Citation: Sharma, I.; Son, M.J.; Motamedi, S.; Hoeft, A.; Teller, C.; Hamby, T.; Ray, A. Utilization of Genomic Tumor Profiling in Pediatric Liquid Tumors: A Clinical Series. Hematol. Rep. 2023, 15, 256–265. https://doi.org/10.3390/ hematolrep15020026 Academic Editor: Claudio Cerchione Received: 29 October 2022 Revised: 9 January 2023 Accepted: 17 April 2023 Published: 19 April 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Article Utilization of Genomic Tumor Profiling in Pediatric Liquid Tumors: A Clinical Series Ishna Sharma 1, * , Min Ji Son 1 , Shoaleh Motamedi 1 , Alice Hoeft 2,3 , Christa Teller 2 , Tyler Hamby 3 and Anish Ray 1,2 1 Texas College of Osteopathic Medicine, The University of North Texas Health Science Center, Fort Worth, TX 76107, USA 2 Department of Hematology/Oncology, Cook Children’s Medical Center, Fort Worth, TX 76104, USA 3 Department of Research Operations, Cook Children’s Medical Center, Fort Worth, TX 76104, USA * Correspondence: isharmamed@gmail.com Abstract: Hematologic tumors are mostly treated with chemotherapies that have poor toxicity profiles. While molecular tumor profiling can expand therapeutic options, our understanding of potential targetable drivers comes from studies of adult liquid tumors, which does not necessarily translate to efficacious treatment in pediatric liquid tumors. There is also no consensus on when profiling should be performed and its use in guiding therapies. We describe a single institution’s experience in integrating profiling for liquid tumors. Pediatric patients diagnosed with leukemia or lymphoma and who underwent tumor profiling were retrospectively reviewed. Ten (83.3%) patients had relapsed disease prior to tumor profiling. Eleven (91.7%) patients had targetable alterations identified on profiling, and three (25%) received targeted therapy based on these variants. Of the three patients that received targeted therapy, two (66.7%) were living, and one (33.3%) decreased. For a portion of our relapsing and/or treatment-refractory patients, genetic profiling was feasible and useful in tailoring therapy to obtain stable or remission states. Practitioners may hesitate to deviate from the ‘standard of therapy’, resulting in the underutilization of profiling results. Prospective studies should identify actionable genetic variants found more frequently in pediatric liquid tumors and explore the benefits of proactive tumor profiling prior to the first relapse. Keywords: leukemia; lymphoma; molecular profiling; targeted therapy; actionable genetic variants 1. Introduction Malignant neoplasms are the third leading cause of death among pediatric patients [1]. Unlike adults, children have higher incidence rates of liquid cancers than solid cancers [1,2]. Liquid cancers are malignancies arising from bone marrow cells or lymph nodes and include leukemias and lymphomas. Acute lymphoblastic leukemia (ALL), followed by acute myeloid leukemia (AML), is the most common leukemia found in children [2,3]. Over the past 60 years, five-year survival rates for pediatric liquid tumor patients have increased from 10% to 80% due to advancements in conventional chemotherapy treatments and supportive care [2,3]. Yet, for those patients with relapsing and/or refractory liquid cancers, prognosis and quality of life are dismal: reinduction treatment for such cancers relies heavily on escalating the intensity of chemotherapy drugs. Such treatment regimens are limited by short-term and long-term treatment toxicities and/or reduced efficacy [4–6]. To overcome similar treatment hurdles in solid adult cancers, precision medicine (i.e., targeted therapy) is often utilized to target particular enzymes and/or signal transduc- ers involved with tumor growth [7]. With a better understanding of the genetics underlying tumor prognosis, molecular profiling use has expanded to adult liquid tumors to guide therapeutic options. Unfortunately, the application of targeted therapy to pediatric liquid tumors is gen- erally limited; frequently, the therapies are developed to target oncogenic mutations that Hematol. Rep. 2023, 15, 256–265. https://doi.org/10.3390/hematolrep15020026 https://www.mdpi.com/journal/hematolrep