Persistent Tn polyagglutination syndrome during febrile neutropenia: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Tn polyagglutination syndrome is a rare disorder that has been reported on only a few occasions in the literature, and, to the best of our knowledge, never before in the context of febrile neutropenia.</p> <p>Case presentation</p> <p>We report the case of a 26-year-old Caucasian woman who presented to our emergency department complaining of a persistent fever over the previous three days. She had a history of long-standing refractory pancytopenia with multi-lineage dysplasia and severe neutropenia, but she had rarely experienced infection. The results of a physical examination and multiple laboratory tests were unremarkable. While investigating the possible causes of the refractory, long-standing pancytopenia, the possibility of a polyagglutinable state was suggested. Blood samples were sent to the laboratory for an analysis of mixed-field seed lectin agglutination assay. A serum lectin panel confirmed the final diagnosis of Tn-activation.</p> <p>Conclusions</p> <p>We should include Tn-activation in our differential whenever we encounter cases of refractory long-standing idiopathic cytopenias and inconclusive bone marrow results displaying multi-lineage dysplasia. Novel genetic techniques have recently revealed the interesting pathophysiology of this phenomenon. The recognition and inclusion of Tn polyagglutination syndrome in our differential diagnoses has important clinical implications, given its main associated features, such as severe thrombocytopenia and neutropenia, which are usually linked to a benign clinical course and prognosis. Increased awareness of the polyagglutinable disorders will potentially decrease the need for invasive and costly medical interventions and also raises the need for monitoring of this specific sub-set of patients. In addition, the study of the expression and implications of Tn, and other similar antigens, offers a fascinating perspective for the study of its role in the diagnosis, prognosis and immunotherapy of solid tumors and hematological malignancies. The infrequency with which Tn polyagglutination syndrome is encountered, its clinical features and its pathophysiology make it a formidable diagnostic challenge.</p

Impact of targeted interventions on heterosexual transmission of HIV in India

<p>Abstract</p> <p>Background</p> <p>Targeted interventions (TIs) have been a major strategy for HIV prevention in India. We evaluated the impact of TIs on HIV prevalence in high HIV prevalence southern states (Tamil Nadu, Karnataka, Andhra Pradesh and Maharashtra).</p> <p>Methods</p> <p>A quasi-experimental approach was used to retrospectively compare changes in HIV prevalence according to the intensity of targeted intervention implementation. Condom gap (number of condoms required minus condoms supplied by TIs) was used as an indicator of TI intensity. Annual average number of commercial sex acts per female sex worker (FSW) reported in Behavioral Surveillance Survey was multiplied by the estimated number of FSWs in each district to calculate annual requirement of condoms in the district. Data of condoms supplied by TIs from 1995 to 2008 was obtained from program records. Districts in each state were ranked into quartiles based on the TI intensity. Primary data of HIV Sentinel Surveillance was analyzed to calculate HIV prevalence reductions in each successive year taking 2001 as reference year according to the quartiles of TI intensity districts using generalized linear model with logit link and binomial distribution after adjusting for age, education, and place of residence (urban or rural).</p> <p>Results</p> <p>In the high HIV prevalence southern states, the number of TI projects for FSWs increased from 5 to 310 between 1995 and 2008. In high TI intensity quartile districts (n = 30), 186 condoms per FSW/year were distributed through TIs as compared to 45 condoms/FSW/year in the low TI intensity districts (n = 29). Behavioral surveillance indicated significant rise in condom use from 2001 to 2009. Among FSWs consistent condom use with last paying clients increased from 58.6% to 83.7% (p < 0.001), and among men of reproductive age, the condom use during sex with non-regular partner increased from 51.7% to 68.6% (p < 0.001). A significant decline in HIV and syphilis prevalence has occurred in high prevalence southern states among FSWs and young antenatal women. Among young (15-24 years) antenatal clinic attendees significant decline was observed in HIV prevalence from 2001 to 2008 (OR = 0.42, 95% CI 0.28-0.62) in high TI intensity districts whereas in low TI intensity districts the change was not significant (OR = 1.01, 95% CI 0.67-1.5).</p> <p>Conclusion</p> <p>Targeted interventions are associated with HIV prevalence decline.</p

Abstract P6-07-01: Multigene profiling to identify clinically relevant actionable mutations in breast cancer: An Indian study

Abstract Background: Numerous chemotherapeutic agents are available against breast cancer (BC), but a vast majority of patients diagnosed with this disease still develop treatment resistance and eventually succumb to disease. It remains an unmet need to identify specific molecular defects against which targeted therapy are available for improving clinical outcomes in BC. Our study aims to identify frequent hotspot mutations in BCs and determine their clinical impact. Methods: 200 women with BC(early diagnosed and/or metastatic) aged 26-75 yrs (median age 50.5yrs) diagnosed at HCG from April 2013-15 were consented to be profiled by targeted deep sequencing for hotspot mutations in 48 cancer-related genes using Illumina's TSCAP panel and MiSeq technology in an IRB-approved prospective study in a CLIA compliant laboratory. All the cases had pathology review for stage, histological type, hormonal status and Ki67. The average coverage across 220 hot spots was greater than 1000X. Data was processed using Strand Avadis NGS™. Mutations identified in the tumor were assessed for 'actionability' i.e. response to therapy and impact on prognosis. Results: Somatic variants were detected in 75% of cases with direct impact on therapy or prognosis. Genetic aberrations were identified in PI3K/AKT/ mTOR signalling pathway in substantial fraction (27%) of breast cancer cases, out of which 17% had PIK3CA activating mutations,13 and 5 cases had PTEN and AKT deletions or truncating mutations respectively. Aberration in this pathway was more prevalent in HR+ve (53%) and HER2-ve including TNBC (61%) than in HR+/HER2+ve tumors (10.6%) of IDC histology. However, no correlation was found with stage and Ki67 index of the tumor. Notably 80% of BC cases presented with liver metastasis at the time of diagnosis were detected with PIK3CA mutation indicating its role as a surrogate marker of organ specific metastasis. PIK3CA was found to be co mutated with p53 in 16 cases (9%) of which 4 cases showed npCR post NACT. Also disruptive and non-disruptive mutations in TP53 alone were found in 25% of BC, varying widely among different histologies. A follow up of few cases showed shorter PFS and poor outcome in resected BC treated with NACT indicating its robust prognostic value in NACT setting. Furthermore, two patients were detected with cKIT mutations indicating sensitivity to imatinib and therefore enrolled on a clinical trial. The other variants were found in RB1(n=8),Her2 (n=2),FGFR amplification(n=1), KRAS(n=2),NRAS(n=3)CDH1(n=1),FBXW7(n=2) and EGFR(n=1).All these variants detected indicated resistance to conventional therapy and suggested sensitivity to available targeted therapy, either approved or in clinical trials. The response and outcome are being monitored in about 20 (10%) patients who have been enrolled in clinical trials and receiving mutation specific targeted therapy. Conclusions: This study confirms the utility of multigene profiling in early diagnosed and advanced BC patients, to stratify them on their molecular profile who could potentially benefit from targeted therapy. Prospective studies and randomized clinical trials are ongoing to confirm the independent prognostic and therapeutic value of the mutations in a larger cohort of Indian population. Citation Format: Ghosh M, Sheela ML, Choudhury S, Bahadur U, Patil S, Satheesh CT, Murugan K, Nayak R, Sridhar PS, Rao N, Mahesh B, Shashidhara HP, Krishnamoorthy N, Gupta V, Sankaran S, Subramanian K, Ajaikumar BS. Multigene profiling to identify clinically relevant actionable mutations in breast cancer: An Indian study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-07-01.</jats:p