scholarly journals Prediction of Early Death After Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia With Pretreatment Risk Scores: A Novel Paradigm for Treatment Assignment

2011 ◽  
Vol 29 (33) ◽  
pp. 4417-4424 ◽  
Author(s):  
Roland B. Walter ◽  
Megan Othus ◽  
Gautam Borthakur ◽  
Farhad Ravandi ◽  
Jorge E. Cortes ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Group Performance ◽  
Predictive Accuracy ◽  
Characteristic Curve ◽  
Performance Status ◽  
Risk Scores ◽  
Newly Diagnosed ◽  
Risk Of Death ◽  
Acute Myeloid

Purpose Outcome in acute myeloid leukemia (AML) worsens with age, at least in part because of higher treatment-related mortality (TRM) in older patients. Eligibility for intensive AML treatment protocols is therefore typically based on age as the implied principal predictor of TRM, although other health- and disease-related factors modulate this age effect. Patients and Methods We empirically defined TRM using estimated weekly hazard rates in 3,365 adults of all ages administered intensive chemotherapy for newly diagnosed AML. We used the area under the receiver operator characteristic curve (AUC) to quantify the relative effects of age and other covariates on TRM in a subset of 2,238 patients. In this approach, an AUC of 1.0 denotes perfect prediction, whereas an AUC of 0.5 is analogous to a coin flip. Results Regardless of age, risk of death declined once 4 weeks had elapsed from treatment start, suggesting that patients who die during this time comprise a qualitatively distinct group. Performance status (PS) and age were the most important individual predictors of TRM (AUCs of 0.75 and 0.65, respectively). However, multicomponent models were significantly more accurate in predicting TRM (AUC of 0.83) than PS or age alone. Elimination of age from such multicomponent models only minimally affected their predictive accuracy (AUC of 0.82). Conclusion These data suggest that age is primarily a surrogate for other covariates, which themselves add significantly to predictive accuracy, thus challenging the wisdom of using age as primary or sole basis for assignment of intensive, curative intent treatment in AML.

scholarly journals Prediction of Treatment-Related Mortality in Patients with Relapsed and Refractory Acute Myeloid Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2277-2277
Author(s):  
Colin Godwin ◽  
Megan Othus ◽  
Vicky Sandhu ◽  
Elihu H. Estey ◽  
Roland B. Walter
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Characteristic Curve ◽  
Performance Status ◽  
Newly Diagnosed ◽  
Treatment Related Mortality ◽  
Related Mortality ◽  
Acute Myeloid ◽  
Refractory Aml

