scholarly journals Antithyroid Antibodies and Thyroid Function in Pediatric Patients with Celiac Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Derya Kalyoncu ◽  
Nafiye Urganci
Keyword(s):  
Celiac Disease ◽  
Thyroid Function ◽  
Pediatric Patients ◽  
Thyroid Stimulating Hormone ◽  
Free Triiodothyronine ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Antithyroid Antibodies ◽  
Significant Difference

Objective. Aim of the study was to determine the prevalence of autoimmune thyroid disease, persistence of antithyroid antibodies, effect of gluten-free diet, and long-term outcome of thyroid function in pediatric patients with celiac disease (CD).Methods. 67 patients with CD aged from 1 year to 16 years were screened for thyroid antithyroperoxidase, antithyroglobulin and anti-TSH receptor antibodies, serum free triiodothyronine, free thyroxine, and thyroid-stimulating hormone (TSH) at diagnosis and during follow-up.Results. None of the patients had antithyroid antibodies at diagnosis. Antithyroid antibodies became positive in 16.4% of the patients (11/67) 2 to 3 years after the diagnosis of CD. Clinical hypothyroidism was observed only in 3 of 11 CD patients with positive antithyroid antibodies (27.2%). The antithyroid antibodies positive and negative patients did not differ significantly according to compliance to GFD (P>0.05). A statistically significant difference was observed only in age, in which the patients with positive antithyroid antibodies were younger than the patients with negative antithyroid antibodies (P=0.004). None of the patients had any change in their thyroid function and antibody profile during their follow-up.Conclusion. Antithyroid antibodies were detected in younger pediatric patients with CD and the prevalence of antithyroid antibodies did not correlate with the duration of gluten intake.

scholarly journals Correlation of Triiodothyronine Level with In-Hospital Cardiac Function and Long-Term Prognosis in Patients with Acute Myocardial Infarction

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Jianqing She ◽  
Jiahao Feng ◽  
Yangyang Deng ◽  
Lizhe Sun ◽  
Yue Wu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Survival Analysis ◽  
Cardiac Function ◽  
Thyroid Function ◽  
Major Adverse Cardiovascular Events ◽  
Free Triiodothyronine ◽  
Kaplan Meier ◽  
Significant Difference

Objective. The pathophysiologic mechanism of how thyroid function is related to the development and prognosis of acute myocardial infarction (AMI) remains under explored, and there has been a lack of clinical investigations. In this study, we investigate the relationship between triiodothyronine (T3) level and cardiac ejection fraction (EF) as well as probrain natriuretic peptide (NT-proBNP) on admission and subsequent prognosis in AMI patients. Methods. We measured admission thyroid function, NT-proBNP, and EF by echocardiography in 345 patients diagnosed with AMI. Simple and multiregression analyses were performed to investigate the correlation between T3 level and EF as well as NT-proBNP. Major adverse cardiovascular events (MACE), including new-onset myocardial infarction, acute heart failure, and cardiac death, were documented during the follow-up. 248 participants were separated into three groups based on T3 and free triiodothyronine (FT3) levels for survival analysis during a 2-year follow-up. Results. 345 patients diagnosed with AMI were included in the initial observational analysis. 248 AMI patients were included in the follow-up survival analysis. The T3 levels were found to be significantly positively correlated with EF (R square=0.042, P<0.001) and negatively correlated with admission NT-proBNP levels (R square=0.059, P<0.001), which is the same with the correlation between FT3 and EF (R square=0.053, P<0.001) and admission NT-proBNP levels (R square=0.108, P<0.001). Kaplan-Meier survival analysis revealed no significant difference with regard to different T3 or FT3 levels at the end of follow-up. Conclusions. T3 and FT3 levels are moderately positively correlated with cardiac function on admission in AMI patients but did not predict a long-time survival rate. Further studies are needed to explain whether longer-term follow-up would further identify the prognosis effect of T3 on MACE and all-cause mortality.

scholarly journals Thyroid Function Changes and Pubertal Progress in Females: A Longitudinal Study in Iodine-Sufficient Areas of East China

2021 ◽  
Vol 12 ◽  
Author(s):  
Yingying Wang ◽  
Dandan He ◽  
Chaowei Fu ◽  
Xiaolian Dong ◽  
Feng Jiang ◽  
...  
Keyword(s):  
Linear Regression ◽  
Multiple Linear Regression ◽  
Thyroid Function ◽  
Pubertal Development ◽  
Thyroid Stimulating Hormone ◽  
East China ◽  
Regression Analyses ◽  
Free Triiodothyronine ◽  
Serum Tsh

