scholarly journals Enrolling children with acute lymphoblastic leukaemia on a clinical trial improves event-free survival: a population-based study

2018 ◽  
Vol 118 (5) ◽  
pp. 744-749 ◽  
Author(s):  
Caron Strahlendorf ◽  
Jason D Pole ◽  
Randy Barber ◽  
David Dix ◽  
Ketan Kulkarni ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Population Based ◽  
Event Free Survival ◽  
Population Based Study ◽  
Free Survival

The Presence Of Normal B and T Lymphocytes In Bone Marrow At Diagnosis Predicts Overall and Event Free Survival In Childhood B- Lineage Acute Lymphoblastic Leukaemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4993-4993
Author(s):  
Claire Edwin ◽  
Joanne elizabeth Dean ◽  
Russell Keenan
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Cell Populations ◽  
Event Free Survival ◽  
Free Survival ◽  
Cell Numbers ◽  
B Lineage ◽  
B And T Lymphocytes

Abstract Introduction  The absolute lymphocyte count (ALC) in peripheral blood has been shown to be a prognostic indicator in both adult and paediatric leukaemia. (Hudson et al 2004, Rabin et al 2012)The ALC is far easier and cheaper to measure than minimal residual disease in both developed and developing countries [1]. It is not known which lymphocytes in peripheral blood are important in predicting outcome or the mechanism for this. Aims We aimed to investigate the presence and subtype of normal lymphocytes present in the bone marrow at diagnosis in patients with B lineage acute lymphoblastic leukaemia and correlate with clinical outcome. We collected retrospective patient data from 101 patients at Alder Hey Children’s hospital diagnosed with B lineage ALL between 2002 and 2008. We aimed to identify normal non-tumour B and T lymphocytes present at diagnosis in bone marrow and correlate their presence with event free(EFS) and overall survival(OS). Methods Patient data was collected from 101 patients’ records  (including clinical prognostic information cytogenetics and MRD status). All patients had at least 5 years follow up.  Diagnostic flow cytometry list mode data files were analysed using WinMDI 2.9 software to determine the tumour populations, and proportions of non-tumour lymphocytes using CD20 and CD7 monoclonal antibodies, which were included in the original diagnostic panel. Proportions of these normal cell populations were correlated with patient outcome. One patient was excluded from the normal B cell analysis due to a high CD20 tumour expression. Results The analysis of CD7 lymphocytes is shown in figure 1. We analysed CD7+ cells as a % of the non-leukaemia cells. Using a threshold of 29.1% those with high CD7 cell numbers OS was 96.8% below the threshold OS was 85.3% (p=0.0017).  Event free survival was 93.6%v 82.3% in those with high v low numbers (p=0.004) see figure 1. The mean proportion of CD20+ cells was 3.86% (SD +/- 7.66)% in the alive patients (n=94) and 1.21 (SD +/-0.75)% in deceased patients (n=6). Using a threshold value of 2.4% the overall survival in those with high CD20 cell numbers was 100.00% v 89.65% in those with low numbers, (p-= 0.03). Similarly a strong trend was observed with CD20 numbers and event-free survival in patients above or below 2.7%, EFS was 97.1% and 87.9% respectively p= 0.129. Conclusion/Discussion  With modern therapy fortunately most children survive their leukaemia.  However there is a group of patients that remain not possible to cure with current chemotherapy approaches. We present that the presence of normal CD7+ and CD20+ lymphocytes in the bone marrow at diagnosis are strongly associated with overall and event free survival. The mechanism of this effect is not known. We postulate that within these cell populations, that we have identified, is a specific immune response to the individuals own leukaemia. If this is the case these normal lymphocytes could be harvested and used as a potential individualised therapy. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Parental occupational exposure to benzene and the risk of childhood and adolescent acute lymphoblastic leukaemia: a population-based study