Abstract Introduction Despite improvements in supportive care, treatment-related mortality (TRM) remains a significant problem for patients with acute myeloid leukemia (AML). In order to quantify fitness for intensive AML therapies, we recently developed a multivariate model for predicting TRM, defined as death within 28 days of treatment initiation in patients undergoing intensive induction chemotherapy for newly-diagnosed AML. Here, we examine the performance of this TRM model in patients with relapsed or refractory AML and assess whether the model can be improved for this population. Methods Using a database of patients treated for AML at our institution since 2003, we identified patients with relapsed or refractory disease treated with intensive chemotherapy, defined as regimens that were at least as intense as typical “7+3” regimens; patients who received treatment protocols with cytarabine <100 mg/m2/day or demethylating agents alone were excluded. We collected the following variables required to calculate the TRM score: ECOG performance status, age, platelet count, albumin, presence or absence of secondary AML, WBC, peripheral blood blast percentage, and creatinine. TRM scores were then calculated as described in J Clin Oncol 2011;29:4417. For a subset of these patients, the following additional variables were collected: duration of prior complete remission, number of prior chemotherapy regimens, number of prior hematopoietic cell transplants, and the number of antibiotics prescribed for treatment of presumed or documented infections at the time of chemotherapy initiation. For this smaller subset, we used a logistic regression model to create a preliminary updated TRM model that included these clinical variables in addition to the variables in the original TRM score. Finally, we used the area under the receiver operator characteristic curve (AUC) to quantify the ability of a model to predict TRM; in this approach, an AUC of 1 indicates perfect prediction of TRM while an AUC of 0.5 indicates no prediction; AUC values of 0.6-0.7, 0.7-0.8, and 0.8-0.9 are commonly considered as poor, fair, and good, respectively. Results A total of 270 patients met our study inclusion criteria. Fifteen (5.6%) died within 28 days of starting chemotherapy, i.e. experienced TRM. The AUC for the previously published TRM score in predicting early death in this population was 0.66. For comparison, in our original study of 2,238 patients with newly-diagnosed AML, we obtained an AUC of 0.82. Expanding the definition of TRM to include those patients who died within 60 (N = 47, 17.4%) or 90 days (N = 75, 27.8%) of starting chemotherapy did not improve the original model’s performance in our cohort (AUCs of 0.62 and 0.59, respectively). The additional variables described above were available for 133 of the 270 patients in our cohort. Within this subset, the AUC for the original TRM score was 0.65 in predicting death within 28 days. Incorporation of these new covariates in a preliminary TRM model yielded an improved AUC of 0.81 for this smaller subset. Conclusions Our data indicate that the TRM score, originally developed for patients with newly-diagnosed AML, only has a fair ability to predict TRM in patients with relapsed and refractory AML. However, with inclusion of additional covariates, such as prior CR duration and number of prior chemotherapies, TRM can be predicted quite well, to a degree similar to the accuracy demonstrated by the original model in newly-diagnosed patients. While our findings need to be confirmed in larger, independent cohorts of patients, they suggest the possibility of developing an objective measure to determine fitness for intensive salvage chemotherapy in AML. Disclosures No relevant conflicts of interest to declare.

Daunorubicine, Cytarabine and Cladribine (DAC) Vs Daunorubicine and Cytarabine (DA) Induction Treatment in Elderly Acute Myeloid Leukemia (AML) Patients – Results of the Prospective, Multicenter, Randomized Trial of the Polish Adult Leukemia Group (PALG)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3602-3602
Author(s):  
Agnieszka Pluta ◽  
Tadeusz Robak ◽  
Agata Wrzesien-Kus ◽  
Bozena Katarzyna Budziszewska ◽  
Kazimierz Sulek ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Treatment Option ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Hematological Toxicity ◽  
Proportional Hazard ◽  
Newly Diagnosed ◽  
Acute Myeloid

