Long-term outcome of NPM1 mutated acute myeloid leukemia: A single-institution experience

2016 ◽  
Vol 92 (2) ◽  
pp. E17-E18 ◽  
Author(s):  
Hamid Sayar ◽  
Parvaneh Bashardoust ◽  
Larry Cripe ◽  
Sujata Chakraborty ◽  
Shaochun Bai
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Single Institution ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Acute Myeloid

Superior Long-Term Outcome With Idarubicin Compared With High-Dose Daunorubicin in Patients With Acute Myeloid Leukemia Age 50 Years and Older

2013 ◽  
Vol 31 (3) ◽  
pp. 321-327 ◽  
Author(s):  
Claude Gardin ◽  
Sylvie Chevret ◽  
Cécile Pautas ◽  
Pascal Turlure ◽  
Emmanuel Raffoux ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Random Assignment ◽  
Cure Rate ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Younger Age ◽  
Acute Myeloid

Purpose Although standard chemotherapy remains associated with a poor outcome in older patients with acute myeloid leukemia (AML), it is unclear which patients can survive long enough to be considered as cured. This study aimed to identify factors influencing the long-term outcome in these patients. Patients and Methods The study included 727 older patients with AML (median age, 67 years) treated in two idarubicin (IDA) versus daunorubicin (DNR) Acute Leukemia French Association trials. Prognostic analysis was based on standard univariate and multivariate models and also included a cure fraction model to focus on long-term outcome. Results Age, WBC count, secondary AML, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and adverse-risk and favorable-risk AML subsets (European LeukemiaNet classification) all influenced complete remission (CR) rate and overall survival (OS). IDA random assignment was associated with higher CR rate, but not with longer OS (P = .13). The overall cure rate was 13.3%. Older age and ECOG-PS more than 1 negatively influenced cure rate, which was higher in patients with favorable-risk AML (39.1% v 8.0% in adverse-risk AML; P < .001) and those treated with IDA (16.6% v 9.8% with DNR; P = .018). The long-term impact of IDA was still observed in patients younger than age 65 years, although all of the younger patients in the DNR control arm received high DNR doses (cure rate, 27.4% for IDA v 15.9% for DNR; P = .049). In multivariate analysis, IDA random assignment remained associated with a higher cure rate (P = .04), together with younger age and favorable-risk AML, despite not influencing OS (P = .11). Conclusion In older patients with AML, younger age, favorable-risk AML, and IDA treatment predict a better long-term outcome.

Addition of Cladribine to the Standard AML Treatment Improves Long-Term Outcome in High Tumor Burden and Older Than 40 Years Acute Myeloid Leukemia Patients. Five-Year Follow-Up of the Polish Adult Leukemia Group (PALG 1999 DAC vs. DA Study).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1795-1795
Author(s):  
Jerzy Holowiecki ◽  
Sebastian Grosicki ◽  
Tadeusz Robak ◽  
Slawomira Krzemien ◽  
Sebastian Giebel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Tumor Burden ◽  
Consolidation Therapy ◽  
Term Outcome ◽  
Long Term Outcome ◽  
High Tumor Burden ◽  
Acute Myeloid

Abstract The goal of the study was to evaluate long-term outcome of acute myeloid leukemia (AML) patients treated within the PALG 1999 DAC vs, DA Study. Between 1999–2002, 445 patients, aged 18–60 years, were randomized to the induction DAC-7: daunorubicin 60 mg/m2/d iv 1–3; cytarabine 200 mg/m2/d ci 1–7; cladribine 5 mg/m2 2h inf. iv d 1–5 or standard DA-7 regimen (the same regimen without cladribine). Patients achieving CR received two courses of subsequent intensive consolidation: 1) HAM (HD AraC, mitoxantrone) 2) HD AraC with or without cladribine in the DAC-7 or DA-7 arm, respectively. In case of PR after the first induction course the same regimen was repeated, NR patients received CLAG (2-CDA, HD-AraC, G-CSF), regardless the randomization arm. Post-consolidation therapy was in both arms comparable. As previously reported, a single course of DAC-7 induction resulted in 17% higher CR rate compared to the DA-7 treatment. The difference was particularly pronounced in a population of patients >40 years and for those with initial WBC >100x109/L. In the latter subgroup also the overall CR rate (achieved after >=1 induction course) was higher in the DAC-7 arm (71% vs. 43%). [Leukemia. 2004 May;18(5):989–97] In the present report we analyzed long-term outcome (median follow-up 3.2 years) in the whole study group and in pre-defined subgroups taking into account initial tumor burden, age, cytogenetics, FAB subtype, and preceding myelodysplasia. At five years the overall survival (OS) rate equaled 31% for DAC-7 and 25% for DA-7 arm (p=0.42) and leukemia free survivall (LFS) 32% vs. 29% (p=0.38), respectively. The subgroup analysis revealed higher probability of the OS in patients with initial WBC ≥100 G/l assigned to DAC-7 compared to DA-7 arm (39% vs. 11%, p=0.02). The LFS rate and the probability of relapse equaled 50% and 32% (p=NS) and 36% and 68% (p=0.0497), respectively. In patients aged >40 years, the therapy containing cladribine was associated with improved LFS (30% for DAC-7 vs. 20% for DA-7, p=0.01), and a tendency to improved OS (28% vs. 18%, p=0.09). In this subgroup DAC-7 therapy resulted in reduced relapse incidence (60% vs. 69%, p=0.04).We conclude that addition of cladribine to induction/consolidation therapy of AML may improve long-term outcome in higher age ranges patients and in those with high tumor burden. The improvement results mainly from reduced risk of relapse, and, in patients with high initial WBC, from higher CR rate.

