tbuckley/cabot-search huggingface dataset:
European leukemia net (ELN) 2013 response categories: Impact on clinical outcomes across four frontline tyrosine kinase inhibitor (TKI) modalities in chronic phase CML.
Authors: Preetesh Jain, Hagop M. Kantarjian, Dasarathula Jyothsna, Alfonso Quintas-Cardama, Elias Jabbour, Marylou Cardenas-Turanzas, Sara Dellasala, Sherry Pierce, Farhad Ravandi, Susan Mary O'Brien, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2014)

7089 Background: In 2013 ELN proposed new response categories applicable to TKI frontline therapy for CML. We analyzed the outcome by ELN category of patients (pts) on different TKI as frontline therapy for CML-CP. Methods: 487 pts treated by TKI from 2000-2013 were analyzed. Pts received imatinib 400 mg/d (IM400; n=70), imatinib 800 mg/d (IM800; n=201), dasatinib (n=107) or nilotinib (n=109) in consecutive or parallel trials. Median follow-up was 99 months (mo). Pts were followed uniformly with cytogenetics and PCR every 3 mo for the first 12 mo, then every 6 mo. Results: Median follow-up was 144 mo for IM400, 119 mo for IM800, 54 mo for dasatinib and 49 mo for nilotinib. Cumulative CCyR rates were 85%, 90%, 98% and 93%, and MMR rates were 84%, 88%, 91%, and 94%, respectively. ITT analysis indicated the proportion of pts falling into optimal, warning and failure categories were 89%, 6%, 6% at 3 mo, 78%, 17% and 6% at 6 mo, and at 12 mo 75%, 13% and 13%, respectively. Rates of optimal response at 3 mo were 75% for IM400, 90% for IM800, 89% for dasatinib and 97% for nilotinib; 41%, 80%, 86% and 89% at 6 mo; and 47%, 77%, 76% and 87% at 12 mo, respectively. Pts with optimal response had longer EFS, FFS, TFS and OS compared to those with warning and failure at all-time points. Within each response category, type of TKI did not affect long-term outcome. (Table) Conclusions: Imatinib 400 induces optimal response in fewer pts at all times. Optimal responses predict for better outcomes irrespective of the TKI modality. Event-free and overall survival probabilities with different TKI modalities stratified by ELN response. % 5-year EFS Response category IM400 N=70 IM800 N=201 Dasatinib N=107 Nilotinib N=109 Overall N=487 3 mo Optimal 81 89 95 84 88 Warning 37 64 100 100 53 Failure 57 19 83 67 49 6 mo Optimal 96 91 97 90 93 Warning 67 79 61 57 70 Failure 36 19 100 50 36 12 mo Optimal 91 94 96 90 93 Warning 100 81 86 80 85 Failure 50 52 60 100 54 % 5-year OS Response category IM400 IM800 Dasatinib Nilotinib Overall 3 mo Optimal 92 94 99 90 94 Warning 90 100 100 100 96 Failure 71 71 83 67 72 6 mo Optimal 92 97 97 93 96 Warning 100 90 100 67 94 Failure 64 75 100 75 71 12 mo Optimal 100 98 100 95 98 Warning 100 94 92 80 93 Failure 85 83 100 100 85
Outcomes of Patients with Newly-Diagnosed Acute Myeloid Leukemia and Hyperleukocytosis Who Did Not Undergo Intensive Chemotherapy: Results from a Large International Database
Authors: Rory M Shallis, Maximilian Stahl, Wei Wei, Pau Montesinos, Etienne Lengline, Judith Neukirchen, Vijaya R. Bhatt, Mikkael A. Sekeres, Amir T. Fathi, Heiko Konig, Selina Luger, Irum Khan, Gail J. Roboz, Thomas Cluzeau, David Martínez-Cuadron, Emmanuel Raffoux, Ulrich Germing, Jayadev Manikkam Umakanthan, Sudipto Mukherjee, Andrew M. Brunner, Adam M. Miller, Christine M. McMahon, Ellen K. Ritchie, Rebeca Rodríguez-Veiga, Raphael Itzykson, Blanca Boluda, Florence Rabian, Mar Tormo, Evelyn Gloria Acuna Cruz, Nikolai Podoltsev, Steven D. Gore, Amer M. Zeidan
Journal: Blood (2018)
Comment on Prevalence and Correlates of Prescription Stimulant Use, Misuse, Use Disorders, and Motivations for Misuse Among Adults in the United States
Authors: Lawrence Diller
Journal: American Journal of Psychiatry (2019)

EDITOR: I wrote my first Ritalin prescription in 1978.I am also a student of stimulant history (1).Therefore, I read with particular interest the article by Compton et al.(2), published in the August 2018 issue of the Journal, on the prevalence and correlates of prescription stimulant use, misuse, use disorders, and motivations for misuse in the U.S. adult population.The authors are to be congratulated for bringing up to date data on current patterns of use, misuse, abuse, and addiction of drugs like Adderall.However, I feel the recommendations of the researchers and the accompanying editorial (3) to clinicians fall short by not specifically discouraging physicians from prescribing immediaterelease formulations of methylphenidate (Ritalin) and amphetamine (Adderall), which are the "drugs of choice" in the misuse, abuse, and addiction of prescription stimulants (4).There is virtually no clinical indication for the prescription of immediate-release stimulants to teenagers and adults for the treatment of attention deficit hyperactivity disorder (ADHD).Indeed, immediate-release stimulants allow for a flexibility of time of use that may actually facilitate or promote an ADHD lifestyle of disorganization and procrastination.Long-acting stimulant preparations require planning of use and discourage stimulant use for a lastminute "all-nighter" cram session.Immediate-release stimulant preparations are also the easiest to crush for intranasal snorting for "power" studying or getting high.Responsible physicians should not only alert teenage and adult users about not sharing their stimulant medication, they should be prescribing only the long-acting stimulant preparations to their patients.