Abstract Abstract 3602 Background: AML in elderly patients is associated with very poor prognosis. The best treatment option for this group of patients is not established, yet. The intensity of treatment depends on performance status and comorbidities. The previous PALG AML study showed that addition of cladribine (2CdA) to conventional induction therapy; especially in patients above 40 yrs, is associated with better outcome (Ho3owiecki 2004). Based on this observation we designed a study addressed to newly diagnosed AML patients above 60 yrs old, who were fit enough to intensive treatment. Aim: To verify whether addition of 2CdA has an impact to clinical outcome in newly diagnosed AML patients older than 60 years old. Methods: From October 2004 to November 2011, 178 patients from 16 hematological PALG centers were randomly assigned to DA induction therapy consisting of daunorubicine (DNR) 45mg/m2, intravenously (iv), day 1–3 and cytarabine (AraC) 100 mg/m2, iv, day 1–7 (DA) or DA with addition of 2CdA 5mg/m2, iv, day 1–5 (DAC). Patients, who achieved complete remission (CR), received one course of consolidation with mitoxantron 6mg/m2 iv day1–2 and AraC 100mg/m2 iv day 1–5, followed by six cycles of maintenance consisting of (DNR 30mg/m2 iv day 1–2 with AraC 100mg/m2 sc day 1–5 and tioguanine 100mg/m2, p.o., twice day, day 1–5 with AraC 100mg/m2 s.c. day 1–5, alternately). Response criteria were determined according to revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia (Chesson 2003). Statistical analysis: Pairwise comparisons between patient characteristics were performed by the Mann-Whitney U-test for continuous variables and by χ2-statistics or Fisher's exact test for categorical variable. The Kaplan-Meier estimates of survival were calculated and compared using the log-rank test. For multivariate analysis, the Cox proportional hazard regression model was applied. P values < 0.05 were considered significant. Results: 88 pts with median age 66 yrs (range 60–79 yrs) were randomized to DA and 90 pts with median age 64 yrs (range 60–79 yrs) was enrolled to DAC schema. The both groups were comparable in terms of age, sex, performance status, white blood cell count, hemoglobin level, platelets count, tumor burden parameters, cytogenetic, between the both groups. The overall CR rate was 38%. In DA and DAC groups CR was achieved in 33% and 43% pts, respectively (p=0.12). However, in patients under 65 yrs the trend towards higher CR rate in DAC arm than DA group was observed (47% vs. 29%, p=0.09). In pts above 65 yrs the CR rate was comparable (39% vs. 38%, p=0.8). The efficacy and hematological toxicity in DA and DAC groups was similar (Table 1). Also no statistical significant differences in non-hematological toxicity were observed (data not shown). Early deaths in DA and DAC did not differ significantly. Median overall survival (OS) in DA and DAC arm was also similar in both groups (Table 1). In proportional hazard Cox analysis only age under 65yo, CR achievement and WBC above 100G/L were important for better OS (p=0.02, p<0.001 and p=0.09). The presence of dysplastic changes, karyotype, LDH, number of bone marrow blasts did not influenced OS. Conclusions: Our data suggest that prolonged overall survival can be achieved in elderly AML patients mainly till 65yrs. Intensive therapy, especially in patients older than 65yrs, may be associated with high number of complications what results withdrawing from intensive treatment protocol. Hematological and non-hematological toxicity of DA and DAC schema is comparable, however higher CR rate in DAC group in patient till 65yrs may suggest, that addition of 2CdA to DA does not increase toxicity and may be a treatment option in this patient population. Disclosures: Wiktor-Jedrzejczak: Janssen-Cilag: Consultancy; Amgen: Consultancy; Novartis: Consultancy, Speakers Bureau; Pfizer: Consultancy; Bayer: Consultancy; Genopharm: Speakers Bureau; Celgene: Speakers Bureau; Genzyme: Speakers Bureau; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

scholarly journals An External Validation Study for Current Risk Scoring Models in Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3861-3861
Author(s):  
Chia-Jen Liu ◽  
Hong Ying-Chung ◽  
Chiu-Mei Yeh ◽  
Chun-Kuang Tsai ◽  
Liang-Tsai Hsiao ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Group Performance ◽  
Early Mortality ◽  
Prognostic Models ◽  
Newly Diagnosed ◽  
Discrimination Ability ◽  
Elderly Aml ◽  
Acute Myeloid

