The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial

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 < .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 < .001 for all). In multivariate analysis, presence of a mutation was the most significant prognostic factor predicting RR and DFS (P < .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.

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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 ◽

10.1182/blood-2009-11-254441 ◽

2010 ◽

Vol 116 (3) ◽

pp. 354-365 ◽

Cited By ~ 1119

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.

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Performance of the Medical Research Council (MRC) and the Leukemia Research Foundation (LRF) score in predicting survival benefit with hypomethylating agent use in patients with relapsed or refractory acute myeloid leukemia

Leukemia & Lymphoma ◽

10.1080/10428194.2018.1468893 ◽

2018 ◽

Vol 60 (1) ◽

pp. 246-249

Author(s):

Maximilian Stahl ◽

Michelle DeVeaux ◽

Pau Montesinos ◽

Raphaël Itzykson ◽

Ellen K. Ritchie ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Medical Research ◽

Survival Benefit ◽

Myeloid Leukemia ◽

Research Council ◽

Medical Research Council ◽

Hypomethylating Agent ◽

Refractory Acute Myeloid Leukemia ◽

Acute Myeloid

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

Leukemia & Lymphoma ◽

10.1080/10428190902964768 ◽

2009 ◽

Vol 50 (7) ◽

pp. 1132-1137 ◽

Cited By ~ 10

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

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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 ◽

10.1182/blood.v98.6.1714 ◽

2001 ◽

Vol 98 (6) ◽

pp. 1714-1720 ◽

Cited By ~ 95

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 < .001), and they had a higher incidence of translocations involving chromosome 11q23 (P < .001). The distribution of French-American-British (FAB) types also varied with age; FAB types M5 (P < .001) and M7 (P < .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 < .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).

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