scholarly journals Economic impact of genomic diagnostics for intermediate‐risk acute myeloid leukaemia

2016 ◽  
Vol 174 (4) ◽  
pp. 526-535 ◽  
Author(s):  
Sonya Cressman ◽  
Aly Karsan ◽  
Donna E. Hogge ◽  
Emily McPherson ◽  
Corneliu Bolbocean ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Economic Impact ◽  
Intermediate Risk ◽  
Acute Myeloid

scholarly journals Acute Myeloid Leukaemia in Children: Preliminary Results of a National Protocol in Casablanca, Morocco

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4898-4898
Author(s):  
Nabila Chellakhi ◽  
Nissrine Khoubila ◽  
Siham Cherkaoui ◽  
Abdallah Madani ◽  
Uma Athale ◽  
...  
Keyword(s):  
Survival Rate ◽  
Complete Remission ◽  
Acute Myeloid Leukaemia ◽  
Supportive Care ◽  
Myeloid Leukaemia ◽  
Risk Group ◽  
Emerging Countries ◽  
Intermediate Risk ◽  
Wbc Count ◽  
Acute Myeloid

Abstract Introduction: The outcome of acute myeloid leukaemia (AML) in emerging countries is very dismal. In Morocco,the complete remission rate (CR) has improved from less of 10% in 1980s to more than 60% in 2000s. However this improvement is far from satisfactory to improve five year survival rate. The aim of study was to evaluate preliminary outcomes of children ≤15years treated according to AML- MA 11protocol. Methods : Between the first January 2011 to December 2014, we carrieed a prospective study of all children aged 15 years or less, diagnosed AML. The diagnosis was according by cytological study with cytochemestry: MPO positive (FAB classification), supplemented by immunophenotyping. The prognosis is evaluated by conventional cytogenetic study. AML-MA 2011 protocol consisted of prephase(whenwhite blood cell (WBC) count ≥ 50 G/l) by Hydroxyurea (HU) (50 mg/m2/day for 4 days). The response to HU was evaluated after 2 days; patients were considered responsers if >50% reduction of the initial WBC count. Then 2 inductions based on daunorubicin 50 mg/m2 (3 days), cytarabine 100mg/m2/12 hours (10 days) and etoposide 100 mg/m2 (5 days) for the second course, followed by 3 consolidations with high dose of cytarabine 1-3 g/m2/12 hours (3 days), with intrathecal therapy. The supportive care is assured during all phases of treatment. Results: Forty four patients were enrolled with a median age of 8 years [1-15] and M:F ratio of 1.2. The median WBC count was 22710 elements/mm3; it exceeded 50 000/mm3 in 18 % of cases, more than 100 000/mm3 in 13 % of cases.The cytological studies showed the predominance of AML subtype 2 (31%) followed by subtype 5 (11, 3%). The immunophenotyping was done in 88% of cases. Karyotype performed in 40 out of 44 cases revealed: 9 (22,5%) favorable risk group [8 had the t(8,21); 1 had inv16], 25 (62,5%) intermediate risk, and 6 (15%) unfavorable-risk group. Seven patients received hydroxy urea with 5 good response (71% of cases; 2 patients had favorable risk and 3 had intermediate risk). Four of this patients died. Thirty five patients were treated (3 death before treatment, 4 abandonment of treatment, 1 myelodysplasea syndroma, and 1 bad condition). After the induction cycles; complete remission was achieved in 22 cases (62%), failure in 6 cases, and 7 children dead (20%) [4 septic choc, 2 haemorrhage and 1 acute pulmonary edema]. One patient died between 0 to 14 days during the cure and 6 others after 14 days of treatment. After a mean follow-up of 9months (1 to 43 months), continuous complete remission was achieved in 45,7% of cases, failure in 20%, relapse in 11%, and death in 45,45 % of cases. (toxic death in 25% of cases with high frequence in induction phases: 88%). Theoverall survival rate in 2 years was 41,2%. Table. Evolution of patients according to prognostic groups Status/cytogenetic groups CR (%) Failure (%) Death (%) Relapse (%) OS (%) favorable 55 0 11 22 53,3 intermediate 32 32 16 4 34,4 unfavorable 33 16 16 16 55,6 Conclusion: With aggressive chemotherapy, it is feasible to achieve high CR even in emerging countries. If supportive care is optimal with particular focus on prevention and management of infection and with improved transfusion support, then it's feasible to improve the overall outcome of patients. Finally it is necessary to make the molecular biology in our patients topreciselyindividualize the pronostic groups. Disclosures No relevant conflicts of interest to declare.

