Person: Chen, Yi-Bin
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Chen
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Yi-Bin
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Chen, Yi-Bin
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Publication Non-invasive detection of severe neutropenia in chemotherapy patients by optical imaging of nailfold microcirculation(Nature Publishing Group UK, 2018) Bourquard, Aurélien; Pablo-Trinidad, Alberto; Butterworth, Ian; Sánchez-Ferro, Álvaro; Cerrato, Carolina; Humala, Karem; Fabra Urdiola, Marta; Del Rio, Candice; Valles, Betsy; Tucker-Schwartz, Jason M.; Lee, Elizabeth S.; Vakoc, Benjamin; Padera, Timothy; Ledesma-Carbayo, María J.; Chen, Yi-Bin; Hochberg, Ephraim; Gray, Martha L.; Castro-González, CarlosWhite-blood-cell (WBC) assessment is employed for innumerable clinical procedures as one indicator of immune status. Currently, WBC determinations are obtained by clinical laboratory analysis of whole blood samples. Both the extraction of blood and its analysis limit the accessibility and frequency of the measurement. In this study, we demonstrate the feasibility of a non-invasive device to perform point-of-care WBC analysis without the need for blood draws, focusing on a chemotherapy setting where patients’ neutrophils—the most common type of WBC—become very low. In particular, we built a portable optical prototype, and used it to collect 22 microcirculatory-video datasets from 11 chemotherapy patients. Based on these videos, we identified moving optical absorption gaps in the flow of red cells, using them as proxies to WBC movement through nailfold capillaries. We then showed that counting these gaps allows discriminating cases of severe neutropenia (<500 neutrophils per µL), associated with increased risks of life-threatening infections, from non-neutropenic cases (>1,500 neutrophils per µL). This result suggests that the integration of optical imaging, consumer electronics, and data analysis can make non-invasive screening for severe neutropenia accessible to patients. More generally, this work provides a first step towards a long-term objective of non-invasive WBC counting.Publication Phase I study of the aurora A kinase inhibitor alisertib with induction chemotherapy in patients with acute myeloid leukemia(Ferrata Storti Foundation, 2017) Fathi, Amir; Wander, Seth; Blonquist, Traci M.; Brunner, Andrew; Amrein, Philip; Supko, Jeffrey; Hermance, Nicole M.; Manning, Amity L.; Sadrzadeh, Hossein; Ballen, Karen K.; Attar, Eyal C.; Graubert, Timothy; Hobbs, Gabriela; Joseph, Christelle; Perry, Ashley M.; Burke, Meghan; Silver, Regina; Foster, Julia; Bergeron, Meghan; Ramos, Aura Y.; Som, Tina T.; Fishman, Kaitlyn M.; McGregor, Kristin L.; Connolly, Christine; Neuberg, Donna; Chen, Yi-BinAberrant expression of aurora kinase A is implicated in the genesis of various neoplasms, including acute myeloid leukemia. Alisertib, an aurora A kinase inhibitor, has demonstrated efficacy as monotherapy in trials of myeloid malignancy, and this efficacy appears enhanced in combination with conventional chemotherapies. In this phase I, dose-escalation study, newly diagnosed patients received conventional induction with cytarabine and idarubicin, after which alisertib was administered for 7 days. Dose escalation occurred via cohorts. Patients could then receive up to four cycles of consolidation, incorporating alisertib, and thereafter alisertib maintenance for up to 12 months. Twenty-two patients were enrolled. One dose limiting toxicity occurred at dose level 2 (prolonged thrombocytopenia), and the recommended phase 2 dose was established at 30mg twice daily. Common therapy-related toxicities included cytopenias and mucositis. Only three (14%) patients had persistent disease at mid-cycle, requiring “5+2” reinduction. The composite remission rate (complete remission and complete remission with incomplete neutrophil recovery) was 86% (nineteen of twenty-two patients; 90% CI 68–96%). Among those over age 65 and those with high-risk disease (secondary acute leukemia or cytogenetically high-risk disease), the composite remission rate was 88% and 100%, respectively. The median follow up was 13.5 months. Of those treated at the recommended phase 2 dose, the 12-month overall survival and progression-free survival were 62% (90% CI 33–81%) and 42% (90% CI 17–65%), respectively. Alisertib is well tolerated when combined with induction chemotherapy in acute myeloid leukemia, with a promising suggestion of efficacy. (clinicaltrials.gov Identifier:01779843).Publication