scholarly journals TLR4 T399I Polymorphism and Endometriosis in a Cohort of Italian Women

Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 255 ◽  
Author(s):  
Enrica Marchionni ◽  
Maria Grazia Porpora ◽  
Francesca Megiorni ◽  
Ilaria Piacenti ◽  
Agnese Giovannetti ◽  
...  

Background: Endometriosis is a widespread multifactorial disease in which environmental, genetic, and epigenetic factors contribute to the phenotype. Single Nucleotide Polymorphisms (SNPs) in genes implicated in pivotal molecular mechanisms have been investigated as susceptible risk factors in distinct populations. Among these, Toll-like receptor 4 (TLR4) represents a good candidate due to its role in the immune/inflammatory response and endometriosis pathogenesis. Methods: The TRL4 gene T399I SNP (C/T transition, rs4986791) was investigated in 236 Italian endometriosis patients and 150 controls by using the PCR-RFLP method. One-tailed Fisher’s exact test was used to compare differences between categorical variables. T399I genotype distribution was evaluated for Hardy–Weinberg equilibrium in both groups using the Chi-squared test for given probabilities. Results: Fisher’s exact test comparing C and T allele frequencies showed a difference in the frequency of T alleles between patients and controls (OR = 1.96, 95% confidence interval 0.91–4.23; p-value = 0.0552). Genotype frequencies did not show any significant difference between patients and controls. The homozygous TT genotype was observed in 2% of endometriosis women and not in controls. Conclusions: Our results show that the TLR4 rs4986791 T variant may be considered a genetic risk factor for endometriosis in Italian women. More extensive studies in other populations are needed to confirm this result.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 78-78
Author(s):  
Helen O Donovan ◽  
Kate Murphy ◽  
Brian Richard Bird ◽  
Conleth G. Murphy

78 Background: 4 cycles ofAC chemotherapy are given as a component of several important and widely used chemotherapy regimens in the adjuvant treatment of breast cancer. We queried whether the use of dose-dense (every 2 week) AC chemotherapy is associated with a lower rate of hospitalization and resource utilization in clinical practice. Methods: We identified patients with early stage breast cancer treated with 3-weekly AC chemotherapy in a single institution. Cases were matched to controls by year of diagnosis and age. Rates of hospitalization during AC chemotherapy as well as duration of hospitalization, associated costs and use of pegfilgrastim were compared between the two groups. Fisher's exact test was used to compare categorical variables, and paired t-test was used to compare continuous variables. Results: 26 patients were included in the analysis. The mean age was 56 in both groups. As expected, rates of growth factor support with pegfilgrastim were higher in the dose dense versus 3-weekly group (52 versus 23 cycles, 2-tailed p = 0.0003). There was no difference in the likelihood of hospitalization among patients treated with dose dense versus 3-weekly AC (Fisher's exact test, p-value = 1.00). There was no difference in the mean duration of hospitalization between groups (mean 2.31 versus 1.23 days, 2-tailed p = 0.3352).Costs pertaining to pegfilgrastim use and hospitalization will be compared. Conclusions: In this clinical setting, dose dense administration of AC was not associated with lower rates or mean duration of hospitalization.