Background Acute myeloid leukemia (AML) is a common hematologic neoplasm in the elderly. The high mortality in elderly AML patients is reported to be associated with old age, poor performance status, and several disease characteristics. Several risk stratification models have been reported. Our aims were to explore risk factors for early mortality in older AML patients and compare the discrimination ability of existing prognostic models. Methods We enrolled newly diagnosed AML patients age 60 and above at Taipei Veterans General Hospital, a national medical center in Taiwan, between July 1, 2008 and May 31, 2017. Our primary endpoint was early mortality, defined as death within two months after initial AML diagnosis. Performance of several existing scoring systems were compared by using the Akaike information criteria (AIC) and Bayesian information criterion (BIC) calculations. Model discrimination ability was also estimated by Harrell's C statistics. Results A total of 478 AML patients were diagnosed during the eight-year follow-up period. After excluding young patients (age < 60) and those without a histopathologic diagnosis, the final cohort included 277 patients. The median age was 74 (range 60-96), and 171 (61.7%) of them were male. One hundred sixteen patients (41.9%) had Eastern Cooperative Oncology Group performance (ECOG) ≥ 2 and 33.9% patients had poor/adverse cytogenetics or molecular abnormalities. The two-month mortality rate was 29.9% (95% confidence interval [CI] 24.8%-35.9%). Age ≥ 80 (adjusted HR 1.95, 95% CI 1.12-3.42), having an antecedent hematologic disorder (adjusted HR 1.86, 95% CI 1.01-3.43), ECOG ≥ 2 (adjusted HR 2.06, 95% CI 1.20-3.54), complex karyotype (adjusted HR 3.13, 95% CI 1.76-5.55), BM blasts ≥ 70% (adjusted HR 1.79, 95% CI 1.02-3.13), WBC ≥ 100 ×109/L (adjusted HR 3.27, 95% CI 1.58-6.75), and creatinine > 1.3 mg/dL (adjusted HR 2.04, 95% CI 1.23-3.39) were identified as independent predictors for early mortality in the multivariate analysis. Furthermore, we systematically reviewed existing prognostic models for elderly AML. We found five scoring models that don't require additional specific examinations beyond clinical practice and later applied them to our elderly AML cohort. The performance of the five models is shown in Table. Kantarjian's prognostic model (Kantarjian H, et. al. Blood 2010) had the highest Harrell's C statistic and the ALMA score (Ramos F, et. al.Leukemia Research 2015) had the lowest AIC and BIC compared with the other prognostic models. Conclusion We identified seven risk factors for early mortality and compared the performance of five prognostic models for elderly AML patients. The finding may help clinicians to stratify patients and initiate appropriate management. Table Disclosures No relevant conflicts of interest to declare.

A Scoring System for Prediction of FLT3-ITD Positivity in Patients with Newly Diagnosed Acute Myeloid Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2590-2590
Author(s):  
Fabiana Ostronoff ◽  
Megan Othus ◽  
Hagop M. Kantarjian ◽  
Soheil Meshinchi ◽  
Farhad Ravandi ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Scoring System ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Cancer Center ◽  
Newly Diagnosed ◽  
Wbc Count ◽  
Acute Myeloid

Abstract Abstract 2590 Background FLT3-internal tandem duplication (ITD) is found in about 30% of patients with acute myeloid leukemia (AML) at diagnosis and confers a high risk of relapse. Thus allogeneic hematopoietic transplant (HCT) is recommended for these patients in first complete remission (CR) and after HCT they become candidates for trials of FLT3-ITD inhibitors (such as quizartinib) to prevent relapse. However at referral to tertiary centers after reaching CR, FLT3-ITD status at diagnosis is often unknown, complicating decisions about HCT. FLT3-ITDs are known to be associated with a normal karyotype (NK), translocation 6;9 and a high white blood cell (WBC) count, and we hypothesized that assessment of likely FLT3-ITD status at diagnosis in patients presenting in CR not tested at diagnosis would be improved by examining these covariates simultaneously. Methods Our initial analysis included 434 adult patients with newly diagnosed AML (excluding APL) treated on three SWOG trials (S9031, S9333, and S0106) in whom FLT3-ITD status (positive/negative) was established at diagnosis. Univariate and then multivariate analyses were used to identify covariates independently associated with FLT3-ITD positivity. The relative abilities of these to predict FLT3-ITD positivity were quantified using the area under the receiver operator characteristic curve (AUC); an AUC of 1.0 denotes perfect prediction, whereas an AUC of 0.5 is analogous to a coin flip. The log odds ratios (ORs) from the multivariate models were used to assign a score to each covariate and scores were summed; such that the higher the score, the greater is the likelihood of the FLT3-ITD positivity at diagnosis. We tested the performance of the scoring system in 2 newly-diagnosed populations that had not contributed to the system's development and in whom FLT3-ITD status at diagnosis was known: (a) 210 patients treated at FHCRC (Fred Hutchinson Cancer Research Center) and (b) 1,401 patients treated at MDACC (M.D. Anderson Cancer Center). Covariates examined were: age, sex, performance status (PS), WBC count, platelet count, bone marrow blast percentage, secondary AML, and cytogenetic risk (using SWOG/Eastern Cooperative Oncology Group criteria). Results FLT3- ITD was present in 101 of the 434 SWOG patients (23%) in the scoring system development population. The log OR were rounded to the nearest half point to create the scoring system. Only WBC > 20,000 (reference, WBC < 20,000) and cytogenetics (reference, normal) had non-zero scores, which are summarized below: Scores less than −0.5 were called low, ≥−0.5 and <0.5 intermediate, ≥ 0.5 high. The AUC was 0.75 and contrasted with 0.66 and 0.69 when only WBC or cytogenetics were considered. However when this system was tested in the FHCRC population (16% FLT3-ITD positive) its AUC was only 0.58, not better than when each covariate was examined separately (AUC 0.54 and 0.6 for WBC and cytogenetics, respectively). Similarly at MDACC (17% FLT3-ITD positive) the system's AUC was 0.68 vs. 0.59 and 0.68 for WBC and cytogenetics, respectively. Conclusion Although this scoring system seemed useful tool within the population it was developed (SWOG), such was not the case in two independent cohorts of AML patients with known FLT3-ITD status (FHCRC and MDACC). This indicates that there is no obvious substitute for actual data on FLT3-ITD status. Disclosures: No relevant conflicts of interest to declare.

