tbuckley/cabot-search huggingface dataset:
Prevalence and patterns of cancer in patients with congenital disease: A national-based cohort study.
Authors: Po-Han Lin, Chih-Hsin Muo, Long-Yuan Li, Hwai-I Yang, Chang-Fang Chiu, Fuu-Jen Tsai
Journal: Journal of Clinical Oncology (2013)

1600 Background: Association of congenital disease (CD) and malignancy was noted in some studies. However, the cancer risk and patterns of different CD was unclear. In this study, we aimed to assess and quantify the relationships between CD and cancers. Methods: In the National Health System of Taiwan, 2.9 million children were born between 1998 and 2010. Patients with CD were identified using ICD-9-CM 740-759. Cox’s proportional hazards regression analysis was used to assess the cancer risk of CD. Results: A total of 32358 CD patients were identified and 87 of them developed malignancy. The cancer diagnostic age was significantly younger in patients with CD (2.44 ± 2.28 years) than patients without CD (3.97 ± 3.04 years; p&lt;0.001). The hazard ratio (HR) of cancer incidence was 2.70 (95% confidential interval (CI) 2.12-3.44). Subgroup analysis showed that significantly increased risk of cancer development was noted among patients with cardiac anomalies (N=26, HR=1.91, 95% CI 1.28-2.86), digestive anomalies (N=8, HR=3.32, 95% CI 1.64-6.70), cutaneous anomalies (N=2, HR=21.5, 95% CI 5.35-86.40) and chromosomal anomalies (N=29, HR=17.5, 95% CI 12.00-25.70); other congenital diseases did not. Considering cancer types, patients with cardiac anomalies had higher rate of hematological cancers (N=12, HR=2.09, 95% CI. 1.15-3.79), especially acute myeloid leukemia (AML; N=9, HR=12.2, 95% CI. 5.36-28.0). Patients with digestive anomalies also had higher rate of hematological cancers (N=4, HR=3.95, 95% CI. 1.46-10.70), and the dominant type was non-Hodgkin lymphoma (N=2, HR=14.70, 95% CI. 3.38-64.0). Patients with chromosomal anomalies had superior rate to have retroperitoneal sarcoma (N=1, HR=8.54, 95% CI. 1.14-63.90), anterior mediastinal tumor (N=1, HR=8.54, 95% CI. 1.14-63.90), and hematological cancers (N=23, HR=33.20, 95% CI. 21.20-51.80), especially the AML (N=21, HR=231, 95% CI. 119-448). Down syndrome patients had extremely high risk of AML (N=8, HR=388, 95% CI. 164-918). Conclusions: Patients with cardiac, digestive, cutaneous and chromosomal CD were at increased risk and younger age to develop cancer. Hematological malignancies, especially AML, were the most common cancer type among these patients.
Brief Report: Anti–Carbamylated Protein Antibodies in Rheumatoid Arthritis Patients Are Reactive With Specific Epitopes of the Human Fibrinogen β‐Chain
Authors: Jonathan D. Jones, B. JoNell Hamilton, William F. C. Rigby
Journal: Arthritis & Rheumatology (2017)

Anti-carbamylated protein (anti-CarP) antibodies are associated with the risk and severity of rheumatoid arthritis (RA) and are primarily directed against fibrinogen. The lack of understanding of anti-CarP antibody reactivity has limited analysis of the immunopathogenic associations in RA. To address this shortcoming, we mapped anti-CarP antibody epitope reactivity in RA patient sera.Immunoblotting identified a patient serum sample with specific reactivity to the carbamylated human fibrinogen β-chain. Liquid chromatography mass spectrometry (LC-MS) identified sites of homocitrullines (carbamylated lysines) present in the human fibrinogen β-chain. The reactivity of an anti-CarP antibody-positive cohort to specific peptides containing carbamylated lysines was determined by enzyme-linked immunosorbent assay, through direct binding (n = 63 sera) and by competition assays (n = 40 sera).Serum with specific reactivity to carbamylated, but not citrullinated, fibrinogen β-chain was identified in a specimen obtained from an RA patient. LC-MS identified carbamylation of 9 of 34 lysines in the human fibrinogen β-chain. Mapping of immunoreactivity to tryptic peptide fragments demonstrated several candidate carbamylated epitopes that were confirmed by competition experiments. Peptides containing a homocitrulline at position 83 appeared to be an immunodominant epitope in some RA patient sera, with additional reactivity to peptides containing homocitrullines at positions 52, 264, 351, 367, and 374.Anti-CarP antibodies appear to preferentially target specific regions of the human fibrinogen β-chain that contain homocitrullines. Interestingly, humoral immunoreactivity appears to be relatively restricted in some patients, which may enable detection of specific relationships with disease phenotype.
