Age-Dependent Frequencies of NPM-1/FLT3-ITD Mutations in Patients with Normal Karyotype AML

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2531-2531 ◽  
Author(s):  
Friederike Schneider ◽  
Eva Hoster ◽  
Michael Unterhalt ◽  
Stephanie Schneider ◽  
Annika Dufour ◽  
...  

Abstract Background: Long-term survival in NK-AML is influenced by different clinical and molecular markers. Whereas the presence of a NPM-1 mutation is associated with a positive prognostic effect on long-term outcome, the presence of a FLT3-ITD mutation has a negative impact on survival. Interestingly, a significant interaction between NPM-1 and FLT3-ITD mutations has been shown. The positive prognostic impact on clinical outcome was evident predominantly in patients with NK-AML carrying NPM1 gene mutations when FLT3-internal tandem duplications (ITD) were absent. In contrast, the survival in all other groups of NPM-1 and FLT3-ITD combinations was not different so far. A clinical parameter with negative impact on all outcome parameters (OS, EFS, RFS, CR) is patient age at diagnosis. Certainly the worse prognosis in elderly patients is due to adverse patient characteristics and comorbidities. Nevertheless also disease-associated parameters reveal differences between older and younger patients with AML. Therefore we investigated the frequencies of NPM-1/FLT3-ITD mutations in different age groups. Patients and methods: Analyses were based on 803 patients with NK-AML included in the AMLCG (German AML Cooperative Group) 2000 trial until 01/2006. Patient age ranged from 17 to 85 years (median: 60 yrs). Information about the mutation status of NPM-1 and FLT3-ITD mutations at diagnosis was available in 689 patients. Patients were divided into six age groups (1: 17–30yrs; 2: 31–40yrs; 3: 41–50yrs; 4: 51–60yrs; 5: 61–70yrs; 6: 71–85yrs). The incidence of the molecular markers NPM-1 and FLT3-ITD as well as the four NPM-1 and FLT3-ITD combinations were calculated in cross tables (Pearson’s Chi Square test) in the different age groups. Results: In 689 patients with available mutations status we found a significant decrease in the frequency of the two molecular markers with higher age. Whereas the incidence of NPM-1 mutation decreased abruptly in patients >60 yrs [Group 1: 18/28 (64.3%), 2: 35/59 (59.3%), 3: 70/114 (61.4%), 4: 84/143 (58.7%), 5: 98/234 (41.9%), 6: 46/111 (41.4%); p<0.0001], the incidence of a FLT3-ITD decreased continuously with increasing age [Group 1: 14/28 (50.0%), 2: 21/59 (35.6%), 3: 36/114 (31.6%), 4: 47/143 (32.9%), 5: 60/234 (25.6%), 6: 22/111 (19.8%); p=0.013)]. Combining both markers we found a significant relative increase of NPM-1−/FLT3-ITD− patients (p<0.0001) with a sharp cut at 60 years whereas the NPM-1+/FLT3-ITD+ group diminished continuously (p=0.020). The proportion of the positive prognostic group of NPM-1+/FLT3-ITD− patients showed an increase between 40–60 years and a decrease afterwards (p=0.024) (see table 1 and figure 1). Conclusions: Our data show in a large cohort of 689 patients with NK-AML that the presence of mutations of the molecular markers NPM-1 and FLT3-ITD significantly decreases with age. Consequently the proportion of NPM-1−/FLT3-ITD− patients increases over time. This observation sheds light on the disease biology in older patients with AML. Table 1: Distribution of the NPM-1, FLT3-ITD and the 4 NPM-1/FLT3-ITD subgroups in different age groups age groups NPM-1 + % FLT3-ITD+ (%) NPM-1−/FLT3-ITD−(%) NPM-1+/FLT3-ITD+ (%) NPM-1−/FLT3-ITD+ (%) NPM-1+/FLT3-ITD− (%) 17–30 64.3 50.0 25.0 39.3 10.7 25.0 31–40 59.3 35.6 30.5 25.4 10.2 33.9 41–50 61.4 31.6 28.9 21.9 9.6 39.5 51–60 58.7 32.9 31.5 23.1 9.8 35.7 61–70 41.9 25.6 51.3 18.8 6.8 23.1 71–85 41 4 19.8 50.5 11.7 8.1 29.7 all age groups (%) 50.9 29.0 40.5 20.5 8.5 30.5 p-value < 0.0001*** 0.013* < 0.0001*** 0.020* 0.886 0.024* Figure 1: Proportions of the four NPM-1/FLT3-ITD subgroups in different age groups Figure 1:. Proportions of the four NPM-1/FLT3-ITD subgroups in different age groups

2021 ◽  
Vol 10 (12) ◽  
pp. 2685
Author(s):  
Andre J. Burnham ◽  
Phillip A. Burnham ◽  
Edwin M. Horwitz