Sequence-Based Discovery of Bradyrhizobium enterica in Cord Colitis Syndrome(New England Journal of Medicine (NEJM/MMS), 2013) Bhatt, Ami; Freeman, Sam; Herrera, Alex Francisco; Pedamallu, Chandra Sekhar; Gevers, Dirk; Duke, Fujiko; Jung, Joonil; Michaud, Monia; Walker, Bruce; Young, Sarah; Earl, Ashlee M.; Kostic, Aleksander D.; Ojesina, Akinyemi Ifedapo; Hasserjian, Robert; Ballen, Karen Kuhn; Chen, Yi-Bin; Hobbs, Gabriela; Antin, Joseph; Soiffer, Robert; Baden, Lindsey; Garrett, Wendy; Hornick, Jason; Marty, Francisco; Meyerson, MatthewBACKGROUND—Immunosuppression is associated with a variety of idiopathic clinical syndromes that may have infectious causes. It has been hypothesized that the cord colitis syndrome, a complication of umbilical-cord hematopoietic stem-cell transplantation, is infectious in origin. METHODS—We performed shotgun DNA sequencing on four archived, paraffin-embedded endoscopic colon-biopsy specimens obtained from two patients with cord colitis. Computational subtraction of human and known microbial sequences and assembly of residual sequences into a bacterial draft genome were performed. We used polymerase-chain-reaction (PCR) assays and fluorescence in situ hybridization to determine whether the corresponding bacterium was present in additional patients and controls. RESULTS—DNA sequencing of the biopsy specimens revealed more than 2.5 million sequencing reads that did not match known organisms. These sequences were computationally assembled into a 7.65-Mb draft genome showing a high degree of homology with genomes of bacteria in the bradyrhizobium genus. The corresponding newly discovered bacterium was provisionally named Bradyrhizobium enterica. PCR identified B. enterica nucleotide sequences in biopsy specimens from all three additional patients with cord colitis whose samples were tested, whereas B. enterica sequences were absent in samples obtained from healthy controls and patients with colon cancer or graft-versus-host disease. CONCLUSIONS—We assembled a novel bacterial draft genome from the direct sequencing of tissue specimens from patients with cord colitis. Association of these sequences with cord colitis suggests that B. enterica may be an opportunistic human pathogen.Publication Bortezomib-based immunosuppression after reduced-intensity conditioning hematopoietic stem cell transplantation: randomized phase II results(Ferrata Storti Foundation, 2018) Koreth, John; Kim, Haesook; Lange, Paulina B.; Poryanda, Samuel J.; Reynolds, Carol G.; Rai, Sharmila Chamling; Armand, Philippe; Cutler, Corey; Ho, Vincent; Glotzbecker, Brett; Yusuf, Rushdia; NIkiforow, Sarah; Chen, Yi-Bin; Dey, Bimalangshu; McMasters, Malgorzata; Ritz, Jerome; Blazar, Bruce R.; Soiffer, Robert; Antin, Joseph; Alyea, Edwin P.Aprior phase I/II trial of bortezomib/tacrolimus/methotrexate prophylaxis after human leukocyte antigen (HLA)-mismatched reduced intensity conditioning allogeneic hematopoietic stem cell transplantation documented low acute graft-versus-host disease incidence, with promising overall and progression-free survival. We performed an open-label three-arm 1:1:1 phase II randomized controlled trial comparing grade II–IV acute graft-versus-host disease between conventional tacrolimus/methotrexate (A) versus bortezomib/tacrolimus/methotrexate (B), and versus bortezomib/sirolimus/tacrolimus (C), in reduced intensity conditioning allogeneic transplantation recipients lacking HLA-matched related donors. The primary endpoint was grade II–IV acute graft-versus-host disease incidence rate by day +180. One hundred and thirty-eight patients (A 46, B 45, C 47) with a median age of 64 years (range: 24–75), varying malignant diagnoses and disease risk (low 14, intermediate 96, high/very high 28) received 7–8/8 HLA-mismatched (40) or matched unrelated donor (98) grafts. Median follow up in survivors was 30 months (range: 14–46). Despite early immune reconstitution differences, day +180 grade II-IV acute graft-versus-host disease rates were similar (A 32.6%, B 31.1%, C 21%; P=0.53 for A vs. B, P=0.16 for A vs. C). The 2-year non-relapse mortality incidence was similar (A 14%, B 16%, C 6.4%; P=0.62), as were relapse (A 32%, B 32%, C 38%; P=0.74), chronic graft-versus-host disease (A 59%, B 60% C 55%; P=0.66), progression-free survival (A 54%, B 52%, C 55%; P=0.95), and overall survival (A 61%, B 62%, C 62%; P=0.98). Overall, the bortezomib-based regimens evaluated did not improve outcomes compared with tacrolimus/methotrexate therapy. clinicaltrials.gov Identifier: 01754389