FUNCTIONAL CONSEQUENCES OF MYOCARDIAL SCAR AFTER MYOCARDIAL INFARCTION: CHARACTERIZATION OF MYOCARDIAL SCAR EXTENT WITH LATE GADOLINIUM CONTRAST ENHANCED CARDIAC MAGNETIC RESONANCE AND IMPACT ON MULTILAYER GLOBAL LONGITUDINAL STRAIN ON SPECKLE TRACKING ECHOCARDIOGRAPHY
Authors: Rachid Abou, Laurien Goedemans, Rob J. van der Geest, Martin Schalij, Nina Ajmone Marsan, Victoria Delgado, Jeroen Bax
Journal: Journal of the American College of Cardiology (2017)
A RANDOMIZED COMPARISON OF FREQUENCY OF RADIAL ARTERY OCCLUSION AND SYMPTOMATIC RADIAL ARTERY SPASM ASSOCIATED WITH TRANSRADIAL CORONARY INTERVENTION USING 6.5-FR SHEATHLESS GUIDE CATHETERTM VERSUS 6.0-FR GLIDESHEATH SLENDERTM
Authors: Kazunori Horie, Norio Tada, Tsuyoshi Isawa, Takashi Matsumoto, Taku Honda, Tatsushi Otomo, Naoto Inoue
Journal: Journal of the American College of Cardiology (2017)
Erratum: The HIPOP-OHP Research Group: A prospective study of passive smoking and risk of diabetes in a cohort of workers: The High-Risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) study (Diabetes Care (2008) 31 (732-734))
Authors: Y. Hayashino, S. Fukuhara, T. Okamura, H. Yamato, H. Tanaka, T. Tanaka, T. Kadowaki, H. Ueshima
Journal: Diabetes Care (2008)
Abstract #3651: Transcriptional down-regulation of c-Myc and Bcl-2 via DNA secondary structure stabilization as novel therapy for Non-Hodgkin lymphoma
Authors: Robert Brown, Vanessa Gaerig, Cristina Beman, Misha Pangasa, Matthew Karolak, Laurence Hurley, Tracy Brooks
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Lymphoma is the most common cancer of the blood, with an estimated 74,340 new cases in 2008. Almost 90% of these cases are non-Hodgkin lymphoma (NHL), a B-cell malignancy characterized by the bcl2 (t(14:18)) and c-myc (t(8:14)) oncogenic translocation events that result in aberrant transcriptional gene regulation leading to oncogenic addiction. Of important note, both Bcl-2 and c-Myc have unique tandem DNA repeats of polyguanine/polycytosine in their promoter regions, which capable of forming DNA secondary structures, termed G-quadruplex and i-motifs. These are globular entities, analogous to tertiary protein folding, that allow them to be targeted by small molecules; and as transcription factors do not appear to bind to G-quadruplexes, stabilization leads to transcriptional downregulation for most oncogenes. Thus, targeting these oncogenes at the transcriptional level through their DNA secondary structures offers a unique opportunity for treatment and selectivity over normal cells and provides potentially a wide therapeutic window. After an extensive library and homology screen, four compounds (GQC-03-06) have been selected as lead c-Myc and Bcl-2 interactive agents. Circular dichroism studies further confirmed G-quadruplex and i-motif stabilization, with shifts in thermal stability as high as 16C with 1 equivalence of compound (GQC-04). The PCR stop assay was used to examine specificity for the target G-quadruplex, as compared to other oncogenic G-quadruplexes. Compounds GQC-06 and GQC-03 had the highest fidelity, while GQC-04 was a promiscuous G-quadruplex binder. The thiazole orange displacement assay differentiates DNA secondary structure binding from dsDNA binding, and again compounds GQC-06 and GQC-03 demonstrated the better selectivity profile, with a maximal ratio of 7.6. In vitro cytotoxicity in six NHL cell lines, representing three major subtypes, were in the low micromolar (GQC-03, -05, and -06) to nanomolar (GQC-04) range. At these same concentrations dose- and time-dependent downregulation of Bcl-2 and/or c-Myc mRNA and protein was observed, which correlated to significant caspase-3 activation, for all but compound GQC-03. To confirm that the mechanism of cell kill is via DNA secondary structure stabilization, promoter specific effects were examined by chromatin immunoprecipitations for key transcription factors that bind to the G-rich tandem repeats. The compounds identified in this study have high potential to lead to novel and specific compounds target oncogenic addiction in NHL, with great benefits to patient toxicity profiling and survival.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3651.
