TY - JOUR
T1 - Clinical Applications and Utility of a Precision Medicine Approach for Patients With Unexplained Cytopenias
AU - Mangaonkar, Abhishek A.
AU - Ferrer, Alejandro
AU - Pinto e Vairo, Filippo
AU - Cousin, Margot A.
AU - Kuisle, Ryan J.
AU - Gangat, Naseema
AU - Hogan, William J.
AU - Litzow, Mark R.
AU - McAllister, Tammy M.
AU - Klee, Eric W.
AU - Lazaridis, Konstantinos N.
AU - Stewart, A. Keith
AU - Patnaik, Mrinal M.
N1 - Funding Information:
Grant Support: This study was supported by “The Gerstner Family Career Development Award,” Mayo Clinic Center for Individualized Medicine and CTSA Grant number KL2 TR000136 from the National Center for Advancing Translational Sciences. Grant Support: This study was supported by “ The Gerstner Family Career Development Award,” Mayo Clinic Center for Individualized Medicine and CTSA Grant number KL2 TR000136 from the National Center for Advancing Translational Sciences. Text within this manuscript does not necessarily represent the official views of the U.S National Institutes of Health and authors are solely responsible for its contents. Drs Mangaonkar and Ferrer contributed equally to this work. Grant Support: This study was supported by “ The Gerstner Family Career Development Award,” Mayo Clinic Center for Individualized Medicine and CTSA Grant number KL2 TR000136 from the National Center for Advancing Translational Sciences.
Publisher Copyright:
© 2019 Mayo Foundation for Medical Education and Research
PY - 2019/9
Y1 - 2019/9
N2 - Objective: To demonstrate experience and feasibility of a precision medicine approach for patients with unexplained cytopenias, defined as low blood counts in one or more cell lineages, persistent for 6 months or longer, in the absence of known nutritional, autoimmune, infectious, toxic, and neoplastic (secondary) causes. Patients and Methods: Patients were evaluated in our clinic between November 8, 2016, and January 12, 2018. After a thorough evaluation of known causes, family history, and appropriate clinical assays, genomic evaluation was performed in a stepwise manner, through Sanger, targeted, and/or whole-exome sequencing. Variants were analyzed and discussed in a genomics tumor board attended by clinicians, bioinformaticians, and molecular biologists. Results: Sixty-eight patients were evaluated in our clinic. After genomic interrogation, they were classified into inherited bone marrow failure syndromes (IBMFS) (n=24, 35%), cytopenias without a known clinical syndrome which included idiopathic and clonal cytopenias of undetermined significance (CCUS) (n=30, 44%), and patients who did not fit into the above two categories (“others,” n=14, 21%). A significant family history was found in only 17 (25%) patients (9 IBMFS, 2 CCUS, and 6 others), whereas gene variants were found in 43 (63%) patients (34 [79%] pathogenic including 12 IBMFS, 17 CCUS, and 5 others]. Genomic assessment resulted in a change in clinical management in 17 (25%) patients, as evidenced by changes in decisions with regards to therapeutic interventions (n=8, 47%), donor choice (n=6, 35%), and/or choice of conditioning regimen for hematopoietic stem cell transplantation (n=8, 47%). Conclusion: We show clinical utility of a real-world algorithmic precision medicine approach for unexplained cytopenias.
AB - Objective: To demonstrate experience and feasibility of a precision medicine approach for patients with unexplained cytopenias, defined as low blood counts in one or more cell lineages, persistent for 6 months or longer, in the absence of known nutritional, autoimmune, infectious, toxic, and neoplastic (secondary) causes. Patients and Methods: Patients were evaluated in our clinic between November 8, 2016, and January 12, 2018. After a thorough evaluation of known causes, family history, and appropriate clinical assays, genomic evaluation was performed in a stepwise manner, through Sanger, targeted, and/or whole-exome sequencing. Variants were analyzed and discussed in a genomics tumor board attended by clinicians, bioinformaticians, and molecular biologists. Results: Sixty-eight patients were evaluated in our clinic. After genomic interrogation, they were classified into inherited bone marrow failure syndromes (IBMFS) (n=24, 35%), cytopenias without a known clinical syndrome which included idiopathic and clonal cytopenias of undetermined significance (CCUS) (n=30, 44%), and patients who did not fit into the above two categories (“others,” n=14, 21%). A significant family history was found in only 17 (25%) patients (9 IBMFS, 2 CCUS, and 6 others), whereas gene variants were found in 43 (63%) patients (34 [79%] pathogenic including 12 IBMFS, 17 CCUS, and 5 others]. Genomic assessment resulted in a change in clinical management in 17 (25%) patients, as evidenced by changes in decisions with regards to therapeutic interventions (n=8, 47%), donor choice (n=6, 35%), and/or choice of conditioning regimen for hematopoietic stem cell transplantation (n=8, 47%). Conclusion: We show clinical utility of a real-world algorithmic precision medicine approach for unexplained cytopenias.
UR - http://www.scopus.com/inward/record.url?scp=85067870363&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85067870363&partnerID=8YFLogxK
U2 - 10.1016/j.mayocp.2019.04.007
DO - 10.1016/j.mayocp.2019.04.007
M3 - Article
C2 - 31256854
AN - SCOPUS:85067870363
SN - 0025-6196
VL - 94
SP - 1753
EP - 1768
JO - Mayo Clinic proceedings
JF - Mayo Clinic proceedings
IS - 9
ER -