Author(s):  
Suwartono Herdhana ◽  
Andrijono

Objective: To investigate the effectiveness TCA 85% compared to cryotherapy to treat patients with positive IVA result.Method: This is a non-inferiority randomized controlled trial study. Patients with positive VIA result referred to Jatinegara Primary Health Center were included in this study. Eligible samples were then treated with either TCA 85% or cryotherapy. The treatment was determined using a random block sampling method. Samples were then followed up 3 months after treatment in order to determine VIA result conversion.Result: Thirty-six patients were treated with TCA 85% and 36 others were treated with cryotherapy. 35 (97,2%) patients treated with TCA 85% converted to negative VIA, whereas all of the patients that were treated with cryotherapy converted to negative VIA. Bivariate analysis fisher’s exact test was then conducted with a result P-value of 1.00 (p > 0,05).Conclusion: There was no statistically significant difference of result between TCA 85% and cryotherapy for treating patients with positive VIA result.Keywords: cervical cancer, cryotherapy, TCA 85%, VIA test. Abstrak Tujuan: Mengetahui efikasi TCA 85% pada tatalaksana IVA positif dibandingkan dengan krioterapiMetode: Penelitian ini merupakan penelitian randomized control trial menggunakan metode non-inferiority study. Subyek penelitian ini merupakan pasien dengan hasil IVA positif yang dirujuk ke Puskesmas Kecamatan Jatinegara, Jakarta Timur. Tatalaksana yang diberikan ditentukan menggunakan metode random block sampling. Subyek diikuti selama 3 bulan setelah tindakan untuk menentukan hasil konversi pemeriksaan IVA.Hasil: Sbenyak 36 subjek diterapi dengan TCA 85% dan 36 lainnya diterapi dengan krioterapi. Sebanyak 35 (97,2%) pasien yang ditatalaksana dengan TCA 85% mengalami konversi menjadi IVA negatif pada follow-up bulan ke-3, sedangkan seluruh pasien yang ditatalaksana dengan krioterapi menjadi konversi menjadi IVA negatif. Dilakukan analisis bivariat fisher’s exact test dan didapatkan nilai p sebesar 1,00 (p>0,05).Kesimpulan:Tidak ada perbedaan bermakna dari efikasi penggunaan TCA 85 % dibandingkan dengan krioterapi pada terapi IVA positif.Kata kunci: kanker serviks, krioterapi, pemeriksaan IVA, TCA 85%.


BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hassan Osman Alhassan Elsaid ◽  
Tarteel Gadkareim ◽  
Tagwa Abobakr ◽  
Eiman Mubarak ◽  
Mehad A. Abdelrhem ◽  
...  

Abstract Background Male factor is the major contributor in roughly half of infertility cases. Genetic factors account for 10–15% of male infertility. Microdeletions of azoospermia factors (AZF) on the Yq region are the second most frequent spermatogenesis disorder among infertile men after Klinefelter syndrome. We detected in our previous study a frequency of 37.5% AZF microdeletions which investigated mainly the AZFb and AZFc. We attempted in this study for the first time to evaluate the frequencies of all AZF sub-regions microdeletions and to analyze reproductive hormonal profiles in idiopathic cases of azoospermic and oligozoospermic men from Sudan. Methods A group of 51 medically fit infertile men were subjected to semen analysis. Four couples have participated in this study as a control group. Semen analysis was performed according to WHO criteria by professionals at Elsir Abu-Elhassan Fertility Centre where samples have been collected. We detected 12 STSs markers of Y chromosome AZF microdeletions using a multiplex polymerase chain reaction. Analysis of reproductive hormone levels including Follicle Stimulating, Luteinizing, and Prolactin hormones was performed using ELISA. Comparisons between outcome groups were performed using Student’s t-test Chi-square test or Fisher’s exact test. Results AZF microdeletion was identified in 16 out of 25 Azoospermic and 14 out of 26 of the Oligozoospermic. Microdeletion in the AZFa region was the most frequent among the 30 patients (N = 11) followed by AZFc, AZFd (N = 4 for each) and AZFb (N = 3). Among the Oligozoospermic participants, the most frequent deletions detected were in the AZFa region (N = 10 out of 14) and was significantly associated with Oligozoospermic phenotype, Fisher's Exact Test (2-sided) p = 0.009. Among the Azoospermic patients, the deletion of the AZFc region was the most frequent (N = 9 out of 16) and was significantly associated with Azoospermia phenotype Fisher's Exact Test p = 0.026. There was a significant difference in Y chromosome microdeletion frequency between the two groups. The hormonal analysis showed that the mean levels of PRL, LH, and FSH in Azoospermic patients were slightly higher than those in oligozoospermic. A weak negative correlation between prolactin higher level and Azoospermic patients was detected. (AZFa r = 0.665 and 0.602, p = 0.000 and 0.0004, AZFb r = 0.636 and 0.409, p = 0.000 and 0.025, and AZFd r = 0.398 and 0.442, p = 0.029 and 0.015). The correlation was positive for AZFa and negative for AZFb and AZFd. Conclusions We concluded in this study that the incidences of microdeletions of the Y chromosome confined to AZF a, b, c and d regions is 58.8% in infertile subjects with 31.4% were Azoospermic and 27.5% were Oligozoospermic. This might provide a piece of evidence that these specified regions of the Y chromosome are essential for controlling spermatogenesis. These findings will be useful for genetic counseling within infertility clinics in Sudan and to adopt appropriate methods for assisted reproduction.


