Clinical Applications and Utility of a Precision Medicine Approach for Patients With Unexplained Cytopenias

Abhishek A. Mangaonkar, Alejandro Ferrer, Filippo Pinto e Vairo, Margot A. Cousin, Ryan J. Kuisle, Naseema Gangat, William Hogan, Mark R Litzow, Tammy M. McAllister, Eric W Klee, Konstantinos N Lazaridis, A. Keith Stewart, Mrinal M Patnaik

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalMayo Clinic proceedings
DOIs
StatePublished - Jan 1 2019

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Precision Medicine
Exome
Poisons
Hematopoietic Stem Cell Transplantation
Cell Lineage
Genomics
Tissue Donors

ASJC Scopus subject areas

  • Medicine(all)

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Clinical Applications and Utility of a Precision Medicine Approach for Patients With Unexplained Cytopenias. / Mangaonkar, Abhishek A.; Ferrer, Alejandro; Pinto e Vairo, Filippo; Cousin, Margot A.; Kuisle, Ryan J.; Gangat, Naseema; Hogan, William; Litzow, Mark R; McAllister, Tammy M.; Klee, Eric W; Lazaridis, Konstantinos N; Stewart, A. Keith; Patnaik, Mrinal M.

In: Mayo Clinic proceedings, 01.01.2019.

Research output: Contribution to journalArticle

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title = "Clinical Applications and Utility of a Precision Medicine Approach for Patients With Unexplained Cytopenias",
abstract = "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.",
author = "Mangaonkar, {Abhishek A.} and Alejandro Ferrer and {Pinto e Vairo}, Filippo and Cousin, {Margot A.} and Kuisle, {Ryan J.} and Naseema Gangat and William Hogan and Litzow, {Mark R} and McAllister, {Tammy M.} and Klee, {Eric W} and Lazaridis, {Konstantinos N} and Stewart, {A. Keith} and Patnaik, {Mrinal M}",
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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

AU - Litzow, Mark R

AU - McAllister, Tammy M.

AU - Klee, Eric W

AU - Lazaridis, Konstantinos N

AU - Stewart, A. Keith

AU - Patnaik, Mrinal M

PY - 2019/1/1

Y1 - 2019/1/1

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.

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