A Phase 1 Study of TTI-621, a Novel Immune Checkpoint Inhibitor Targeting CD47, in Patients with Relapsed or Refractory Hematologic Malignancies
Authors: Stephen Ansell, Robert W Chen, Ian W. Flinn, Michael B. Maris, Owen A. O'Connor, Lisa DS Johnson, Meghan Irwin, Penka S. Petrova, Robert A. Uger, Eric L Sievers
Journal: Blood (2016)
A Novel Upregulation of Fanconi Anemia/BRCA DNA Repair Pathway Is Observed Upon Co-Culture of Bone Marrow Stroma with Multiple Myeloma Cell Lines: A Potential New Participant(s) in Environment Mediated Drug Resistance.
Authors: Kenneth H Shain, Vasco Oliveira, Danielle Yarde, Linda Mathews, William S. Dalton
Journal: Blood (2009)
DLX1 Affects Cell Cycle and Proliferation of Myeloid Leukemia Cells In Vitro and In Vivo
Authors: Katerina Rejlova, Miroslava Kardosova, Martina Slamova, Marketa Zaliova, Meritxell Alberich-Jorda, Jan Trka, Julia Starkova
Journal: Blood (2016)
Upfront Single Versus Double Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma: An Intergroup, Multicenter, Phase III Study of the European Myeloma Network (EMN02/HO95 MM Trial)
Authors: Michele Cavo, Maria Teresa Petrucci, Francesco Di Raimondo, Elena Zamagni, Barbara Gamberi, Claudia Crippa, Giulia Marzocchi, Mariella Grasso, Stelvio Ballanti, Donatella Iolanda Vincelli, Paola Tacchetti, Massimo Offidani, Gianpietro Semenzato, Anna Marina Liberati, Anna Pascarella, Giulia Benevolo, Rossella Troia, Angelo D. Palmas, Nicola Cantore, Rita Rizzi, Fortunato Morabito, Mario Boccadoro, Pieter Sonneveld
Journal: Blood (2016)
ADDRESSING REFERENCE ECHOCARDIOGRAPHIC PARAMETERS IN ATHLETIC SCREENING: A COLLEGE FOOTBALL-BASED STUDY FOCUSING ON THE IMPLICATIONS OF RACE AND CORRECTION FOR BODY COMPOSITION
Authors: Kegan Moneghetti, Tamanna Singh, Zoe Kooreman, Jeffrey Christle, Victor Froelicher, Matthew Wheeler, Euan Ashley, Francois Haddad
Journal: Journal of the American College of Cardiology (2017)
IMPACT OF CANCER DISEASE ON OUTCOME OF PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Norman Mangner, Felix Woitek, Stephan Haussig, Florian Schlotter, Anna Lindner, Georg Stachel, Robert Hoellriegel, Sergey Leontyev, David Holzhey, Friedrich Mohr, Gerhard Schuler, Axel Linke
Journal: Journal of the American College of Cardiology (2017)
CD20 Tcb (RG6026), a Novel "2:1" T Cell Bispecific Antibody for the Treatment of B Cell Malignancies
Authors: Marina Bacac, Pablo Umaña, Sylvia Herter, Sara Colombetti, Johannes Sam, Marine Le Clech, Anne Freimoser-Grundschober, Marine Richard, Valeria Nicolini, Christian Gerdes, Laurent Lariviere, Christiane Neumann, Christian Klein
Journal: Blood (2016)
Acute Kidney Injury in Children With Type 1 Diabetes Hospitalized for Diabetic Ketoacidosis
Authors: Brenden E. Hursh, Rebecca Ronsley, Nazrul Islam, Cherry Mammen, Constadina Panagiotopoulos
Journal: JAMA Pediatrics (2017)

Acute kidney injury (AKI) in children is associated with poor short-term and long-term health outcomes; however, the frequency of AKI in children hospitalized for diabetic ketoacidosis (DKA) has not been previously examined.To determine the proportion of children hospitalized for DKA who develop AKI and to identify the associated clinical and biochemical markers of AKI.This medical record review of all DKA admissions from September 1, 2008, through December 31, 2013, was conducted at British Columbia Children's Hospital, the tertiary pediatric hospital in British Columbia, Canada. Children aged 18 years or younger with type 1 diabetes and DKA and with complete medical records available for data analysis were included (n = 165). All data collection occurred between September 8, 2014, and June 26, 2015. Data analysis took place from August 25, 2015, to June 8, 2016.Acute kidney injury was defined using Kidney Disease/Improving Global Outcomes serum creatinine criteria. Multinomial logistic regression was used to identify potential factors associated with AKI.Of the 165 children hospitalized for DKA, 