Comprehensive Geriatric Assessment Does Not Predict Overall Survival in Older Patients with Acute Myeloid Leukemia (AML)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3689-3689 ◽  
Author(s):  
Ellen K. Ritchie ◽  
Danielle C. Marshall ◽  
Molly D. Greenberg ◽  
Tania J. Curcio ◽  
Ashley E. Giambrone ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Geriatric Assessment ◽  
Comprehensive Geriatric Assessment ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Newly Diagnosed ◽  
Wbc Count ◽  
Acute Myeloid

Abstract Background Age and cytogenetics are the strongest predictors of overall survival (OS) in older patients with acute myeloid leukemia (AML), but practitioners recognize that outcomes are also affected by medical comorbidities, physical function and a variety of psychosocial factors. Recent data suggest that geriatric assessment, including measures of physical, cognitive and psychological function, may be predictive of OS and helpful for risk stratification in AML (Klepin 2013). We evaluated the ability of a comprehensive geriatric assessment (CGA) to predict overall survival in newly diagnosed older patients with AML. Patients and Methods All newly diagnosed AML patients age ≥60 years treated at Weill Cornell Medical Center and The New York Presbyterian Hospital completed a CGA including the OARS Physical Health Section, Mental Health Inventory (MHI-17), MOS Social Activity Survey, Activities of Daily Living (ADL) subscale of the MOS Physical Health, OARS Instrumental ADL subscale, Timed Up & Go, Blessed-Orientation-Memory-Concentration Test, and Karnofsky Performance Status (KPS). Laboratory data, medications, transfusions and days of hospitalization were also collected. Comorbidities were assessed using the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI). OS was estimated by the Kaplan-Meier method and the log-rank test was used to compare survival profiles. The independent effects of the CGA and clinical risk factor variables on OS were estimated using hazard ratios in an adjusted Cox regression model. Results In total, 126 patients were evaluated (median age 74, range 60-90). Fifty-one percent of patients had a HCT-CI score >1, with the most common comorbidities being a history of cancer (28.57%), cardiac disease (20.6%), and psychiatric disturbances (17.5%). Half of the patients had prior hematologic disorders and 29% had poor-risk cytogenetics. Most patients (84.9%) received decitabine-based induction strategies; 44 of these patients (34.9%) subsequently received intensive salvage regimens (median age 69). The other 19 patients (15.1%) were treated with standard induction chemotherapy, and 29 patients (21%) underwent allogeneic stem cell transplantation (median age 68). One hundred twenty-three patients (96.6%) completed the CGA with a mean time to completion of 26 minutes (± 8.9 minutes). Thirty-five percent of patients did not complete the entire assessment and only 61.1% completed the follow up CGA. Median OS was 11.1 months (range 0.36-52.64), with 1-year survival of 47.6%, complete remission (CR) rate of 39.8%, and 30-day mortality of 2.4%. In univariate analysis, age (P=0.0289), physician-assigned KPS (P=0.0031), sex (P=0.0074), ELN cytogenetic risk (P=0.0194), creatinine (P=0.027), albumin (P=0.0052), white blood cell (WBC) count (P=0.0135), LDH (P=0.0004), and treatment response (P=0.0001) were significant clinical predictors of OS. Significant CGA variables included Blessed Orientation-Memory-Concentration score (P=0.0035), Bend-Kneel-Stoop (P=0.0239), “someone to prepare your meals” (P=0.0253) and self-reporting of heart disease (P<0.001). In a multivariate analysis controlling for age and cytogenetic risk, physician-assigned KPS (HR, 1.804; 95% CI 1.175 to 2.768), self-reported cardiac history (HR, 2.290; 95% CI 1.383 to 3.794), and WBC count <11.2/ul (HR, 2.360; 95% CI 1.415 to 3.936) were the only independent prognostic factors for overall survival. Conclusion In this study, age and cytogenetics remain the strongest predictors of OS in older patients with AML. While completion of the CGA was feasible, only performance status (KPS) was predictive of OS. Many measures previously reported as significant predictors of outcome, including impaired physical function (Klepin 2013), medication intake (Hurria 2011), pain (Sherman 2013), and HCT-CI score (Sorror 2005, 2009) were not predictive in our study population. The role of the CGA as a predictor of OS in AML requires further evaluation. The utility of the CGA in predicting functional performance and/or quality of life for older AML patients throughout treatment should also be investigated. Disclosures Ritchie: Celgene, Incyte: Speakers Bureau. Feldman:Ariad: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau.