A Network Meta-Analysis of Clinical Trials Assessing Induction Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia Among Young Adults
Authors: Nour Tlimat, Salman Muddassir, Saad Ullah Malik, Warda Faridi, Qurat Ul Ain Riaz Sipra, Faiz Anwer
Journal: Blood (2018)
Allogeneic stem cell transplantation (SCT) using a CAT-bu conditioning regimen in patients with advanced myelodysplastic/myeloproliferative disorders (MDS-MPDs).
Authors: Julie Cote, Guy Cantin, Julie Lemieux, Genevieve Gallagher
Journal: Journal of Clinical Oncology (2014)

7035 Background: Many patients with MDS-MPDs are ineligible to allogeneic SCT using a standard myeloablative approach. In this population, we evaluated the efficacy and safety of a novel conditioning regimen called CAT-Bu. Methods: The conditioning regimen consisted of CAT (cyclophosphamide IV 300 mg/m2 every 12 hours from day 1 to 3, Cytarabine IV 2000 mg/m2 from day 2 to 6, topotecan 1.25 mg/m2/day by continuous IV perfusion from day 2 to 6) and oral Busulfan adjusted dose from day 14 to 18. Peripheral blood stem cells were infused on day 20. Tacrolimus and mycophenolate were used as graft vs. host disease (GVHD) prophylaxis. All patients received prophylactic trimethoprim/sulfamethoxazole, valacyclovir and posaconazole. Charts from patients who received this regimen between July 2009 and September 2012 were reviewed. Results: Sixteen patients received the CAT-Bu regimen. The median age was 60.5 years old. The Hematopoietic Cell Transplant Comorbidity Index was low in 63%. The disorder at diagnosis was MDS in 56% and MPD in 44%. At SCT, active disease was noted in 75% of the population. Nearly half of the patients had transformation to AML (44%). No patient was in complete remission (CR). The majority of donors were fully matched siblings (81%). Median follow up was 729 days for alive patients and 159 days for dead patients. CR was the best response obtained after SCT in 63%. The OS and PFS at 6 months, 1 year and 2 years were respectively: 75%, 56%, 48% and 50%, 44%, 35%. All deaths were related to the hematological neoplasia. Common adverse events were febrile neutropenia (81%), oral mucositis (56%), diarrhea (38%) and hepatic cytolysis (38%). Two grade 4 respiratory distresses were noted. One was probably related to Busulfan’s pulmonary toxicity. Conclusions: This new sequential approach offers satisfactory efficacy with acceptable toxicity for the studied population, which, for the majority, presented active disease at time of SCT. Engraftment success 15/16 Median time from SCT to neutrophil recovery (days) 18 Median time from SCT to platelet recovery (days) 13 aGVHD 6/16 aGVHD maximum grade 1 2 1/6 5/6 cGVHD 10/16 cGVHD maximum grade Limited Extensive 6/10 4/10
Risk of serious infections in patients with rheumatoid arthritis treated in routine care with abatacept, rituximab and tocilizumab in Denmark and Sweden
Authors: Kathrine Lederballe Grøn, Elizabeth V Arkema, Bente Glintborg, Frank Mehnert, Mikkel Østergaard, Lene Dreyer, Mette Nørgaard, Niels Steen Krogh, Johan Askling, Merete Lund Hetland
Journal: Annals of the Rheumatic Diseases (2019)

Objective To estimate (1) crude and age-and gender-adjusted incidence rates (IRs) of serious infections (SI) and (2) relative risks (RR) of SI in patients with rheumatoid arthritis (RA) initiating treatment with abatacept, rituximab or tocilizumab in routine care. Methods This is an observational cohort study conducted in parallel in Denmark and Sweden including patients with RA in Denmark (DANBIO) and Sweden (Anti-Rheumatic Treatment in Sweden Register/Swedish Rheumatology Quality Register) who started abatacept/rituximab/tocilizumab in 2010–2015. Patients could contribute to more than one treatment course. Incident SI (hospitalisations listing infection) and potential confounders were identified through linkage to national registries. Age- and gender-adjusted IRs of SI per 100 person years and additionally adjusted RRs of SI during 0–12 and 0–24 months since start of treatment were assessed (Poisson regression). Country-specific RRs were pooled using inverse variance weighting. Results We identified 8987 treatment courses (abatacept: 2725; rituximab: 3363; tocilizumab: 