2012 ◽  
Author(s):  
Γεώργιος Γαλανόπουλος

Στόχος της παρούσας διδακτορικής διατριβής ήταν η πειραματική μελέτη της επίδρασης της ιλοπρόστης (ανάλογο της προστακυκλίνης) στην επούλωση αναστομώσεων του παχέος εντέρου επίμυων σε συνθήκες αποφρακτικού ειλεού. Για τη μελέτη χρησιμοποιήθηκαν 80 άρρενες επίμυες, οι οποίοι χωρίστηκαν τυχαιοποιημένα σε 4 (1, 2, 3, 4) ομάδες, με 2 (α, β) ισοδύναμες υποομάδες έκαστη. Στην ομάδα 1 (ελέγχου) και 3 (ιλοπρόστη) διενεργήθηκε τμηματική εντερεκτομή και τελικοτελική αναστόμωση. Στην ομάδα 2 (ειλεός) και 4 (ειλεός και ιλοπρόστη) επιτεύχθηκαν αρχικά συνθήκες αποφρακτικού ειλεού και 24 ώρες μετά διενεργήθηκε τμηματική εντερεκτομή και τελικοτελική αναστόμωση. Η ιλοπρόστη χορηγήθηκε στις ομάδες 3 και 4 σε δόση 2μg/kg Β.Σ. σε 3ml διαλύματος NaCl 0,9% ενδοπεριτοναϊκά, διεγχειρητικά και κάθε ημέρα μέχρι τη θυσία, ενώ αντίστοιχα στις ομάδες 1 και 2 στα πειραματόζωα χορηγούνταν 3ml διαλύματος NaCl 0,9%. Σε κάθε ομάδα τα μισά πειραματόζωα (υποομάδα 1α, 2α, 3α, 4α) θυσιάστηκαν την 4η μετεγχειρητική ημέρα και τα υπόλοιπα (υποομάδα 1β, 2β, 3β, 4β) την 8η. Κατά τη νεκροτομή γινόταν μακροσκοπικός έλεγχος για ρήξη της αναστόμωσης, ύπαρξη περιτονίτιδος ή περιαναστομωτικού αποστήματος καθώς και ποσοτική αξιολόγηση των συμφύσεων σύμφωνα με την κλίμακα Van der Hamm. Ακολουθούσε μέτρηση της πίεσης διάσπασης και στη συνέχεια τμήμα της αναστόμωσης αποστέλλονταν για ιστολογική εξέταση κατά την οποία αξιολογούνταν η φλεγμονώδης αντίδραση (διήθηση από ουδετερόφιλα), η νεοαγγειογένεση, ο αριθμός των ινοβλαστών και η εναπόθεση νεοκολλαγόνου. Η ταξινόμηση των μικροσκοπικών ευρημάτων έγινε σύμφωνα με την κλίμακα Ehrlich και Hunt με τις τροποποιήσεις κατά Phillips. Επιπλέον, προσδιορίστηκε βιοχημικά η συγκέντρωση υδροξυπρολίνης και κολλαγενάσης I επί της αναστόμωσης. Για την συνοπτική παρουσίαση των αποτελεσμάτων υπολογίστηκαν απόλυτες και σχετικές συχνότητες (ποσοστά %), δείκτες κεντρικής τάσης (μέσοι όροι, διάμεσες τιμές) και δείκτες διασποράς (ελάχιστες τιμές, μέγιστες τιμές, τυπικές αποκλίσεις). Για τη σύγκριση των μέσων όρων χρησιμοποιήθηκε το κριτήριο της Ελάχιστης Σημαντικής Διαφοράς (Least Significant Difference-LSD), μετά από την εφαρμογή της μεθόδου ANOVA (Analysis of Variance). Για τις συγκρίσεις των ποσοστών, εφαρμόστηκε ο ακριβής έλεγχος του Fisher (Fisher’s Exact Test). Από την ανάλυση των πειραματικών δεδομένων προέκυψε ότι η ενδοπεριτοναϊκή χορήγηση ιλοπρόστης σε συνθήκες αποφρακτικού ειλεού, έχει ως αποτέλεσμα τον περιορισμό της αρνητικής δράσης του ειλεού στην επούλωση των αναστομώσεων του παχέος εντέρου. Συγκεκριμένα, την 4η και 8η μετεγχειρητική ημέρα ελαττώνει σημαντικά την απώλεια σωματικού βάρους. Επίσης, προάγει τη νεοαγγειογένεση, ενώ συγχρόνως αυξάνει τον πολλαπλασιασμό των ινοβλαστών και τη συγκέντρωση υδροξυπρολίνης. Επιπλέον, την 4η μετεγχειρητική ημέρα ελαττώνει τη φλεγμονώδη αντίδραση και μειώνει τη συγκέντρωση κολλαγενάσης Ι. Σταδιακά, την 8η μετεγχειρητική ημέρα αυξάνει τη σύνθεση νεοκολλαγόνου στην περιοχή της αναστόμωσης. Οι παραπάνω δράσεις έχουν ως αποτέλεσμα την αύξηση της μηχανικής ισχύος των αναστομώσεων, κατά την 4η και 8η μετεγχειρητική ημέρα, όπως αυτή προκύπτει από τη μέτρηση των πιέσεων διάσπασης. Συμπερασματικά, η άμεση μετεγχειρητική ενδοπεριτοναϊκή χορήγηση ιλοπρόστης ενισχύει τους μηχανισμούς επούλωσης και αντισταθμίζει την αρνητική δράση του ειλεού στην επούλωση των αναστομώσεων του παχέος εντέρου.


