Comorbidity Indices Predict Survival Among Elderly Patients with Acute Myelogenous Leukemia but Do Not Aid in Selecting Between Traditional Induction Chemotherapy and 5-Azacytidine Treatment.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1040-1040
Author(s):  
Stuart L. Goldberg ◽  
Aisha Masood ◽  
Jayshree Shah ◽  
Jack W. Hsu ◽  
Neelesh Rastogi ◽  
...  

Abstract Abstract 1040 Poster Board I-62 Treatment of the elderly patient with acute myelogenous leukemia remains problematic as many have poor performance status precluding aggressive therapy and others have high risk features including abnormal cytogenetics. The success of 5-azacitidine among patients with advanced myelodysplastic syndromes in controlling blast cells and prolonging survival has led to its use in AML. However choosing between potentially curative hospital-based induction chemotherapy and palliative outpatient hypomethylating treatments is difficult. The availability of predictive comorbidity scores may aid in guiding patients in this decision. Methods: Patients with a new diagnosis of AML, ages 60 and older, were offered traditional in-patient induction therapy (7 days cytarabine 100 mg/m2 CI with 3 days idarubicin 12mg/m2) or out-patient therapy (5-azacitidine 75 mg/m2 IV 5 days per month). We report a retrospective review of clinical outcomes among patients treated between June 2003 and August 1, 2009. A review of presenting clinical features, placing patients into prognostic groupings by the Charlson Comorbidity Index (J Chronic Dis 1987; 40:373), Hematopoietic Cell Transplantation – Specific Comorbidity Index (Blood 2007; 110:4606), and the Myelodysplastic Syndrome – Specific Comorbidity Index (Blood 2008; 112: abstr 2677) was performed. Points for a diagnosis of leukemia were excluded from the indices. Results: 99 patients with AML were treated at our center, all with leukemic blasts >20% (median 48%). 75 chose traditional 7+3 and 24 chose 5-aza. The median age was younger for those choosing 7+3 (67 vs 77 years, p<0.001). The median survival for all patients was 340 days (95% CI 258, 422). The median survival was longer with 7+3 at 367 days (95% CI 306,428) compared to a median survival with 5-aza of 186 days (95% CI 122, 250) (p=0.07). Only one patient age <65 chose 5-aza. The median survival for pts with 7+3 was similar by age groups: <65 yrs (n=34) 367 days, 65-69 yrs (n=19) 340 days, and ≥70 yrs (n=22) 467 days (log-rank p=0.31). Cytogenetic features (SWOG criteria) at baseline correlated with survival: good risk (n=3) 186 days, intermediate risk (n=54) 604 days, and poor risk (n=28) 241 days. (p=0.03). Similarly, cytogenetic risk continued to remain significant regardless of treatment choice: 7+3: intermediate/poor risk karyotype 664 days vs 340 days, and 5-aza: intermediate/poor risk 604 days vs 67 days (p=0.03). All 3 examined comorbidity indices were able to predict overall survival for the entire cohort (n=99). Using the CCI, better scores led to improved outcome (log-rank p=0.007): Score 0 (n=41): 475 days; score 1 (n=23): 213 days; score 2 (n=25): 196 days; score 3 (n=8): 186 days; score 4 (n=2) 1404 days. Similar results were obtained using the HCTS-CI (log-rank p=0.01): Score 0 (n=33): 475 days; score 1 (n=24): 353 days; score 2 (n=13): 146 days; score 3 (n=17): 196 days; score 4 (n=5) 1113 days; score 5 (n=5) 337 days; score 8 (n=1) 1404 days. And using the MDS-CI (log-rank p=0.02) better scores predicted improved survival: Score 0 (n=64): 375 days; score 1 (n=18): 241 days; score 2 (n=13): 186 days; score 3 (n=3): 69 days; score 4 (n=1) 1404 days. In addition, patients who scored well on the CCI did better (p=0.005) than patients with poor scores by type of treatment (ie, a low score patient treated with 7+3 did better than a high score patient treated with 7+3, and a low score patient treated with 5-aza did better than a high score patient treated with 5-aza). Similar relationships were noted between scores on the HCTS-CI and MDS-CI and treatment choice. However, in all CCI score categories, 7+3 treatment was superior to 5-aza (score 0: 839 vs 298 days; score 1: 276 vs 69 days; score 2: 279 vs 106 days; score 3: 435 vs 90 days) (p=0.08). Similarly 7+3 treatment appeared superior to 5-aza by HCTS-CI score (p=0.02) and MDS-CI (p=0.05). Conclusions: Elderly patients with AML can achieve survivals approaching one year with current treatment options. 5-azacytidine is a reasonable option for patients declining aggressive hospital based treatments especially if cytogenetic features are favorable, however overall survival may be inferior to standard induction chemotherapy. Although comorbidity indices are able to stratify potential outcomes among elderly patients with AML choosing a particular treatment, in our series we could not identify a comorbidity score that would dissuade aggressive treatment in favor of less intensive therapy. Disclosures: Goldberg: Celgene: Speakers Bureau. Off Label Use: 5-azacytidine use in AML. Masood:Celegene: Speakers Bureau.