2019 ◽  
Vol 76 (8) ◽  
pp. 527-529 ◽  
Author(s):  
Julia E Heck ◽  
Di He ◽  
Zuelma Arellano Contreras ◽  
Beate Ritz ◽  
Jørn Olsen ◽  
...  
Keyword(s):  
Occupational Exposure ◽  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Conditional Logistic Regression ◽  
Population Based ◽  
Population Based Study ◽  
Benzene Exposure ◽  
Shoe Industry ◽  
Increased Risk ◽  
Parental Occupational Exposure

ObjectivesOnly a small number of studies have reported on the association of parental occupational exposure to benzene and risk of childhood and adolescent leukaemias. We examined associations with acute lymphoblastic leukaemia (ALL) in this population-based study in Denmark.MethodsBenzene was largely banned from Danish workplaces after 1975, thus this case-control study focused on the immediately prior years. Paediatric cancer cases (<age 20) were ascertained from the Danish Cancer Registry among children born 1968–1974, and controls were selected from population records. Paternal occupation within the 3 months preconception and maternal pregnancy occupation were identified from nationwide pension fund records. Blinded, we assigned benzene exposure using a job-exposure matrix that had been developed for the Danish population. Risk for ALL was estimated using conditional logistic regression. In an exploratory analysis, we also examined other cancers with at least five case parents exposed.ResultsWe identified 217 employed case fathers and 169 employed case mothers, of which 22 (10.1%) and 11 (6.5%), respectively, were exposed to benzene (vs 6.7% and 2.9% of control fathers and mothers). Most exposed parents worked as machine or engine mechanics, or in the shoe industry. Maternal occupational exposure to benzene in pregnancy was related to increased risk of ALL in offspring (adjusted OR=2.28, 95% CI 1.17 to 4.41), while paternal preconceptional benzene exposure was not as strongly associated (adjusted OR=1.40, 95% CI 0.88 to 2.22).ConclusionsOur study supports an increased risk for ALL with parental occupational benzene exposure.

scholarly journals Are survival and mortality rates associated with recruitment to clinical trials in teenage and young adult patients with acute lymphoblastic leukaemia? A retrospective observational analysis in England

BMJ Open ◽  
2017 ◽  
Vol 7 (10) ◽  
pp. e017052 ◽  
Author(s):  
Rachael Hough ◽  
Sabrina Sandhu ◽  
Maria Khan ◽  
Anthony Moran ◽  
Richard Feltbower ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Clinical Trials ◽  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Relative Survival ◽  
Data Repository ◽  
Trial Participation ◽  
Patient Benefit ◽  
Cancer Data

ObjectiveParticipation rates in clinical trials are low in teenagers and young adults (TYA) with cancer. Whilst the importance of clinical trials in informing best practice is well established, data regarding individual patient benefit are scarce. We have investigated the association between overall survival and trial recruitment in TYA patients with acute lymphoblastic leukaemia (ALL).DesignRetrospective.SettingNational (England) TYA patients treated for ALL.Participants511 patients aged 15–24 years diagnosed with ALL between 2004 and 2010 inclusive, of whom 239 (46.7%) participated in the UKALL2003 trial.Outcome measuresPatients were identified using National Clinical Trial (UKALL2003) and Cancer Registry (National Cancer Data Repository, English National Cancer Online Registration Environment) Databases. Relative survival rates were calculated for trial and non-trial patients and observed differences were modelled using a multiple regression approach. The numbers and percentages of deaths in those patients included in the survival analysis were determined for each 3-month period, p values were calculated using the two-tailed z-test for difference between proportions and 95% CIs for percentage deaths were derived using the binomial distribution based on the Wilson Score method.ResultsPatients treated on the trial had a 17.9% better 2-year survival (85.4% vs 67.5%, p<0.001) and 8.9% better 1-year survival (90.8% vs 81.9%, p=0.004) than those not on the trial. 35 (14.6%) patients recruited to the trial died in the 2 years following diagnosis compared with 86 (32.6%) of those not recruited (p<0.001).ConclusionsTYA patients recruited to the clinical trial UKALL 2003 in England had a lower risk of mortality and a higher overall survival than contemporaneous non-trial patients. These data underline the potential for individual patient benefit in participating in a clinical trial and the importance of international efforts to increase trial participation in the TYA age group.Trial registration numberISRCTN07355119.

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