BackgroundThe onset of puberty is influenced by thyroid function, and thyroid hormones (THs) fluctuate substantially during the period of pubertal development. However, it needs to be further clarified how THs change at specific puberty stages and how it influences pubertal development in girls. So far, longitudinal data from China are scarce.MethodsA cohort study was conducted among girls during puberty in iodine-sufficient regions of East China between 2017 to 2019. Serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were determined for each participant. Thyroid homeostasis structure parameters (THSPs), including the ratio of FT4 to FT3 (FT4/FT3), Jostel’s TSH index (TSHI), and thyroid feedback quantile-based index (TFQI), were calculated. Puberty category scores (PCS), calculated based on the Puberty Development Scale (PDS), was used to assess the stage of puberty. Girls were grouped into three categories according to PCS changes (△PCS) and six categories according puberty stage (BPFP: pre-pubertal at both baseline and follow-up; BPFL: pre-pubertal at baseline and late-pubertal at follow-up, respectively; BPFT: pre-pubertal at baseline and post-pubertal at follow-up, respectively; BLFL: late-pubertal at both baseline and follow-up; BLFT: late-pubertal at baseline and post-pubertal at follow-up, respectively; BTFT: post-pubertal at both baseline and follow-up). Multiple linear regression analyses were used to evaluate the associations of THs changes with pubertal progress.ResultsThe levels of serum TSH and FT3 decreased while serum FT4 increased during the study period (P&lt;0.001). In multiple linear regression analyses, after adjustment for covariables, FT3 decreased by an additional 0.24 pmol/L (95% CI: -0.47 to -0.01) in the higher △PCS group than the lower △PCS group. Compared with the BLFL group, the BPFT group showed an additional decline in FT3 (β= -0.39 pmol/L, 95%CI: -0.73 to -0.04), the BTFT group showed a lower decline in TSH (β=0.50 mU/L, 95% CI: 0.21 to 0.80) and a lower decline in TSHI (β=0.24, 95%CI: 0.06 to 0.41), respectively. There was no association of △FT4 or △TFQI with △PCS or the puberty pattern.ConclusionsSerum TSH and FT3 decreased while serum FT4 increased among girls during puberty. Both the initial stage and the velocity of pubertal development were related to thyroid hormone fluctuations.

Peri-interventional endothelin-A receptor blockade improves long-term outcome in patients with ST-elevation acute myocardial infarction

2014 ◽  
Vol 112 (07) ◽  
pp. 176-182 ◽  
Author(s):  
Michael Humenberger ◽  
Martin Andreas ◽  
Bassam Redwan ◽  
Klaus Distelmaier ◽  
Günter Klappacher ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Receptor Blockade ◽  
Event Free Survival ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Free Survival ◽  
Amino Terminal ◽  
Significant Difference ◽  
St Elevation

SummaryEndothelin (ET)-1 is a pro-fibrotic vasoconstrictive peptide causing microvascular dysfunction and cardiac remodelling after acute ST-elevation myocardial infarction (STEMI). It acts via two distinct receptors, ET-A and ET-B, and is involved in inflammation and atherogenesis. Patients with posterior-wall STEMI were randomly assigned to intravenous BQ-123 at 400 nmol/minute (min) or placebo over 60 min, starting immediately prior to primary percutaneous coronary intervention (n=54). Peripheral blood samples were drawn at baseline as well as after 24 hours and 30 days. Myeloperoxidase (MPO), as a marker of neutrophil activation and matrix metalloproteinase 9 (MMP-9), a marker of extracellular matrix degradation were measured in plasma. Clinical follow-up was conducted by an investigator blinded to treatment allocation over three years. During the median follow-up period of 3.6 years (interquartile range [IQR] 3.3–4.1) we observed a longer event-free survival in patients randomised to receive BQ-123 compared with patients randomised to placebo (mean 4.5 years (95% confidence interval: 3.9–5) versus mean 3 years (2.2–3.7), p=0.031). Patients randomised to ET-A receptor blockade demonstrated a greater reduction of MPO levels from baseline to 24 hours compared to placebo-treated patients (-177 ng/ml (IQR 103–274) vs –108 ng/ml (74–147), p=0.006). In addition, a pronounced drop in MMP-9 levels (-568 ng/ml (44–1157) vs –117 ng/ml (57–561), p=0.018) was observed. There was no significant difference in amino-terminal propetide of pro-collagen type III levels. In conclusion, short-term administration of BQ-123 leads to a reduction in MPO, as well as MMP-9 plasma levels and to a longer event-free survival in patients with STEMI.ClinicalTrials.gov Identifier: NCT00502528