2899). At treatment start, rituximab-treated patients were older, had longer disease duration and more previous malignancies; tocilizumab-treated patients had higher C reactive protein. During 0–12 and 0–24 months of follow-up, 456 and 639 SI events were identified, respectively. The following were the age- and gender-adjusted 12-month IRs for abatacept/rituximab/tocilizumab: 7.1/8.1/6.1 for Denmark and 6.0/6.4/4.7 for Sweden. The 24-month IRs were 6.1/7.5/5.2 for Denmark and 5.6/5.8/4.3 for Sweden. Adjusted 12-month RRs for tocilizumab versus rituximab were 0.82 (0.50 to 1.36) for Denmark and 0.76 (0.57 to 1.02) for Sweden, pooled 0.78 (0.61 to 1.01); for abatacept versus rituximab 0.94 (0.55 to 1.60) for Denmark and 0.86 (0.66 to 1.13) for Sweden, pooled 0.88 (0.69 to 1.12); and for abatacept versus tocilizumab 1.15 (0.69 to 1.90) for Denmark and 1.14 (0.83 to 1.55) for Sweden, pooled 1.13 (0.91 to 1.42). The adjusted RRs for 0–24 months were similar. Conclusion For patients starting abatacept, rituximab or tocilizumab, differences in baseline characteristics were seen. Numerical differences in IR of SI between drugs were observed. RRs seemed to vary with drug (tocilizumab &lt; abatacept &lt; rituximab) but should be interpreted with caution due to few events and risk of residual confounding.
Generation of hepatobiliary organoids from human induced pluripotent stem cells
Authors: Fenfang Wu, Di Wu, Yong Ren, Yuhua Huang, Bo Feng, Nan Zhao, Taotao Zhang, Xiaoni Chen, Shangwu Chen, Anlong Xu
Journal: Journal of Hepatology (2019)

Highlights•We established a system to generate hiPSC-derived hepatobiliary organoids in vitro.•To varying degrees, this model recapitulated several key aspects of hepatobiliary organogenesis.•The hepatobiliary organoids displayed a series of hepatic and biliary functional attributes.•This system does not rely on any exogenous cells or genetic manipulation.Graphical abstractAbstractBackground & AimsHuman induced pluripotent stem cell (hiPSC)-derived liver modeling systems have the potential to overcome the shortage of donors for clinical application and become a model for drug development. Although several strategies are available to generate hepatic micro-tissues, few have succeeded in generating a liver organoid with hepatobiliary structure from hiPSCs.MethodsAt differentiation stages I and II (day 1–15), 25% of mTeSR™ culture medium was added to hepatic differentiation medium to induce endodermal and mesodermal commitment and thereafter hepatic and biliary co-differentiation. At stage III (day 15–45), 10% cholesterol+ MIX was added to the maturation medium to promote the formation and maturation of the hepatobiliary organoids. Phenotypes and functions of organoids were determined by specific markers and multiple functional assays both in vitro and in vivo.ResultsIn this system, hiPSCs were induced to form 3D hepatobiliary organoids and to some extent recapitulated key aspects of early hepatogenesis in a parallel fashion. The organoids displayed a series of functional attributes. Specifically, the induced hepatocyte-like cells could take up indocyanine green, accumulate lipid and glycogen, and displayed appropriate secretion ability (albumin and urea) and drug metabolic ability (CYP3A4 activity and inducibility); the biliary structures in the system showed gamma glutamyltransferase activity and the ability to efflux rhodamine and store bile acids. Furthermore, after transplantation into the immune-deficient mice, the organoids survived for more than 8 weeks.ConclusionThis is the first time that functional hepatobiliary organoids have been generated from hiPSCs. The organoid model will be useful for in vitro studies of the molecular mechanisms of liver development and has important potential in the therapy of liver diseases.Lay summaryHerein, we established a system to generate human induced pluripotent stem cell-derived functional hepatobiliary organoids in vitro, without any exogenous cells or genetic manipulation. To some extent this model was able to recapitulate several key aspects of hepatobiliary organogenesis in a parallel fashion, holding great promise for drug development and liver transplantation.
