tbuckley/cabot-search huggingface dataset:
Biomarker analysis from the KEYNOTE-199 trial of pembrolizumab in patients (pts) with docetaxel-refractory metastatic castration-resistant prostate cancer (mCRPC).
Authors: Emmanuel S. Antonarakis, Jose Maria M. Piulats Rodriguez, Marine Gross-Goupil, Jeffrey C. Goh, Ulka N. Vaishampayan, Ronald De Wit, Tuomo Alanko, Satoshi Fukasawa, Kenichi Tabata, Susan Feyerabend, Raanan Berger, Haiyan Wu, Jeri Kim, Charles Schloss, Ping Qiu, Leah Suttner, Razvan Cristescu, Matthew John Marton, Johann S. De Bono
Journal: Journal of Clinical Oncology (2020)

5526 Background: In the phase II KEYNOTE-199 study (NCT02787005), pembrolizumab monotherapy demonstrated antitumor activity in pts with docetaxel-refractory mCRPC (n = 258). Here we evaluated the association between prespecified molecular biomarkers and clinical outcomes. Methods: Cohorts 1 (C1) and 2 (C2) enrolled pts with RECIST-measurable PD-L1–positive (combined positive score [CPS] ≥1 using immunohistochemistry) and PD-L1–negative (CPS &lt;1) disease, respectively. C3 enrolled pts with nonmeasurable, bone-predominant disease, irrespective of PD-L1 status. Biomarkers evaluated in this analysis were tumor mutational burden ([TMB; mutations/exome] n = 155), PD-L1 CPS (n = 255), tumor microenvironment–based 18-gene RNA expression profile ([GEP] n = 196), and microsatellite instability ([MSI] as determined by Promega PCR analysis; n = 147). Outcomes evaluated for C1 and C2 (n = 200) were ORR, disease control rate (DCR), and radiographic PFS (rPFS) per blinded, independent central review per PCWG-modified RECIST v1.1. Outcomes evaluated for C1-C3 (n = 258) were prostate-specific antigen (PSA) response, time to PSA progression, and OS. Significance of continuous biomarkers (CPS; TMB; GEP) was prespecified at 0.05 for one-sided P values from logistic (ORR; DCR; PSA response) and Cox proportional hazard regression (rPFS; OS; PSA progression) adjusted for Eastern Cooperative Oncology Group performance status. Binary biomarkers (MSI) were analyzed using Fisher’s exact test (ORR; DCR; PSA response). Clinical data cutoff date: Jun 24, 2019. Results: Median TMB was 53.0 (interquartile range [IQR], 40.5 to 78.0), median CPS was 1 (IQR, 0 to 5), and median GEP was –0.64 (IQR, –0.88 to –0.46); 6 pts (2.3%) had MSI-high tumors. In C1-C3, TMB was associated with PSA response (one-sided nominal P = 0.0016) and time to PSA progression (one-sided nominal P = 0.00092). In C1-C3, PD-L1 CPS was associated with PSA response (one-sided nominal P = 0.046) and time to PSA progression (one-sided nominal P = 0.021). In C1-C3, GEP was not significantly associated with response. In C1-C3, MSI was associated with PSA response (one-sided nominal P = 0.019). Conclusions: In this biomarker analysis from KEYNOTE-199 C1-C3, TMB and PD-L1 CPS were associated with better PSA response; however, small pt numbers limit definitive conclusions on ORR, DCR, and OS. Further evaluation of molecular biomarkers in pts with mCRPC treated with pembrolizumab is warranted. Clinical trial information: NCT02787005 .
鼻内镜下等离子低温消融治疗青少年腺样体肥大59例
Authors: 孙麦青, 张红伟, 李泳文, 蔡纪堂
Journal: BMJ (2007)

腺样体肥大是儿童期较常见的疾病,也可见于青年和成年人,其临床症状以鼻阻塞为主,并经常伴有鼻及鼻窦急慢性炎症[1].我们自2003年2月至2005年2月采用鼻内镜下DNR数字温控等离子低温消融技术治疗青少年腺样体肥大59例,取得满意效果,现报告如下。
Non-motor symptoms in Parkinson′s disease patients with different motor types
Authors: Lingling Zhong, Yaqi Song, Hua Cao, Keju Ju
Journal: BMJ (2018)

One hundred ten patients with Parkinson′s disease (PD) and 110 age-matched healthy controls were enrolled in the study. The non-motor symptoms (NMS) were assessed with Non-motor symptoms of Parkinson′s disease questionnaire (PDNMSQ30). The PD patients were classified as gait abnormality posture type (PIGD, n=73) and tremor type (TD, n=37). The non-motor symptoms were compared between two groups.


