Increased Serum Levels of N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) in Mobilized Healthy Donors with G-CSF: A Cohort Study.

Limited data regarding elevation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in mobilized donors with G-CSF is available. We extended these findings by examining serum NT-proBNP in a cohort study including 35 healthy donors and 69 patients who received G-CSF for CD34+ mobilization as well as 54 patients who did not receive G-CSF but who underwent collection of CD3+ cells for chimeric antigen receptor (CAR) T-cell manufacturing. No donor in the three cohorts experienced significant cardiac adverse events. NT-proBNP levels were measured before and after G-CSF administration and after finishing apheresis procedure. NT-proBNP increase was observed in mobilized healthy donors after G-CSF administration, but was not observed in mobilized or non-mobilized patients. Only in the cohort of healthy donors, pairwise comparisons using Wilcoxon signed ranks test showed a significant increase between the mean serum NT-proBNP level after G-CSF administration and the mean serum NT-proBNP level measured before G-CSF administration (231.09 ± 156.15 pg/mL vs. 58.88 ± 26.84 pg/mL; P < .01). No correlation was observed between NT-proBNP increase and G-CSF dose (rs = 0.09; n = 32; P = .6) and no other variables contributing to predict serum NT-proBNP increase were detected. In conclusion, we observed a statistically, although not clinically, significant increase of NT-proBNP in healthy donors who received G-CSF as CD34+ cell mobilization.

Evaluation of cell collection efficiency in non-mobilized adult donors for autologous chimeric antigen receptor T-cell manufacturing.

BACKGROUND AND OBJECTIVES: Data about collection efficiency 1 (CE1), which takes into account blood cell counts before and after collection, thus providing a more accurate estimate, in the collection of autologous T lymphocytes by apheresis for chimeric antigen receptor (CAR) T-cells remain scarce. We evaluated donor- and procedure-related characteristics that might influence the CE1 of lymphocytes. MATERIALS AND METHODS: We retrospectively reviewed all mononuclear cell (MNC) collections) performed for CAR T-cell manufacturing in our institution from May 2017 to June 2021 in adult patients. Age, gender, weight, total blood volume (TBV), prior haematopoietic cell transplant, diagnosis, days between last treatment and apheresis, pre-collection cell counts, duration of apheresis, TBV processed, vascular access, inlet flow and device type were analysed as potential factors affecting CE1 of lymphocytes. RESULTS: A total of 127 autologous MNC collections were performed on 118 patients diagnosed with acute lymphoblastic leukaemia (n = 53, 45%), non-Hodgkin lymphoma (n = 40, 34%), multiple myeloma (n = 19, 16%), and chronic lymphocytic leukaemia (n = 6, 5%). The median CE1 of lymphocytes was 47% (interquartile range: 32%-65%). In multiple regression analysis, Amicus device was associated with higher CE1 of lymphocytes (p = 0.01) and lower CE1 of platelets (p < 0.01) when compared with Optia device. CONCLUSION: The knowledge of the MNC and lymphocyte CE1 of each apheresis device used to collect cells for CAR T therapy, together with the goal of the number of cells required, is essential to define the volume to be processed and to ensure the success of the collection.

Comparison Between Standard and High Dose of G-CSF for Mobilization of Hematopoietic Progenitors Cells in Patients and Healthy Donors.

A standard dose of 10 µg/kg/day granulocyte colony stimulating factors (G-CSF) is currently recommended for hematopoietic progenitor cells (HPCs) mobilization. Our aim was to analyze whether certain patients or healthy donors could benefit from high dose of G-CSF.We performed a retrospective multicenter analysis of HPCs mobilization procedures (2015-2020) in patients and healthy donors. Those who received standard dose of G-CSF (10 µg/Kg/day for 4 days to patients and healthy donors) and those that received higher dose (24 µg/Kg/day for 4 days to patients and 16 µg/Kg/day for 4 days to healthy donors) were compared.496 individuals were included (201 standard dose and 295 higher dose). Between standard or higher dose, we did not find significant differences in median number of mobilized CD34+ cells/mL, neither among healthy donors (77 100 vs 75 500 respectively, P = .895), nor in patients (34 270 vs 33 704 respectively, P = .584). Additionally, among those with the same underlaying pathology the comparison between standard and higher dose did not showed differences. High G-CSF dose was not associated with a less frequent incidence of poor mobilizers (<20 000 CD34+ cells/mL) neither in healthy donors (1 [1.3%] vs 0; P = .218) nor patients (30 [24.4%] vs 32 [18.1%]; P = .165). Multivariate analysis showed that age, gender, and G-CSF dose did not influence median number of mobilized CD34+ cells/mL in healthy donors or patients. However, the underlying pathology among patients significantly influenced the CD34+ cells mobilization. In healthy donors, cellular blood count showed significantly higher leukocytes and platelets count with G-CSF high-dose, while in patients just a higher platelets count was found. To conclude, high dose of G-CSF compared to standard dose did not show significant benefit in terms of mobilization of CD34+ cells in healthy donors or in patients, also without a decrease in the incidence of poor mobilizers.

