approach combining proteomics, lipidomics, and isotopic profiling of [U-13C] glucose and [U-13C] glutamine cultures with more classical biochemical analyses, we studied the impact of the IDH1 R132H mutation in AML cells on lipid biosynthesis. Results: Global proteomic and lipidomic approaches showed a dysregulation of lipid metabolism, especially an increase of phosphatidylinositol, sphingolipids (especially few species of ceramide, sphingosine, and sphinganine), free cholesterol and monounsaturated fatty acids in IDH1 mutant cells. Isotopic profiling of fatty acids revealed that higher lipid anabolism in IDH1 mutant cells corroborated with an increase in lipogenesis fluxes. Conclusions: This integrative approach was efficient to gain insight into metabolism and dynamics of lipid species in leukemic cells. Therefore, we have determined that lipid anabolism is strongly reprogrammed in IDH1 mutant AML cells with a crucial dysregulation of fatty acid metabolism and fluxes, both being mediated by 2-HG (2-Hydroxyglutarate) production.

scholarly journals Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemia

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Adriana E. Tron ◽  
Matthew A. Belmonte ◽  
Ammar Adam ◽  
Brian M. Aquila ◽  
Lawrence H. Boise ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Specific Inhibitor ◽  
Acute Myeloid

scholarly journals Low expression of MN1 associates with better treatment response in older patients with de novo cytogenetically normal acute myeloid leukemia

Blood ◽  
2011 ◽  
Vol 118 (15) ◽  
pp. 4188-4198 ◽  
Author(s):  
Sebastian Schwind ◽  
Guido Marcucci ◽  
Jessica Kohlschmidt ◽  
Michael D. Radmacher ◽  
Krzysztof Mrózek ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Hox Genes ◽  
De Novo ◽  
Prognostic Significance ◽  
The Impact ◽  
Favorable Group ◽  
Acute Myeloid

AbstractLow MN1 expression bestows favorable prognosis in younger adults with cytogenetically normal acute myeloid leukemia (CN-AML), but its prognostic significance in older patients is unknown. We analyzed pretherapy MN1 expression in 140 older (≥ 60 years) de novo CN-AML patients treated on cytarabine/daunorubicin-based protocols. Low MN1 expressers had higher complete remission (CR) rates (P = .001), and longer overall survival (P = .03) and event-free survival (EFS; P = .004). In multivariable models, low MN1 expression was associated with better CR rates and EFS. The impact of MN1 expression on overall survival and EFS was predominantly in patients 70 years of age or older, with low MN1 expressers with mutated NPM1 having the best outcome. The impact of MN1 expression was also observed in the Intermediate-I, but not the Favorable group of the European LeukemiaNet classification, where low MN1 expressers had CR rates and EFS similar to those of Favorable group patients. MN1 expresser-status-associated gene- and microRNA-expression signatures revealed underexpression of drug resistance and adverse outcome predictors, and overexpression of HOX genes and HOX-gene–embedded microRNAs in low MN1 expressers. We conclude that low MN1 expression confers better prognosis in older CN-AML patients and may refine the European LeukemiaNet classification. Biologic features associated with MN1 expression may help identify new treatment targets.

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