Faculty Opinions recommendation of Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials.

2010 ◽  
Author(s):  
Peter Wiernik
Keyword(s):  
Acute Myeloid Leukemia ◽  
Medical Research ◽  
Myeloid Leukemia ◽  
Research Council ◽  
Medical Research Council ◽  
Chromosomal Abnormalities ◽  
Prognostic Significance ◽  
The United Kingdom ◽  
Acute Myeloid

Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials

Blood ◽  
2010 ◽  
Vol 116 (3) ◽  
pp. 354-365 ◽  
Author(s):  
David Grimwade ◽  
Robert K. Hills ◽  
Anthony V. Moorman ◽  
Helen Walker ◽  
Stephen Chatters ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Medical Research ◽  
Myeloid Leukemia ◽  
Research Council ◽  
Medical Research Council ◽  
Chromosomal Abnormalities ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
All Trans Retinoic Acid ◽  
Acute Myeloid

Abstract Diagnostic karyotype provides the framework for risk-stratification schemes in acute myeloid leukemia (AML); however, the prognostic significance of many rare recurring cytogenetic abnormalities remains uncertain. We studied the outcomes of 5876 patients (16-59 years of age) who were classified into 54 cytogenetic subgroups and treated in the Medical Research Council trials. In multivariable analysis, t(15;17)(q22;q21), t(8;21)(q22;q22), and inv(16)(p13q22)/t(16;16)(p13;q22) were the only abnormalities found to predict a relatively favorable prognosis (P < .001). In patients with t(15;17) treated with extended all-trans retinoic acid and anthracycline-based chemotherapy, additional cytogenetic changes did not have an impact on prognosis. Similarly, additional abnormalities did not have a significant adverse effect in t(8;21) AML; whereas in patients with inv(16), the presence of additional changes, particularly +22, predicted a better outcome (P = .004). In multivariable analyses, various abnormalities predicted a significantly poorer outcome, namely abn(3q) (excluding t(3;5)(q25;q34)), inv(3)(q21q26)/t(3;3)(q21;q26), add(5q)/del(5q), −5, −7, add(7q)/del(7q), t(6;11)(q27;q23), t(10;11)(p11∼13;q23), other t(11q23) (excluding t(9;11)(p21∼22;q23) and t(11;19)(q23;p13)), t(9;22)(q34;q11), −17, and abn(17p). Patients lacking the aforementioned favorable or adverse aberrations but with 4 or more unrelated abnormalities also exhibited a significantly poorer prognosis (designated “complex” karyotype group). These data allow more reliable prediction of outcome for patients with rarer abnormalities and may facilitate the development of consensus in reporting of karyotypic information in clinical trials involving younger adults with AML. This study is registered at http://www.isrctn.org as ISRCTN55678797 and ISRCTN17161961.

scholarly journals The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials

Blood ◽  
2001 ◽  
Vol 98 (6) ◽  
pp. 1752-1759 ◽  
Author(s):  
Panagiotis D. Kottaridis ◽  
Rosemary E. Gale ◽  
Marion E. Frew ◽  
Georgina Harrison ◽  
Stephen E. Langabeer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Medical Research ◽  
Myeloid Leukemia ◽  
Research Council ◽  
Tandem Duplication ◽  
Medical Research Council ◽  
Internal Tandem Duplication ◽  
Free Survival ◽  
The United Kingdom ◽  
Acute Myeloid

Abstract In acute myeloid leukemia (AML), further prognostic determinants are required in addition to cytogenetics to predict patients at increased risk of relapse. Recent studies have indicated that an internal tandem duplication (ITD) in the FLT3 gene may adversely affect clinical outcome. This study evaluated the impact of a FLT3/ITD mutation on outcome in 854 patients, mostly 60 years of age or younger, treated in the United Kingdom Medical Research Council (MRC) AML trials. An FLT3/ITD mutation was present in 27% of the patients and was associated with leukocytosis and a high percentage of bone marrow blast cells (P &lt; .001 for both). It had a borderline association with a lower complete remission rate (P = .05) and a higher induction death rate (P = .04), and was associated with increased relapse risk (RR), adverse disease-free survival (DFS), event-free survival (EFS), and overall survival (OS) (P &lt; .001 for all). In multivariate analysis, presence of a mutation was the most significant prognostic factor predicting RR and DFS (P &lt; .0001) and was still significant for OS (P = .009) and EFS (P = .002). There was no evidence that the relative effect of a FLT3/ITD differed between the cytogenetic risk groups. More than one mutation was detected in 23% of FLT3/ITD+ patients and was associated with worse OS (P = .04) and EFS (P = .07). Biallelic disease or partial/complete loss of wild-type alleles was present in 10% of FLT3/ITD+ patients. The suggestion is made that detection of a FLT3/ITD should be included as a routine test at diagnosis and evaluated for therapeutic management.

