scholarly journals Pretreatment prognostic factors and treatment outcome in elderly patients with de novo acute myeloid leukemia

2005 ◽  
Vol 16 (8) ◽  
pp. 1366-1373 ◽  
Author(s):  
C.-C. Chen ◽  
C.-F. Yang ◽  
M.-H. Yang ◽  
K.-D. Lee ◽  
W.-K. Kwang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Treatment Outcome ◽  
Prognostic Factors ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Acute Myeloid

Priming with Granulocyte Colony-Stimulating Factor (G-CSF) Has No Impact on Treatment Outcome but Impairs Mobilization of Peripheral Blood Stem Cells (PBSC) in Elderly Patients with Acute Myeloid Leukemia: Results of a Randomized Oligocenter Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 867-867
Author(s):  
Gesine Bug ◽  
Steffen Koschmieder ◽  
S. Wiebe ◽  
Gerd Heil ◽  
Carla Delfs ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Treatment Outcome ◽  
Elderly Patients ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Secondary Aml ◽  
Remission Duration ◽  
Cd34 Cells ◽  
Acute Myeloid

Abstract Treatment of elderly patients with acute myeloid leukemia (AML) is characterized by a low complete remission (CR) rate of less than 50% and short remission duration with a median disease-free survival (DFS) of less than one year (Rowe et al., Blood 2004). Sensitization of leukemic cells with growth factors may enhance the efficacy of chemotherapy in AML patients. Aims of this randomized prospective, oligocenter study were 1) to assess whether induction chemotherapy given simultaneously with and followed by G-CSF (G-CSFpriming) was superior to G-CSF following induction (G-CSFpost) with regard to CR rate and DFS in pts aged older than 60 yrs with previously untreated de novo and secondary AML and 2) to examine the feasibility of an early consolidation therapy followed by autologous stem cell transplantation (ASCT) as late consolidation. Between 01/00 and 04/04, a total of 116 eligible patients (median age 67 yrs) were randomly assigned to receive G-CSFpriming (n=57) or G-CSFpost (n=59) during two remission-induction cycles consisting of idarubicin, cytarabine and etoposide (IdAV) with daily application of 5μg/kg G-CSF (Neupogen®, Amgen). Pts achieving a CR received early consolidation using fludarabine, cytarabine, idarubicin, G-CSF (mini-FlagIda) and PBSC harvest, followed by ASCT. Pts lacking PBSC due to mobilization failure were optionally treated with a second cycle of mini-FlagIda. After induction chemotherapy, 74 out of 116 pts (63.8%) achieved CR. Response was not significantly different in the G-CSFpost vs. G-CSFpriming group (67.8 vs. 59.6%), nor was recovery of neutrophils. Of 74 complete responders, 44 have relapsed and 3 died in CR. Median remission duration was 15.2 and 14.7 months in the G-CSFpost and G-CSFpriming group, resp. Median DFS was 16.5 months and the probability of DFS at 4 yrs 21.2%, with no significant difference between the treatment groups and a median follow-up of 22 months at the time of this interim analysis. Mini-FlagIda consolidation was administered to 51 out of 74 CR patients (68.9%). The number of circulating CD34+ cells was monitored in 43 patients. The probability of mobilizing at least 1x106/kg CD34+ cells was significantly lower in the G-CSFpriming compared to the G-CSFpost group with 29.4% (5/17 pts) and 59.2% (16/26 pts), resp (p<0.05). ASCT was performed in 10 pts resulting in a significantly better 4-yr DFS (55%) compared to 10 pts treated with a second course of mini-FlagIda (22%, p<0.05). The major reason for not being autografted in spite of efficient collecting of CD34+ cells was early relapse. Conclusion: In elderly pts with de novo or secondary AML, G-CSF priming did not enhance the antileukemic efficacy of induction chemotherapy and had no significant impact on overall treatment outcome compared with G-CSF administered after induction. As ASCT proved to be an effective consolidation modality for CR patients mobilizing sufficient amounts of CD34+ cells, the detrimental effect of G-CSF priming on the collection of PBSC is clinically relevant.>

Addition of Lomustine to Idarubicin and Cytarabine Improves the Outcome of Elderly Patients With De Novo Acute Myeloid Leukemia: A Report From the GOELAMS

