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The effect of repeated stimulated granulocyte donations on hematopoietic indexes in donors: a 24-year donor center experience.

ABSTRACT: BACKGROUND:Short- and long-term effects of mobilization regimens in hematopoietic stem cell and granulocyte donors have been well characterized. In this study, we examined the longitudinal hematopoietic changes related to repeat stimulated granulocyte donation. STUDY DESIGN AND METHODS:Complete blood counts for consecutive granulocyte donors between October 1994 and May 2017 were compared to unstimulated granulocyte donors. Plateletpheresis donors served as controls. The longitudinal change in precollection white blood cell (WBC) counts for these donor groups were modeled using a linear mixed-effects model. The investigated variables were granulocyte, lymphocyte, and monocyte counts and the granulocyte collection yield. Contrasts were performed to explore the effect of donation number on precollection counts. RESULTS:For the granulocyte-colony-stimulating factor plus dexamethasone (G-CSF/Dex)-stimulated group, both the granulocyte and the lymphocyte counts decreased 6.51 × 109 /L (-23.1%, p < 0.001) and 0.21 × 109 /L (-20.4%, p < 0.001), respectively, between Donation 1 and Donation 20. This effect was still present at the 3- to 4-year interval (b = -0.0008313, SE = 0.00029, p = 0.004). For the unstimulated donor group between Donation 1 and Donation 20, the lymphocyte count decreased by 0.62 × 109 /L (-51.5%, p < 0.001). This effect was only significant up to Year 2 (b = -0.0026, SE = 0.0010, p = 0.013). CONCLUSIONS:Past granulocyte donations were found to have a statistically strong negative effect on precollection granulocyte counts and lymphocyte counts and decreased granulocyte yield both in the G-CSF/Dex-stimulated donors and the unstimulated donors. In this statistical model, for both these groups, the effect of past donations on granulocyte and WBC counts were still detectable 2 years later.

SUBMITTER: Szymanski J

PROVIDER: S-EPMC7365331 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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The effect of repeated stimulated granulocyte donations on hematopoietic indexes in donors: a 24-year donor center experience.

Szymanski James J Troendle James J Leitman Susan S Hong Hong H Yau Yu Ying YY Cantilena Cathy C

Transfusion 20181116 1

<h4>Background</h4>Short- and long-term effects of mobilization regimens in hematopoietic stem cell and granulocyte donors have been well characterized. In this study, we examined the longitudinal hematopoietic changes related to repeat stimulated granulocyte donation.<h4>Study design and methods</h4>Complete blood counts for consecutive granulocyte donors between October 1994 and May 2017 were compared to unstimulated granulocyte donors. Plateletpheresis donors served as controls. The longitudi ...[more]

PMID: 30444537

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Project description:IntroductionPeripheral blood stem cells mobilized by granulocyte colony-stimulating factor (G-CSF) from healthy donors are commonly used for allogeneic stem cell transplantation. The effect of G-CSF administration on global serum metabolite profiles has not been investigated before.ObjectivesThis study aims to examine the systemic metabolomic profiles prior to and following administration of G-CSF in healthy adults.MethodsBlood samples were collected from 15 healthy stem cell donors prior to and after administration of G-CSF 10 µg/kg/day for 4 days. Using a non-targeted metabolomics approach, metabolite levels in serum were determined using ultrahigh performance liquid chromatography-tandem mass spectrometry and gas chromatography/mass spectrometry.ResultsComparison of the metabolite profiles of donors before and after G-CSF treatment revealed 239 metabolites that were significantly altered. The major changes of the metabolite profiles following G-CSF administration included alteration of several fatty acids, including increased levels of several medium and long-chain fatty acids, as well as polyunsaturated fatty acids; while there were lower levels of other lipid metabolites such as phospholipids, lysolipids, sphingolipids. Furthermore, there were significantly lower levels of several amino acids and/or their metabolites, including several amino acids with known immunoregulatory functions (methionine, tryptophan, valine). Lastly, the levels of several nucleotides and nucleotide metabolites (guanosine, adenosine, inosine) were also decreased after G-CSF administration, while methylated products were increased. Some of these altered products/metabolites may potentially have angioregulatory effects whereas others may suggest altered intracellular epigenetic regulation.ConclusionOur results show that G-CSF treatment alters biochemical serum profiles, in particular amino acid, lipid and nucleotide metabolism. Additional studies are needed to further evaluate the relevance of these changes in healthy donors.

