Desai, Pinkal M
Mayo Clinic
Division of Hematology and Oncology, Weill Cornell Medicine, New York, NY 10065, USA.
Citations 2
The genetic determinants of recurrent somatic mutations in 43,693 blood genomes
Weinstock, Joshua S. , Laurie, Cecelia , Broome, Jai , Taylor, Kent D. , Guo, Xiuqing , Shuldiner, Alan R. , O’Connell, Jeffrey R. , Lewis, Joshua P. , Boerwinkle, Eric , Barnes, Kathleen C. , Chami, Nathalie , Loos, Ruth J. F. , Fornage, Myriam , Redline, Susan , Cade, Brian E. , Chen, Zhanghua , Gauderman, W. James , Schleimer, Robert P. , Bis, Joshua C. , Brody, Jennifer A. , Silverman, Edwin K. , Qiao, Dandi , Lasky‐Su, Jessica , DeMeo, Dawn L. , Palmer, Nicholette D. , Bowden, Donald W. , Johnson, Andrew D. , Yanek, Lisa R. , Becker, Lewis C. , Kardia, Sharon L.R., Kaplan, Robert C. , Heckbert, Susan R. , Smith, Nicholas L. , Arnett, Donna K. , Irvin, Marguerite R. , Tiwari, Hemant K., Raffield, Laura M. , Gao, Yan , Rotter, Jerome I. , Wheeler, Marsha M. , Duggirala, Ravindranath , Xiao, Shujie, Williams, L. Keoki , Meyers, Deborah A. , Ortega, Victor E. , McGarvey, Stephen T. , Chen, Yii‐Der Ida , Lee, Wen‐Jane , Shoemaker, M. Benjamin , Roden, Dan M. , Blackwell, Thomas W. , Smith, Albert V. , Kang, Hyun Min , Mathias, Rasika A. , Natarajan, Pradeep , Jaiswal, Siddhartha , Reiner, Alex P. , Bick, Alexander G. , Kaplan, Robert C. , Broome, Jai , Kenny, Eimear E , Loos, Ruth J F , Fornage, Myriam , Redline, Susan , Cade, Brian E , Gauderman, W James , Grammer, Leslie , Schleimer, Robert P , Bis, Joshua C , Brody, Jennifer A , Silverman, Edwin K , Yun, Jeong H , Qiao, Dandi , Weiss, Scott T , Palmer, Nicholette D , Freedman, Barry I , Cho, Michael H , Vasan, Ramachandran S , Johnson, Andrew D , Yanek, Lisa R , Becker, Lewis C , He, Jiang , Heckbert, Susan R , Wiggins, Kerri L , Arnett, Donna K , Correa, Adolfo , Raffield, Laura M , Gao, Yan , Rotter, Jerome I , Rich, Stephen S , Manichaikul, Ani W , Konkle, Barbara A , Johnsen, Jill M , Custer, Brian S , Duggirala, Ravindranath , Curran, Joanne E , Li, Xingnan , McGarvey, Stephen T , Gu, C Charles , Lee, Wen-Jane , Darbar, Dawood , Roden, Dan M. , Kooperberg, Charles , Desai, Pinkal M , Smith, Albert V , Kang, Hyun M , Mathias, Rasika A , Natarajan, Pradeep , Jaiswal, Siddhartha , Bick, Alexander G , Weinstock, Joshua S , Shuldiner, Alan R , Taylor, Kent D , Guo, Xiuqing , Lasky-Su, Jessica , Gilliland, Frank D. , Kumar, Rajesh , Psaty, Bruce M. , Yun, Jeong H. , Weiss, Scott T. , Freedman, Barry I. , Cho, Michael H. , Vasan, Ramachandran S. , He, Jiang , Wiggins, Kerri L. , Andrade, Mariza de , Rich, Stephen S. , Manichaikul, Ani , Konkle, Barbara A. , Custer, Brian , Curran, Joanne E. , Blangero, John , Gui, Hongsheng , Li, Xingnan , Darbar, Dawood , Albert, Christine M. , Kooperberg, Charles , Desai, Pinkal , Abecasis, Gonçalo R.