Long-Term Follow-Up Analysis of HD9601 Trial Comparing ABVD Versus Stanford V Versus MOPP/EBV/CAD in Patients With Newly Diagnosed Advanced-Stage Hodgkin's Lymphoma: A Study From the Intergruppo Italiano Linfomi

2011 ◽  
Vol 29 (32) ◽  
pp. 4227-4233 ◽  
Author(s):  
Teodoro Chisesi ◽  
Monica Bellei ◽  
Stefano Luminari ◽  
Antonella Montanini ◽  
Luigi Marcheselli ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Disease Free Survival ◽  
Hodgkin's Lymphoma ◽  
Advanced Stage ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Free Survival ◽  
Significant Difference

Purpose The Intergruppo Italiano Linfomi HD9601 trial compared doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) versus doxorubicin, vinblastine, mechloretamine, vincristine, bleomycin, etoposide, and prednisone (Stanford V [StV]) versus the combination of mechlorethamine, vincristine, procarbazine, prednisone (MOPP) with epidoxorubicin, bleomycin, vinblastine (EBV), lomustine, doxorubicin, and vindesine (CAD) (MOPP/EBV/CAD [MEC]) for the initial treatment of advanced-stage Hodgkin's lymphoma to select which regimen would best support a reduced radiotherapy program (limited to two or fewer sites of either previous bulky or partially remitting disease). Superiority of ABVD and MEC to StV was demonstrated. We report analysis of long-term outcome and toxicity. Patients and Methods Patients with stage IIB, III, or IV were randomly assigned among six cycles of ABVD, three cycles of StV, and six cycles of MEC; radiotherapy was administered in 76, 71, and 50 patients in the three arms, respectively. Results Currently, the median follow-up is 86 months; in the prolonged observation period, eight additional failures, including two relapses, both in the StV arm, and six additional deaths in complete response were recorded. The 10-year overall survival rates were 87%, 80%, and 78% for ABVD, MEC, and StV, respectively (P = .4). The 10-year failure-free survival was 75%, 74%, and 49% in the ABVD, MEC, and StV arms, respectively (P < .001). The 10-year disease-free survival of patients treated or not with radiotherapy (RT) showed no difference for ABVD or MEC (85% v 80% and 93% v 68%), and a statistically significant difference for StV (76% v 33%; P = .004). No significant long-term toxicity was recorded. Conclusion The long-term analysis confirmed ABVD and MEC superiority to StV. The use of RT after StV was established as mandatory. ABVD is still to be considered as the standard treatment with a good balance between efficacy and toxicity.

scholarly journals Variation in thyroid function in subclinical hypothyroidism: importance of clinical follow-up and therapy

2011 ◽  
Vol 164 (3) ◽  
pp. 317-323 ◽  
Author(s):  
Jesper Karmisholt ◽  
Stig Andersen ◽  
Peter Laurberg
Keyword(s):  
Thyroid Function ◽  
Subclinical Hypothyroidism ◽  
Repeated Measurements ◽  
Thyroid Peroxidase ◽  
Biochemical Tests ◽  
Free Triiodothyronine ◽  
Significant Difference ◽  
Hypothyroid Patients ◽  
Symptoms And Signs

Subclinical hypothyroidism (SCH) is a common condition that is often observed without therapy. However, no evidence-based recommendation exists with regards to how patients with untreated SCH should be monitored.Monitoring involves regular assessment of symptoms and signs of hypothyroidism (HYPO) and biochemical tests of thyroid function. An important question when repeated tests of thyroid function are performed is how large a difference in test results is needed to be confident that the change is real and not just due to chance variation.Recent data show that the least significant difference between two tests in SCH is 40% for TSH and 15% for free thyroxine and free triiodothyronine, with 90% confidence. Furthermore, monitoring has to be based on biochemical function testing because serial evaluation of symptoms and signs related to HYPO is rather insensitive in detecting worsening of thyroid insufficiency.When the presence of thyroid peroxidase auto-antibodies (TPO-Ab) in serum has been demonstrated, repeated measurements do not add much useful information in the monitoring of individual subclinical hypothyroid patients, as levels of TPO-Ab vary in parallel with TSH in these patients.Lastly, we discuss how differences in the monitoring procedure influence the diagnostic outcome, and we suggest a follow-up approach for untreated subclinical hypothyroid patients.