2014 ◽  
Vol 96 (4) ◽  
pp. 289-293 ◽  
Author(s):  
IG Panagiotopoulou ◽  
D Fitzrol ◽  
RA Parker ◽  
J Kuzhively ◽  
N Luscombe ◽  
...  

Introduction We receive fast track referrals on the basis of iron deficiency anaemia (IDA) for patients with normocytic anaemia or for patients with no iron studies. This study examined the yield of colorectal cancer (CRC) among fast track patients to ascertain whether awaiting confirmation of IDA is necessary prior to performing bowel investigations. Methods A review was undertaken of 321 and 930 consecutive fast track referrals from Centre A and Centre B respectively. Contingency tables were analysed using Fisher’s exact test. Logistic regression analyses were performed to investigate significant predictors of CRC. Results Overall, 229 patients were included from Centre A and 689 from Centre B. The odds ratio for microcytic anaemia versus normocytic anaemia in the outcome of CRC was 1.3 (95% confidence interval [CI]: 0.5–3.9) for Centre A and 1.6 (95% CI: 0.8–3.3) for Centre B. In a logistic regression analysis (Centre B only), no significant difference in CRC rates was seen between microcytic and normocytic anaemia (adjusted odds ratio: 1.9, 95% CI: 0.9–3.9). There was no statistically significant difference in the yield of CRC between microcytic and normocytic anaemia (p=0.515, Fisher’s exact test) in patients with anaemia only and no colorectal symptoms. Finally, CRC cases were seen in both microcytic and normocytic groups with or without low ferritin. Conclusions There is no significant difference in the yield of CRC between fast track patients with microcytic and normocytic anaemia. This study provides insufficient evidence to support awaiting confirmation of IDA in fast track patients with normocytic anaemia prior to requesting bowel investigations.