106 (64.2%) developed AKI (AKI stage 1, 37 [34.9%]; AKI stage 2, 48 [45.3%]; and AKI stage 3, 21 [19.8%]). Two children required hemodialysis. In the adjusted multinomial logistic regression model, a serum bicarbonate level less than 10 mEq/L (compared with ≥10 mEq/L) was associated with a 5-fold increase in the odds of severe (stage 2 or 3) AKI (adjusted odds ratio [aOR], 5.22; 95% CI, 1.35-20.22). Each increase of 5 beats/min in initial heart rate was associated with a 22% increase in the odds of severe AKI (aOR, 1.22; 95% CI, 1.07-1.39). Initial corrected sodium level of 145 mEq/L or greater (compared with 135-144 mEq/L) was associated with a 3-fold increase in the odds of mild (stage 1) AKI (aOR, 3.29; 95% CI, 1.25-8.66). There were no cases of mortality in patients with or without AKI.This study is the first to date to document that a high proportion of children hospitalized for DKA develop AKI. Acute kidney injury was associated with markers of volume depletion and severe acidosis. Acute kidney injury is concerning because it is associated with increased morbidity and mortality as well as increased risk of chronic renal disease, a finding that is especially relevant among children who are already at risk for diabetic nephropathy. Strategies are needed to improve the diagnosis, management, and follow-up of AKI in children with type 1 diabetes.
Activity, efficacy, and safety of nab-paclitaxel (Nab-P) and gemcitabine (G) in heaviliy pretreated advanced pancreatic cancer (APDAC) patients (pts): A multicenter retrospective analysis.
Authors: Antonio Febbraro, Alberto Zaniboni, Vittorina Zagonel, Francesco Di Costanzo, Luigi Maiorino, Paola Bertocchi, Francesca Bergamo, Elisa Giommoni, Guido Giordano
Journal: Journal of Clinical Oncology (2014)

e15255 Background: There is no standard of care for APDAC pts who have progressed to a first line chemotherapy (CT) and all investigated drugs have showed only moderate activity and limited efficacy. Nab-P has shown efficacy in combination with G as first line therapy in APDAC in a randomised phase III trial and it seems to be active in G resistant pts. Methods: APDAC pts who received off-label combination of nab-P 125 mg/m2 and G 1000 mg/m2 on days 1, 8, and 15 of a 28 day cycle as 2ndor further line of treatment in five Italian centers were retrospectively analyzed. We evaluated activity in terms of Disease Control Rate (DCR: Stable Disease + Partial Response + Complete Response, SD+PR+CR), efficacy (Progression Free Survival, PFS and Overall Survival, OS) and safety. Results: 34 pts (M/F: 20/14) median age of 60 (range 41-83) and ECOG Performance Status of 0/1/2: 8/17/9 respectively, were evaluated in our analysis. Median CA19.9 baseline level was 892 U/I, 17.6% pts had biliary stent, 21 pts (61.8%) had liver metastases and 10 (29.4%) had multiple metastatic sites. 10 pts underwent to prior radical surgery and 8 (23.5%) received G-based adjuvant CT. 50% received FOLFIRINOX as first line CT. Nab-P+G was administered as 2nd/3rd/4th/5thline of therapy in 18/12/2/2 pts respectively for a median number of 4 cycles (range 1-14). 1 CR, 12 PR and 6 SD were obtained with 55.9% DCR. Median PFS was 4.5 months (95% CI 1-8); 3- and 6- month PFS rate were 58% and 22.6% respectively. Median OS was 6.5 months (95% CI 1.5-11.5); 6- and 12-month OS rate were 54% and 29% respectively. Treatment was mildly tolerated with only 1 G4 neutropenia. G3 toxicities were represented by neutropenia (14.7%), piastrinopenia (11.7%), diarrhea and neurotoxicity (5%), nausea and anemia (2.9%). Twenty percent dose reduction was needed in 29% of pts. Conclusions: Nab-P+G represents a standard of care in first line CT for APDAC pts. At authors knowledge this one represent the first analysis evaluating Nab-P+G in APDAC pretreated pts. Our data shows that Nab-P+G is active, efficacious and mildly tolerated and it could be considered as a valid therapeutic option also in this setting of pts.