FLAG-IDA Regimen (Fludarabine, Cytarabine, Idarubicin and G-CSF) in the Treatment of Patients with High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndromes.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2866-2866
Author(s):  
Pau Montesinos ◽  
Javier de la Rubia ◽  
Guillermo Orti ◽  
Jaime Sanz ◽  
David Martinez ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Term Outcome ◽  
Long Term Outcome ◽  
First Relapse ◽  
Subsequent Relapse ◽  
Acute Myeloid ◽  
Refractory Aml

Abstract Background: Preliminary results with the combination of fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor (G-CSF) (FLAG-IDA), reported complete response (CR) rates of 47–95% in patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), with acceptable toxicity. These results lead to a generalized use of FLAG-IDA regimen in this set of patients. However, these studies have been made in small series and the long-term outcome of patients have not been described. Objectives: Analyze the results of FLAG-IDA regimen, in terms of CR rate and long-term outcome, in a large series of patients with high-risk AML and MDS treated in a single institution. Methods: From 1997 to 2007, 158 adult patients (median age 60 years, range 16–79) received FLAG-IDA regimen (Fludarabine, 30 mg/m2 intravenous (iv) for 4 days, cytarabine 2 g/m2 iv for 4 days, idarubicin 10 mg/m2 iv for 3 days and glycosylated G-CSF at a daily dose of 300 mcg/m2, from day -1 until day 5). Post-remission therapy consisted of allogeneic transplantation (Allo-HSCT) in eligible patients, or consolidation (idarubicin, 10 mg/m2 iv for 3 days and cytarabine, 200 mg/m2 iv for 5 days), followed by intensification with Auto-HSCT or one cycle of carboplatin (300 mg/m2 for 4 days, as a 24 h continuous infusion). Patients were diagnosed with high-risk MDS (11%), treatment related AML (10%), AML secondary to MDS (29%), primary refractory AML (17%), AML in first relapse (27%), and AML in second or subsequent relapse (6%). Median follow-up of the cohort was 40 months (range 2–104). We calculated the Kaplan-Meier estimates curves for overall survival (OS), disease-free (DFS) and relapse-free survival (RFS). Results: CR and partial remission (PR) was achieved in 84 patients (53%) and in 19 patients (12%), respectively. Twenty-three patients (15%) died during induction, mostly due to infection (19 patients). The CR rates according to the disease status were the following: high-risk MDS 61%, treatment related AML 73%, AML secondary to MDS 52%, primary refractory AML 54%, AML in first relapse 49%, and AML in second or subsequent relapse 30%. Post-remission therapy consisted of Allo-HSCT in 16 patients (8 related and 8 unrelated), Auto-HSCT in 15 patients, and chemotherapy alone in 53 patients. The 1 and 5 year OS, DFS and RFS of the entire cohort were 36% and 11%, 40% and 11%, and 51% and 23%, respectively. The 1 and 5 year OS in patients achieving CR, PR and resistance were 64% and 22%, 26% and 7%, and 4% and 0%, respectively (p<0.0001). The 5 year RFS of patients treated with chemotherapy alone, Auto-HSCT and Allo-HSCT were 13%, 16% and 64%, respectively (p=0.09). The 5 year RFS of patients aged >55 years and ≤55 years were 4% and 53%, respectively (p=0.0005). The 5 year DFS of patients treated with chemotherapy alone, Auto-HSCT and Allo-HSCT were 7%, 13% and 35%, respectively (p=0.22). Conclusion: Our results confirm the acceptable toxicity and high response rate observed with FLAG-IDA regimen in this very high-risk subgroup of patients. This regimen can be a bridge towards Allo-HSCT, that appear to be the most curative therapy in this setting.

scholarly journals How I treat acute myeloid leukemia presenting with preexisting comorbidities

Blood ◽  
2016 ◽  
Vol 128 (4) ◽  
pp. 488-496 ◽  
Author(s):  
Yishai Ofran ◽  
Martin S. Tallman ◽  
Jacob M. Rowe
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Pulmonary Insufficiency ◽  
Curative Intent ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Clinical Scenarios ◽  
Definitive Therapy ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a devastating disease with an incidence that progressively increases with advancing age. Currently, only ∼40% of younger and 10% of older adults are long-term survivors. If untreated, the overall prognosis of AML remains dismal. Initiation of therapy at diagnosis is usually urgent. Barriers to successful therapy for AML are the attendant toxicities directly related to chemotherapy or those associated with inevitable aplasia. Organ dysfunction often further complicates such toxicities and may even be prohibitive. There are few guidelines to manage such patients and the fear of crossing the medico-legal abyss may dominate. Such clinical scenarios provide particular challenges and require experience for optimal management. Herein, we discuss select examples of common pretreatment comorbidities, including cardiomyopathy, ischemic heart disease; chronic renal failure, with and without dialysis; hepatitis and cirrhosis; chronic pulmonary insufficiency; and cerebral vascular disease. These comorbidities usually render patients ineligible for clinical trials and enormous uncertainty regarding management reigns, often to the point of withholding definitive therapy. The scenarios described herein emphasize that with appropriate subspecialty support, many AML patients with comorbidities can undergo therapy with curative intent and achieve successful long-term outcome.

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