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Umbilical cord blood as a hematopoietic stem cell source in transplantation for pediatric sickle cell disease: current challenges and strategies

  • Megha Malhotra
    Affiliations
    Washington University School of Medicine, Division of Pediatric Hematology Oncology, Department of Pediatrics, 660 S. Euclid Avenue, Campus Box 8116, St. Louis, MO 63110, USA
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  • Shalini Shenoy
    Correspondence
    Correspondence to: Washington University School of Medicine in St. Louis, Department of Pediatrics, 660 S. Euclid Avenue, Campus Box 8116, St. Louis, MO 63110, USA.
    Affiliations
    Washington University School of Medicine, Division of Pediatric Hematology Oncology, Department of Pediatrics, 660 S. Euclid Avenue, Campus Box 8116, St. Louis, MO 63110, USA
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      Highlights

      • Stem cell transplantation can eradicate disease symptoms in sickle cell disease.
      • Cord blood can be mismatched and hence expands donor availability for transplant.
      • Advantages include availability for ethnic minorities and low risk of chronic GVHD.
      • Advances targeting engraftment/infection challenges continue to improve outcomes.

      Abstract

      Allogeneic hematopoietic stem cell transplant (HSCT) is the only established cure for sickle cell disease (SCD), a hemolytic disorder that arises due to a point mutation in the hemoglobin A gene. The result is an abnormal sickle hemoglobin (HbS) replacing hemoglobin A. Of the spectrum of sickle hemoglobinoapthies, homozygous (HbSS) and HbSβ0 thalassemia manifest severe forms of disease characterized by chronic endothelial injury/vasculopathy, ischemic pain, and vital organ damage that commence in childhood and escalate with age resulting in impaired quality of life, increased healthcare burden, and early mortality. HSCT has demonstrated durable disease control and regression of symptoms. Human leukocyte antigen (HLA) matched sibling donor (MSD) transplantation can achieve disease-free survival of > 90%. However, < 18% of SCD patients in the United States have a MSD. Familial mismatched and unrelated donors from registries provide alternate stem cell sources. Umbilical cord blood (UCB) from family or cord blood banks expand donor sources and are attractive due to donor-independent ease of use and availability. These naïve cells tolerate greater degrees of HLA-mismatch. The primary challenge with UCB is optimizing cell dose toward successful engraftment and timely immune reconstitution while minimizing graft-versus-host disease (GVHD). This review summarizes evidence that UCB remains a promising stem cell source where modern methods of graft expansion, conditioning, GVHD prophylaxis, and infection control can overcome these challenges and retain the value of this intervention.

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