BRCA carrier status as an independent prognostic factor associated with earlier biochemical relapse in local prostate cancer.
Authors: Elena Castro, David Olmos, Chee Leng Goh, Ed Saunders, Daniel Leongamornlert, Malgorzata Tymrakiewicz, Elizabeth Bancroft, Elizabeth Page, Tokhir Dadaev, Koveela Govindasami, Michelle Guy, Emma Sawyer, Rosemary Wilkinson, Steve Ellis, Debra Frost, Susan Peock, Antonis C. Antoniou, Doug Easton, Zsofia Kote-Jarai, Ros A. Eeles
Journal: Journal of Clinical Oncology (2012)

1545 Background: Biochemical relapse after local treatment for prostate cancer (PCa) indicates recurrent disease and is associated with shorter survival. Germline BRCA mutations are associated with worse PCa outcomes. BRCA carriers are currently treated with the same protocols used for non-carriers. We analyzed biochemical-progression free survival (bPFS) after conventional treatment for localized PCa in a cohort of BRCA patients (pts). Methods: In this retrospective case-control study, each BRCA carrier (9 BRCA1 and 34 BRCA2) treated with radical prostatectomy (RP) or external beam radiotherapy (RT) was matched with 3 non-carriers (NC) by age at diagnosis (±5 yrs), TNM stage, Gleason score, presenting PSA, local treatment , androgen-deprivation therapy (ADT) and year of treatment (±3 yrs). All NC were screened for BRCA1 and BRCA2 mutations. Biochemical failure was reviewed according to ASTRO and NCCN criteria. The Kaplan-Meier method and a multivariate Cox regression model adjusted by matching factors were employed. Results: 172 pts were included. Median follow-up was 76 months (ms). Median age at diagnosis was 58 yrs (43-75). Tumour stages were I 11%, IIA 19%, IIB 28%, III 28%, IV 14%. 80 pts received RT (18 BRCA2, 5 BRCA1, 57NC) and 85% also received ADT (70% for ≥6 months). 92 pts underwent RP (16 BRCA2, 4 BRCA1 and 72 NC), and 9% of them received ADT (&lt;6months). Overall, median bPFS was 71ms. For those treated with RT, median bPFS was 65ms in NC vs 39ms in BRCA carriers (p=0.023). bPFS was not affected by ADT duration. Median bPFS after RP was 65ms in BRCA carriers. No difference was observed in 3yrs-bPFS between BRCA carriers and NC (73% vs 76%). The adjusted MVA confirmed the independent prognostic value of tumour stage (p=0.004) and BRCA status (p=0.032) for bPFS. Among BRCA carriers, the risk was greater when the analysis was limited to BRCA2 pts (p=0.013, HR 2.1,.95%CI 1.2-3.7). Conclusions: Our results suggest that BRCA carriers with PCa have worse local disease control than NC when treated with RT, regardless of ADT duration. No differences in bPFS were observed in pts treated with RP after &gt;6 yrs median follow-up. These results may have implications for tailoring clinical management for these patients.
Outcomes after Unrelated Umbilical Cord Blood Transplantation for Children with Osteopetrosis.
