Disease severity impacts plerixafor-mobilized stem cell collection in patients with sickle cell disease

Abstract

Recent studies suggest that plerixafor mobilization and apheresis in patients with sickle cell disease (SCD) is safe and can allow collection of sufficient CD34+ hematopoietic stem cell (HSC) collection for clinical gene therapy applications. However, the quantities of plerixafor-mobilized CD34+ cells vary between different SCD patients for unknown reasons. Twenty-three participants with SCD underwent plerixafor mobilization followed by apheresis, processing, and HSC enrichment under a phase 1 safety and efficacy study conducted at 2 institutions. Linear regression or Spearman's correlation test was used to assess the relationships between various hematologic and clinical parameters with total CD34+ cells/kg collected. Median CD34+ cells/kg after 2 or fewer mobilization and apheresis cycles was 4.0 × 106 (range, 1.5-12.0). Similar to what is observed generally, CD34+ yield correlated negatively with age (P < .001) and positively with baseline (P = .003) and preapheresis blood CD34+ cells/µL (P < .001), and baseline white blood cell (P = .01) and platelet counts (P = .03). Uniquely for SCD, CD34+ cell yields correlated positively with the number of days hydroxyurea was held (for up to 5 weeks, P = .01) and negatively with markers of disease severity, including hospitalization frequency within the preceding year (P = .01) and the number of medications taken for chronic pain (P = .002). Unique SCD-specific technical challenges in apheresis were also associated with reduced CD34+ cell collection efficiency and purification. Here, we describe factors that impact plerixafor mobilization success in patients with SCD, confirming known factors as described in other populations in addition to reporting previously unknown disease specific factors in patients with SCD. This trial was registered at www.clinicaltrials.gov as #NCT03226691.

Graphical abstract

Figure 1.

Total CD34⁺collection. Total CD34⁺ cells/kg were assessed in the final product after 1 (n = 19) or 2 (n = 4) mobilization and apheresis procedures. Median values with 95% confidence interval shown.

Figure 2.

Correlation of total CD34⁺collection with participant CD34⁺cells/µL, age, and sex. (A) Association of preapheresis CD34⁺ cells/µL to total CD34⁺ cells/kg. (B) Association of age with total CD34⁺ cells/kg. (C) Median CD34⁺ cell/kg for males vs females. Median values with 95% confidence interval shown. □, Participants on chronic transfusion and hydroxyurea (HU); ○, participants on chronic transfusions; ●, participants on HU.

Figure 3.

Correlation of total CD34⁺collection with hematologic parameters. (A-D) Association of hematologic parameters (WBC [A], platelets [B], hemoglobin [C], and ARC [D]) with total CD34⁺ cells/kg. □, Participants on chronic transfusion and hydroxyurea (HU), ○, participants on chronic transfusions; ●, participants on HU.

Figure 4.

Correlation of total CD34⁺collection with disease severity and duration of HU washout. (A) Association of self-reported number of hospitalizations in the year before enrollment and total CD34⁺ cells/kg. (B) Association of self-reported number of medications taken on a daily basis to control chronic pain and total CD34⁺ cells/kg. (C) Association of number of days hydroxyurea (HU) was held before mobilization and apheresis total CD34⁺ cells/kg. □, Participants on chronic transfusion and hydroxyurea (HU), ○, participants on chronic transfusions; ●, participants on HU.