Increased collection efficiency of CD34+ cells after mobilization with preemptive use of plerixafor followed by leukocytapheresis on the same day.

BACKGROUND: Plerixafor should be administered 6 to 11 hours before starting leukocytapheresis. However, we have been using plerixafor followed by leukocytapheresis according to different time schedules since 2007. Our objective was to compare the CD34+ cell collection efficiency (CE1) of the first leukocytapheresis performed after using plerixafor at different time intervals. STUDY DESIGN AND METHODS: Same-day schedule refers to the administration of plerixafor at 10:00 AM and starting the leukocytapheresis on the same day at 4:00 PM (6 hours interval). Next-day schedule refers to the administration of plerixafor at 8:00 PM and starting the leukocytapheresis on the next day (10:00 AM or 4:00 PM; either a 14- or 20-hr interval). Variables that might influence the CE1 of CD34+ cells were analyzed by longitudinal linear regression with a random effects model derived by generalized estimating equations. RESULTS: The median CE1 of CD34+ cells was higher in the group of 30 patients who underwent leukocytapheresis on the same day when compared with the group of 62 patients who underwent leukocytapheresis on the next day (65.8% vs. 56.7%; p < 0.01). In the longitudinal linear regression analysis, only the time from plerixafor administration to leukocytapheresis start was associated with a statistically significant decrease in the CE1 of CD34+ cells (CE1 change -0.034%; p < 0.01). CONCLUSION: Higher CE1 of CD34+ cells was observed when patients underwent leukocytapheresis on the same day after receiving plerixafor in comparison with administering plerixafor and underwent leukocytapheresis on the next day. Larger studies are necessary to confirm present results.

Leukocytapheresis in nonmobilized donors for cellular therapy protocols: Evaluation of factors affecting collection efficiency of cells.

INTRODUCTION: Collection efficiency (CE1) of cells refers to the number of cells that are collected from the total number of cells processed by the apheresis device. Limited data are available about the CE1 of cells when performing leukocytapheresis in nonmobilized donors for cellular therapy purposes. The aim of our study was to evaluate donor- and procedure-related characteristics that might influence the CE1 of cells. MATERIAL AND METHODS: Variables that predicted the CE1 of cells were analyzed by longitudinal linear regression in a series of 1071 leukocytapheresis procedures on 249 nonmobilized donors. Donor-related characteristics considered were gender, age, total blood volume, and complete blood count (CBC) data. Procedure-related characteristics considered were vascular access and device used. RESULTS: Older donor age was associated with a decrease in the CE1 of leukocytes, lymphocytes, monocytes, and mononuclear cells (MNCs; sum of leukocytes and monocytes) and with an increase in the CE1 of platelets (P < .05). Preprocedure CBC data (leukocytes, lymphocytes, monocytes, and platelets) were associated with either a statistically significant increase or decrease in the CE1 of cells. Central line used as vascular access was associated with a statistically significant decrease in the CE1 of MNCs (P = .02). CONCLUSION: Donor's age, preprocedure CBC data as well as central line used as vascular access were factors associated with CE1 of cells. Knowing these characteristics is helpful in the apheresis unit when designing cellular therapy protocols in order to maximize the CE1 of the desired cell and to personalize collection variables for each donor.

Efficacy and safety of one-day offline extracorporeal photopheresis schedule processing one total blood volume for treating patients with graft-versus-host disease.