Olfactory neuroblastoma (ONB) is a rare neuroepithelial-derived malignancy that usually presents in the nasal cavity. The rarity of ONB has led to conflicting reports regarding associations of patient age and ONB survival and outcome. Moreover, long-term outcomes of chemotherapy and other treatment modalities are speculated. Here, we aimed to compare survival outcomes across age groups through time and determine associations between treatment modality and survival. In this retrospective population-based study, we analyzed the SEER 2000–2016 Database for patients with ONB tumors. Using Kaplan–Meier survival analysis, a significant effect of age and cancer-specific survival (CSS) was observed; geriatric ONB patients had the lowest CSS overall. Generalized linear models and survival analyses demonstrated that CSS of the pediatric patient population was similar to the geriatric group through 100 months but plateaued thereafter and was the highest of all age groups. Radiation and surgery were associated with increased CSS, while chemotherapy was associated with decreased CSS. GLM results showed that tumor grade, stage and lymph node involvement had no CSS associations with age or treatment modality. Our results provide insight for future investigations of long-term outcomes associated with ONB patient age and treatment modality, and we conclude that survival statistics of ONB patients should be analyzed in terms of trends through time rather than fixed in time.


2018 ◽  
Vol 7 (12) ◽  
pp. 506 ◽  
Author(s):  
Katarina Boršič ◽  
Rok Blagus ◽  
Tjaša Cerar ◽  
Franc Strle ◽  
Daša Stupica

Infected elderly people often present with signs and symptoms that differ from those in younger adults, but data on the association between patient age and presentation of early Lyme borreliosis (LB) are limited. In this study, the association between patient age (18–44 years, young vs. 45–64 years, middle-aged vs. ≥ 65 years, elderly) and disease course, microbiologic characteristics, and the long-term outcome of treatment was investigated prospectively in 1220 adult patients with early LB manifesting as erythema migrans (EM) at a single-center university hospital. Patients were assessed at enrolment and followed-up for 12 months. Age was associated with comorbidities, previous LB, presenting with multiple EM, and seropositivity to borreliae at enrolment. The time to resolution of EM after starting antibiotic treatment was longer in older patients. At 12 months, 59/989 (6.0%) patients showed incomplete response. The odds for incomplete response decreased with time from enrolment (odds ratio (OR) of 0.49, 0.50, and 0.48 for 2-month vs. 14-days, 6-month vs. 2-month, and 12-month vs. 6-month follow-up visits, respectively), but were higher with advancing age (OR 1.57 for middle-aged vs. young, and 1.95 for elderly vs. young), in women (OR 1.41, 95% confidence interval (CI) 1.01–1.96), in patients who reported LB-associated constitutional symptoms at enrolment (OR 7.69, 95% CI 5.39–10.97), and in those who presented with disseminated disease (OR 1.65, 95% CI 1.09–2.51). The long-term outcome of EM was excellent in patients of all age groups. However, older patients had slower resolution of EM and higher odds for an unfavorable outcome of treatment (OR 1.57, 95% CI 1.05–2.34 for middle-aged vs. young; and OR 1.95, 95% CI 1.14–3.32 for elderly vs. young), manifested predominantly as post-LB symptoms. The presence of LB-associated constitutional symptoms at enrolment was the strongest predictor of incomplete response.


Perfusion ◽  
2018 ◽  
Vol 33 (8) ◽  
pp. 687-695 ◽  
Author(s):  
Julia Merkle ◽  
Anton Sabashnikov ◽  
Carolyn Weber ◽  
Georg Schlachtenberger ◽  
Johanna Maier ◽  
...  

Objectives: Stanford A acute aortic dissection (AAD) is a life-threatening emergency, typically occurring in older patients and requiring immediate surgical repair. The aim of this study was to evaluate early outcome and short- and long-term survival of patients under and above 65 years of age. Methods: Two hundred and forty patients with Stanford A AAD underwent aortic surgical repair from January 2006 to April 2015 in our center. After statistical analysis and logistic regression analysis, Kaplan-Meier survival estimation was performed, with up to 9-year follow-up, comprising patients under and above 65 years of age. Results: The proportion of patients above 65 years of age suffering from Stanford A AAD was 50% (n=120). The group of patients above 65 years of age compared to the group under 65 years of age showed statistically significant differences in terms of higher odds ratios (OR) for hypertension (p=0.012), peripheral vascular disease (p=0.026) and tachyarrhythmia absoluta (p=0.004). Patients over 65 years of age also showed significantly poorer short- and long-term survival. Our subgroup analysis revealed that male patients (Breslow p=0.001, Log-Rank p=0.001) and patients suffering with hypertension (Breslow p=0.003, Log-Rank p=0.001) were reasonable for these results whereas younger and older female patients showed similar short- and long-term outcome (Breslow p=0.926, Log-Rank p=0.724). After stratifying all patients into 4 age groups (<45; 55-65; 65-75; >75years), short-term survival of the patients appeared to be significantly poorer with increasing age (Breslow p=0.026, Log-Rank p=0.008) whereas long-term survival of patients free from cerebrovascular events (Breslow p=0.0494, Log-Rank p=0.489) remained similar. Conclusions: All patients referred to our hospital for repair of Stanford A AAD with higher age had poorer short- and long-term survival, caused by male patients and patients suffering from hypertension, whereas survival of women and survival free from cerebrovascular events of the entire patient cohort was similar, irrespective of age.