Low Expression of FUS1 Is Negatively Correlated with miR-378 and May Predict Adverse Prognoses in Acute Myeloid Leukemia

2018 ◽  
Vol 139 (2) ◽  
pp. 89-95 ◽  
Author(s):  
Xi Tang ◽  
Jiao Zhou ◽  
Jing Zhang ◽  
Ling-Yu Zhou ◽  
Ling-Ling  Zhai ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Mononuclear Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Characteristic Curve ◽  
Transcript Level ◽  
Suppressor Gene ◽  
Newly Diagnosed ◽  
Low Expression ◽  
Acute Myeloid

FUS1 is a tumor suppressor gene that has been found to be frequently lost in a variety of solid tumors. In this study, we aimed to investigate the expression status of the FUS1 gene in acute myeloid leukemia (AML), as well as its clinical significance. We further explored the correlation between the expression of FUS1 and miR-378 in AML. We detected expression of the FUS1 transcript in bone marrow mononuclear cells from 23 controls and 158 newly diagnosed AML patients by real-time quantitative polymerase chain reaction. Downregulated FUS1 expression was found in 139 out of 158 (87.97%) AML cases; this rate was significantly lower than that in all 23 controls (p = 0.012). Receiver operating characteristic curve analysis revealed that the FUS1 transcript level could discriminate AML patients from controls effectively (area under the ROC curve = 0.663). Kaplan-Meier analysis demonstrated that non-M3-AML patients with a low FUS1 expression had a shorter overall survival (p = 0.049) and leukemia-free survival (p = 0.051) than those with a high FUS1 expression. Furthermore, we studied the correlation between the expression of FUS1 and miR-378 in 53 newly diagnosed AML patients. We found that the correlation coefficient was –0.346, which showed that FUS1 and miR-378 were negatively correlated in AML patients (p = 0.011). These results indicate that the low expression of FUS1 is a common molecular event in AML.

scholarly journals Epigenetic therapy is associated with similar survival compared with intensive chemotherapy in older patients with newly diagnosed acute myeloid leukemia