Results
showed that the NMS in PD patients was higher than that in healthy controls[(35.2±3.0) vs. (6.0±2.0) symptoms, t=6.43, P=0.01]. The NMS score of PIGD group was higher than that of TD group[(28.9±1.1)vs.(6.2±0.7)symptoms, t=2.73, P<0.01]; Mini-mental state examination (MMSE) and Montreal cognitive assessment scale (MoCA) scores of TD group were significantly higher than those of PIGD group(t=11.52, P<0.01; t=8.79, P<0.01). The results indicate that for PD patients with different motor types, their NMS are different, and PD patients with PIGD have more axial involvement, and more NMS.


Key words: 
Parkinsons disease; Motor types; Non-motor symptom; Hoehn-Yahr classification; Tremor dominant
The impact of next generation sequencing on sarcoma diagnosis.
Authors: Gang Zhao, Lu Xie, Wei Guo, Yanfeng Xi, Yanzhi Cui, Siying Yu, Qing Wan, Donglin Chen, Xuedong Pan, XiaoWei Dong, Kai Wang, Jian WANG
Journal: Journal of Clinical Oncology (2020)

e23528 Background: The rarity and heterogeneity of sarcoma has been complicating the diagnosis of sarcoma for years. Even expert pathologists of sarcoma could make mistakes in the diagnosis of this disease. The availability of Next Generation Sequencing (NGS) data enabled more accurate diagnosis of sarcoma. In this study, we systematically described the application of NGS on the diagnosis of sarcoma and the contribution of NGS to the diagnostic accuracy of sarcoma. Methods: A multi-center, retrospective study included 235 sarcoma patients’ tumor and paired normal samples that were sent from 56 hospitals to a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory, at Shanghai, China for Next Generation Sequencing (NGS) was performed. Using next generation sequencing based YS panel consisting 450 genes, these 235 sarcoma patients’ sample were sequenced and the NGS data was analyzed. The initial diagnosis without NGS information was reconsidered by expert pathologists. Results: Taking into consideration both the initial diagnosis and the NGS results, the final diagnosis of these 235 sarcoma cases included 8 low grade malignant fibromyxoid tumors, 11 dermatofibrosarcoma protuberans (DFSP), 38 myxoliposarcomas, 22 alveolar rhabdomyosarcomas, 11 alveolar soft tissue sarcoma, 2 desmoplastic small round cell tumors, 37 NTRK rearrangement spindle cell tumors, 40 Ewing’s sarcoma and 66 synoviosarcomas. In total, 29% initial diagnoses were changed according to NGS identified fusions, including 13% low grade malignant fibromyxoid tumors (1 FUS- CREB3L2 fusion), 27% DFSPs (3 COL1A1- PDGFB fusions), 11% myxoliposarcomas (3 FUS- DDIT3 fusions and 1 EWSR1- DDIT3 fusion), 14% alveolar rhabdomyosarcomas (2 PAX7- FOXO1 fusions and 1 FOXO1- LINC00598 fusion), 18% alveolar soft tissue sarcomas (2 ASPSCR1- TFE3 fusions), 50% desmoplastic small round cell tumor (1 EWSR1- WT1 fusion), 95% NTRK rearrangement spindle cell tumors, 13% Ewing’s sarcomas (3 EWSR1- FLI1 fusions and 2 EWSR1- ERG fusions) and 21% synoviosarcomas (9 SS18- SSX1 fusions and 5 SS18- SSX2 fusions). Conclusions: NGS would be highly recommended for accurate diagnosis of sarcoma, especially for NTRK rearrangement spindle cell tumor, the majority of which were confirmed according to NGS identified fusions.
原发性高血压患者尿微量白蛋白检测的临床意义
Authors: 李庆祥, 郭路芬, 吴寿岭, 王烜, 吴海英, 张宇清, 颜红兵, 刘国仗
Journal: BMJ (2006)