2020 ◽  
Vol 9 (1) ◽  
pp. 111-118
Author(s):  
Lumastari Ajeng Wijayanti ◽  
Eny Sendra ◽  
Ratih Novitasari ◽  
Tanti Dwi Pujaningsih

This research used cross sectional design. The population was 194 respondents and the sample was 54 respondents which are taken by using simple random sampling technique. Independent variable in this research was demographic status that was measured by questionnaire and nutritional status that was measured based on Body Mass Index (BMI). Meanwhile, dependent variable in this research was the occurrence of anemia that was measured by using spectrophotometry. Data analysis used Fisher's Exact test and Two-Sample Kolmogorov-Smirnov test (α = 0,05). Result of Fisher's Exact test was obtained that p value = 1,000 > 0,05, which meant that there was no significant correlation between demographic status and the occurrence of anemia. Meanwhile, result of Two-Sample Kolmogorov-Smirnov test was obtained that p value = 0,017 < 0,05, which meant that there was a significant correlation between nutritional status and the occurrence of anemia.


Author(s):  
M Zamzani ◽  
Hamam Hadi ◽  
Dewi Astiti

<p><strong>ABSTRACT</strong></p><p><strong><em>Background</em></strong><strong><em>s</em></strong><strong><em>:</em></strong><em> The increasing prevalence of obesity is caused by imbalance between energy input to energy output. Physical activity in children both at school and at home plays an important role in determining the nutritional status of children, including the risk of obesity. </em></p><p><strong><em>Objectives:</em></strong><em> To determine the relationship between children physical activity with obesity in Ngebel Elementary School, Tamantirto Kasihan Bantul. </em></p><p><strong><em>Methods:</em></strong><em> This study was an observational study with cross sectional design. The study population is all children grades 3, 4, and 5 Ngebel Elementary School, Tamantirto Kasihan Bantul. These samples included 96 children who met the inclusion and exclusion criteria obtained with less total sampling technique. Weight children measured using digital bathroom scales to the nearest 0.1 kg and height was measured using the nearest 0.1 cm microtoice assisted by trained enumerators. Physical activity data were obtained using a physical activity questionnaire was adopted from previous studies. Nutritional status data is calculated using the WHO software Anthro 2005. Univariate analysis using frequency distribution and bivariate analysis using </em><em>Fisher’s Exact Test</em><em>. Data were analyzed using software statistic.</em></p><p><strong><em>Results:</em></strong><em> Results analisis showed physical activity had a significant relationship with the incidence of obesity in children, with p Value 0.015 (&lt;0,05) with OR of 4.78 (95% CI: 1.36 to 16.82), </em><em>in other words children who do moderate to severe activity ≤1 hour/day had 5 times higher chance to be obese than children with moderate to severe activity &gt;1 hour/day.</em></p><p><strong><em>Conclusions:</em></strong><em> Physical activity has a significant association with obesity.</em><em> </em></p><p><strong>KEYWORDS<em>:</em></strong><em> physical activity, obesity, elementary school children</em><em></em></p><p> </p><p><strong>ABSTRAK</strong></p><p><strong><em>Latar belakang: </em></strong><em>Peningkatan prevalensi obesitas disebabkan oleh adanya ketidakseimbangan antara masukan energi dengan keluaran energi. Aktivitas fisik pada anak-anak baik di sekolah maupun di rumah berperan penting dalam penentuan status gizi anak, termasuk risiko terjadinya obesitas.<strong></strong></em></p><p><strong><em>Tujuan: </em></strong><em>Untuk mengetahui </em><em>hubungan antara aktivitas fisik dengan kejadian obesitas pada anak Sekolah Dasar Negeri Ngebel, Tamantirto Kasihan Bantul.</em></p><p><strong><em>Metode: </em></strong><em>Penelitian ini merupakan penelitian observasional dengan rancangan cross sectional. Populasi penelitian adalah semua anak kelas 3, 4, dan 5 SDN Ngebel, Tamantirto Kasihan Bantul. Sampel penelitian berjumlah </em><em>96 </em><em>anak yang memenuhi kriteria inklusi dan eksklusi diperoleh dengn teknik total sampling. Berat anak-anak diukur dengan menggunakan timbangan injak digital dengan ketelitian 0,1 kg, sedangkan tinggi badan diukur menggunakan microtoise dengan ketelitian 0,1 cm dibantu oleh enumerator terlatih. Data aktivitas fisik diperoleh menggunakan kuesioner aktivitas fisik yang diadopsi dari</em><em> penelitian sebelumnya</em><em>. Data status gizi dihitung dengan menggunakan software WHO Anthro 2005. Analisis univariat menggunakan distribusi frekuensi dan analisis bivariat menggunakan</em><em> Fisher’s Exact Test</em><em>. Data dianalisis dengan menggunakan program software statistic.</em></p><p><strong><em>Hasil: </em></strong><em>Hasil a</em><em>nalisis </em><em>menunjukkan aktivitas fisik memiliki hubungan yang signifikan dengan kejadian obesitas pada anak dengan </em><em>nilai p value 0,009 (&lt;0,05) dengan nilai OR 5,69 (95% CI: 1,42-22,65), dengan kata lain anak yang melakukan aktivitas sedang-berat ≤1 jam/hari berpeluang 5 kali lebih besar untuk mengalami obesitas daripada anak dengan aktivitas sedang-berat &gt;1 jam/hari.</em></p><p><strong><em>Kesimpulan: </em></strong><em>Aktivitas fisik memiliki hubungan secara bermakna dengan obesitas.</em><strong><em></em></strong></p><p><strong>KATA KUNCI: </strong><em>aktivitas fisik, obesitas, anak SD</em></p>