Improved treatment results in Mexican children with acute myeloid leukemia using a Medical Research Council (MRC)-acute myeloid leukemia 10 modified protocol

2009 ◽  
Vol 50 (7) ◽  
pp. 1132-1137 ◽  
Author(s):  
Sergio Gallegos-Castorena ◽  
Aurora Medina-Sanson ◽  
Oscar Gonzalez-Ramella ◽  
Fernando Sánchez-Zubieta ◽  
Armando Martínez-Avalos
Keyword(s):  
Acute Myeloid Leukemia ◽  
Medical Research ◽  
Myeloid Leukemia ◽  
Research Council ◽  
Medical Research Council ◽  
Treatment Results ◽  
Mexican Children ◽  
Acute Myeloid

Relationships between age at diagnosis, clinical features, and outcome of therapy in children treated in the Medical Research Council AML 10 and 12 trials for acute myeloid leukemia

Blood ◽  
2001 ◽  
Vol 98 (6) ◽  
pp. 1714-1720 ◽  
Author(s):  
David K. H. Webb ◽  
Georgina Harrison ◽  
Richard F. Stevens ◽  
Brenda G. Gibson ◽  
Ian M. Hann ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Medical Research ◽  
Myeloid Leukemia ◽  
Research Council ◽  
Medical Research Council ◽  
Disease Free Survival ◽  
Older Children ◽  
Free Survival ◽  
Severe Diarrhea ◽  
Acute Myeloid

Abstract Between May 1988 and June 2000, 698 children were treated in the Medical Research Council acute myeloid leukemia 10 and 12 trials. The presenting features and outcomes of therapy in these children were compared by age. Although there was no single cutoff in age, younger children were more likely to have intermediate risk and less likely to have favorable cytogenetics (P &lt; .001), and they had a higher incidence of translocations involving chromosome 11q23 (P &lt; .001). The distribution of French-American-British (FAB) types also varied with age; FAB types M5 (P &lt; .001) and M7 (P &lt; .001) were more common in early childhood, whereas older children were more likely to have FAB types M0 (P = .03), M1 (P = .04), M2 (P = .005), and M3 (P &lt; .001). Involvement of the central nervous system at diagnosis was also more common in the youngest children (P = .01). Younger children had more severe diarrhea (P = .002), whereas older children had worse nausea and vomiting (P = .01) after chemotherapy. When adjusted for other important factors, complete remission rates were similar (P = .5) and although there was less resistant disease in younger children (P = .003), this was partially balanced by a slight increase in deaths during induction therapy in younger patients (P = .06). On multivariate analysis overall survival (P = .02), event-free survival (P = .02), and disease-free survival were better (P = .06) in younger children due to a lower relapse rate (P = .02) especially in the bone marrow (P = .02).

scholarly journals The possible significance of trisomy 8 in acute myeloid leukemia

2017 ◽  
Vol 5 (6) ◽  
pp. 2652 ◽  
Author(s):  
Salil N. Vaniawala ◽  
Monika V. Patel ◽  
Pratik D. Chavda ◽  
Shivangi H. Zaveri ◽  
Pankaj K. Gadhia
Keyword(s):  
Acute Myeloid Leukemia ◽  
Chromosomal Aberrations ◽  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Prognostic Significance ◽  
Chromosomal Translocation ◽  
Banding Technique ◽  
Trisomy 8 ◽  
Increased Risk ◽  
Acute Myeloid

Background: Acute myeloid leukemia (AML) is a heterogeneous disorder that results from a block in the differentiation of haematopoietic progenitor cells along with uncontrolled proliferation. Trisomy 8 is the most common recurring numerical chromosomal aberrations in acute myeloid leukemia (AML). It occurs either as a sole anomaly or together with other additional chromosomal aberrations. The prognostic significance of trisomy 8 in presence of other additional chromosomal abnormality depends on clonal cytogenetic changes. The patients with trisomy 8 had shorter survival with significantly increased risk with other chromosomal abnormality.Methods: Total 139 patients were screened between January 2016 to November 2016 who were suspected of AML cases. Bone marrow cultures were set up using conventional cytogenetic methods. Chromosomal preparation was made and subjected to GTG banding technique. Banded metaphases were analysed and karyotyped for further analysis.Results: Cytogenetic evaluation of karyotyped of 139 suspected AML patients showed 52 with t(8;21)(q22;q22), 36 with t(15;17)(q22;q12), and 11 with inv(16)(p13;q22). The rest 40 cases found with additional chromosomal abnormalities, of which 16 were sole trisomy 8 and 24 cases were found with other chromosomal abnormalities In addition, only one person found with t(8;21) and trisomy 8, while  three person having t(15;17) with trisomy 8.Conclusions: AML is considered to be one of the most important cytogenetic prognostic determinants. Recurrent chromosomal translocation with trisomy 8 varying 1.9% for t(8;21) and 8.3% for t(15;17). In the present study trisomy 8 in AML with known favourable anomalies is very small. Therefore, it cannot be taken as a prognostic marker.