对502例原发性高血压患者进行尿微量白蛋白检测,结果显示213例(42.4%)患者尿微量白蛋白异常,尿微量白蛋白异常组收缩压、舒张压高于正常组(P值分别为0.005、0.04);logistic回归分析表明,收缩压增高是高血压早期肾损害的独立危险因素(P=0.008).提示原发性高血压患者应常规检查尿微量白蛋白。
Effects of gonadotropin-releasing hormone analogs on height in girls with idiopathic central precocious puberty
Authors: Yong-hong Wang, Yu-min Shi, Jian Yu, Yi-qun Zhang, Wen Sun, Hong Hu
Journal: BMJ (2010)

Objective The purpose of this study was to evaluate effects of gonadotropin-releasing hormone analogs (GnRHa) on improvement of predicted adult height (PAH) in girls with idiopathic central precocious puberty (ICPP) initiating treatment at age of eight years or over and analyze its related factors.Methods Forty-nine girls with ICPP aged eight years and over were treated with GnRHa for ( 17.4 ±5.6) months initiating at age of (9.3 ± 0.6) years during 2005 and 2008.They were followed-up every three to six months to evaluate its effects on growth velocity (GV), height standard deviation score for chronological age (HtSDS-CA), height SDS for bone age (HtSDS-BA), PAH, and so on, as well as their related factors.Results PAH increased after GnRHa treatment, from ( 157.7 ± 4.5) cm six months after treatment to ( 159.2 ±4.4) cm 12 months after treatment, and to ( 160.8 ±5.0) cm by the end of treatment from ( 155.5 ±5.1 ) cm at its initiation (P ＜0.01 ).There was significant difference in PAH by the end of treatment and target height (TH) [( 157.6 ±3.4) cm].HtSDS-BA increased since six months after GnRHa treatment, from ( -0.64 ±0.68) six months to ( -0.52 ±0.70) 12 months after it and ( -0.36 ±0.68)by the its end, all significantly different from ( - 0.94 ± 0.68 ) that at the initiation of treatment ( P ＜0.01 ).There was no significant difference in HtSDS-CA before and after treatment.GV decreased from the initiation (6.3 ± 1.3) cm/yr to (4.8 ± 1.5) cm/yr by the end of treatment ( P ＜ 0.01 ).No significant association between PAH and age of the initiation of treatment and between PAH and age by the end of treatment were found (P ＞ 0.05 ).But, PAH reversely correlated with bone age, and positively correlated with HtSDS-CA, HtSDS-BA, GV, TH and length of treatment ( P ＜ 0.01 ).Conclusions GnRHa can remarkably improves PAH in girl with ICPP.PAH mainly correlates with HtSDS-BA, TH and GV at the initiation and the end of treatment.

Key words: 
Puberty, precocious;  Body height;  Gonadotropin-releasing hormone analogs
原发性气管非何杰金淋巴瘤一例并文献复习
Authors: 徐锋, 徐作军
Journal: BMJ (2006)

通过报道一例原发于气管的非何杰金淋巴瘤病例并复习文献,探讨该病的临床特点、诊断、治疗,以提高对其的认识.气管非何杰金淋巴瘤患者常表现有呼吸困难、喘息、咳嗽,常被误诊为哮喘;多数除有气道受累外还伴发胸内其他病变;原发性气管非何杰金淋巴瘤以低分化组织细胞学更常见,很多患者显示出黏膜相关的淋巴组织学特点,可采用手术、化疗、放疗单独或联合治疗.局限发生在气管和支气管的非何杰金淋巴瘤很罕见,在气道阻塞性疾病的鉴别诊断中应考虑到非何杰金淋巴瘤,气管镜是诊断的重要手段。
A phase Ia/Ib dose-escalation study of intravenously administered SB 11285 alone and in combination with nivolumab in patients with advanced solid tumors.
Authors: Filip Janku, James Strauss, Raghad Karim, Anthony J. Olszanski, Jason J. Luke, Kevin Leach, Radhakrishnan Iyer, Atif Abbas
Journal: Journal of Clinical Oncology (2020)

