Dataset Information

Hematopoietic progenitor cell mobilization is more robust in healthy African American compared to Caucasian donors and is not affected by the presence of sickle cell trait.

ABSTRACT:

Background

Granulocyte-colony-stimulating factor (G-CSF)-stimulated hematopoietic progenitor cells (HPCs) collected by apheresis have become the predominant graft source for HPC transplantation in adults. Among healthy allogeneic donors, demographic characteristics (age, sex, body mass index [BMI]) and baseline hematologic counts affect HPC mobilization, leading to variability in CD34+ apheresis yields. Racial differences in HPC mobilization are less well characterized.

Study design and methods

We retrospectively analyzed data from 1096 consecutive G-CSF-stimulated leukapheresis procedures in healthy allogeneic African American (AA) or Caucasian donors.

Results

In a multivariate analysis, after adjusting for age, sex, BMI, baseline platelet and mononuclear cell counts, and daily G-CSF dose, peak CD34+ cell mobilization was significantly higher among AAs (n = 215) than Caucasians (n = 881; 123 ± 87 × 10(6) cells/L vs. 75 ± 47 × 10(6) cells/L; p < 0.0001). A ceiling effect was observed with increasing G-CSF dose (10 µg/kg/day vs. 16 µg/kg/day) in AAs (123 ± 88 × 10(6) cells/L vs. 123 ± 87 × 10(6) cells/L) but not in Caucasians (74 ± 46 × 10(6) cells/L vs. 93 ± 53 × 10(6) cells/L; p < 0.001). In AA donors, the presence of sickle cell trait (SCT; n = 41) did not affect CD34+ mobilization (peak CD34+ 123 ± 91 × 10(6) cells/L vs. 107 ± 72 × 10(6) cells/L, HbAS vs. HbAA; p = 0.34). Adverse events were minimal and similar across race.

Conclusions

AAs demonstrated significantly better CD34 mobilization responses to G-CSF than Caucasians. This was independent of other demographic and hematologic variables. Studying race-associated pharmacogenomics in relation to G-CSF may improve dosing strategies. Adverse event profile and CD34 mobilization were similar in AA donors with and without SCT. Our findings suggest that it would be safe to include healthy AA donors with SCT in unrelated donor registries.

SUBMITTER: Panch SR

PROVIDER: S-EPMC5500229 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Publications

Hematopoietic progenitor cell mobilization is more robust in healthy African American compared to Caucasian donors and is not affected by the presence of sickle cell trait.

Panch Sandhya R SR Yau Yu Ying YY Fitzhugh Courtney D CD Hsieh Matthew M MM Tisdale John F JF Leitman Susan F SF

Transfusion 20160501 5

<h4>Background</h4>Granulocyte-colony-stimulating factor (G-CSF)-stimulated hematopoietic progenitor cells (HPCs) collected by apheresis have become the predominant graft source for HPC transplantation in adults. Among healthy allogeneic donors, demographic characteristics (age, sex, body mass index [BMI]) and baseline hematologic counts affect HPC mobilization, leading to variability in CD34+ apheresis yields. Racial differences in HPC mobilization are less well characterized.<h4>Study design a ...[more]

