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 < .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).

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 < .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.

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.

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

Clinical relevance of P-glycoprotein expression in de novo acute myeloid leukemia

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1997-2004 ◽  
Author(s):  
G Del Poeta ◽  
R Stasi ◽  
G Aronica ◽  
A Venditti ◽  
MC Cox ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Normal Karyotype ◽  
Free Survival ◽  
Negative Phenotype ◽  
Acute Myeloid

Abstract Cytofluorimetric detection of the multidrug resistance (MDR)-associated membrane protein (P-170) was performed at the time of diagnosis in 158 patients with acute myeloid leukemia using the C219 monoclonal antibody (MoAb). In 108 of these cases the JSB1 MoAb was also tested. An improved histogram subtraction analysis, based on curve fitting and statistical test was applied to distinguish antigen-positive from antigen-negative cells. A marker was considered positive when more than 20% of the cells were stained. At onset, P-170 was detected in 43% of cases with C219 and in 73% of cases with JSB1. There was a strict correlation between C219 and JSB1 positivity, as all C219+ cases were also positive for JSB1 MoAb (P < .001). No relationship was found between sex, age, organomegaly, and MDR phenotype. Significant correlation was found between CD7 and both C219 and JSB1 expression (P < .001 and .001, respectively). C219-negative phenotype was more often associated with a normal karyotype (24 of 55 with P = .030). Rhodamine 123 (Rh123) staining and flow cytometry analysis showed a significantly decreased mean fluorescence in 51 C219+ and 38 JSB1+ patients compared to 42 MDR negative ones (P < .001). The rate of first complete remission (CR) differed both between C219+ and C219- cases and between JSB+ and JSB- ones (30.9% v 71.1% and 35.4% v 93.1%, respectively, P < .001). Of the 21 C219+ patients who had yielded a first CR, 19 (90.4%) relapsed, compared with 28 of 64 (43.7%) C219- patients (P < .001). Of the 28 JSB1+ patients in first CR, 17 (60.7%) relapsed relative to 8 (29.6%) of 27 JSBI- ones (P = .021). A higher rate of relapses among MDR+ compared with MDR- patients was observed both for C219 and JSB1 MoAbs taken separately (C219 80% v 44%; JSB1 52% v 27%), with no relationship to age. The survival rates (Kaplan-Meyer method) were significantly shorter both in C219+ patients and in JSB1+ cases (P < .001). Disease-free survival curves followed this same trend. The combination (C219- JSB1+) identified a subset of patients with an intermediate outcome compared to C219 positive cases. The prognostic value of both markers (C219 and JSB1) was confirmed in multivariate analysis. These results suggest that the assessment of MDR phenotype by flow cytometry may be an important predictor of treatment outcome.

Low Platelet Counts at Diagnosis Predict Better Survival for Patients with Intermediate-Risk Acute Myeloid Leukemia

2019 ◽  
Vol 143 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Yimin Zhang ◽  
Haihui Gu ◽  
Qi Chen ◽  
Ying Zhang ◽  
Hui Cheng ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Negative Impact ◽  
Disease Free Survival ◽  
Intermediate Risk ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Risk Patients ◽  
Immature Cells ◽  
Acute Myeloid

Background: Aggressive growth of primitive and immature cells in the bone marrow results in reductions in megakaryocyte and platelet (PLT) counts, leading to thrombocytopenia in acute myeloid leukemia (AML). However, not all AML patients show thrombocytopenia at the time of diagnosis, and the association of PLT count with patient survival is largely unknown. Methods: A retrospective study was performed to determine PLT counts at diagnosis in the peripheral blood in 291 newly diagnosed AML patients and assess the association of PLT counts with the overall survival (OS) and disease-free survival (DFS) of these patients. Results: Low PLT counts (≤40 × 109/L) were associated with better outcomes for the whole cohort (5-year OS, 55.1 ± 3.8 vs. 35.3 ± 3.5%, p < 0.001; 5-year DFS, 49.1 ± 3.8 vs. 25.7 ± 4.0%, p < 0.001) and intermediate-risk patients (5-year OS, 64.5 ± 5.4 vs. 41.0 ± 4.8%, p < 0.001; 5-year DFS, 60.8 ± 5.6 vs. 28.6 ± 5.6%, p < 0.001). Moreover, low PLT counts were related to deeper molecular remission. Low PLT counts correlated with better survival of intermediate-risk AML patients treated with chemotherapy only. Allogeneic hematopoietic stem cell transplantation attenuated the negative impact of high PLT counts on the survival of intermediate-risk patients. Furthermore, univariate and multivariate analyses demonstrated that PLT count at diagnosis was an independent prognostic factor for intermediate-risk AML. Conclusion: PLT count at diagnosis predicts survival for patients with intermediate-risk AML.

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