2010 ◽  
Vol 28 (18) ◽  
pp. 3028-3034 ◽  
Author(s):  
Arnaud Pigneux ◽  
Jean-Luc Harousseau ◽  
Francis Witz ◽  
Mathieu Sauvezie ◽  
Marie-Christine Bene ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Elderly Patients ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Group I ◽  
Acute Myeloid

Purpose No significant improvement in treatment outcome has been seen in elderly patients with acute myeloid leukemia (AML) over the past 20 years. This retrospective analysis investigated the prognostic factors for complete remission (CR) and survival in older patients with AML. Patients and Methods The study involved 847 patients older than 60 years enrolled onto three trials carried out in France between 1995 and 2005. Induction therapy consisted of idarubicin (8 mg/m2, days 1 through 5) and cytarabine (100 mg/m2, days 1 through 7; group I, 339 patients) or the same drugs plus lomustine (200 mg/m2 orally on day 1; group II, 508 patients). Consolidation therapy consisted of anthracycline and cytarabine courses at lower doses, preceded or not by a first course of intermediate-dose cytarabine. Results The rate of CR was significantly higher in patients in group II compared with group I (68% v 58%; P = .002). The rate of toxic death was similar in the two groups. In multivariate analysis, two prognostic factors were linked to CR: nonadverse cytogenetic (P < .003) and addition of lomustine to induction chemotherapy (P = .002). Median overall survival was significantly improved in patients treated with lomustine (median and SE, 12.7 ± 2.2 months v 8.7 ± 2.7 months; P = .004). In multivariate analysis, five prognostic factors positively affected overall survival: addition of lomustine (P = .002), age ≤ 69 years (P < .001), Eastern Cooperative Oncology Group performance status lower than 2 (P = .002), French-American-British subgroup 1/2 (P = .02), and nonadverse cytogenetic (P < .001). Conclusion Lomustine improves the rate of CR and survival in elderly patients with de novo AML when added to standard induction therapy.

scholarly journals Survival and Prognostic Factors in Adults Acute Myeloid Leukemia: A Retrospective Analysis of 119 Cases

2013 ◽  
Vol 1 (2) ◽  
pp. 70-73
Author(s):  
Alina M Gridjac ◽  
Cristian Daniel Pirlog ◽  
Anca Simona Bojan
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Risk Groups ◽  
Developed Countries ◽  
Risk Level ◽  
Secondary Aml ◽  
Cytogenetic Testing ◽  
Acute Myeloid

Background: Acute myeloid leukemia (AML) is a malignant disease with significant identified prognostic factors. Therefore our aim was to develop an Assessment Scheme of Prognosis in AML based on prognostic factors. In some counties, such as Romania or other less-highly developed countries, this scheme would be beneficial particularly when cytogenetic testing is unavailable or time-intensive. Methods: We analyzed 119 adult patients with AML during a five year-period from a single-center in Romania. We retrospectively collected and analyzed data with Epi Info and Excel using patient medical records. Results: According to age, the group A1 (<60 years) had a 40 months survival, in contrast with the group B1 (≥60 years) with a survival of 19 months (p=0,0063). The group A2 (secondary AML) survived 15 months, whereas the group B2 (AML de novo) survived 40 months (p=0.0021). Additionally, the group A3 (mild comorbidities) achieved a 40 months survival, the group B3 (moderate comorbidities) survived 19 months, whereas the group C3 (severe comorbidities) survived 7 months (p=0,0059). According to WBC and blast number, the group A4 (high levels) had a 25 months survival, whereas the group B4 (low levels) survived 40 months (p=0,0057). Conclusion: The prognostic factors studied are useful to identify the risk level of AML disease for each patient at diagnosis. We developed an assessment scheme of prognosis with three risk groups according to age, secondary AML, comorbidity, WBC and blasts and cytogenetic examination.