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 7026-7026 ◽  
Author(s):  
G. J. Schiller ◽  
D. DeAngelo ◽  
N. Vey ◽  
S. Solomon ◽  
R. Stuart ◽  
...  

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2146-2146
Author(s):  
Ellin Berman ◽  
Molly Maloy ◽  
Sean M. Devlin ◽  
Esperanza B Papadopoulos ◽  
Ann A. Jakubowski

Abstract Introduction Optimal therapy for older adults with acute myelogenous leukemia (AML) who achieve remission following induction chemotherapy has not been determined. Options include consolidation chemotherapy (CC) or stem cell transplant (SCT) if an appropriate donor is identified. In order to determine whether SCT improved overall survival (OS) or whether associated toxicity was increased, we performed a retrospective study comparing SCT with CC in this older age group. Methods All adult patients ages 60 to 75 years with AML in 1st remission (CR1) who underwent a SCT at MSKCC between 2001 and 2013 were reviewed and compared to age-matched patients with AML who achieved CR1 and received CC. A landmark analysis at 3 months following CR1 was used to compare OS for the 2 patient groups. Only SCT patients transplanted by landmark time were included in the analysis. Overall survival was compared using Kaplan-Meier methodology. Results Sixty-eight patients were identified for the SCT group. Thirty-two patients were identified for the CC group (Table). Stem cell sources included: peripheral blood (n=63), cord blood (n=4) and bone marrow (n=1). Fifty-six patients received a T cell depleted transplant (32 with ClinMACsTM and 24 with IsolexTM ) and 12 received an unmodified product. Conditioning regimens were busulfan/melphalan/ fludarabine (n=54), melphalan/fludarabine (n=4), cyclophosphamide/fludarabine/thiotepa/ TBI (n=4), fludarabine/busulfan (n=3), busulfan/melphalan (n=2) and thiotepa/fludarabine/TBI (n=1). Donors included matched unrelated (n=28), matched related (n=25), mismatched unrelated (n=11) and mismatched cord blood (n=4). For patients in the CC group, induction chemotherapy included cytarabine in combination with either idarubicin (n=21), daunorubicin (n=10), or mitoxantrone plus etoposide (n=1). Forty-four patients received their transplant by the 3 month landmark and 30 patients in the CC group were alive at the landmark and were included in the OS analysis. Deaths in the SCT group included 4 patients from infection, 1 from treatment-related toxicity, and 1 from relapsed disease. The estimated OS at 2 years in the landmark groups were 64% in the SCT group and 42% in the CC group (p=0.04). Conclusions Recognizing the inherent bias when retrospective studies compare SCT and CC, these data support the use of SCT for older patients with AML in CR1 who have an appropriate donor. Despite the older age, there was a statistically significant better OS with low 100 day mortality for those patients who underwent SCT. Disclosures: No relevant conflicts of interest to declare.


1995 ◽  
Vol 13 (3) ◽  
pp. 560-569 ◽  
Author(s):  
A J Mitus ◽  
K B Miller ◽  
D P Schenkein ◽  
H F Ryan ◽  
S K Parsons ◽  
...  

PURPOSE Despite improvement in chemotherapy and supportive care over the past two decades, overall survival for patients with acute myelogenous leukemia (AML) remains poor; only 25% to 30% of individuals with this disorder will be cured. In 1987, we initiated a prospective multiinstitution study designed to improve long-term survival in adults with AML. METHODS We modified the usual 7-day treatment scheme of daunorubicin and cytarabine with high-dose cytarabine (HiDAC) on days 8 through 10 (3 + 7 + 3). Allogeneic or autologous bone marrow transplantation (BMT) was offered to all patients who entered complete remission (CR) to decrease the rate of leukemic relapse. Data were analyzed by intention to treat. RESULTS CRs were achieved in 84 of 94 patients (89%; 95% confidence interval [CI], 83 to 95). Because of the high remission rate, factors previously thought to predict outcome, such as cytogenetics, WBC count, French-American-British (FAB) classification, sex, and age, were not useful prognostic variables. The overall survival rate for the entire cohort of patients from data of diagnosis is 55% at 5 years. Sixty percent of all patients who achieved a CR underwent marrow grafting. There was no significant difference in event-free survival (EFS) at 5 years comparing patients assigned to receive allogeneic BMT with patients assigned to receive autologous BMT (56% v 45%, P = .54). CONCLUSION The long-term disease-free survival observed in this study is excellent compared with historical data. This improvement in survival is probably due to the high rate of remission induction, as well as to the effective nature of the consolidation therapy.


Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 315-319 ◽  
Author(s):  
HJ Weinstein ◽  
RJ Mayer ◽  
DS Rosenthal ◽  
FS Coral ◽  
BM Camitta ◽  
...  