scholarly journals Relationship between Different Psoriasis Types and Thyroid Dysfunction: A Retrospective Analysis

Scanning ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Juan Du ◽  
Chunyue Ma ◽  
Runnan Wang ◽  
Lanmei Lin ◽  
Luhui Gao ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Peroxidase ◽  
Thyroid Function Tests ◽  
Free Triiodothyronine ◽  
Hormone Levels ◽  
Significant Difference ◽  
Total Thyroxine

Objective. The aim of this study was to investigate the relationship between different psoriasis types and thyroid dysfunction. Methods. The data of patients diagnosed with psoriasis between January 2013 and October 2018 who underwent thyroid function tests were collected. Free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), total thyroxine (TT4), thyroid-stimulating hormone (TSH), thyroglobulin antibody (TGAb), and thyroid peroxidase antibody (TPOAb) were measured. The thyroid function of patients with psoriasis vulgaris, pustular psoriasis, erythrodermic psoriasis, and psoriatic arthritis was evaluated, and the differences in hormone levels and antibodies in the pituitary-thyroid axis with psoriasis type were analyzed. Results. The data of a total of 468 patients were analyzed in this study. The proportion of normal hormone levels was higher among vulgaris patients ( P < 0.001 ), while the erythrodermic patients were more likely to have decreased FT3 or FT4 but normal TSH ( P < 0.001 ). FT3 levels were lower in pustular patients ( P < 0.05 ), FT4 levels were lower in erythrodermic patients ( P < 0.05 ), and TSH levels were higher in patients with psoriatic arthritis ( P < 0.05 ). TPOAb levels were higher than normal in all patients, but there was no significant difference in the levels of TPOAb and TGAb among 4 types of the patients. Conclusion. Psoriasis is related to thyroid dysfunction, especially in patients with atypical psoriasis types. The possibility of complications should be considered in erythrodermic patients.

P2267CTEPH patients long term follow-up: results from a single center

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Mladoniczky ◽  
M Szegedi ◽  
Z S Piroth ◽  
J Nemeth ◽  
L Ablonczy ◽  
...  
Keyword(s):  
Nyha Class ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Walking Distance ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Post Surgery ◽  
Significant Difference ◽  
Long Term Follow Up

Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a thrombotic pulmonary disease associated with pulmonary vasculopathy. Pulmonary endarterectomy (opus, PEA) is the first treatment choice in CTEPH, and specific PAH medication when there is a contraindication for surgery or residual pulmonary arterial hypertension (rPAH) occurs. In the presence of PAH balloon pulmonary angioplasty (BPA) might be also recommended if available. Objective We investigated the long term outcome of our CTEPH patients. Methods CTEPH from our institution retrospectively analyzed (data between 2003 and 2018). Baseline, treatment and outcome data were documented. We compared the outcome, together with mortality in those with and without surgery (PEA vs. non PEA group). NYHA class, 6 minutes walking distance (6MWD) and NT-proBNP were also reported during follow-up. Results Of 29 CTEPH patients (mean age was 62±19 years, 52% male) 16 (55%) were accepted for PEA, and further 12 of them had a long term follow-up post surgery (n=3 periop exit, n=1 waiting for surgery). Half of the PEA patients were cured (n=6) and the other half (n=6) required specific PAH treatment (n=1, in combination with BPA) for rPAH. All patients from the non-PEA group (n=13) were started on specific PAH treatment (n=1 in combination with BPA). Patients with or without PEA did not differ hemodynamically. At the late follow-up there was a significant improvement in PEA group for NYHA class and NT-proBNP (p<0,001, and p=0,046), and in non PEA group for NYHA class and the 6MWD (p=0,012, and 0,006). We found significant difference in mortality at 1,3,5 year (Kaplan-Meier survival analysis) follow-up, for PEA group 100%-100%-100% and non PEA group 100%-85%-78% (p=0,013), respectively. Conclusions 55% of CTEPH patients were suitable for PEA, and those who survived the surgery 50% were cured. Non PEA patients improved functionally on the long term, but had worse survival.

scholarly journals SAT-LB60 Discordant Biological Parameters of Remission in Acromegaly Do Not Increase the Risk of Hypertension or Diabetes: A Study With the Liege Acromegaly Survey Database

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Vincent Amodru ◽  
Patrick Petrossians ◽  
Annamaria Colao ◽  
Brigitte Delemer ◽  
Luigi Maione ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Biochemical Parameters ◽  
Biological Parameters ◽  
Tertiary Referral ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Significant Difference ◽  
Active Disease