Elderly Patients with Acute Myeloid Leukemia Are Not All the Same: Results of the Prospective DSIL AML96 Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1840-1840
Author(s):  
Markus Andreas Schaich ◽  
Walter E. Aulitzky ◽  
Heinrich Bodenstein ◽  
Martin Bornhaeuser ◽  
Thomas Illmer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
High Risk ◽  
Elderly Patients ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Low Risk ◽  
Severe Toxicity ◽  
Elderly Aml ◽  
Acute Myeloid

Abstract The majority of patients with acute myeloid leukemia (AML) are older than 60 years at diagnosis. However, treatment results for these elderly patients are still unsatisfactory. This is thought to be due to a more aggressive disease, preexisting co-morbidities or a decreased tolerance for intensive treatment approaches. As for younger patients there is growing evidence that elderly AML patients may be divided into prognostic subgroups. So far data on prognostic factors in this group of patients are still sketchy. Between February 1996 and March 2005 a total of 827 elderly AML patients with a median age of 67 (61–87) years were treated within the prospective AML96 trial of the German Study Initiative Leukemia (DSIL). 643 patients had de novo and 184 patients secondary disease. All patients were scheduled to receive a double induction therapy with Daunorubicin and Ara-C (DA3+7). The consolidation therapy consisted of one course of m-Amsacrine and intermediate-dose (10g/m2) Ara-C. 265 (32%) patients reached CR criteria after double induction therapy. Forty-two patients (5%) had only a PR, 307(37%) displayed refractory disease, 126(15%) died during induction therapy and 77(10%) received only one course of induction therapy due to severe toxicity. Out of the 265 patients in CR 120 (45%) patients received the consolidation course. The strongest independent prognostic factors for achieving a CR were less than 10% blasts in the day 15 bone marrow, the presence of a NPM mutation or a low-risk karyotype (p&lt;0.0001 each). The 3-year overall (OS) and relapse-free survival (RFS) rates were 18% for all patients and 17% for all patients in CR, respectively. In the multivariate analysis the strongest prognostic factors for survival were age, LDH and cytogenetics (p&lt;0.0001 each). Using these three parameters a prognostic model for survival was established. Patients older than 70 years with intermediate- or high-risk cytogenetics and a high LDH level at diagnosis (n=213) had a 3-year OS of only 9%, whereas patients with low-risk cytogenetics or patients with intermediate-risk cytogenetics, younger than 70 years and a low LDH level (n=237) had a 3-year OS of 32%. All other patients (n=377) had an intermediate 3-year OS of 15% (p&lt;0.0001). In conclusion, elderly AML patients can be stratified into prognostic groups. AML patients older than 70 years with high LDH levels and intermediate- or high-risk cytogenetics at diagnosis do not profit from conventional chemotherapy.

Interim results of protracted low doses of temozolomide in high-risk acute myeloid leukemia

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7052-7052
Author(s):  
B. C. Medeiros ◽  
J. R. Gotlib ◽  
S. E. Coutre ◽  
C. Jones ◽  
S. A. Khan ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Elderly Patients ◽  
Promoter Methylation ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Normal Karyotype ◽  
Low Doses ◽  
Npm1 Mutation ◽  
Acute Myeloid

7052 Background: High treatment-related mortality and low response rates often discourage elderly patients with acute myeloid leukemia from receiving treatment. Previous data demonstrate that only patients lacking expression of O6-alkylguanine-DNA alkyltransferase (AGAT) in leukemic blasts are sensitive to temozolomide. Protracted exposure to low doses of temozolomide can significantly inhibit AGAT enzymatic activity. Methods: Phase II clinical trial of tailored temozolomide therapy to high-risk AML patients according to AGAT methylation promoter status. Patients demonstrating evidence of AGAT promoter methylation were stratified to conventional doses of temozolomide at 200 mg/m2 orally x 7 days. Patients demonstrating lack of AGAT promoter methylation (unmethylated) received protracted doses of temozolomide (100 mg/m2 orally x 14 days) followed by conventional doses of temozolomide. Patients who achieved CR were given up to 5 consolidation treatments. Results: Fifteen patients have completed treatment to date. The median age was 78 (68–83) and nine were male. De novo AML was diagnosed in eight patients and five patients had s-AML. Nine patients had a normal karyotype and three patients had a complex karyotype. Two patients had only a NPM1 mutation and one had NPM1mut/FLT3-ITD. In 13 patients, the AGAT promoter was found to be unmethylated. AGAT protein was present in 5/11 patients. All patients had an intact mismatch repair pathway. Thirteen patients had HCT-CI scores of 0–2. Six patients (6/13) achieved a complete remission (CR) after 1 cycle of therapy (1/2 for patients with methylated and 5/11 for patients with unmethylated AGAT promoter). Nonhematologic toxicities were minimal. Drug-related hematologic toxicities were difficult to distinguish from disease-related cytopenias. Three patients remain in CR with a median duration of 22 weeks (14–36 weeks). Seven patients have died from disease progression, while two patients died of neutropenic sepsis (early deaths). With a median follow-up of 38 weeks (10–48), the median overall survival for the entire population is 12 weeks (3.5 - 38) weeks (responders 26.5 weeks). Conclusions: These preliminary results suggest that temozolomide therapy may be individually tailored to elderly patients with AML according to AGAT promoter status. [Table: see text]