Prognostic importance of CD56 expression in intermediate risk acute myeloid leukaemia

2016 ◽  
Vol 176 (3) ◽  
pp. 498-501 ◽  
Author(s):  
Juan L Coelho-Silva ◽  
Luany E Carvalho ◽  
Mayara M Oliveira ◽  
Pedro L Franca-Neto ◽  
Adryanna T Andrade ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Intermediate Risk ◽  
Cd56 Expression ◽  
Prognostic Importance ◽  
Acute Myeloid

scholarly journals Prognostic Significance and Risk Stratification in Acute Myeloid Leukaemia Patients in the Absence of Successful Cytogenetic Analysis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1379-1379
Author(s):  
Lucy Chilton ◽  
Christine Harrison ◽  
Anthony V. Moorman ◽  
Iona Ashworth ◽  
Alan K. Burnett ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Cytogenetic Analysis ◽  
Prognostic Significance ◽  
Intermediate Risk ◽  
Younger Patients ◽  
Risk Patients ◽  
Acute Myeloid ◽  
Better Than

Abstract Cytogenetic analysis is a key tool in risk stratification of patients with acute myeloid leukaemia (AML). Sometimes samples are not sent or metaphase analysis fails (~10% cases). In these situations, a cytogenetic risk score cannot be assigned, preventing risk stratification. It has been suggested that in the absence of cytogenetic data, both missing and failed, patients have a poor outcome (Mederios et al (Br. J. Haematol. 2014 164(2): 245-50); Lazarevic et al (Eur. J. Haematol. 2015 94(5): 419-23)). In this study, we investigated the characteristics and prognostic significance of the provision of samples, and their successful analysis across the MRC UK series of AML trials (AML10 - AML16). Data from 14265 non-APL patients recruited to successive UK AML trials (1988 - 2012) were analysed. Patients were classified based on whether a sample was sent for cytogenetic analysis and the outcome of the analysis. Rates of successful cytogenetic analysis were higher in patients treated on intensive chemotherapy protocols (intensive: 11104/13081 (85%); non-intensive 850/1184 (72%), p<.0001). In intensively treated patients, there was a significant association between increasing age and missing or failed cytogenetic samples (p<.0001). Stratification of intensively treated patients with successful cytogenetics, according to the criteria of Grimwade et al (Blood 2010 116(3):354-65), into favourable (18%), intermediate (62%) and adverse risk (19%) were analysed for outcomes and showed 10 year survival of 66%, 30% and 12%, respectively. Survival at 10 years was 24% when no sample was sent compared to 32% when a sample failed cytogenetic analysis. Survival for patients with failed cytogenetics was not significantly different from those with intermediate risk cytogenetics in either univariate analysis (p=0.10) or after adjustment for age, performance status, white cell count and secondary disease (p=0.06). Outcomes were significantly better than those for adverse risk patients (p<.0001 for both analyses). For those with no sample, survival was significantly worse than for the intermediate risk (p<.0001 in both analyses), although the effect size was not large (HR 1.18 in adjusted analyses), yet significantly better than adverse risk patients (p<.0001, HR 0.57). While outcomes worsened with increasing age, a similar pattern was seen across all age groups (favourable/intermediate/adverse/no sample/failed: age<16 81%/57%/49%/63%/62%; age 16-59 67%/36%/13%/30%/41%; age 60+ 32%/12%/2%/8%/9%). In the most recent trial, AML17 (2009-14) of younger patients, 97% had successful cytogenetic analysis, compared to 86% in AML10-15. Here too, there was no suggestion of poor outcomes for those patients with no cytogenetic result. These results indicate that cytogenetic analysis is possible in the vast majority of younger patients, and suggest that absence of cytogenetic information is not in itself an adverse prognostic factor. This poor prognosis identified in other studies may be due to selection bias in the decision to send samples. The experience of AML17 demonstrates that, when cytogenetic analysis is required to guide treatment decisions, if results can be provided in real time, high levels of compliance can be achieved, not only in sending, but also in the quality of samples. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Fluorescence in Situ Hybridisation (FISH) Detection of Prognostically Relevant Chromosomal Abnormalities in Childhood Acute Myeloid Leukaemia (AML)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2897-2897
Author(s):  
Claire Schwab ◽  
Deniz Bakkalci ◽  
Brenda Gibson ◽  
Christine Harrison
Keyword(s):  
Risk Stratification ◽  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Chromosomal Abnormalities ◽  
Intermediate Risk ◽  
Chromosome 5 ◽  
Monosomy 7 ◽  
Poor Risk ◽  
Childhood Aml ◽  
Acute Myeloid