Effect of body mass index and menopausal disorders during menopause on vasomotor symptoms of postmenopausal Japanese breast cancer patients treated with anastrozole: A prospective multicenter cohort study of patient-reported outcomes.
Authors: Kaori Tane, Chiyomi Egawa, Shintaro Takao, Masaru Miyashita, Kazuhiko Yamagami, Masashi Baba, Shigetoshi Ichii, Muneharu Konishi, Yuichiro Kikawa, Junya Minohata, Toshitaka Okuno, Keisuke Miyauchi, Yasuo Miyoshi
Journal: Journal of Clinical Oncology (2014)

9619 Background: Although vasomotor symptoms induced by aromatase inhibitors are frequently recognized, risk factors are ill-defined. To identify risk factors for vasomotor symptoms of Japanese breast cancer patients treated with adjuvant anastrozole, we conducted a prospective cohort study based on patient-reported outcomes (PROs). Patients and Methods: For this prospective cohort study (SAVS-JP, UMIN000002455), 391 postmenopausal Japanese estrogen receptor-positive breast cancer patients who were treated with adjuvant anastrozole were recruited from 28 centers. The PRO assessment was obtained from a self-reported questionnaire at baseline, 3, 6, 9 and 12 months between August 2009 and April 2012. Vasomotor symptoms, comprising hot flashes, night sweats, and cold sweats, were categorized into four grades (none, Grade 1: mild, Grade 2: moderate, Grade 3: severe). Pre-existing symptoms were only included if they worsened post-baseline. Results: Hot flashes, night sweats, and cold sweats at baseline were reported by 80 (20.5%), 59 (15.1%), and 32 (8.2%) patients respectively. New or worsening symptoms were experienced by 139 (38.4%), 106 (29.3%), and 104 (28.7%) patients. About 80% of newly occurring symptoms were grade 1, and less than 5% were grade 3. Overall vasomotor symptoms were reported by 201 (55.5%) out of 362 patients. Patients with vasomotor symptoms were significantly younger, had higher body mass index (BMI), shorter time period aftermenopause, and more menopausal disorders during menopause. Multivariate analysis showed that BMI (odds ratio: 1.09, 95% confidence interval: 1.02-1.16, P=0.009) and experience of menopausal disorders (2.11, 1.35-3.30, P=0.001) were significantly associated with vasomotor symptoms. Conclusions: We found that high BMI and experience of menopausal disorders at menopause were significantly associated with occurrence of vasomotor symptoms. These data are expected to prove useful for management of postmenopausal Japanese women treated with aromatase inhibitors. Clinical trial information: UMIN000002455.
Protein macroarray identification of biomarkers in HER2-positive breast cancer.
Authors: Dearbhaile Collins, Sinead Cocchiglia, Hong Chen, Derek Murphy, Arnold D. Hill, Leonie S Young
Journal: Journal of Clinical Oncology (2014)

e11575 Background: The holy grail of breast cancer diagnosis and management is the identification of biomarkers that can simplify diagnosis, predict response to treatment and facilitate follow-up to detect early recurrence and metastasis. We set out to identify autoantibodies in the serum of HER2-overexpressing breast cancer patients using protein macroarrays. Methods: We utilized a PEX protein macroarray comprising a human protein expression library containing 16,000 antigens to proteins known to be involved in tumorigenesis, dissemination and recurrence. Preoperative blood was collected from fifteen matched patients in three groups: HER2-positive, HER2-negative and non-cancer controls. Clinicopathological characteristics were prospectively obtained. Results: The macroarray uncovered 1,186 autoantibody-antigen interactions in breast cancer patient’s sera. Comparative analysis identified only seven common to three HER2-positive patients and forty-nine proteins common to two patients. No antibodies were exclusive to all or four of the HER2-positive patients. Secondary data revealed four antibodies exclusive to three HER2-negative patients. Two autoantibodies were expressed in all ten breast cancer patients, regardless of HER2 status and not in the control group, including the MYC-associated zinc ring finger protein. In the estrogen receptor (ER) positive cohort, two antibodies were exclusive to five out of six ER-positive patients and six antibodies were common to four ER-negative patients. One autoantibody in the HER2-positive group identified as Ada3 was further investigated with reverse ELISA techniques and validated in a prospective breast cancer cohort comprising seventy one patient’s sera and sixteen controls but failed to show significance. Conclusions: The PEX protein macroarray identified autoantibodies present in the sera of breast cancer patients and discovered common and unique autoantibodies in our primary cohort of HER2-positive breast cancer as well as in secondary HER2-negative and ER-positive cohorts that may prove to be important in the diagnosis, prognosis, tumour response prediction and follow-up of breast cancer patients.