Age-Specific Differences in Oncogenic Pathway Dysregulation in Patients With Acute Myeloid Leukemia

2009 ◽  
Vol 27 (33) ◽  
pp. 5580-5586 ◽  
Author(s):  
Arati V. Rao ◽  
Peter J.M. Valk ◽  
Klaus H. Metzeler ◽  
Chaitanya R. Acharya ◽  
Sascha A. Tuchman ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Treatment Strategies ◽  
Gene Set Enrichment Analysis ◽  
Oncogenic Signaling ◽  
Younger Patients ◽  
Pathway Activation ◽  
Acute Myeloid

Purpose To define the biology driving the aggressive nature of acute myeloid leukemia (AML) in elderly patients. Patients and Methods Clinically annotated microarray data from 425 patients with newly diagnosed de novo AML from two publicly available data sets were analyzed after age-specific cohorts (young ≤ 45 years, n = 175; elderly ≥ 55 years; n = 144) were prospectively identified. Gene expression analysis was conducted utilizing gene set enrichment analysis, and by applying previously defined and tested signature profiles reflecting dysregulation of oncogenic signaling pathways and altered tumor environment. Results Elderly AML patients as expected had worse overall survival and event-free survival compared with younger patients. Analysis of oncogenic pathways revealed that older patients had higher probability of RAS, Src, and tumor necrosis factor (TNF) pathway activation (all P < .0001). Hierarchical clustering revealed that younger patients with AML in cluster 2 had clinically worse survival, with high RAS, Src, and TNF pathway activation compared with patients in cluster 1. However, among elderly patients with AML, those in cluster 1 also demonstrated high RAS, Src, and TNF pathway activation but this did not translate into differences in survival. Conclusion AML in the elderly represents a distinct biologic entity characterized by unique patterns of deregulated signaling pathway variations that contributes to poor survival. These insights should enable development and adjustments of clinically meaningful treatment strategies in the older patient population.

scholarly journals Risk factors affect accurate prognosis in ASXL1-mutated acute myeloid leukemia

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yi Fan ◽  
Linxiao Liao ◽  
Yajun Liu ◽  
Zhenzhen Wu ◽  
Chong Wang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Primary Data ◽  
Hematopoietic Stem ◽  
Mutational Spectrum ◽  
Double Hit ◽  
Acute Myeloid

