How do we consistently provide high-dose granulocyte products for transfusions in neutropenic patients?

BACKGROUND: The therapeutic use of granulocyte transfusions for the treatment of infections in immunocompromised patients has been a controversial practice. Randomized controlled trials suggest that benefit may be provided when a high-dose product, defined as providing a dose of at least 0.6 × 109 /kg, is offered. Here we describe the collection process and granulocyte product yield over a four-year period at a donation center supplying a large, tertiary academic medical center. METHODS: A retrospective chart review was performed for apheresis granulocyte donations collected between 2018 and 2021 following implementation of combined G-CSF and dexamethasone donor stimulation at our institution. Data collected includes donor demographics, G-CSF administration timeline, pre-collection cell counts, product yields, donor adverse events, and post-transfusion ANC increments. RESULTS: A total of 269 granulocyte units were collected from 184 unique donors. The median neutrophil yield (ANC) following G-CSF implementation was 7.5 × 1010 /unit. The proportion of granulocyte products meeting or exceeding a yield of 4.0 × 1010 per unit was 96.5%. These products resulted in measurable median ANC increment of 550/µL in transfused adult patients (n = 166 transfusions). DISCUSSION: In order to properly assess the effectiveness of granulocyte transfusions in patients, it is necessary to ensure that the products being transfused contain an adequate granulocyte dose. This study demonstrates that the combination of G-CSF and dexamethasone donor stimulation, followed by apheresis granulocyte collection, is safe and can reliably yield a high-dose product. Consistent production of high-dose units allows for better assessment of patient outcomes by reducing dosage variability.

Blood, sweat, and tears: Red Blood Cell-Omics study objectives, design, and recruitment activities.

BACKGROUND: The Red Blood Cell (RBC)-Omics study was initiated to build a large data set containing behavioral, genetic, and biochemical characteristics of blood donors with linkage to outcomes of the patients transfused with their donated RBCs. STUDY DESIGN AND METHODS: The cohort was recruited from four US blood centers. Demographic and donation data were obtained from center records. A questionnaire to assess pica, restless leg syndrome, iron supplementation, hormone use, and menstrual and pregnancy history was completed at enrollment. Blood was obtained for a complete blood count, DNA, and ferritin testing. A leukocyte-reduced RBC sample was transferred to a custom storage bag for hemolysis testing at Storage Days 39 to 42. A subset was recalled to evaluate the kinetics and stability of hemolysis measures. RESULTS: A total of 13,403 racially/ethnically diverse (12% African American, 12% Asian, 8% Hispanic, 64% white, and 5% multiracial/other) donors of both sexes were enrolled and ranged from 18 to 90 years of age; 15% were high-intensity donors (nine or more donations in the prior 24 mo without low hemoglobin deferral). Data elements are available for 97% to 99% of the cohort. CONCLUSIONS: The cohort provides demographic, behavioral, biochemical, and genetic data for a broad range of blood donor studies related to iron metabolism, adverse consequences of iron deficiency, and differential hemolysis (including oxidative and osmotic stress perturbations) during RBC storage. Linkage to recipient outcomes may permit analysis of how donor characteristics affect transfusion efficacy. Repository DNA, plasma, and RBC samples should expand the usefulness of the current data set.

Intradonor reproducibility and changes in hemolytic variables during red blood cell storage: results of recall phase of the REDS-III RBC-Omics study.