TPS3162 Background: Activation of the Stimulator of Interferon Genes (STING) pathway in immune cells in the tumor microenvironment (TME) and tumor cells results in the induction of innate and adaptive immunity and subsequent activation of cytotoxic T cells and NK cells for durable anti-tumor responses. SB 11285 is a novel agonist of the STING pathway leading to the activation of tumor-resident APCs and priming of tumor antigen specific CD8+ T cells. In our preclinical studies using multiple tumor-derived cell lines, SB 11285 has been observed to cause the induction of cytokines, such as INF-b, INF- a, TNFa and others consistent with engagement of the STING target, as well as tumor cell death by STING-mediated apoptosis. SB 11285 reduced tumor volumes in multiple rodent tumor models when administered intravenously, intraperitoneally or intratumorally as monotherapy or in combination with checkpoint inhibitors such as anti-CTLA-4 or anti-PD-1 antibody. Systemic administration could additionally facilitate trafficking of newly activated CD8+T cells from periphery into the tumor site. Methods: This open-label, multicenter phase 1a/1b clinical trial (NCT04096638) aims to enroll approximately 110 patients in the dose escalation (Part 1) and expansion cohorts (Part 2). Part 1 of the trial is a dose escalation study with IV SB 11285 monotherapy followed by combination with the checkpoint inhibitor nivolumab. Part 1 Dose Escalation of the study will evaluate ascending doses of intravenously administered SB 11285 with respect to dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), recommended phase 2 dose (RP2D) and the pharmacokinetic (PK)/pharmacodynamic profile as monotherapy and in combination with nivolumab. SB 11285, with a starting dose of 0.3μg/kg, will be administered as monotherapy weekly on Days 1, 8, 15, and 22 of repeated 28-day cycles in escalating doses and in combination with nivolumab administered on Q4W schedule. Part 2 Expansion Cohorts of the study will explore initial signs of efficacy in pre-specified tumor types (such as Melanoma, Head and Neck squamous cell carcinoma) using the recommended phase 2 dose (RP2D) of SB 11285 in combination with nivolumab. In addition, the biological effects of SB 11285 will be evaluated by changes in immune cell types and activation state, serum cytokines, and gene expression patterns indicative of activation of the immune compartment. The trial is being conducted at multiple sites in the U.S . Clinical trial information: NCT04096638 .
Prognostic role of pre-treatment neutrophil-to-lymphocyte ratio in patients with soft tissue sarcoma.
Authors: Se Jun Park, Jinsoo Lee, Kabsoo Shin, Hyunho Kim, In-Ho Kim, Ji Eun Lee
Journal: Journal of Clinical Oncology (2020)

e23537 Background: Recent studies suggest that the neutrophil-to-lymphocyte ratio (NLR) may be associated with prognosis in several cancers. However, it has not been widely accepted in a clinical situation. In this study, we investigated the clinical significance of NLR as prognostic marker in patients with soft tissue sarcoma. Methods: Between January 2008 to December 2018, 168 patients with STS who had available blood counts at the time of diagnosis were retrospectively evaluated. Receiver operator characteristic (ROC) curve analysis was used to identify the optimal cut-off value for NLR in predicting overall survival. The association between NLR and overall survival (OS) and disease-free survival (DFS) was analyzed with Kaplan-meier method and multivariate Cox proportional models. Results: A total of 168 patients were analyzed, 116 (69.0%) patients were initially resectable disease. Based on the results of ROC curve analysis, patients were classified into two groups as; high-NLR ( &gt; 1.8) and low-NLR (≤1.8). High-NLR was presented in 107 (63.7%) patients which was significantly associated initial disease status (HR 3.30; 95% CI 1.51-7.20, p= 0.002), but not with age at diagnosis ( p= 0.167). High-NLR was significantly correlated with worse OS (HR 3.14; 95% CI 1.62-6.10, p &lt; 0.001). 3-year DFS was 26.2% for high-NLR group versus 37.3% for low-NLR group. DFS tended to be better in low-NLR group, though not statistically significant (HR 1.65; 95% CI 0.95-2.87, p= 0.078). Conclusions: Pre-treatment NLR is a useful predictive factor for prognosis in patients with soft tissue sarcoma. Further studies are needed to evaluate the association between factors representing of host inflammatory status and cancer prognosis.
艾滋病的行为干预
Authors: 庞琳
Journal: BMJ (2006)

自美国1981年诊断首例艾滋病(AIDS)患者以来,人类免疫缺陷病毒(HIV)在全球范围内以惊人的速度传播.根据联合国艾滋病规划署(UNAIDS)公布的最新统计数字,截至2005年年底,全球估计共有3 860万名HIV感染者[1].艾滋病防治已成为全球关注的重要公共卫生和社会热点问题。
Clinical features of 138 patients with ulcerative colitis
Authors: Tao Peng, Yu-lan Liu
Journal: BMJ (2008)

