scholarly journals Prognosis of acute myeloid leukemia patients up to 60 years of age exhibiting trisomy 8 within a non-complex karyotype: individual patient data-based meta-analysis of the German Acute Myeloid Leukemia Intergroup

Haematologica ◽  
2007 ◽  
Vol 92 (6) ◽  
pp. 763-770 ◽  
Author(s):  
M. Schaich ◽  
R. F. Schlenk ◽  
H. K. Al-Ali ◽  
H. Dohner ◽  
A. Ganser ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Patient Data ◽  
Complex Karyotype ◽  
Trisomy 8 ◽  
Acute Myeloid

Individual Patient Data–Based Meta-Analysis of Patients Aged 16 to 60 Years With Core Binding Factor Acute Myeloid Leukemia: A Survey of the German Acute Myeloid Leukemia Intergroup

2004 ◽  
Vol 22 (18) ◽  
pp. 3741-3750 ◽  
Author(s):  
R.F. Schlenk ◽  
A. Benner ◽  
J. Krauter ◽  
T. Büchner ◽  
C. Sauerland ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Patient Data ◽  
Survival Duration ◽  
Core Binding Factor ◽  
Binding Factor ◽  
Acute Myeloid

PurposeTo evaluate prognostic factors for relapse-free survival (RFS) and overall survival (OS) and to assess the impact of different postremission therapies in adult patients with core binding factor (CBF) acute myeloid leukemias (AML).Patients and MethodsIndividual patient data–based meta-analysis was performed on 392 adults (median age, 42 years; range, 16 to 60 years) with CBF AML (t(8;21), n = 191; inv(16), n = 201) treated between 1993 and 2002 in prospective German AML treatment trials.ResultsRFS was 60% and 58% and OS was 65% and 74% in the t(8;21) and inv(16) groups after 3 years, respectively. For postremission therapy, intention-to-treat analysis revealed no difference between intensive chemotherapy and autologous transplantation in the t(8;21) group and between chemotherapy, autologous, and allogeneic transplantation in the inv(16) group. In the t(8;21) group, significant prognostic variables for longer RFS and OS were lower WBC and higher platelet counts; loss of the Y chromosome in male patients was prognostic for shorter OS. In the inv(16) group, trisomy 22 was a significant prognostic variable for longer RFS. For patients who experienced relapse, second complete remission rate was significantly lower in patients with t(8;21), resulting in a significantly inferior survival duration after relapse compared with patients with inv(16).ConclusionWe provide novel prognostic factors for CBF AML and show that patients with t(8;21) who experience relapse have an inferior survival duration.

scholarly journals Individual patient data meta-analysis of randomized trials evaluating IL-2 monotherapy as remission maintenance therapy in acute myeloid leukemia

Blood ◽  
2011 ◽  
Vol 117 (26) ◽  
pp. 7007-7013 ◽  
Author(s):  
Marc Buyse ◽  
Pierre Squifflet ◽  
Beverly J. Lange ◽  
Todd A. Alonzo ◽  
Richard A. Larson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Maintenance Therapy ◽  
Myeloid Leukemia ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Patient Data ◽  
Free Survival ◽  
Remission Maintenance ◽  
Acute Myeloid

IL-2 is a natural, T cell–derived cytokine that stimulates the cytotoxic functions of T and natural killer cells. IL-2 monotherapy has been evaluated in several randomized clinical trials (RCTs) for remission maintenance in patients with acute myeloid leukemia (AML) in first complete remission (CR1), and none demonstrated a significant benefit of IL-2 monotherapy. The objective of this meta-analysis was to reliably determine IL-2 efficacy by combining all available individual patient data (IPD) from 5 RCTs (N = 905) and summary data from a sixth RCT (N = 550). Hazard ratios (HRs) were estimated using Cox regression models stratified by trial, with HR < 1 indicating treatment benefit. Combined IPD showed no benefit of IL-2 over no treatment in terms of leukemia-free survival (HR = 0.97; P = .74) or overall survival (HR = 1.08; P = .39). Analyses including the sixth RCT yielded qualitatively identical results (leukemia-free survival HR = 0.96, P = .52; overall survival HR = 1.06; P = .46). No significant heterogeneity was found between the trials. Prespecified subset analyses showed no interaction between the lack of IL-2 effect and any factor, including age, sex, baseline performance status, karyotype, AML subtype, and time from achievement of CR1 to initiation of maintenance therapy. We conclude that IL-2 alone is not an effective remission maintenance therapy for AML patients in CR1.