Authors: R Chiesa, A Ruggeri, A Paviglianiti, M Zecca, M Gonzelez Vicent, Bordon, J Stein, S Lawson, Sophie Dupont, E Lanino, M Abecacis, A Al Seraihy, C Kenzey, M Bierings, F Locatelli, E Gluckman, A Schulz, A Gennery, K Page, J Kurtzberg, Rocha
Journal: Blood (2016)
The 'Next-in-Cml' Study: A Prospective Multicenter Study of Deep Sequencing of the BCR-ABL1 Kinase Domain in Philadelphia Chromosome-Positive Patients with Non-Optimal Responses to Tyrosine Kinase Inhibitor Therapy
Authors: Simona Soverini, Caterina De Benedittis, Stefania Stella, Anna Serra, Francesca Carnuccio, Santa Errichiello, Luana Bavaro, Fausto Castagnetti, Alessandra Iurlo, Nicola Orofino, Federica Sorà, Simona Sica, Sara Galimberti, Claudia Baratè, Federica Mottadelli, Margherita Martelli, Elisabetta Novella, Eros Di Bona, Giorgina Specchia, Francesco Albano, Elisabetta Abruzzese, Fabio Ciceri, Francesca Lunghi, Carmen Fava, Giovanna Rege Cambrin, Luigia Luciano, Massimo Breccia, Clementina Caracciolo, Marco Santoro, Francesco Di Raimondo, Gabriele Gugliotta, Cristina Papayannidis, Giovanni Cazzaniga, Manuela Mancini, Rosaria Sancetta, Renato Bassan, Caterina Musolino, Giuseppina Spinosa, Silvana Franca Capalbo, Mario Annunziata, Michele Cavo, Gianantonio Rosti, Michele Baccarani, Paolo Vigneri, Giuseppe Saglio, Fabrizio Pane, Giovanni Martinelli
Journal: Blood (2016)
OUTCOMES AND THEIR PREDICTORS IN ACUTE TRANSCATHETER AORTIC HEART VALVE-IN-TRANSCATHETER AORTIC HEART VALVE THERAPY
Authors: Ruchir Patel, Elsheikh Abdelrahim, Mahmoud Ali, Nirmit Desai, Aditya Singh, Daryl Sudasena, Dee Dee Wang, Marvin H. Eng, William O'Neill, Adam Greenbaum
Journal: Journal of the American College of Cardiology (2017)
INCIDENCE, PREDICTORS, AND OUTCOME OF POSTOPERATIVE ATRIAL FIBRILLATION IN PATIENTS RECEIVING CONTINUOUS FLOW LEFT VENTRICULAR ASSIST DEVICES
Authors: Amrish Deshmukh, Ankit Bhatia, Emeka Anyanwu, Nir Uriel, Roderick Tung, Valluvan Jeevanandam, Cevher Ozcan
Journal: Journal of the American College of Cardiology (2017)
Thrombocytopenia associated with ipilimumab therapy of advanced melanoma at a single institution.
Authors: Monique Z. Sajjad, Timothy George, Jeffrey S. Weber, Lubomir Sokol
Journal: Journal of Clinical Oncology (2013)

9072 Background: Ipilimumab (IPi) is a monoclonal IgG1κ antibody targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) that was approved for the treatment of metastatic melanoma (MM). IPi therapy is associated with immune-related adverse events (irAEs) (Weber et al. J Clin Oncol2012 Jul 20;30(21):2691-7). Hematologic toxicity has rarely been reported. Methods: We analyzed 172 pts with MM treated adjuvantly or for metastatic disease with IPi on 2 clinical studies and an expanded access program (protocols MCC15283, MCC15722 and MCC15977). Clinical characteristics and hematologic parameters related to therapy were recorded. Medications, infections, comorbidities, prior therapies, and pathology reports from bone marrow (BM) biopsies were reviewed. Results: Of 172 subjects, 10 (5.8%) pts with normal platelet counts prior to therapy, developed thrombocytopenia (TCP) following IPi. Median number of doses was 8.5 (range 1-19). Median age at development of TCP was 64 years (range 21-93). Median time to development of TCP was 16.5 months (range 0.25 – 39). Of ten pts, three developed grade (gr) 1 or 2 TCP, three developed gr 3 and four pts developed gr 4 thrombocytopenia. BM analysis in pts with gr 4 TCP showed normal hematopoiesis and no evidence of melanoma. Six of 10 (60%) pts required therapy and were initiated on prednisone, but were deemed steroid refractory. No sustained responses to subsequent treatments with IVIG, rituximab, danazol, and/or splenectomy were observed. Three pts with grade 4 TCP were treated with eltrombopag. One of them achieved a sustained complete response lasting &gt; 20 months. The other 2 pts who received eltrombopag discontinued treatment due to vascular events. Three out of 10 (30%) pts with any gr of TCP experienced mild bleeding episodes in the form of epistaxis. One pt with gr 4 thrombocytopenia experienced severe gastrointestinal bleeding requiring hospitalization. No deaths related to bleeding occurred. Conclusions: This is the first case series of hematologic irAEs in pts treated with IPi on clinical trials, suggesting that steroid refractory TCP may occur with IPi treatment . The timing and severity of IPi associated TCP is highly variable so careful hematologic monitoring should be considered.