BACKGROUND: Extracorporeal photopheresis (ECP) has been increasingly used as a second-line therapy for graft-versus-host disease (GVHD) but there is no consensus regarding the best therapeutic schedule. STUDY DESIGN AND METHODS: Our offline ECP schedule for treating patients with GVHD was retrospectively reviewed. Patients with acute GVHD were treated on 2 days per week for the first 2 weeks, followed by 1 day per week for 2 more weeks. After the first month of treatment, patients received treatment 1 day every 2 weeks for a minimum of 16 ECP procedures. Patients with chronic GVHD were treated on 1 day per week for 4 weeks followed by 1 day every 2 weeks for a minimum of 14 ECP procedures. RESULTS: Our series comprises 21 (45%) patients with acute GVHD and 26 (55%) patients with chronic GVHD who received 667 ECP procedures. A median (interquartile range [IQR]) of 1.0 (1.0-1.12) total blood volume was processed. Patients with acute and chronic GVHD received ECP procedures during a median of 49 (IQR, 14-103) and 180 (IQR, 111-274) days, respectively. Mild citrate-induced symptoms were present in 98 (46%) and 232 (51%) procedures in patients with acute and chronic GVHD, respectively. Overall response rate (ORR) and overall survival (OS) were 57 and 38% (95% confidence interval [CI], 17%-59%), respectively, for patients with acute GVHD. For patients with chronic GVHD, ORR and OS were 77 and 61% (95% CI, 18%-87%), respectively. CONCLUSION: Our new offline ECP schedule for treating patients with acute and chronic GVHD was efficacious and safe.

The Barcelona Hospital Clínic therapeutic apheresis database.

INTRODUCTION: A therapeutic apheresis (TA) database helps to increase knowledge about indications and type of apheresis procedures that are performed in clinical practice. The objective of the present report was to describe the type and number of TA procedures that were performed at our institution in a 10-year period, from 2007 to 2016. MATERIAL AND METHODS: The TA electronic database was created by transferring patient data from electronic medical records and consultation forms into a Microsoft Access database developed exclusively for this purpose. Since 2007, prospective data from every TA procedure were entered in the database. RESULTS: A total of 5940 TA procedures were performed: 3762 (63.3%) plasma exchange (PE) procedures, 1096 (18.5%) hematopoietic progenitor cell (HPC) collections, and 1082 (18.2%) TA procedures other than PEs and HPC collections. The overall trend for the time-period was progressive increase in total number of TA procedures performed each year (from 483 TA procedures in 2007 to 822 in 2016). The tracking trend of each procedure during the 10-year period was different: the number of PE and other type of TA procedures increased 22% and 2818%, respectively, and the number of HPC collections decreased 28%. CONCLUSION: The TA database helped us to increase our knowledge about various indications and type of TA procedures that were performed in our current practice. We also believe that this database could serve as a model that other institutions can use to track service metrics.

Transfusion of irradiated red blood cell units with a potassium adsorption filter: A randomized controlled trial.

BACKGROUND: The irradiation of red blood cells (RBCs) causes damage of the RBC membrane with increased potassium (K) leak during storage compared with nonirradiated RBC units of similar age. A previous in vitro study showed a mean reduction of K of 94 ± 5% with a potassium adsorption filter (PAF). STUDY DESIGN AND METHODS: A prospective, single-center, nonblinded, randomized controlled trial (RCT) was designed to evaluate the safety and efficacy of transfusing irradiated RBC units with the PAF. Patients 18 years of age or older who received irradiated RBC units due to chemotherapy-induced anemia were randomly assigned to receive irradiated RBC units with the PAF (PAF group) or with the standard blood infusion set (control group). Primary outcome measures were safety and efficacy of the PAF (absolute change in hemoglobin [Hb] and K, respectively, in patient's blood values after transfusing the irradiated RBC units with or without the PAF). RESULTS: A total of 63 irradiated RBC units were transfused to 17 patients in the control group, and a total of 56 irradiated RBC units were transfused to 13 patients in the PAF group. The absolute change of Hb (9.3 ± 6.3 g/L vs. 8.1 ± 5.8 g/L; p = 0.3) and the absolute change of K (-0.01 ± 0.4 mmol/L vs. -0.01 ± 0.3 mmol/L; p = 0.2) were comparable between the two groups of the trial. CONCLUSION: The transfusion of 1 irradiated RBC unit with the PAF was as safe and efficacious as the transfusion of 1 irradiated RBC unit with the standard blood infusion set in patients with chemotherapy-induced anemia.

