Children with sickle cell disease are more likely than other children to develop a clonal growth of precancerous blood cells called clonal hematopoiesis (CH), which is associated in older people with a higher risk of blood cancer, according to new research from Vanderbilt Health.  

However, the clones in children with sickle cell disease did not expand as readily as they do in older people with CH, suggesting that they may be more transitory and have different health consequences, the researchers reported March 26 in the journal Blood.  

In addition, hydroxyurea, which reduces painful episodes and the need for blood transfusions in people with sickle cell disease, did not increase the risk of developing CH. That is good news for patients for whom hydroxyurea is “an essential therapy,” the researchers reported.  

While questions remain about the link between CH and sickle cell disease, these findings shed light on disruptions in normal blood cell development (hematopoiesis) that may be shared by both diseases.  

Chronic hematopoietic stress within the hypoxic (low oxygen), inflammatory bone marrow environment of sickle cell disease may predispose to the accumulation of somatic mutations (in nonreproductive cells) and/or the outgrowth of affected hematopoietic stem cell clones at an earlier age, the researchers hypothesized.  

The researchers used a highly sensitive sequencing technique to determine the prevalence of CH in 1,025 children with sickle cell disease, and in a matched control group of 2,957 children without the disease. The results were validated in an independent cohort of 1,293 children with sickle cell disease.  

Jessica Ulloa, a graduate student in the Vanderbilt Human Genetics Program, is the paper’s first author.   

Contributing equally to the study were the paper’s corresponding author, Alexander Bick, MD, PhD, the Edward Claiborne Stahlman Professor and director of the Division of Genetic Medicine and Clinical Pharmacology at Vanderbilt Health; Michael DeBaun, MD, MPH, the J.C. Peterson, MD Professor of Pediatrics and director of the Vanderbilt-Meharry Sickle Cell Disease Center of Excellence; Santosh Saraf, MD, University of Illinois; and Mitchell Weiss, MD, PhD, St. Jude Children’s Research Hospital.  

Other co-authors from Vanderbilt Health were Kristin Wuichet, PhD, Yash Pershad, and Connor Shore.  

Support for the study was provided in part by National Institutes of Health grants R01HL168179, T32GM145734 and T32GM007347, and the Vanderbilt Undergraduate Summer Research Program.  

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Researchers from Vanderbilt-Ingram Cancer Center will present findings from clinical trials, laboratory discoveries and innovations in caring for patients with hematologic cancers and other blood diseases at ASH 2025 in Orlando, Florida, Dec. 6-9. 

ASH 2025 is the American Society of Hematology Annual Meeting and Exposition. Established in 1958, ASH is the world’s largest professional organization for clinicians and scientists who study blood diseases.  

Three of the presentations from Vanderbilt-Ingram researchers will focus on chimeric antigen receptor T-cell (CAR-T) therapies, a form of immunotherapy that involves treating cancer with white blood cells that have been reengineered to attack cancer cells. Vanderbilt-Ingram is an international leader in advancing the efficacy of and expanding access to CAR-T therapies.

Olalekan Oluwole, MBBS, MPH, associate professor of Medicine, who leads the cellular therapy research program at Vanderbilt-Ingram, will present data on health care resource utilizations of the therapies in U.S. patients treated at newly authorized treatment centers. He will also provide an overview of outcomes for inpatient and outpatient CAR-T treatment. Grace Mercadante, MD, will present data on the impact of clonal hematopoiesis on CAR-T therapy. 

Michael DeBaun, MD, MPH, the J.C. Peterson, MD, Professor of Pediatrics and founder and director of the Vanderbilt-Meharry Sickle Cell Disease Center of Excellence, will speak at a special session focusing on ASH’s sickle cell disease initiative. He will present findings from “Sickle Cell Trait Does Not Cause ‘Sickle Cell Crisis’ Leading to Exertion Related Death: A Systematic Review.” 

Other topics researchers will address include acute myeloid leukemia, myelodysplastic syndrome, drug resistance, potential adverse reactions and risk comparisons of treatments, pediatric blood disorders, multiple myeloma, bispecific antibody treatment, and graft-versus-host disease. 

A complete list of presentations from Vanderbilt researchers follows: 

Sally Momoh, MD – Sex-related differences in silent cerebral infarction burden among adults with sickle cell disease 

Jamila Mammadova, MD – Behind the blood-brain barrier: Contemporary screening practice patterns and trends of central nervous system involvement in acute myeloid leukemia treated with intensive regimens and hypomethylating agent/venetoclax 

Alyssa Jarabek – Impact of innate immune memory on myelodysplastic syndrome progression by TET2-driven inflammation 

Raymond Zhang – VISTA contributes to disease progression in high-risk myelodysplastic syndrome 

Mattew Villaume, MD, PhD – EB2023 primes mitochondria for BCL2 dependence and induces pyroptotic cell death via AMPK signaling and the unfolding protein response 

Grace Mercadante, MD – The impact of clonal hematopoiesis on CAR-T cell therapy outcomes: a single-center analysis 

Ghadeer Dawwas, PhD, MSc, MBA – Risk of serious bleeding with concomitant use of apixaban or rivaroxaban with amiodarone compared to flecainide or sotalol in patients with atrial fibrillation  

Olalekan Oluwole, MBBS, MPH – Real-world health care utilization following CAR-T cell therapy in U.S. patients treated in newly authorized treatment centers 

Erin Christensen, MS, DO – A case series of pediatric patients with congenital thrombotic thrombocytopenia purpura treated with recombinant ADAMTS13 

Andrew Jallouk, MD, PhD – Real-world outcomes of mosunetuzumab use in indolent and aggressive lymphomas  

Bhagirathbhai Dholaria, MBBS – Characterization of a population with newly diagnosed standard risk multiple myeloma by 2025 ims/IMWG definition with exceptional long-term outcomes after fixed duration therapy 

Y. Emily Chu – The acute myeloid leukemia microenvironment is defined by ineffective immune surveillance despite the presence of activated, clonally-expanded CD8 T cells with preserved effector function 

Michael DeBaun, MD, MPH – Findings from “Sickle cell trait does not cause ‘sickle cell crisis’ leading to exertion related death: a systematic review ”

Mattew Villaume, MD, PhD – F1 subunit-specific ATP synthase inhibition disrupts AML mitochondrial metabolism distinctly from other electron transport chain inhibitors 

Lauren Klein, MD, – Early weight gain predicts nutritional recovery in children with sickle cell anemia and severe acute malnutrition in Nigeria 

Olalekan Oluwole, MBBS, MPH – U.S. cost consequence and time toxicity model for advanced therapies in the treatment for relapsed/refractory third-line or later diffuse large B-cell lymphoma: a comparison of axicabtagene ciloleucel with bispecific antibodies 

Olalekan Oluwole, MBBS, MPH – Outcomes of inpatient and outpatient CAR-T in newly authorized treatment centers in the United States 

Elizabeth Pollard, MD – Leukapheresis for acute leukemia with hyperleukocytosis: line complications, resource utilization, and early mortality outcomes 

Carrie Kitko, MD – Long-term treatment duration and safety of axatilimab among patients with chronic graft-versus-host disease in AGAVE-201 

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