Objective To investigate the clinical features of ulcerative colitis(UC).Methods Based on typical clinical manifestation,enteroscopy and pathological results,138 in-hospital patients were diagnosed UC during 1998 to 2006.Their clinical features were analyzed in this report.Results UC was more commonly seen in people aged 20～60(n=108,78.3％).Nearly forty-six percent of the patients (n=63,45.7％)had the disease less than one year.More patients(n=100,72.4％)showed mild or moderate UC.Bloody stool was the most common manifestation.erythrocyte sedimentation rate,hemoglobin,albumin and α1 or α2 globulin levels were closely related with the condition.The mean value of platelet counting was in the upper limit of the normal value.Enteroscopy found more lesion located in the whole colon (n=78,56.5％).Pathological results showed infiltration of inflammatory cells,especially in patients with chronic inflammation.Salieylazosulfapyridine(SASP)and/or 5-Aminosalicyclic(5-ASA)were effective in most UC patients(n=70,50.7％).Conclusions Chinese patients usually had mild to moderate UC,and their courses were often shorter than abroad.The disease was closely related with α1 and α2 globulin levels.Most of the patients had response to SASP and/or 5-ASA.

Key words: 
Ulcerative colitis; Diagnosis; Therapy
A review of gynecological cancers studies of concordance with individual clinicians or multidisciplinary tumor boards for an artificial intelligence-based clinical decision-support system.
Authors: Yull Edwin Arriaga, Rezzan Hekmat, Karlis Draulis, Suwei Wang, Anita M Preininger, Winnie Felix, Irene Dankwa-Mullan, Kyu Rhee, Gretchen Purcell Jackson
Journal: Journal of Clinical Oncology (2020)

e14070 Background: Watson for Oncology (WfO) is an artificial intelligence-based clinical decision-support system that offers potential therapeutic options to cancer-treating physicians. We reviewed studies of concordance between therapeutic options offered by WfO and treatment decisions made by individual clinicians (IC) and multidisciplinary tumor boards (MTB) in practice in gynecological cancers. Methods: We searched PubMed and an internal database to identify peer-reviewed WfO concordance studies of gynecological cancers published between 01/01/2015 and 06/30/2019. Concordance was defined as agreement between therapeutic options recommended or offered for consideration by WfO and treatment decisions made by IC or MTB. Mean concordance was calculated as a weighted average based on the number of patients per study. Statistical significance was evaluated by z-test of two proportions. Results: Our search identified 5 retrospective studies with 635 patients with cervical and ovarian cancers in China and Thailand; 4 compared WfO to MTB and 1 to IC. Overall WfO concordance with MTB and IC for both cancers was 77.2% (SD 11.6%). The concordance between MTB and WfO in cervical and ovarian cancers was 80.5% and 86.2%, respectively ( P = .21); IC concordance with WfO in cervical and ovarian cancers was 65.2% and 73.2%, respectively ( P = .18). MTB concordance with WfO for both cancers combined was 81.5%, significantly higher than the 67.9% IC concordance with WfO for both cancers ( P = .01). Conclusions: Studies of cervical and ovarian cancers demonstrated a statistically significantly higher concordance of MTB and WfO than IC and WFO, suggesting a role for WfO in supporting treatment-decision making in gynecological cancers that aligns with decisions made by MTB. Larger prospective studies are needed to evaluate the technical performance, usability, workflow integration, and clinical impact of WfO in gynecological cancers.[Table: see text]
Low-dose cisplatin administration through the superficial temporal artery combined with definitive radiotherapy for maxillary sinus squamous cell carcinoma.
Authors: Tatsuo Masubuchi, Yosuke Kitani, Chihiro Fushimi, Daisuke Kawakita, Hideaki Takahashi, Etsuro Takeishi, Tetsuharu Kaneko, Chihiro Kanno, Morio Yamazaki, Junpei Tanaka, Tatsuya Kitajima, Kenji Hanyu, Kazuhito Toya, Akane Takahashi, Naoki Okura, Masaaki Akahane, Kouki Miura, Shin-etsu Kamata, Yuichiro Tada
Journal: Journal of Clinical Oncology (2020)