Blood ◽  
2012 ◽  
Vol 120 (24) ◽  
pp. 4840-4845 ◽  
Author(s):  
Alfonso Quintás-Cardama ◽  
Farhad Ravandi ◽  
Theresa Liu-Dumlao ◽  
Mark Brandt ◽  
Stefan Faderl ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Survival Rates ◽  
Epigenetic Therapy ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Similar Survival ◽  
Acute Myeloid

Abstract We reviewed the outcome of 671 patients 65 years of age or older with newly diagnosed acute myeloid leukemia (AML) treated at our institution between 2000 and 2010 with intensive chemotherapy (n = 557) or azacitidine- or decitabine-based therapy (n = 114). Both groups were balanced according to cytogenetics and performance status. The complete response rates with chemotherapy and epigenetic therapy were 42% and 28%, respectively (P = .001), and the 8-week mortality 18% and 11%, respectively (P = .075). Two-year relapse-free survival rates (28% vs 39%, P = .843) and median survival (6.7 vs 6.5 months, P = .413) were similar in the 2 groups. Multivariate analysis identified older age, adverse cytogenetics, poor performance status, elevated creatinine, peripheral blood and BM blasts, and hemoglobin, but not type of AML therapy, as independent prognostic factors for survival. No outcome differences were observed according to cytogenetics, FLT3 mutational status, age, or performance status by therapy type. Decitabine was associated with improved median overall survival compared with azacitidine (5.5 vs 8.8 months, respectively, P = .03). Survival after failure of intensive chemotherapy, azacitidine, or decitabine was more favorable in patients who had previously received decitabine (1.1 vs 0.9 vs 3.1 months, respectively, P = .109). The results of the present study show that epigenetic therapy is associated with similar survival rates as intensive chemotherapy in older patients with newly diagnosed AML. The studies reviewed are registered at www.clinicaltrials.gov as 2009-0172 (NCT00926731) and 2009-0217 (NCT00952588).

Untreated Patients with Acute Myeloid Leukemia, Age 50–59 Years and Performance Status 2 Should Be as Eligible for Targeted Therapy as Older Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2864-2864
Author(s):  
Apostolia M. Tsimberidou ◽  
Hagop M. Kantarjian ◽  
Stefan Faderl ◽  
Sherry Pierce ◽  
Emil J. Freireich ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Newly Diagnosed ◽  
Death Rates ◽  
Targeted Treatments ◽  
High Death ◽  
And Performance ◽  
Acute Myeloid

Abstract Background: The early mortality rates in older patients (generally defined as those > 60 years) following standard therapy for acute myeloid leukemia (AML), has spurred numerous trials of “targeted” treatments, typically limited to this age group. Here we examine whether younger patients with Zubrod performance status (PS) 2 might also be candidates for these therapies. Patients and Methods: We reviewed the records of 1841 patients 40 years or older with newly diagnosed AML (no acute promyelocytic leukemia) who received cytarabine-containing therapy at M. D. Anderson from 1980 to 2007. We chose patients with the following pretreatment characteristics because they are conventional criteria for entry onto trials of new therapies: PS 0–2, bilirubin < 2 mg/dL, and creatinine < 2 mg/dL. We calculated death rates by age and PS at 28 and 42 days after initiation of induction therapy. Results: Induction death rates in patients with AML by age and performance status The 28-day death rates in patients age 50–59 years with PS 2 were similar to those in patients ≥ 60 years with PS 0–1, and the 42-day death rates in the patients age 50–59 years with PS 2 were similar to those in patients age 60–79 with PS 0–1. Conclusion: Because of the high death rates following AML therapy in patients age 50–59 with PS 2, these patients should be eligible for targeted treatments now limited to older patients. Age, yrs Performance Status No. of Patients Dead by day 28, % Dead by day 42 % 40–49 0–1 288 7 9 40–49 2 38 5 5 50–59 0–1 405 4 6 50–59 2 85 14 15 60–69 0–1 423 8 11 60–69 2 111 17 17 70–79 0–1 301 12 16 70–79 2 124 23 33 ≥80 0–1 45 13 20 ≥ 80 2 21 38 43

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