Pooled Data Analysis of Acute Myeloid Leukemia Patients <= 60 Years with Trisomy 8 Treated within the Studies of the German Acute Myeloid Leukemia Intergroup.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2374-2374
Author(s):  
Markus Andreas Schaich ◽  
Silke Soucek ◽  
Hartmut Döhner ◽  
Gerhard Ehninger ◽  
Arnold Ganser ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
Autologous Transplantation ◽  
Disease Free Survival ◽  
High Dose ◽  
Age Difference ◽  
Complex Karyotype ◽  
Trisomy 8 ◽  
Acute Myeloid

Abstract Trisomy 8 (+8) occurs in about 8–13% of patients with acute myeloid leukemia (AML). However, so far the prognostic impact of this recurrent aberration is unclear. Additional prognostic factors and different consolidation therapies may influence prognosis in this disease entity. Therefore, the German AML Intergroup analyzed 198 adult patients (median age 49 (17–60) years; 172 de novo and 26 secondary AML) with trisomy 8 treated between 1993 and 2002 in eight prospective German AML treatment trials. Patients with t(8;21), inv(16) or abn11q23 and an additional +8 were not included in the study. Clinical, diagnostic and laboratory data were reviewed for consistency and completeness before analysis by a central coordination center. Ninety-two (46%) patients had +8 as a sole aberration, 39 (20%) had one additional secondary aberration and 67 (34%) had +8 within complex karyotypes with at least three independent abnormalities. Trisomy 8 was frequently accompanied by other trisomies (53/198), especially by +21 (16/198) or +22 (13/198). Complete remission rate after two induction therapies was 62% for all patients. An additional +21 (odds ratio 0.17; 95% CI 0.05–0.57) and a secondary AML (odds ratio 0.38; 95% CI 0.16–0.90) were negative prognostic factors for treatment response. Only 25% of patients with an additional +21 reached CR criteria. Disease free survival (DFS) was 18% and overall survival (OS) 19% after 5 years for all patients, respectively. Patients with +8 as a sole aberration had a 5-year OS of 20%, with one additional secondary aberration of 32% and with a complex karyotype of only 8% (p=0.005). All but one patient with an additional +21 died within the first two years (p&lt;0.001). Multivariate analysis revealed age (difference 10 years hazard ratio (HR) 1.30; p&lt;0.001), an additional +21 (HR 2.32; p=0.004), a complex karyotype (HR 1.58; p=0.02) and logarithm of white blood cell count (WBC) (HR 1.41; p=0.01) as prognostic factors for overall survival and age (difference of 10 years HR 1.22; p=0.01) and a complex karyotype (HR 1.63; p=0.04) for disease free survival in all patients. Post remission therapy (i.e. high-dose Ara-C vs. autologous transplantation vs. conventional allogeneic transplantation) did not enter in the multivariate models. Looking on the group of patients with +8 as sole aberration only extramedullary disease (HR 2.05; p=0.02) influenced survival. In conclusion, the data of this large cohort of patients indicate that AML with trisomy 8 is a heterogeneous entity. Neither allogeneic nor autologous transplantation proved superiority compared to high-dose cytarabine based consolidation therapy. For the majority of patients alternative therapeutic approaches are needed to achieve durable remissions in the future.