BACKGROUND: Genetic determinants may underlie the susceptibility of red blood cells (RBCs) to hemolyze in vivo and during routine storage. This study characterized the reproducibility and dynamics of in vitro hemolysis variables from a subset of the 13,403 blood donors enrolled in the RBC-Omics study. STUDY DESIGN AND METHODS: RBC-Omics donors with either low or high hemolysis results on 4°C-stored leukoreduced (LR)-RBC samples from enrollment donations stored for 39 to 42 days were recalled 2 to 12 months later to donate LR-RBCs. Samples of stored LR-RBCs from the unit and from transfer bags were evaluated for spontaneous and stress-induced hemolysis at selected storage time points. Intradonor reproducibility of hemolysis variables was evaluated in transfer bags over two donations. Hemolysis data at serial storage time points were generated on LR-RBCs from parent bags and analyzed by site, sex, race/ethnicity, and donation frequency. RESULTS: A total of 664 donors were successfully recalled. Analysis of intradonor reproducibility revealed that osmotic and oxidative hemolysis demonstrated good and moderate reproducibility (Pearson's r = 0.85 and r = 0.53, respectively), while spontaneous hemolysis reproducibility was poor (r = 0.40). Longitudinal hemolysis in parent bags showed large increases over time in spontaneous (508.6%) and oxidative hemolysis (399.8%) and smaller increases in osmotic (9.4%) and mechanical fragility (3.4%; all p < 0.0001). CONCLUSION: Spontaneous hemolysis is poorly reproducible in donors over time and may depend on site processing methods, while oxidative and osmotic hemolysis were reproducible in donors and hence could reflect consistent heritable phenotypes attributable to genetic traits. Spontaneous and oxidative hemolysis increased over time of storage, whereas osmotic and mechanical hemolysis remained relatively stable.

Estimates of total body iron indicate 19 mg and 38 mg oral iron are equivalent for the mitigation of iron deficiency in individuals experiencing repeated phlebotomy.

Iron deficiency anemia is a common clinical condition often treated with tablets containing 65 mg of elemental iron. Such doses can elicit gastrointestinal side effects lowering patient compliance. Oral iron supplements also increase hepcidin production causing decreased fractional absorption of subsequent doses. Frequent blood donors often become iron deficient. Therefore, they were enrolled in a two-year study involving continued blood donations and randomization to receive no pill, placebo, 19, or 38 mg ferrous gluconate for 60 days. Total body iron (TBI) did not change for the subset of donors in the no pill and placebo groups who completed both enrollment and final visits (P = .21 and P = .28, respectively). However, repeated measures regression analysis on the complete dataset estimated a significant decrease in TBI of 52 mg/year for the placebo and no pill groups (P = .001). The effects of 19 and 38 mg iron supplementation on TBI were indistinguishable (P = .54). TBI increased by 229 mg after the initial 60 days of iron supplementation (P < .0001) and was maintained at this higher level with continued iron supplementation following each subsequent donation. The TBI increase was apportioned 51 mg to red cell iron (P < .0001) and 174 mg to storage iron (P < .0001). Changes in storage iron were negatively impacted by 57 mg due to concurrent antacid use (P = .04). These findings in blood donors suggest that much lower doses of iron than are currently used will be effective for clinical treatment of iron deficiency anemia.

Qualitative assessment of pica experienced by frequent blood donors.

BACKGROUND: Pica, the compulsive consumption of ice or other nonnutritious substances, is associated with iron deficiency, a common negative consequence of frequent blood donation. Because of this, blood donors, such as those participating in the Strategies to Reduce Iron Deficiency (STRIDE) study, are an ideal population to explore pica and iron deficiency. STUDY DESIGN AND METHODS: STRIDE was a 2-year intervention trial to assess the effectiveness of iron supplementation for mitigating iron deficiency in frequent blood donors. Subjects completed baseline and follow-up questionnaires that included questions about pica symptoms. In-depth telephone interviews were conducted with 14 of these subjects reporting pica symptoms and eight presumed controls (casual ice chewers) to gain a deeper understanding of pica symptoms and their impact on daily life and to make a final determination on the presence of pica. RESULTS: Pica was confirmed in five of the 14 subjects reporting symptoms and in two of eight controls. Outcome misclassification based on the questionnaire was attributed to inadequate assessment of several pica symptoms identified during the interview. Comparison of subjects' repeated quantitative iron measurements taken throughout STRIDE with subjects' final adjudicated pica status revealed a positive relationship between development of pica and worsening iron status; the opposite was found in those whose pica symptoms resolved. CONCLUSION: Continued refinement of pica symptom questions will allow for rapid and accurate detection of pica in frequent blood donors and confirmation of successful treatment with iron supplements.

A randomized, blinded, placebo-controlled trial of education and iron supplementation for mitigation of iron deficiency in regular blood donors.