Abstract We designed a protocol (VAPA) that featured 14 mo of intensive postremission induction chemotherapy in an effort to improve remission durations for patients with acute myelogenous leukemia (AML). One hundred and seven patients under 50 yr of age were entered into this study. The rate of complete remission is 70%. A Kaplan-Meier analysis of patients entering remission predicts that 56% +/- 7% (+/-SE) of patients less than 18 yr and 45% +/- 9% of patients aged 18–50 yr will remain in remission at 3 yr (median follow-up is 43 mo). Patients with the monocytic subtype had a statistically significant shorter duration of remission (2-sided p less than 0.05). There was a high incidence of primary CNS relapse in children. Thirty-one of 41 patients who completed the regimen remain in remission without maintenance therapy. We conclude that the VAPA protocol continues to offer a promising approach to treatment of AML.


2020 ◽  
Vol 10 ◽  
Author(s):  
Jiafeng Zheng ◽  
Tongqiang Zhang ◽  
Wei Guo ◽  
Caili Zhou ◽  
Xiaojian Cui ◽  
...  

BackgroundAcute myelogenous leukemia (AML) is a common pediatric malignancy in children younger than 15 years old. Although the overall survival (OS) has been improved in recent years, the mechanisms of AML remain largely unknown. Hence, the purpose of this study is to explore the differentially methylated genes and to investigate the underlying mechanism in AML initiation and progression based on the bioinformatic analysis.MethodsMethylation array data and gene expression data were obtained from TARGET Data Matrix. The consensus clustering analysis was performed using ConsensusClusterPlus R package. The global DNA methylation was analyzed using methylationArrayAnalysis R package and differentially methylated genes (DMGs), and differentially expressed genes (DEGs) were identified using Limma R package. Besides, the biological function was analyzed using clusterProfiler R package. The correlation between DMGs and DEGs was determined using psych R package. Moreover, the correlation between DMGs and AML was assessed using varElect online tool. And the overall survival and progression-free survival were analyzed using survival R package.ResultsAll AML samples in this study were divided into three clusters at k = 3. Based on consensus clustering, we identified 1,146 CpGs, including 40 hypermethylated and 1,106 hypomethylated CpGs in AML. Besides, a total 529 DEGs were identified, including 270 upregulated and 259 downregulated DEGs in AML. The function analysis showed that DEGs significantly enriched in AML related biological process. Moreover, the correlation between DMGs and DEGs indicated that seven DMGs directly interacted with AML. CD34, HOXA7, and CD96 showed the strongest correlation with AML. Further, we explored three CpG sites cg03583857, cg26511321, cg04039397 of CD34, HOXA7, and CD96 which acted as the clinical prognostic biomarkers.ConclusionOur study identified three novel methylated genes in AML and also explored the mechanism of methylated genes in AML. Our finding may provide novel potential prognostic markers for AML.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S387-S388
Author(s):  
Risa Fuller ◽  
Erin Moshier ◽  
Samantha E Jacobs ◽  
Douglas Tremblay ◽  
Guido Lancman ◽  
...  

Abstract Background In the era of increased antibiotic resistance, minimizing the use of broad-spectrum antibiotics is essential. We sought to determine whether there was a difference in risk of recurrent fever in patients with acute myelogenous leukemia (AML) and neutropenic fever without an identifiable source in which antibacterials were de-escalated prior to neutrophil recovery compared with those that continued until recovery. Methods We performed a retrospective chart review of adult patients with AML undergoing induction chemotherapy at Mount Sinai Hospital in New York, NY from 2009–2017. Neutropenic fever was defined as a temperature of 100.4°F for 1 hour or single temperature of 101°F in a patient with an absolute neutrophil count (ANC) of less than 500 cells/μL. Febrile patients were treated with cefepime, piperacillin–tazobactam, or a carbapenem. De-escalation was defined as changing from one of these antibiotics to antibacterial prophylaxis such as levofloxacin, or discontinuing antibiotics. The primary outcome was recurrent neutropenic fever. Secondary outcomes were adverse events related to antibiotics, intensive care unit (ICU) transfer, and all-cause mortality. Results Of 390 AML patients undergoing induction chemotherapy, 135 had a neutropenic fever; of whom, 77 had no identifiable infectious source. Of those 77, 38 had antibiotics de-escalated prior to ANC recovery (“short”) and 39 had antibiotics continued until ANC recovery or discharge (“long”). Demographics were similar (Table 1). The median number of antibiotic days for the first fever was 9 in the short group and 15 in the long group (P = 0.0008) (Table 2). Risk of recurrent fever was 46% lower in the short group compared with the long group (hazard ratio 0.54, 95% CI: 0.34–0.88; P = 0.01). There was no significant difference in ICU transfer (P = 0.11) and in-hospital mortality (P = 0.36) between the short and long groups (Table 2). There were 7 adverse drug outcomes, 2 in the short group and 5 in the long group (Table 3). Conclusion Antibiotic de-escalation in AML patients with neutropenic fever with no identifiable infectious source was associated with a lower rate of recurrent fever without affecting ICU transfer, adverse drug events, and death. Physicians should consider de-escalation prior to ANC recovery in the appropriate setting. Disclosures All authors: No reported disclosures.


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