PMID: 27167356

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Project description:Background and objectivesSickle cell trait and sickle cell disease are associated with faster GFR decline compared with normal hemoglobin phenotypes. We sought to compare the AKI risk in sickle cell trait/disease to normal hemoglobin phenotypes and investigate the association between AKI and GFR decline in sickle cell trait/disease.Design, setting, participants, & measurementsThis multicenter observational study used registry data (January 2005-June 2018) of adult Black patients with sickle cell trait/disease (exposures) and normal hemoglobin phenotype (reference) ascertained by hemoglobin electrophoresis. Outcomes of interest (incident AKI [1.5 times baseline serum creatinine or higher], incident severe AKI [doubling of baseline serum creatinine or higher], and incident sustained AKI [AKI persisting for ≥72 hours]) were adjudicated by chart review and evaluated by Cox regression. The association between AKI and GFR decline (linear mixed models) was also investigated.ResultsWe identified 8968 reference patients, 1279 patients with sickle cell trait, and 254 patients with sickle cell disease with a median follow-up of 7.6 years and mean baseline serum creatinine of 0.8 mg/dl. We observed 796 AKI events, 452 sustained AKI events, and 466 severe AKI events. Compared with people with a normal hemoglobin phenotype, sickle cell trait was associated with higher risk for sustained AKI (adjusted hazard ratio, 1.64; 95% confidence interval, 1.27 to 2.11), but not AKI (adjusted hazard ratio, 1.11; 95% confidence interval, 0.91 to 1.36) or severe AKI (adjusted hazard ratio, 1.26; 95% confidence interval, 0.96 to 1.64). Sickle cell disease was associated with AKI (adjusted hazard ratio, 2.85; 95% confidence interval, 2.13 to 3.81), severe AKI (adjusted hazard ratio, 2.38; 95% confidence interval, 1.65 to 3.42), and sustained AKI (adjusted hazard ratio, 2.50; 95% confidence interval, 1.68 to 3.71). Post-AKI GFR decline was significantly faster in sickle cell trait (0.37 ml/min per 1.73 m2 per year faster, P<0.01) and disease (1.69 ml/min per 1.73 m2 per year faster, P<0.01) compared with the reference.ConclusionsSickle cell trait and disease are associated with higher risk of AKI, which is associated with accelerated decline in eGFR.

Project description:BackgroundClinical manifestations and severity of SARS-CoV-2 infection in individuals with sickle cell disease (SCD) and sickle cell trait (SCT) are not well understood yet.MethodsWe performed a systematic review and meta-analysis to assess COVID-19 outcomes in individuals with SCD or SCT compared to individuals without sickle cell disease or trait. An electronic search on PubMed, Embase, and Cochrane Library was performed on August 3, 2023. Two authors (IFM and ISP) independently screened (IFM and ISP) and extracted data (IFM and ILC) from included studies. Main exclusion criterion was the absence of the non-SCD/SCT group. Exposure effects for binary endpoints were compared using pooled odds ratio (OR) with 95% confidence intervals (CI). I2 statistics was used to assess the heterogeneity and DerSimonian and Laird random-effects models were applied for all analyses to minimize the impact of differences in methods and outcomes definitions between studies. The overall quality of evidence was assessed using the GRADE system. Review Manager 5.4 and R software (v4.2.2) were used for statistical analyses. Registered with PROSPERO, CRD42022366015.FindingsOverall, 22 studies were included, with a total of 1892 individuals with SCD, 8677 individuals with SCT, and 1,653,369 individuals without SCD/SCT. No difference in all-cause mortality was seen between SCD/SCT and non-SCD/SCT (OR 1.18; 95% CI 0.78-1.77; p = 0.429; I2 = 82%). When considering only studies adjusted for confounders (8 studies), patients with SCD/SCT were shown to be at increased risk of death (OR 1.86; 95% CI 1.30-2.66; p = 0.0007; I2 = 34%). No significant difference was seen between individuals with SCD and SCT (p = 0.863). The adjusted for confounders analysis for hospitalisation revealed higher rates for the SCD (OR 5.44; 95% CI 1.55-19.13; p = 0.008; I2 = 97%) and the SCT groups (OR 1.31; 95% CI 1.10-1.55; p = 0.002; I2 = 0) compared to the non-SCD/SCT population. Moreover, it was significantly higher for the SCD group (test for subgroup difference; p = 0.028).InterpretationOur findings suggest that patients with SCD or SCT may present with a higher mortality and hospitalisation rates due to COVID-19 infection.FundingNone.

Dataset Information

Hematopoietic progenitor cell mobilization is more robust in healthy African American compared to Caucasian donors and is not affected by the presence of sickle cell trait.

Background

Study design and methods

Results

Conclusions

Publications

Hematopoietic progenitor cell mobilization is more robust in healthy African American compared to Caucasian donors and is not affected by the presence of sickle cell trait.

Similar Datasets

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