Gerodontology ◽  
1993 ◽  
Vol 10 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Per-Olof J. Glantz ◽  
Krister Niler

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2069-2069 ◽  
Author(s):  
H. Yoon ◽  
A. F. Hottinger ◽  
L. M. DeAngelis ◽  
A. B. Lassman ◽  
L. E. Abrey

2069 Background: Glioblastoma multiforme (GBM) patients generally have a dismal prognosis with average survival of one year. Long-term survival of 3 years or more is rare and the clinical outcome of these patients has been poorly studied. Methods: Retrospective review of patients surviving 3 years or longer following diagnosis of GBM at our institution between 1985 and 2003. Clinical characteristics and long-term outcome were reviewed. Pathology was confirmed at our institution for all patients. Results: 39 long-term survivors of GBM were identified. Median age at diagnosis was 47 years (range: 14 - 69 years). Fifteen patients (pts) were older than 55 at time of diagnosis, and 5 were over 60. Presenting symptoms were headaches (56%), seizures (28%), hemiparesis (12%), aphasia (17%) or confusion (5%). Median KPS at diagnosis was 90 (range: 50–100). One patient (4%) underwent biopsy and X patients each (48%) underwent complete resection and incomplete resections. All patients received focal radiation therapy (RT) with a median dose of 5940 cGy (range: 4500 - 6120 cGy); 7 received concurrent temozolomide. Adjuvant chemotherapy in 35 pts consisted of temozolomide (54%), BCNU (38%), intra-arterial cisplatin (4%), or PCV (4%). Estimated median survival was 6.16 years (range: 3.1 - 18.2). After initial treatment, 11 pts had continuous clinical and radiographic remission, 28 relapsed, and 12 died. Median KPS at last follow-up was 70 (range 40 - 100). However, 19 pts (49%) developed delayed treatment-related complications at a median of 2.7 years (range: 1 -12 years) from initial diagnosis. Six (15%) developed RT necrosis (none of whom received concurrent temozolomide), 12 (31%) developed a subcortical dementia with associated leukoencephalopathy, and 9 (23%) developed strokes thought to be related to prior treatment. Conclusions: Long-term GBM survivors remain rare but occur in all age groups. These patients have a high risk of developing clinically significant long-term complications of their treatment. No significant financial relationships to disclose.


2018 ◽  
Vol 12 (4) ◽  
pp. 369-374 ◽  
Author(s):  
T. Terjesen

PurposeThe aims of this study on late-detected developmental dislocation of the hip (DDH) were to assess the outcome in patients aged 55 to 60 years and to define prognostic factors.MethodsThe study included 60 patients (74 hips). Primary treatment was skin traction to obtain closed reduction, followed by hip spica plaster cast. There were 52 girls and eight boys with a mean age at reduction of 19.6 months (8 to 37). Criteria for good long-term outcome were no osteoarthritis (OA) or total hip arthroplasty (THA) and modified Harris Hip Score ≥ 80 points.ResultsThe mean patient age at follow-up was 57.7 years (55 to 60). Good long-term clinical and radiographic outcome occurred in 39 of 73 hips (53%). In all, 24 hips (32%) had undergone THA at a mean patient age of 48.1 years (31 to 58). Survival analysis with conversion to THA as endpoint showed a reduction in survival from 100% at patient age 30 years to 62% at 58 years. Risk factors for poor outcome were age at reduction ≥ 1.5 years and residual dysplasia (Severin grades III/IV) at skeletal maturity.ConclusionWith a mean follow-up of patient age 58 years, the outcome of late-detected DDH, treated with traction and closed reduction, was satisfactory in more than half the hips. This indicates that the hip will probably last more than 50 years if risk factors like age at reduction ≥ 1.5 years, residual dysplasia and avascular necrosis are avoided.


2010 ◽  
Vol 138 (5) ◽  
pp. S-817-S-817
Author(s):  
Renumathy Dhanasekaran ◽  
Samir Parekh ◽  
Hyun S. Kim

2021 ◽  
Vol 41 (2) ◽  
pp. 1069-1076
Author(s):  
KEISUKE KOSUMI ◽  
KOSUKE MIMA ◽  
ATSUSHI MORITO ◽  
SHINSEI YUMOTO ◽  
TAKASHI MATSUMOTO ◽  
...  

Blood ◽  
2013 ◽  
Vol 122 (25) ◽  
pp. 4111-4118 ◽  
Author(s):  
Attilio Olivieri ◽  
Michele Cimminiello ◽  
Paolo Corradini ◽  
Nicola Mordini ◽  
Roberta Fedele ◽  
...  

Key Points Efficacy of imatinib in steroid-refractory chronic GVHD was prospectively compared across 3 different response systems, with high agreement. Validity of quantitative-based assessment of response with NIH criteria was confirmed by its prognostic impact on long-term survival.


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