2001 ◽  
Vol 47 (4) ◽  
pp. 645-653 ◽  
Author(s):  
Anne Mette Høgh ◽  
Thomas Vauvert F Hviid ◽  
Britta Christensen ◽  
Steen Sørensen ◽  
Rasmus D Larsen ◽  
...  

Abstract Background: Information about the appearance of γ-, ε-, and ζ-globin mRNAs in fetal erythroblasts during gestation and about the presence and amounts of these mRNAs in pregnant and nonpregnant women is important from the perspective of using these molecules as a marker of fetal erythroblasts. A specific marker is necessary for isolation and identification of fetal nucleated red blood cells from maternal blood samples for use in antenatal diagnosis of fetal genetic or chromosomal abnormalities. Methods: We used a very sensitive reverse transcription-PCR (RT-PCR) method, coamplification analysis of γ- and ε-globin cDNA, and quantitative analysis of γ-globin mRNA based on competitive RT-PCR to investigate these aspects. Results: All adult whole-blood samples were negative for ε- and ζ-globin mRNA. Analyses of CD71+ cell fractions showed that specimens from 19 of 20 nonpregnant and 10 of 14 pregnant women (at 9–13 weeks of gestation) were positive for γ-globin mRNA (Fisher’s exact test, P = 0.13), and those from 3 of 20 nonpregnant and 5 of 14 pregnant women were positive for ζ-globin mRNA (Fisher’s exact test, P = 0.23). No ε-globin mRNA was detected in CD71+ cell fractions from 1-mL blood samples from adults. CD71+ cell fractions from eight fetal blood samples (at 17–20 weeks of gestation) were positive for all three globin mRNAs. We found no statistically significant difference between the amounts of γ-globin mRNA in pregnant and nonpregnant women. Conclusions: This study indicates that ε-globin mRNA might function as a marker for fetal CD71+ cells early in pregnancy. Although γ-globin mRNA can be detected in CD71+ cell fractions from most adults, these transcripts also may be of use because of a marked difference between adult and fetal values.


2012 ◽  
Vol 78 (6) ◽  
pp. 693-697
Author(s):  
Alfred John Colfry ◽  
Xu Zhang ◽  
George M. Fuhrman