Science Advances | April 26, 2023 | Volume: 9 | Issue: 17 | Pages: No page available
Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid lineage commitment. In addition, the presence of eight specific RNMSMs associated with blood cell traits at effect sizes comparable to Mendelian genetic mutations. Overall, we found that somatic mutations in blood are an unexpectedly common phenomenon with ancestry-specific determinants and human health consequences.
Open-Label Phase II Prospective, Randomized, Controlled Study of Romyelocel-L Myeloid Progenitor Cells to Reduce Infection During Induction Chemotherapy for Acute Myeloid Leukemia
Desai, Pinkal , Brown, J. Martin , Gill, Saar , Solh, Melham, Akard, Luke P., Hsu, Jack W., Üstün, Celalettin , Frankfurt, Olga, Foran, James M. , Lister, John , Schiller, Gary J. , Wieduwilt, Matthew J. , Pagel, John M. , Stiff, Patrick J. , Liu, Delong , Khan, Irum , Kambhampati, Suman , Tallman, Martin S. , Morris, Lawrence E. , Edwards, John , Pusic, Iskra , Kantarjian, Hagop M. , Mamelok, Richard D., Wong, Alicia , Syoc, Rodney Van, Kellerman, Lois, Panuganti, Swapna, Mandalam, Ramkumar, Abboud, Camille N. , Desai, Pinkal M , Solh, Melham M , Lister, John , Wieduwilt, Matthew J , Pagel, John M , Stiff, Patrick J , Khan, Irum , Stock, Wendy , Edwards, John , Abboud, Camille N , Kantarjian, Hagop , Andreadis, Charalambos Babis , Stock, Wendy , Wong, Alicia, Syoc, Rod Van, Ravandi, Farhad
Journal of Clinical Oncology | June 22, 2021 | Volume: 39 | Issue: 29 | Pages: 3261-3272
PURPOSEStandard cytotoxic induction chemotherapy for acute myeloid leukemia (AML) results in prolonged neutropenia and risk of infection. Romyelocel-L is a universal, allogeneic myeloid progenitor cell product being studied to reduce infection during induction chemotherapy.PATIENTS AND METHODSOne hundred sixty-three patients with de novo AML (age ≥ 55 years) receiving induction chemotherapy were randomly assigned on day 0 (d0), of whom 120 were evaluable. Subjects received either romyelocel-L infusion on d9 with granulocyte colony-stimulating factor (G-CSF) starting daily d14 (treatment group) or G-CSF daily alone on d14 (control) until absolute neutrophil count recovery to 500/µL. End points included days in febrile episode, microbiologically defined infections, clinically diagnosed infection, and days in hospital.RESULTSMean days in febrile episode was shorter in the treatment arm from d15 through d28 (2.36 v 3.90; P = .02). Similarly, a trend toward decreased microbiologically defined infections and clinically diagnosed infection in the treatment arm was observed from d9 to d28 (35.6% v 47.5%; P = .09), reaching a statistically significant difference from d15 to d28 (6.8% v 27.9%; P = .002). Because of this, antibacterial or antifungal use for treatment of an infection was significantly less in the treatment group (d9-d28: 44.1% v 63.9%; P = .01). Significantly fewer patients in the treatment arm received empiric antifungals from d9 tod28 (42.4% v 63.9%; P = .02) and d15-d28 (42.4% v 62.3%; P = .02). Patients in the treatment arm also had 3.2 fewer hospital days compared with control (25.5 v 28.7; P = .001). Remission rates and days to absolute neutrophil count recovery were similar in the two groups. No patients in the romyelocel-L plus G-CSF group died because of infection compared with two patients in the control arm. No graft-versus-host disease was observed.CONCLUSIONSubjects receiving romyelocel-L showed a decreased incidence of infections, antimicrobial use, and hospitalization, suggesting that romyelocel-L may provide a new option to reduce infections in patients with AML undergoing induction therapy.