Project description:BackgroundPassive therapy with convalescent plasma (CP) could be an effective and safe treatment option in COVID-19 patients. Neutralizing antibodies present in CP generated in response to SARS-CoV-2 infection and directed against the receptor-binding domain of the spike protein are considered to play a major role in the viral clearance. CP infusion may also contribute to the modulation of the immune response through its immunomodulatory effect. We describe for the first time the effectiveness of a CP collection protocol from repeated donations in young patients.Materials and methodsWe enrolled health service workers who experienced mild to moderate COVID-19 and from whom several donations have been collected. No minimal severity threshold and no biological cure criteria were required. Donors could return to a second plasma donation 14 days after the first donation. A minimal neutralizing antibody titer of 1:40 was considered for clinical use.ResultsEighty-eight donors were included (median age 35 [28-48] years, 41 women), and 149 plasma products were collected. COVID-19 were mainly WHO stage 2 infections (96%). Among the 88 first donations, 76% had neutralizing antibody titers higher than or equal to 1:40. Eighty-eight percent of donors who came for a second donation had a neutralizing antibody titer of 1:40. Median durations were 15 (15-19) and 38 (33-46) days from the first to the second donation and from recovery to the second donation, respectively. Sixty-nine percent of donors who came for a third donation had a neutralizing antibody titer of 1:40. Median durations were 16 (13-37) and 54 (49-61) days from the second to the third donation and from recovery to the third donation, respectively. No significant difference was observed between the IgG ratio and the age of the donors or the time between recovery and donation. The average IgG ratio did not significantly vary between donations. When focused on repeated blood donors, no significant differences were observed either.ConclusionThe recruitment of young patients with a mild to moderate CO-VID-19 course is an efficient possibility to collect CP with a satisfactory level of neutralizing antibodies. Repeated donations are a well-tolerated and effective way of CP collection.

Project description:IntroductionAzacitidine (AZA) either single-agent or with donor lymphocytes infusions (DLI) has been used as a salvage treatment for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) relapsing after allogeneic hematopoietic stem cell transplantation (HSCT). To date, the majority of data come from patients relapsed after HSCT from full-matched donors.MethodsWe report a multicenter, collaborative, retrospective analysis of 71 patients with hematologic (n = 40, 56%) and molecular relapse (n = 31, 44%) of myeloid neoplasms after HSCT from alternative donors (mismatched unrelated, n = 39, 55%; haploidentical, n = 29, 41%) consecutively treated at three European centers with AZA ± DLI.ResultsMedian time from HSCT to relapse was 9 months. Additional DLI were given to 33 patients (46%). After a median of four cycles, overall response rate (ORR) was 49% and complete response (CR) rate was 38%. CR lasted for a median of 17 months (range 5-89 months). Median follow-up in the entire cohort was 11 months (range 1-115 months). Event-free survival (EFS) and overall survival (OS) at 1 year were 26% and 53%, respectively. Treatment of molecular relapse granted higher CR rate (65% versus 15%; p = 0.0001), 1-year EFS (43% versus 13%; p = 0.006), and 1-year OS (79% versus 34%; p < 0.001) compared to hematologic relapses. Addition of DLI resulted in significantly higher responses and longer 1-year EFS and OS (Mantel-Byar test, p = 0.004 and p = 0.002, respectively). When applied to our cohort, the APSS-R score confirmed its ability to stratify patients into distinct prognostic groups with significantly different response rates (p = 0.0005) and survival (p < 0.0001). Treatment was well tolerated, with the incidence of late acute and chronic graft-versus-host disease of 27% and 18%, respectively.ConclusionAZA ± DLI proved feasible and effective in AML and MDS relapsing after HSCT from alternative donors. Despite modest efficacy among hematologic relapses, pre-emptive treatment with AZA ± DLI fared better in molecular relapse. Additional DLI contributed to improving efficacy and ensuring longer survival.

Dataset Information

The effect of repeated stimulated granulocyte donations on hematopoietic indexes in donors: a 24-year donor center experience.

Publications

The effect of repeated stimulated granulocyte donations on hematopoietic indexes in donors: a 24-year donor center experience.

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