Abstract Background The epigenetic regulator additional sex combs-like 1 (ASXL1) is an adverse prognostic factor in acute myeloid leukemia (AML). However, the mutational spectrum and prognostic factors of ASXL1-mutated (ASXL1+) AML are largely unknown. We aim to evaluate the risk factors influencing the prognosis of ASXL1+ AML. Methods We performed next-generation sequencing (NGS) in 1047 cases of de novo AML and discovered 91 ASXL1+ AML (8.7%). The Log-Rank test and Kaplan-Meier were used to evaluate survival rate, and the Cox regression model was used to analyze multivariate analysis. Results In a total of 91 ASXL1+ AML, 86% had one or more co-mutations. The factors that had adverse impact on overall survival (OS) and event-free survival (EFS) are defined as high risk factors, including age ≥ 60 years, WBC count ≥ 50 × 109/L, FLT3-ITD mutations, RUNX1 mutations, and absence of AML1-ETO fusion gene. ASXL1 mutations without any risk factor were classified as single-hit ASXL1+ AML; ASXL1 mutations accompanied with one of the risk factors was referred to as double-hit ASXL1+ AML; ASXL1 mutations with two or more of the risk factors were designated as triple-hit ASXL1+ AML. The combination of these risk factors had a negative influence on the prognosis of ASXL1+ AML. The median OS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 6.67 months in triple-hit ASXL1+ AML (P = 0.003). The median EFS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 5.47 months in triple-hit ASXL1+ AML (P = 0.002). Allogenic hematopoietic stem cell transplantation (allo-HSCT) improved the prognosis of double/triple-hit ASXL1+ AML patients. Conclusions Our study provided new insights into the mutational spectrum and prognostic factors of ASXL1+ AML patients. Our primary data suggest that the risk factors in ASXL1+ AML contribute to the poor outcome of these patients. The management of ASXL1+ AML patients should be based on the risk factors and allo-HSCT is highly recommended for consolidation.

Clinico-Biological Characteristics and Prognosis of Non-M3 Acute Myeloid Leukemia with High Percentage of Myeloperoxisase Positive Blasts. Single Center Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4462-4462
Author(s):  
Pau Montesinos ◽  
Lorenzo Algarra ◽  
Jaime Sanz ◽  
Mari Luz Perez ◽  
Leonor Senent ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Disease Free Survival ◽  
Favourable Outcome ◽  
Biological Characteristics ◽  
Prognostic Impact ◽  
Acute Myeloid

Abstract Introduction: It has been suggested that acute myeloid leukemia (AML) showing mature phenotype is associated with favourable outcome. In a study recently published by JALSG, myeloperoxidase (MPO) positivity in over 50% of blasts had favourable prognostic impact, independent from karyotype, on achieving complete remission (CR), overall survival (OS) and disease free survival (DFS). No other studies have established the independent prognostic value of MPO expression. Objectives: Analyze the clinico-biological characteristics of AML with high percentage of MPO+ blasts and its impact on CR, OS and DFS. Material and methods: Between 1986 and 2005, 418 adult patients (median 53 years, range 15–80) were diagnosed with de novo non-APL AML and evaluated for percentage of MPO+ blasts. All patients received intensive chemotherapy. Diagnosis was made by optic microscopy of bone marrow (BM) aspirates stained with May-Grumwald giemsa, MPO, butyrate esterase and or non specific esterase. Cytogenetic and immunophenotype analysis was evaluated in 66% and in 76% of the cases respectively. Results: 118 patients (28%) showed a percentage of MPO+ blasts >75%. AML with MPO+ blasts >75% was associated with M1-M2-M4 subtypes, leucocytes >50×109/L, blasts in BM >70% and HLA-DR negativity (p<0.01). It was also significantly associated with favourable karyotype (11% vs 3% favourable, 52% vs 48% intermediate and 3% vs 15% unfavourable). Patients with AML and MPO+ blasts >75% obtained higher CR rate (71% vs 55%), due to less resistant disease (9% vs 22%, p<0.01). In multivariate analysis favourable karyotype, leukocytes <50×109/L and age <60 were favourable prognostic factors for CR. Median OS and DFS was higher in patients with AML and MPO+ blasts >75% (15 vs 7 months, p<0.001, y 41 vs 12 months, p<0.001, respectively). ). In multivariate analysis, favourable karyotype, leukocytes <50×109/L, age <60 years and MPO+ >50% were favourable prognostic factors for OS; and age <60 and MPO+ >75% were the only independent factors for DFS. Median DFS was higher in patients with AML and MPO+ blasts >75% in the intermediate cytogenetic risk group (59 vs 13 months, p=0.015), age <60 (109 vs 15 months, p=0.003), age >60 (13 vs 7 months, p=0.03), autologous stem cell transplantation (100 vs 9 months, p=0.04) and chemotherapy alone (16 vs 8 months, p=0.003). Conclusion: In our series, patients with AML and MPO+ blasts >75% show less chemoresistant disease and a longer remission duration, the latter independently from the karyotype. This biological characteristic could be useful in designing therapeutic strategies in patients that lack other prognostic markers.

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