e18562 Background: Although patients with locoregional advanced maxillary sinus squamous cell carcinoma (MSSCC) are often treated with surgery followed by postoperative radiotherapy (RT), the cosmetic and functional outcomes are unsatisfactory. Moreover, the efficacy and safety of intra-arterial chemoradiotherapy are controversial. Methods: In this study, we investigated the efficacy and safety of low-dose cisplatin administration through the superficial temporal artery (STA) combined with definitive RT in patients with MSSCC. Between January 2009 and December 2018, 57 patients were administered weekly intra-arterial infusions of cisplatin (30–50 mg/m 2 /5h) through the STA with simultaneous intravenous infusions of sodium thiosulfate. Overall response rate (ORR), local progression-free survival (LFS), maxillectomy-free survival (MFS), progression-free survival (PFS), overall survival (OS), and safety were evaluated retrospectively. The impact of clinical factors on survival was investigated using the Cox proportional hazard models. Results: The median follow-up time was 44 months (range, 10–80 months). There were 4, 26, 23, and 4 patients with cT2, cT3, cT4a, and cT4b, respectively. All patients completed the planned treatment except for one patient who discontinued owing to facial palsy. The ORR was 98% with 51 and 5 patients having complete and partial responses, respectively. The 3-year LFS, PFS, and OS were 74%, 63%, and 81%, respectively for all patients and 100%, 81%, and 94%, respectively for 22 patients received 70 Gy irradiation. Notably, the 3-year MFS was 95% for all patients and 100% in patients received 70 Gy RT. The most common grade 3 or more toxic event was oral mucositis (22.8%). Additionally, 4 (7.0%) patients had catheter-related infections. Late grade 3 or more adverse events included optic nerve disorder (8.8%), osteonecrosis (7.0%), encephalopathy (1.8%), and increased creatinine levels (1.8%). Salvage surgery including hard palate resection and orbital exenteration were performed in 2 and 1 patients, respectively. No clinical factor was correlated with survival outcomes in our study cohort. Conclusions: Low-dose cisplatin through STA combined with RT, especially 70 Gy RT, was associated with promising tumor response, high organ preservation rate, and tolerable adverse events in MSSCC patients. Further prospective studies are warranted to compare these outcomes with primary surgery.
Clinicopathologic and molecular profile of Philadelphia like ALL in Hispanic population of Central Valley California.
Authors: Hugo Akabane, Mir Ali, Haifaa Abdulhaq, Mohammed SANI Bukari
Journal: Journal of Clinical Oncology (2020)

7524 Background: Philadelphia-like Acute B-ALL(PHL) are Ph negative B-ALL(PHN) with molecular signatures that mirrors Ph + B ALL. Studies have shown worse prognosis in this subtype of leukemias, but few have reported outcomes with incorporation of novel agents. Our study seeks to describe clinical and molecular profile of a single center experience. Methods: This is a retrospective study of patients treated for PHL in community referral center in central valley of California from 1/2009 to 12/2019. Of the initial 71 patients, 34 met the inclusion and exclusion criteria. 16 of the 34 patients who had Next Generation Sequencing (NGS) by Foundation Medicine (14) or NeoGenomics (2). Data for 34 PHN and 8 with PHL patients were analyzed. Results: There are no differences in mean ages (36.7 x 36) and gender between the PHN and PHL subgroup. There is over representation of Hispanics in both groups (63% x 65%) with slightly male predominance in PHL group (62%). This ratio is slightly higher than reported by 2010 census of 46%. The BMI 38.4(27.5-48.4) vs. 29.1(26.6-39.1), mean WBC (71 vs. 58), bone marrow CD20+ by flow cytometry (90% vs. 63%) and abnormal cytogenetics (50% vs.15%) are all higher in PHL compared to PHN group. The prevalence rate of PHL signature in 16 tested patients is 8(50%). CRLF2 like subtype accounted for 6/8(75%), with 1 each of ABL-like and JAK-Stat subtype. All patients harbored multiple other mutational abnormalities in addition to those associated with Ph-like genetic signatures (Table). The median number of mutations was 4.55(3-7). The distribution of the 20 other mutation is as shown in table. 6 patients had morphological remission after induction chemotherapy of HyperCVAD (37%) and CALGB 10403 (25%) with measurable MRD in 5 of the patients. 7 patients were exposed to novel therapy; Blinatumomab; 2 nd line (6 patients), Cart T cell; 3 rd line (2 patients), Inotuzumab; 3 rd line (3 patients) and ASCT; (3 Patients post second- or third-line remission). 2 patients died at the time of data cut off, 1 from infection and other from refractory leukemia. Conclusions: Our data shows high incidence of PHL signatures in the cohort. The mutational heterogeneity between and within patients, may represent sub-clonal population vs. passenger and hence poor clinical outcomes. [Table: see text]