BACKGROUND: The historical approach of offering dietary advice to donors with low hemoglobin (Hb) is ineffective for preventing iron deficiency in frequent donors. Alternative approaches to maintaining donor iron status were explored. STUDY DESIGN AND METHODS: Frequent blood donors were randomly assigned into five arms for 2 years of follow-up. Three double-blinded arms provided 60 once-daily pills after each donation (38, 19, or 0 mg of iron). Two single-blinded arms provided iron status (ferritin) or no information letters after each donation. Ferritin, soluble transferrin receptor, and complete blood count were measured at each donation. RESULTS: There were 692 subjects enrolled and 393 completed the study. Subjects in pill groups deenrolled more than those in letter groups (39% vs. 7%). Adverse events occurred equally in subjects receiving iron or placebo pills. Of those completing the study, the prevalence of ferritin of less than 12 or less than 26 ng/mL declined by more than 50% and was statistically indistinguishable in the three intervention groups (19 or 38 mg of iron; iron status letter). Longitudinal analyses of all subjects showed improved iron status in iron pill groups and worsening iron status in control groups (placebo; no information letter). The iron pill groups experienced a net increase of approximately 0.6 g/dL Hb compared to control groups. The iron status letter group had little change in Hb. CONCLUSION: Providing 19 or 38 mg of daily iron or iron status information were effective and mostly equivalent interventions for mitigating iron deficiency in regular donors when compared at the end of the 2-year longitudinal phase of the study. Donors without intervention had worsened iron deficiency with continued donation.

Blood donor deferral for men who have sex with men: the Blood Donation Rules Opinion Study (Blood DROPS).

BACKGROUND: In the United States, any man who discloses having had sex with another man (MSM) even once since 1977 is currently deferred from donating blood. A study was conducted to assess noncompliance with the policy at four geographically dispersed blood centers. STUDY DESIGN AND METHODS: Male donors 18+ years of age with e-mail addresses were randomly selected and invited to complete a confidential online survey between August and October 2013. No additional recruitment e-mails were sent. Survey content included demographics, sexual history, donation history, compliance with the policy, and opinions about current and modified policies. RESULTS: Response rate was 11.5% but varied by center (6.3% to 21.7%). Of 3183 completed surveys, 2.6% of respondents (95% confidence interval, 2.1%-3.2%) reported donation after male-male sex. Noncompliance was not statistically different among the centers (p = 0.1), but was related to age with 5.7, 4.6, 2.5, and 1.0% of donors 18 to 24, 25 to 34, 35 to 54, and 50+ years of age, respectively, reporting noncompliance (p < 0.001). Of all respondents, 6.8% reported at least six female and 0.3% reported at least six male sex partners in the past 5 years. Opinions about the current MSM policy were mixed with noncomplying donors more supportive of change than complying donors. Approximatey half of noncompliers indicated they would adhere to a 1-year deferral. CONCLUSION: Noncompliance with the MSM policy is evident and may be increasing compared to earlier data. Any change from the current policy will require close monitoring to determine whether it affects residual risk of HIV in the US blood supply.

Donation frequency of blood donors participating in a prospective cohort study of iron status.

BACKGROUND: Blood centers are interested in understanding determinants of frequent blood donation. We hypothesized that participation in uncompensated research could result in higher donation rates. STUDY DESIGN AND METHODS: Donation rates for 2425 subjects from six US blood centers enrolled in the Retrovirus Epidemiology Donor Study-II Donor Iron Status Evaluation Study were compared to those of nonenrolled donors (n = 202,383). Over 15 months, we compared mean donation rates and adjusted rate ratios (RRs) between enrolled and nonenrolled for three subgroups, first-time, reactivated, and frequent donors, and donation rates before and after the study enrollment period for frequent donors only. RESULTS: Enrolled donors had higher 15-month mean donation rates than nonenrolled donors (first-time, 1.21 [RR = 1.91]; reactivated, 1.68 [RR = 1.83]; frequent, 3.40 [RR = 1.12]). However, frequent donors donated at approximately the same rate after enrollment as they did before enrollment in the study (3.62 per 15 months [RR = 1.12]). CONCLUSION: Donors enrolled in the study donated at a higher rate than nonenrolled donors, but frequent donors remained consistent in their donation frequency both before and after enrollment. Although increased donation rates could have been causally related to study enrollment, we cannot rule out an enrollment bias whereby more committed donors were more likely to enroll in the study.