Prognostic Factors in Adult Patients up to 60 Years Old With Acute Myeloid Leukemia and Translocations of Chromosome Band 11q23: Individual Patient Data–Based Meta-Analysis of the German Acute Myeloid Leukemia Intergroup

2009 ◽  
Vol 27 (18) ◽  
pp. 3000-3006 ◽  
Author(s):  
Jürgen Krauter ◽  
Katharina Wagner ◽  
Irina Schäfer ◽  
Rolf Marschalek ◽  
Claus Meyer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Adult Patients ◽  
Chromosome Band ◽  
Reciprocal Translocations ◽  
Acute Myeloid

Purpose To identify risk factors for induction success and overall survival (OS) and relapse-free survival (RFS) and to evaluate the impact of allogeneic stem-cell transplantation (alloSCT) in adult patients up to 60 years old with acute myeloid leukemia (AML) and reciprocal translocations involving chromosome band 11q23 [t(11q23)]. Patients and Methods An individual patient data-based meta-analysis was performed on 180 adult patients with AML and t(11q23). These patients were identified by cytogenetics and/or molecular techniques and treated within eight prospective multicenter trials of the German AML Intergroup. The median follow-up time was 53 months. Results Complete remission rate was 71%. Favorable factors for induction success were the presence of a t(9;11), t(11q23) as a sole aberration, and de novo leukemia. OS rate at 4 years was 29%. Translocations other than t(9;11), platelets less than the median, secondary leukemia, and peripheral blasts greater than the median were adverse risk factors for OS. RFS rate at 4 years was 29%. The presence of a t(6;11) and peripheral blasts greater than the median had a negative impact on RFS. Three risk groups for OS and RFS could be defined by the combination of these factors with 4-year OS rates of 50%, 28%, and 5% and 4-year RFS rates of 37%, 26%, and 5%. An alloSCT from matched related or unrelated donors in first complete remission was beneficial, especially in t(6;11)-negative patients. Conclusion Risk stratification of AML patients with reciprocal translocations of chromosome band 11q23 is feasible based on the translocation partner and clinical parameters.

Favorable prognosis of biallelicCEBPAgene mutations in acute myeloid leukemia patients: a meta-analysis

2015 ◽  
Vol 94 (5) ◽  
pp. 439-448 ◽  
Author(s):  
Hong-Ying Li ◽  
Dong-Hong Deng ◽  
Ying Huang ◽  
Fang-Hui Ye ◽  
Lu-Lu Huang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Meta Analysis ◽  
Favorable Prognosis ◽  
Acute Myeloid

scholarly journals Tritsomy 8 Acute Myeloid Leukemia Analysis Reveals New Insights of DNA Methylome with Identification of HHEX as Potential Diagnostic Marker

2015 ◽  
Vol 7 ◽  
pp. BIC.S19614 ◽  
Author(s):  
Marwa H. Saied ◽  
Jacek Marzec ◽  
Sabah Khalid ◽  
Paul Smith ◽  
Gael Molloy ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Diagnostic Marker ◽  
Cpg Island ◽  
Global Analysis ◽  
Extra Chromosome ◽  
Chromosome 8 ◽  
Trisomy 8 ◽  
Acute Myeloid

Trisomy 8 acute myeloid leukemia (AML) is the commonest numerical aberration in AML. Here we present a global analysis of trisomy 8 AML using methylated DNA immunoprecipitation-sequencing (MeDIP-seq). The study is based on three diagnostic trisomy 8 AML and their parallel relapse status in addition to nine non-trisomic AML and four normal bone marrows (NBMs). In contrast to non-trisomic DNA samples, trisomy 8 AML showed a characteristic DNA methylation distribution pattern because an increase in the frequency of the hypermethylation signals in chromosome 8 was associated with an increase in the hypomethylation signals in the rest of the chromosomes. Chromosome 8 hypermethylation signals were found mainly in the CpG island (CGI) shores and interspersed repeats. Validating the most significant differentially methylated CGI ( P = 7.88 · 10–11identified in trisomy 8 AML demonstrated a specific core region within the gene body of HHEX, which was significantly correlated with HHEX expression in both diagnostic and relapse trisomy 8 AMLs. Overall, the existence of extra chromosome 8 was associated with a global impact on the DNA methylation distribution with identification of HHEX gene methylation as a potential diagnostic marker for trisomy 8 AML.

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