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 - 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 -