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

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.