Preclinical studies in sickle cell disease (SCD) have demonstrated bone marrow pathology including disordered vasculature and reduced mesenchymal stem cell (MSC) function. Findings from these studies and preliminary testing in SCD patients support the benefits of red blood cell (RBC) transfusion in reducing such bone marrow abnormalities, with important implications for transfusion support and transplant outcomes in this patient population.

In research published in 2020 in Blood, for example, a 6-week transfusion regimen aimed at reducing hemoglobin S (HbS) levels to lower than 30% led to complete reversal of the abnormal bone marrow vasculature observed in humanized SCD mice.1 Additionally, a 2021 study showed that RBC transfusion reduced levels of oxidative stress in the bone marrow in murine models, and similar effects were noted in blood samples derived from patients with SCD.2

To learn more about bone marrow pathology in SCD and related considerations regarding transfusion in the transplant setting, we interviewed one of the authors of both the 2021 study2 and the American Society of Hematology guidelines3 for transfusion support in SCD: Patricia Shi, MD, medical director, head of clinical research in SCD, and assistant member of the Lindsley F. Kimball Research Institute at the New York Blood Center.

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Dr Shi, who is also a clinical associate professor of hematology and oncology at Albert Einstein College of Medicine, discussed this topic in a presentation at the 2022 Association for the Advancement of Blood and Biotherapies (AABB) Virtual Annual Meeting.4

What are some of the commonly observed manifestations of bone marrow pathology in patients with SCD, and what are the proposed mechanisms involved?

Manifestations of bone marrow pathology include inadequate compensatory reticulocytosis for the level of anemia, regardless of the level of renal dysfunction.5 Although this is partly related to an inadequate serum erythropoietin response, patients with SCD and renal dysfunction also tend to require higher doses of erythropoietin compared to other patient populations.6 Clonal hematopoiesis may develop at a younger age, and there exists a small absolute increase in the risk of leukemia.7,8

Underlying mechanisms may include inflammation, stress erythropoiesis, ineffective erythropoiesis, and decreased bone marrow hematopoietic stem cell (HSC) numbers and function.2,9,10 Underlying mechanisms for the decreased HSC numbers and function may include abnormal bone marrow vasculature and decreased numbers and function of bone marrow mesenchymal stromal cells.1,2