Leukemia Cutis in Childhood Acute Myeloid Leukemia: Epidemiological, Clinical, Biological, and Prognostic Characteristics of Patients Included in the ELAM02 Study.
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ABSTRACT:
SUBMITTER: Gouache E
PROVIDER: S-EPMC6407794 | biostudies-literature | 2018 Oct
REPOSITORIES: biostudies-literature
Publications
Leukemia Cutis in Childhood Acute Myeloid Leukemia: Epidemiological, Clinical, Biological, and Prognostic Characteristics of Patients Included in the ELAM02 Study.
Gouache Elodie E Greze Victoria V Strullu Marion M Saultier Paul P Fenneteau Odile O Gandemer Virginie V Ragu Christine C Auvrignon Anne A Boutroux Hélène H Lapillonne Hélène H Pasquet Marlène M Leverger Guy G
HemaSphere 20181002 5
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Project description:ImportanceLeukemia cutis (LC) is an important yet understudied extramedullary manifestation of leukemia. Previous reports have suggested poor prognosis for patients with LC, but these reports have largely consisted of descriptive studies with a limited number of patients.ObjectivesTo identify patient factors associated with LC and characterize the association of LC with the course of acute myeloid leukemia (AML).Design, setting, and participantsThis retrospective, matched-cohort study included 1683 patients with AML diagnosed from January 1, 2005, to April 1, 2017, with and without biopsy-proven LC seen at a single-center, tertiary care hospital in St Louis, Missouri. To specifically evaluate differences in survival, propensity scoring was used to match patients with AML with LC to patients with AML without LC off the logit of propensity score based on age, race/ethnicity, sex, and leukemia type. Kaplan-Meier methods were used to compare cumulative probability survival. Matched survival analysis was performed with extended Cox regression to determine factors associated with leukemia-specific and overall survival.Main outcomes and measuresLeukemia-specific survival and overall survival.ResultsA total of 1683 patients were reviewed, including 78 patients with biopsy-proven LC of the AML type and 1605 patients with AML without LC. A total of 62 of the patients with AML and LC (mean [SD] age, 58.2 [11.7] years; 33 [53.2%] male) were matched in a 1:3 ratio to 186 patients with AML without LC (mean [SD] age, 58.2 [13.5] years; 103 [55.4%] male). The 5-year survival among the 62 patients with AML with LC was 8.6%, shorter than the 28.3% among the 186 matched patients with AML without LC. Matched survival analysis revealed that patients with AML and LC compared with those without LC had hazard ratios of 2.06 (95% CI, 1.26-3.38; P = .004) for leukemia-specific death and of 1.66 (95% CI, 1.06-2.60; P = .03) for all-cause death. In addition, matched patients with LC had greater odds of extramedullary organ burden (odds ratio, 3.48; 95% CI, 1.72-7.05; P < .001).Conclusions and relevanceThe results suggest that the presentation of LC in patients with AML is associated with decreased overall survival and leukemia-specific survival. Patients with AML presenting with LC may require more intensive treatment and monitoring of their leukemic disease.
| S-EPMC6583862 | biostudies-literature
Project description:Acute myeloid leukemia (AML) arises from clonal expansion of malignant hematopoietic precursor cells in the bone marrow. In rare instances, AML can recur with prominent extramedullary manifestations (i.e., leukemia cutis or myeloid sarcoma), either simultaneously or preceding marrow involvement, or as a sole site of primary disease relapse.
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| S-EPMC10400410 | biostudies-literature
Project description:Acute myeloid leukemia (AML) is the fifth most common malignancy in children, and the prognosis for AML in children remains relatively poor. However, its incidence and survival trends based on a large sample size have not been reported. Children diagnosed with AML between 1975 and 2014 were accessed from the Surveillance, Epidemiology, and End Results database. Incidence and survival trends were evaluated by age-adjusted incidence and relative survival rates (RSRs) and Kaplan-Meier analyses. Cox regression was performed to identify independent risk factors for child AML death. The overall incidence of AML in childhood increased each decade between 1975 and 2014, with the total age-adjusted incidence increasing from 5.766 to 6.615 to 7.478 to 7.607 per 1,000,000 persons. In addition, the relative survival rates of AML in childhood improved significantly, with 5-year RSRs increasing from 22.40% to 39.60% to 55.50% to 68.30% over the past four decades (p < 0.0001). Furthermore, survival disparities among different races and socioeconomic statuses have continued to widen over the past four decades. Multivariate Cox regression analyses showed a higher risk of death in Black patients (HR = 1.245, 95% CI: 1.077-1.438, p = 0.003) with Whites as a reference. These results may help predict future trends for AML in childhood, better design clinical trials by eliminating disparities, and ultimately improve clinical management and outcome.