Acid-base balance disturbances in plasma exchange depend on the replacement fluid used.

BACKGROUND: Metabolic alkalosis occurs as a direct result of plasma exchange (PE) because of metabolism of citrate. However, we observed a decrease of serum pH and bicarbonate after PE when albumin was used as replacement fluid. STUDY DESIGN AND METHODS: The acid-base balance in 2730 PEs using different replacement fluids (albumin, fresh-frozen plasma [FFP], or both) was measured, and absolute changes (Δ) in acid-base balance were compared. The frequency of adverse effects (AEs) before and after using prophylactic administration of sodium bicarbonate was compared. RESULTS: A decrease of serum pH and bicarbonate was observed after PEs when albumin was used as replacement fluid (Δ pH = -0.06 ± 0.04; Δ bicarbonate = -4.03 ± 2.29 mmol/L; Δ base excess = -2.54 ± 3.82 mmol/L). An increase of serum pH and bicarbonate was observed after PEs when FFP was used as replacement fluid (Δ pH = +0.04 ± 0.05; Δ bicarbonate = +3.6 ± 3.68 mmol/L; Δ base excess = +1.62 ± 4.51 mmol/L). The prophylactic administration of sodium bicarbonate corrected partially the decrease of serum pH and bicarbonate after finishing PEs when albumin was used as replacement fluid (Δ pH = -0.04 ± 0.04; Δ bicarbonate = -3.1 ± 2.47 mmol/L; Δ base excess = -3.35 ± 3.06 mmol/L). The frequency of AEs after using prophylactic administration of sodium bicarbonate was lower in comparison with the frequency of AEs before using prophylactic administration of sodium bicarbonate (2.0% vs. 4.8%; p < 0.001). CONCLUSION: A decrease of serum pH and bicarbonate appeared in patients after PEs when albumin was used as replacement fluid; it was corrected partially with prophylactic administration of sodium bicarbonate, and it was associated with fewer AEs.

Efficacy and safety of plasma exchange: ann 11-year single-center experience of 2730 procedures in 317 patients.

We reviewed retrospectively 317 patients who received 2730 plasma exchange (PE) procedures. According to guidelines published by the American Society for Apheresis (ASFA) in 2013, there were 220 (69%), 55 (17%), 32 (9%), and 7 (4%) patients who were treated with PE for a disease or condition considered as category I, II, III, and IV, respectively. Overall, 73%, 72%, and 69% of the patients showed an improvement of the underlying disease or condition at the end of the PE, and at 3 months and at 6 months after finishing the PE, respectively. We observed adverse effects in 90 (3%) PEs.

Platelet transfusions from D+ donors to D- patients: a 10-year follow-up study of 1014 patients.

BACKGROUND: Current guidelines recommend that platelets (PLTs) from D- donors should be given to D- patients. However, such evidence comes from studies with a limited number of included patients that reported an incidence of anti-D alloimmunization to be up to 19%. We thus decided to extend these findings by examining anti-D alloimmunization at our institution, where PLT transfusions from D+ donors are transfused to D- patients because of logistic constraints. STUDY DESIGN AND METHODS: From April 1999 to December 2009, we retrospectively reviewed the clinical and transfusion records of all D- patients who received PLT transfusions from D+ donors at our hospital. PLT concentrates (PCs) were obtained from apheresis and from whole blood donations. RhIG was not administered after the transfusion of PCs from D+ donors. The antibody screen test to detect anti-D was performed by low-ionic-strength solution indirect antiglobulin test using the gel test. RESULTS: Our series comprises 1014 D- patients who received 5128 PLT transfusions from D+ donors (89% were pooled PCs). We had 315 (31.1%) patients who had a blood sample to analyze the presence of anti-D 4 or more weeks after the first D+ PLT transfusion with a median follow-up of 29 weeks (range, 4-718 weeks). Anti-D developed in 12 (3.8%) of these 315 patients. CONCLUSIONS: The frequency of anti-D alloimmunization of D- patients after receiving pooled PCs from D+ donors is low. The transfusion of D-incompatible pooled PCs without immunoprophylaxis to D- men or D- women without childbearing potential seems a reasonable and safe alternative.