Phase I Trial of Systemic Administration of Vesicular Stomatitis Virus Genetically Engineered to Express NIS and Human Interferon Beta, in Patients with Relapsed or Refractory Multiple Myeloma (MM), Acute Myeloid Leukemia (AML), and T-Cell Neoplasms (TCL)
Authors: Joselle Cook, Kah-Whye Peng, Brenda F Ginos, Amylou C. Dueck, Marissa Giers, Nandakumar Packiriswamy, Beth Brunton, Mrinal M. Patnaik, Thomas E. Witzig, Francis K. Buadi, Angela Dispenzieri, Morie A Gertz, Ronald S. Go, Suzanne R. Hayman, John A. Lust, David Dingli, S. Vincent Rajkumar, Nelson Leung, Rahma M Warsame, Wilson I Gonsalves, Taxiarchis Kourelis, Eli Muchtar, P. Leif Bergsagel, Stephen Broski, Prashant Kapoor, Robert A. Kyle, Mustaqeem A. Siddiqui, Amie Fonder, Miriam A. Hobbs, Yi L. Hwa, Yi Lin, Shaji K. Kumar, Stephen J. Russell, Martha Q. Lacy
Journal: Blood (2020)
Gastric cancer (GC) among California Asians: Analysis of California Cancer Registry (CCR).
Authors: Afsaneh Barzi, Mariana C. Stern, Juanjuan Zhang, Dennis Deapen, Heinz-Josef Lenz, Lihua Liu
Journal: Journal of Clinical Oncology (2014)

4086 Background: GC is the 4th cause of cancer death worldwide and is associated with significant morbidity in the affected individuals. In the US, California has the highest number of GC cases per year. We designed a study to explore the disparities in the presentation and outcome of GC in the Asians. Methods: Using data from CCR, we investigated the GC incidence, presentation, and survival among Asians from 2000-2010. We explored the significance of race in the anatomic presentation and survival of GC in the Asians compared to non-Hispanic Whites (NHW). We identified 18,377 GC cases in this time period, 70% were NHW, 8% Chinese, 7% Korean and 5% Japanese, the rest included Filipino, Vietnamese and other Asian sub-groups. Results: The frequency of GC by anatomical sites were statistically significantly different between Asians and NWH for both males and females (p<0.001). Compared to NHW, Asians had significantly lower frequency of cardia and fundus cancers (44% in NHW and 14% in Asians). Asians presented at a younger age (p <0.001) and had lower rates of de-novo metastatic disease compared to NHW (p <0.001). Survival rates were higher in Asians compared to NHW when adjusted for age, gender, socio-economic status, nativity, stage, anatomical site, and type of treatment received. Prognostic factors for death from gastric cancer included age > 65 and immigration status, with immigrants doing better than US born. There was significant amount of disparity among Asians form different countries, Koreans had the highest age adjusted incidence rate of GC compared to all other Asians. Conclusions: The differences in the demographics, anatomical distribution of GC, and outcome in the Asians may be due to differences in etiologic factors that deserve further exploration. In Japan and Korea, early detection had resulted in a dramatic decline in mortality and morbidity. Although overall low incidence of the disease in US is prohibitive for a generalized screening program, there are subpopulations that may benefit from screening. Given that early detection has proven to be effective and cost saving in Asian countries with high incidence of gastric cancer consideration of screening for this population is intriguing and should be explored.
Expanding the Utility of Midostaurin in Acute Myeloid Leukemia - Predictive Mutational Signatures in Patient Samples without FLT3 mutations and Clinically Applicable Synergistic Drug Combinations
Authors: Markus Vaha-Koskela, Muhammad Ammad-ud-din, Kirsi Siivola, Tanja Ruokoranta, Laura Turunen, Kimmo Porkka, Pedro Marques Ramos, Celine Pallaud, Tero Aittokallio, Krister Wennerberg
Journal: Blood (2018)