| S-EPMC6775523 | biostudies-literature
Project description:BackgroundLeukemia cutis (LC) is an extramedullary acute myeloid leukemia (AML) infiltrate. No previous study has described the clinical characteristics and outcomes of Thai patients diagnosed with AML with LC.Materials and methodsWe conducted a 7-year retrospective case-control study on Thai AML patients at Siriraj Hospital from November 2013 to July 2020. Patients were divided into LC and non-LC groups. Initial clinical presentations and laboratory findings were examined to identify LC-associated factors. Overall survival (OS) and relapse-free survival (RFS) were assessed. Pathological tissues underwent re-evaluation to validate the LC diagnoses.ResultsThe study included 159 patients in a 2:1 ratio (106 non-LC and 53 LC). The LC group had a mean ± SD age of 54.3 ± 15.5 years; females were predominant. Three-fifths of the LC patients had intermediate-risk cytogenetics; 20.4% had an adverse risk, and 10.2% had a favorable risk. Most were classified as AML-M4 and AML-M5. Leukemic nodules were the primary finding in 58.5% of the cases, mainly on the legs. In the multivariate analysis of predictive factors associated with LC, organomegalies, specifically hepatomegaly, and lymphadenopathy, remained significant factors associated with LC [OR 4.45 (95%CI 1.20, 16.50); p = 0.026 and OR 5.48 (95%CI 1.65, 18.20); p = 0.005], respectively. The LC group demonstrated a significantly reduced OS (log-rank test p = 0.002) (median OS of 8.6 months vs. 32.4 months). RFS was considerably lower in the LC group (log-rank test p = 0.001) (median duration of 10.3 months vs. 24.4 months in the non-LC).ConclusionsAML patients who developed LC tended to experience notably poorer prognoses. Therefore, it is imperative to consider aggressive treatment options for such individuals. The presence of organomegalies in AML patients serves as a strong predictor of the possible occurrence of LC when accompanied by skin lesions.
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Project description:Despite major treatment improvements over the past decades, pediatric acute myeloid leukemia (AML) is still a life-threatening malignancy with relapse rates up to 30% and survival rates below 75%. A better description of the pattern of molecular aberrations in childhood AML is needed to refine prognostication in such patients. We report here the comprehensive molecular landscape using both high-throughput sequencing focused on 36 genes and ligation-dependent RT-PCR in 385 children with de novo AML enrolled in the prospective ELAM02 trial and we evaluated their prognostic significance. Seventy-six percent of patients had at least 1 mutation among the genes we screened. The most common class of mutations involved genes that control kinase signaling (61%) followed by transcription factors (16%), tumor suppressors (14%), chromatin modifiers (9%), DNA methylation controllers (8%), cohesin genes (5%), and spliceosome (3%). Moreover, a recurrent transcript fusion was detected in about a half of pediatric patients. Overall, CBF rearrangements, NPM1 and double CEBPA mutations represented 37% of the cohort and defined a favorable molecular subgroup (3 years OS: 92.1%) while NUP98 fusions, WT1, RUNX1, and PHF6 mutations (15% of the cohort) segregated into a poor molecular subgroup (3 years OS: 46.1%). KMT2A-rearrangements (21% of the cohort) were associated with an intermediate risk. Despite some overlaps, the spectrum of molecular aberrations and their prognostic significance differ between childhood and adult AML. These data have important implications to contribute in refining risk stratification of pediatric AML and show the need for further validations in independent pediatric cohorts.
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Project description:Acute myeloid leukemia (AML) is a highly heterogeneous myeloid malignancy which can be classified by genetic aberrations. To evaluate the impact of the dynamin 2 mutation in AML, we systematically assessed the characteristics and prognostic of DNM2 mutated patients in AML. In 912 AML patients, 20 somatic mutations in the DNM2 gene were identified among the 18 DNM2 mutated AML patients (2%). Of the mutation events, 60% (12/20) were in the dynamin central region of DNM2. DNM2mutations were preferentially occurred in AML with CEBPA mutation (11/18, 61.1%), or RUNX1::RUNX1T1 fusion gene (6/18, 33.3%). DNM2 mutations were associated with better overall survival (P = 0.028), event-free survival (P = 0.0093) and trends towards better relapse-free survival (P = 0.08), which seems potentially attribute to its coexisting with CEBPA mutation and RUNX1::RUNX1T1 fusion gene. Our study demonstrated the clinical characteristics and the role of DNM2 mutations in AML, which might facilitate understanding the pathogenesis of AML.
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