The prognostic significance of IDH1 mutations in younger adult patients with acute myeloid leukemia is dependent on FLT3/ITD status

Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. 2779-2782 ◽  
Author(s):  
Claire L. Green ◽  
Catherine M. Evans ◽  
Robert K. Hills ◽  
Alan K. Burnett ◽  
David C. Linch ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Idh1 Mutation ◽  
Adult Patients ◽  
Npm1 Mutation ◽  
Mutation Status ◽  
The United Kingdom ◽  
Dehydrogenase Gene ◽  
Acute Myeloid

Abstract Mutations in the isocitrate dehydrogenase gene (IDH1) were recently described in patients with acute myeloid leukemia (AML). To investigate their prognostic significance we determined IDH1 status in 1333 young adult patients, excluding acute promyelocytic leukemia, treated in the United Kingdom MRC AML10 and 12 trials. A mutation was detected in 107 patients (8%). Most IDH1+ patients (91%) had intermediate-risk cytogenetics. Mutations correlated significantly with an NPM1 mutation (P < .0001) but not a FLT3/ITD (P = .9). No difference in outcome between IDH1+ and IDH1− patients was found in univariate or multivariate analysis, or if the results were stratified by NPM1 mutation status. However, when stratified by FLT3/ITD status, an IDH1 mutation was an independent adverse factor for relapse in FLT3/ITD− patients (P = .008) and a favorable factor in FLT3/ITD+ patients (P = .02). These results suggest that metabolic changes induced by an IDH1 mutation may influence chemoresistance in a manner that is context-dependent.

scholarly journals Prognostic Significance of NPM1 Mutations in the Absence of FLT3–Internal Tandem Duplication in Older Patients With Acute Myeloid Leukemia: A SWOG and UK National Cancer Research Institute/Medical Research Council Report

2015 ◽  
Vol 33 (10) ◽  
pp. 1157-1164 ◽  
Author(s):  
Fabiana Ostronoff ◽  
Megan Othus ◽  
Michelle Lazenby ◽  
Elihu Estey ◽  
Frederick R. Appelbaum ◽  
...  
Keyword(s):  
Cancer Research ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Research Council ◽  
Medical Research Council ◽  
Prognostic Significance ◽  
Cancer Research Institute ◽  
National Cancer Research Institute ◽  
The Impact ◽  
Acute Myeloid

Purpose Younger patients with acute myeloid leukemia (AML) harboring NPM1 mutations without FLT3–internal tandem duplications (ITDs; NPM1-positive/FLT3-ITD–negative genotype) are classified as better risk; however, it remains uncertain whether this favorable classification can be applied to older patients with AML with this genotype. Therefore, we examined the impact of age on the prognostic significance of NPM1-positive/FLT3-ITD–negative status in older patients with AML. Patients and Methods Patients with AML age ≥ 55 years treated with intensive chemotherapy as part of Southwest Oncology Gorup (SWOG) and UK National Cancer Research Institute/Medical Research Council (NCRI/MRC) trials were evaluated. A comprehensive analysis first examined 156 patients treated in SWOG trials. Validation analyses then examined 1,258 patients treated in MRC/NCRI trials. Univariable and multivariable analyses were used to determine the impact of age on the prognostic significance of NPM1 mutations, FLT3-ITDs, and the NPM1-positive/FLT3-ITD–negative genotype. Results Patients with AML age 55 to 65 years with NPM1-positive/FLT3-ITD–negative genotype treated in SWOG trials had a significantly improved 2-year overall survival (OS) as compared with those without this genotype (70% v 32%; P < .001). Moreover, patients age 55 to 65 years with NPM1-positive/FLT3-ITD–negative genotype had a significantly improved 2-year OS as compared with those age > 65 years with this genotype (70% v 27%; P < .001); any potential survival benefit of this genotype in patients age > 65 years was marginal (27% v 16%; P = .33). In multivariable analysis, NPM1-positive/FLT3-ITD–negative genotype remained independently associated with an improved OS in patients age 55 to 65 years (P = .002) but not in those age > 65 years (P = .82). These results were confirmed in validation analyses examining the NCRI/MRC patients. Conclusion NPM1-positive/FLT3-ITD–negative genotype remains a relatively favorable prognostic factor for patients with AML age 55 to 65 years but not in those age > 65 years.

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