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

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.

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).

Treatment results of childhood acute myeloid leukemia in Serbia

2013 ◽  
Vol 6 (1) ◽  
pp. 63-68 ◽  
Author(s):  
Krstovski Nada ◽  
Kuzmanovic Milos ◽  
Vujic Dragana ◽  
Dokmanovic Lidija ◽  
Micic Dragan ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Results ◽  
Childhood Acute Myeloid Leukemia ◽  
Acute Myeloid

scholarly journals Results of program acute myeloid leukemia therapy use in National Medical Research Center for Hematology of the Ministry of Health of Russian Federation

2018 ◽  
Vol 90 (7) ◽  
pp. 14-22 ◽  
Author(s):  
E N PAROVICHNIKOVA ◽  
I A LOUKIANOVA ◽  
V V TROITSKAYA ◽  
M Y DROKOV ◽  
T I LOBAOVA ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Medical Research ◽  
Myeloid Leukemia ◽  
Risk Group ◽  
Research Center ◽  
Chromosome Inversion ◽  
Landmark Analysis ◽  
Allogenic Blood ◽  
National Medical ◽  
Acute Myeloid

Objective. To analyze treatment results of 172 patients with acute myeloid leukemia (AML) aged 18-60 years in National Medical Research Center for Hematology of MHRF. Materials and methods. Inductive and consolidation program for 139 (80%) patients was based on a standardized protocol: 4 courses “7+3” with different anthracycline use (2 courses of daunorubicin, idarubicin, mitoxantrone) and continuous use of cytarabine on the second inductive course. In 20% of patients cytarabine courses at the dose of 1 g/m2 2 times a day for 1-3 days combined with idarubicin and mitoxantrone were used as two consolidation courses. Allogenic bone marrow transplantation was performed in the first complete remission (CR) period in 40% of patients. Results. The frequency of CR achievement in all patients was 78.6%, refractory forms were observed in 13.9% of patients, early mortality - in 7.5% of patients. Seven-year overall survival (OS) rate was 40.7%, relapse free survival (RFS) - 43.2%. When estimating effectiveness depending on cytogenetic risk group it was demonstrated that 5-year OS and RFS in patients with translocation (8; 21) cannot be considered as satisfying, it accounted for 50 and 34%, respectively. At the same time in patients with 16th chromosome inversion (inv16) these characteristics accounted for 68.6 and 63.5%. Acquired results forced reconsidering of the consolidation program in AML patients of this subgroup. The median time to allogenic blood stem cells transplantation (allo-BSCT) in patients with first CR was 6.5 months that was taken as a reference point in landmark analysis of patients in whom allo-BSCT was not performed. Landmark analysis showed that in AML patients of favorable prognosis group allo-BSCT does not significantly reduce the probability of relapse (0 and 36%) and does not influence RFS (33 and 64%). In patients of border-line and poor prognosis allo-BSCT significantly reduces relapse probability (26 and 66%; 20 and 100%) and significantly increases a 7-year RFS (68.7 and 30%; 45.6 and 0%). Allo-BSCT also results in significant RFS increase and reduces the probability of relapse (25 and 78%) in patients in whom CR was achieved only after the second induction course. At the same time allo-BSCT does not influence patients who achieved CR after the first treatment course: 55 and 50%. Conclusion. Multivariate analysis showed that cytogenetic risk group (HR=2.3), time of CR achievement (HR=2.9), and allo-BSCT transplantation (HR=0.16) are independent factors for disease relapse prognosis after achieving CR.

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