We hypothesize that the diminishing role of axillary node dissection (ALND) in early stage breast cancer could be further reduced in patients with advanced disease depending on the response to neoadjuvant chemotherapy (NC). We reviewed records of patients managed with NC and recorded demographics, tumor characteristics, pre/postoperative axillary nodal status, and NC response. We define a response to NC as follows: T2 tumors at least a 50 per cent reduction in the product of the length and width of the tumor and in T3–4 tumors a reduction in tumor size to less than 2 cm. We defined a negative axillary nodal status as either a negative sentinel node biopsy before or after NC or a negative ALND. We defined a positive axillary nodal status as clinical persistence of nodal disease despite NC or involved nodes determined by ALND. Fisher's exact test was used to evaluate the association between response to NC and nodal status. Over the past 4 years, 35 patients have completed NC and surgical treatment including lymph node assessment. Sixteen cancers demonstrated a response to NC and two (12.5%) had positive lymph nodes. Nineteen cancers failed to respond to NC and 13 (68.4%) had involved lymph nodes. Fisher's exact test shows a strong association between NC response and nodal status (two-tailed P value 0.0016). Patients with advanced locoregional breast cancer that respond to NC are unlikely to benefit from ALND. If this study's findings are confirmed in larger trials, ALND could be limited to patients with advanced locoregional breast cancer unresponsive to NC.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2747-2747
Author(s):  
Chern Siang Lee ◽  
Margaret Ashton-Key ◽  
Sergio Cogliatti ◽  
Susanne Crowe ◽  
Mark S Cragg ◽  
...  

Abstract Abstract 2747 Background: Single-agent immunotherapy with rituximab is a viable treatment option for low risk FL, with limited toxicity and a long duration of response in some patient subsets. We have previously shown that high expression of FcγRIIB promotes rituximab internalisation on various B cell targets, including FL (Blood 2011 118:2530–2540), something not seen with type II anti-CD20 antibodies. The SAKK 35/98 trial examined rituximab monotherapy in FL and now has long-term follow-up data of almost 10 years (JCO 2010 28:4480–4484). We analysed diagnostic tumour samples from this trial to determine the relationship of FcγRIIB expression to responses and clinical outcomes after rituximab treatment in FL. Methods: 202 patients (pts) with newly diagnosed or relapsed FL received induction treatment with rituximab 375 mg/m2 weekly for 4 weeks. Pts with stable or responding disease at week 12 were randomized into 2 groups: no further treatment or prolonged treatment with single infusions of rituximab 375 mg/m2 at weeks 12, 20, 28 and 36. Archived tissue samples from 135 evaluable pts were stained using an anti-human FcγRIIB antibody (clone EP888Y, Abcam) at a dilution of 1:3000 on a Dako autostainer. The samples were pretreated with the Dako EnVisionFLEX target retrieval solution high pH and detection using the Dako AS-Link 48 with Dako EnVision flex plus detection kit. Positive samples were graded into negative/low intensity staining (n=120) versus medium/high (n=13) by an expert lymphoma histopathologist blinded to the clinical outcomes. Data from 2 slides and response at week 12 data for 4 pts were unavailable (1 of whom also has missing slide data), resulting in 130 pts available for analysis. Failure-free survival (FFS) was defined as time from registration until failure to achieve complete/partial response at week 12, progression, relapse, a second cancer or death from any cause. Objective response rate (ORR) was associated with intensity staining levels using Fisher's exact test. All time-to-event endpoints were evaluated using the Kaplan-Meier method; groups were compared using the log-rank test. The hazard ratio (HR) was assessed using Cox proportional hazards models. Results: Registered and randomised pts had very similar baseline characteristics; previously untreated pts had slightly more favourable characteristics but were balanced between the 2 treatment arms. Pts expressing medium/high levels of FcγRIIB were less likely to respond to rituximab by week 12 (ORR 58.1% vs 23.1%, Fisher's exact test, p=0. 02), a finding independent of prior therapy. For FFS, there was a statistically significant difference (p=0.001; HR=0.42; 95% confidence interval (C.I.): 0.23–0.77) between the negative/low staining group (median: 21.4 months; 95% C.I.: 7.0–34.2) and the medium/high staining group (median: 7.0 months; 95% C.I.: Not calculable). The interaction between staining levels and randomised treatment groups for FFS was not statistically significant. There was a non-significant trend towards better overall survival in the low/negative group (median: 140.0 vs 50.0 months; p=0.15; HR=0.57; 95% C.I.: 0.27–1.23); however the event rate was lower (36.8% vs 61.5%). Conclusion: Elevated FcγRIIB expression level is associated with poor response to rituximab in pts with FL. This group may show better results with non-internalising type II antibodies, a hypothesis for validation in future prospective clinical trials. Disclosures: Ghielmini: Roche: Honoraria, Speakers Bureau. Johnson:Roche: Honoraria.


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