Abstract Introduction: Acromegaly is a rare disease due to growth hormone (GH)-secreting pituitary adenoma. GH and IGF-1 levels are usually congruent, indicating either remission or active disease, however a discrepancy between GH and IGF-1 may occur. We aimed to evaluate the outcome of acromegalic comorbidities in patients with congruent GH and/or IGF-1 levels vs discordant biochemical parameters. Methods: Retrospective analysis of the data of 3173 patients from the Liège Acromegaly Survey (LAS) allowed to include 190 patients from 8 tertiary referral centers across Europe, treated by surgery, with available data concerning diabetes mellitus (DM) and hypertension (HT) both at diagnosis and at last follow-up. We recorded for all the patients the number of antihypertensive and antidiabetic drugs used at the first evaluation and at last follow-up. Results: Ninety-nine patients belonged to the REM group (Concordant parameters), sixty-five patients were considered as GHdis and 26 patients were considered as IGF-1dis. At diagnosis, 63 patients (33.1%) had HT and 54 patients had DM (28.4%). There was no statistically significant difference in terms of number of anti-HT and anti-diabetic drugs at diagnosis versus last follow-up (mean duration=7.3+/-4.5years) between all 3 groups. Discussion: The results highlight that the long-term outcome of acromegaly does not tend to be more severe in patients with biochemical discordance in comparison with patients considered as in remission on the basis of concordant biological parameters, suggesting that patients with biochemical discordance do not require a closer follow-up.

Meta-analysis of gender effect for first-line chronomodulated 5-fluorouracil-leucovorin-oxaliplatin (ChronoFLO) compared with FOLFOX or constant infusion (conventional delivery, CONV) against metastatic colorectal cancer (MCC) in three international controlled phase III randomized trials (RT)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4112-4112 ◽  
Author(s):  
F. Levi ◽  
P. Innominato ◽  
A. Poncet ◽  
T. Moreau ◽  
S. Iacobelli ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Constant Infusion ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Significant Difference

4112 Background: Gender predicted for the most effective schedule in a RT of ChronoFLO vs CONV against MCC: overall survival (OS) was significantly increased in men on chronoFLO vs FOLFOX, whereas the reverse was found in women (Giacchetti, JCO 2006). Methods: To assess the relevance of gender for patient (pt) outcome, meta-analysis was performed on individual pt data (IPD) from 3 RT in 845 MCC pts treated with chronoFLO vs CONV (346 F, 499 M at 36 centers in 1990–2002)(Lévi, JNCI 1994; Lancet 1997). Data bases were merged and updated at 9 y after inclusion of the 1st pt. Main prognostic factors were comparable in each RT according to gender and treatment arm (median age: 61y; PS=0, 46% pts; liver M, 85% pts; liver involvement >25%, 41% pts; lung M, 37% pts; CEA>10, 56% pts). Results: No significant difference was found according to delivery schedule or gender in the whole population for Response Rate (RR), Progression-Free Survival (PFS) and OS. However, men on chronoFLO had highest RR, longest PFS and OS. PFS and OS were highest in women on CONV ( Table ). The rate of complete macroscopic resections of liver metastases (R0+R1) was 12.5% in men on chronoFLO vs 7.8–8.5% in men on CONV or in women on either schedule. A complete histologic response of liver metastases was documented in 2.1% of the men on chronoFLO vs 0–1.1% in the other groups. The relative risk of an earlier death in men vs women was 0.76 [95% CL, 0.91 to 0.94] on chronoFLO and 1.24 [0.99 to 1.56] on CONV. Conclusions: This IPD meta-analysis of 3 RT in MCC with a minimum follow up of 5 years confirms that men benefit from chronoFLO as compared to CONV delivery, with regard to long term outcome and medico-surgical strategy. ChronoFLO should be preferred to conventional oxaliplatin-5-FU-LV schedules in men with MCC. Support: ARTBC Internationale, P. Brousse Hospital, Villejuif, France. [Table: see text] No significant financial relationships to disclose.