Abstract Cytogenetics is important in diagnosis of acute myeloid leukaemia (AML) and a number of chromosomal abnormalities have prognostic significance. AML clinical trials use three prognostic cytogenetic groups: good, intermediate and poor risk, for risk stratification of newly diagnosed patients to the most appropriate treatment arm. Many AML studies have combined data from children and adults, although the biology of their disease and treatment responses differ. For example, chromosomal abnormalities are observed in 80% of childhood AML, compared to only 50% of adults. The recent opening of the International Randomised Phase III Clinical Trial in Children with Acute Myeloid Leukaemia, MyeChild01, required extensive review of existing and novel genetic risk factors for stratification of patients in this study. The final consensus was to include the following abnormalities: Good risk; t(8;21)(q22;q22)/RUNX1-RUNX1T1 (approximate expected incidence in childhood AML, 12%), inv(16)(p13q22)/CBFB-MYH11 (6%); Poor Risk: inv(3)(q21q26)/t(3;3)(q21;q26)/abnormalities of 3q/MECOM rearrangements (~1%), monosomy 5/deletion of the long arm of chromosome 5 (5q) (~1%), monosomy 7 (4%), t(6;9)(p23;q34)/DEK-NUP214 (~1%), t(9;22)(q34;q11)/BCR-ABL1 (~1%), t(6;11)(q27;q23)/MLL-MLLT4/t(4;11)(q21;q23)/MLL-AFF1/t(10;11)(p11-p14;q23)/MLL-MLLT10 (5%), t(5;11)(q35;p15.5)/NUP98-NSD1(<5%),abnormalities of the short arm of chromosome 12 (12p) (~4%), inv(16)(p13.3q24.3)/CBFA2T3-GLIS2 (<2%); Intermediate risk; t(9;11)(p21;q23)/MLL-MLLT3/t(11;19)(q23;p13.3)/MLL-MLLT1/other MLL rearrangements (11%) and all other cases (25%). A pilot study was performed to evaluate the role of FISH in accurate detection of these abnormalities using a retrospective cohort of 158 paediatric AML patients. Patients were initially classified according to available karyotype, as t(8;21)(q22;q22) (n=15, 9%), inv(16)(p13q22) (n=12, 8%), t(15;17)(q24;q21) (n=8, 5%, although these patients are excluded from MyeChild01), monosomy 7/abnormalities of long arm of chromosome 7 (7q) (n=13, 8%), chromosome 5 abnormalities (n=3, 2%), t(9;22)(q34:q11) (n=1, 0.6%) and MLL rearrangements (n=49, 31%). Those patients with normal karyotype and other abnormalities were grouped together as other (n=57, 36%). They were analysed using a range of specific FISH probes, either commercially available from CytoCell or Kreatech or home grown, for the abnormalities listed above. No additional patients were identified with RUNX1-RUNX1T1, PML-RARα, CBFβ-MYH11 or BCR-ABL1, although copy number changes involving the chromosomal regions covered by these probes were indicated. No patients were found with the poor risk abnormality, inv(16)(p13.3q24.3)/CBFA2T3-GLIS2, likely due to its rarity.However, a number of previously undetected abnormalities were identified: MLL rearrangement, with poor risk translocations excluded (n=2), MLL-MLLT3 (n=1), 12p abnormalities (n=6), NUP98-NSD1 (n=3), DEK-NUP214 (n=1) and MECOM rearrangement (n=1). These latter 11 patients, accounting for 19 % of the other group, originally classified as intermediate risk became re-classified as poor risk following FISH screening. Cytogenetics is important to identify those significant chromosomal abnormalities involved in paediatric AML, which are used to stratify patients for treatment. FISH enables accurate detection of rare cryptic abnormalities associated with poor risk, meaning that more patients can benefit from appropriate risk stratification. Thus we are confident that FISH provides a reliable detection method to be implemented in MyeChild01, alongside screening for those mutations of prognostic relevance: NPM1, CEBPA and FLT3-ITD. Disclosures No relevant conflicts of interest to declare.

The acute myeloid leukaemia market

2019 ◽  
Vol 19 (4) ◽  
pp. 233-234
Author(s):  
Jorrit Schaefer ◽  
Sorcha Cassidy ◽  
Rachel M. Webster
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Acute Myeloid
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