No Evidence That PTEN Abnormalities Impact on Outcome in Pediatric Patients with T-Cell Acute Lymphoblastic Leukemia (T-ALL) Treated on the MRC UKALL2003 Trial

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1077-1077
Author(s):  
Sarah Jenkinson ◽  
Amy A Kirkwood ◽  
Nicholas Goulden ◽  
Ajay J. Vora ◽  
Chris Mitchell ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Pediatric Patients ◽  
Response To Therapy ◽  
Heteroduplex Analysis ◽  
Pten Gene ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Good Outcome ◽  
Significant Difference

Abstract Although outcome has improved for pediatric patients with T-ALL, ≈25% of cases relapse and prognosis post-relapse remains poor. Molecular characterisation at diagnosis can provide additional information for risk-stratification. We previously reported that patients with double NOTCH1 or NOTCH1+FBXW7 mutations (NOTCH1±FBXW7Double) have a very good outcome and should not be considered for more intensive therapy in first remission, even if slow responders or MRD-positive after induction therapy. However, recent studies have suggested that this may be modulated by the presence of coincident abnormalities such as in the PTEN gene. Truncating mutations and genomic loss of this gene have been described in T-ALL, but their prognostic impact in patients is unclear, with reports of either no effect or reduced event-free survival (EFS). Furthermore, subgroup analysis has shown that the adverse impact of a PTEN mutation is either not seen in the presence of a NOTCH1 mutation or, conversely, that it ablates the benefit of a NOTCH1 mutation. In order to determine whether these abnormalities impact on the good outcome seen in NOTCH1±FBXW7Double cases in our cohort, and whether they can refine stratification of cases with single NOTCH1 mutations (NOTCH1Single) or wild-type NOTCH1 (NOTCH1WT), we investigated PTEN genotype in samples from 145 patients treated on the MRC UKALL2003 trial and correlated this with outcome in the different subgroups. The entire coding region (exons 1-9) of the PTEN gene was screened for mutations using heteroduplex analysis. Samples with abnormal chromatograms were further investigated. Mutations were detected in 21 patients (14%); 17 (81%) had exon 7 mutations, 2 exon 6+7, and 2 exon 5 mutations. All were small insertions, deletions or indels; 89% were predicted to lead to C-terminal truncation and loss of protein function, 11% were in-frame size changes. Exon 7 mutant levels were quantified by size analysis in 19 patients; median total mutant level was 48% of all PTEN alleles (range, 10%-96%). Of note, in the 21 mutated cases, only 7 (33%) had a single mutation; 8 had 2, 3 had 3, and 3 had 4 mutations. Based on total mutant level, 11 cases were considered to have monoallelic (heterozygous) mutations and 10 cases biallelic (homozygous/hemizygous or compound heterozygous) mutations. To investigate loss of genomic material, Illumina CytoSNP-850k SNP array analysis was performed on all samples. Partial or complete loss of the PTEN gene was detected in 15 patients (10%), 12 with heterozygous and 3 homozygous loss. This data was consistent with quantitative analysis of the relative allele levels of two common intronic SNPs (rs1903858 and rs555895) studied in 76 informative patients, which indicated that in 2 of 6 informative cases with heterozygous loss, only the 3’ end of the gene was deleted. Putting together the mutation and SNP data, 32 patients (22%) had abnormalities in the PTEN gene (PTENABN), 19 (59%) scored as monoallelic (PTENMONO), and 13 (41%) biallelic (PTENBI). There was no significant difference according to overall PTEN genotype in either early response to therapy (P>.99) or MRD status at day 29 of induction therapy (P=.28). Long-term outcome also did not significantly differ, EFS at 5 years was 78% in PTENABN and 85% in PTENWT patients (P=.37), overall survival (OS) 81% and 91% respectively (P=.1). These results did not change if grouped according to PTEN type, EFS 74% in PTENMONO and 85% in PTENBI patients (P=.46), although the number of patients in these groups was very small. The incidence of PTEN abnormalities did not differ according to NOTCH1/FBXW7 genotype, 59% PTENABN patients had a NOTCH1/FBXW7 mutation compared to 67% PTENWT patients (P=.7). There was no evidence that PTEN genotype impacted on the favorable outcome of the NOTCH1±FBXW7Double group, none of the 5 PTENABNNOTCH1±FBXW7Double patients relapsed and all remain alive. Similarly, no significant difference was observed in the NOTCH1Single and NOTCH1WT patients. In conclusion, although we found that loss of PTEN through either gene mutation or genomic deletion was relatively common in pediatric T-ALL patients, including total loss of PTEN in nearly one-half of mutated patients, this appeared to have no effect on either response to treatment or long-term outcome with current therapies, and therefore screening of PTEN is not warranted in pediatric T-ALL for potential use in risk-adapted therapy. Disclosures No relevant conflicts of interest to declare.

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