BACKGROUND: A study was undertaken to investigate whether granulocyte-colony-stimulating factor (G-CSF) injection in lower adipose tissue-containing sites (arms and legs) would result in a lower exposure and reduced stem cell collection efficiency compared with injection into abdominal skin.
STUDY DESIGN AND METHODS: We completed a prospective randomized study to determine the efficacy and tolerability of different injection sites for patients with multiple myeloma or lymphoma undergoing stem cell mobilization and apheresis. Primary endpoints were the number of CD34+ cells collected and the number of days of apheresis. Forty patients were randomly assigned to receive cytokine injections in their abdomen (Group A) or extremities (Group B). Randomization was stratified based on diagnosis (myeloma, n = 29 vs. lymphoma, n = 11), age, and mobilization strategy and balanced across demographic factors and body mass index.
RESULTS: Thirty-five subjects were evaluable for the primary endpoint: 18 in Group A and 17 in Group B. One evaluable subject in each group failed to collect a minimum dose of at least 2.0 × 106 CD34+ cells/kg. The mean numbers of CD34+ cells (±SD) collected were not different between Groups A and B (9.15 × 106 ± 4.7 × 106/kg vs. 9.85 × 106 ± 5 × 106/kg, respectively; p = NS) after a median of 2 days of apheresis. Adverse events were not different between the two groups.
CONCLUSION: The site of G-CSF administration does not affect the number of CD34+ cells collected by apheresis or the duration of apheresis needed to reach the target cell dose.
Background
In September 2009, the National, Heart, Lung, and Blood Institute (NHLBI) convened a State of the Science Symposium in Transfusion Medicine to identify phase II/III clinical trials that would provide important information to advance transfusion medicine.
Methods
Seven multidisciplinary Subcommittees developed proposals in the following areas: a) platelet product use, b) neonatal/pediatric transfusion practice, c) surgical transfusion practice, d) intensive care unit (ICU) and/or in trauma transfusion practice, e) plasma/cryoprecipitate product use, and therapeutic apheresis practice, f) red blood cell (RBC) product use/blood conservation management, and g) medical transfusion practice or blood donor studies. The committees consisted of transfusion medicine specialists, hematologists, cardiovascular surgeons, anesthesiologists, neonatologists, critical care physicians, and clinical trial methodologists. Proposals were presented and an External Panel evaluated and prioritized each concept for scientific merit, clinical importance, and feasibility.
Results
24 concepts were presented by the Subcommittees. Ten concepts addressed four areas deemed most important: 1) platelet transfusion strategies to prevent/mitigate bleeding in neonates and patients with hematologic malignancies, 2) RBC transfusion trigger strategies to improve overall outcomes in different patient populations, 3) evaluation of optimal plasma:platelet:RBC ratios in trauma resuscitation , and 4) pathogen inactivation of platelets to improve platelet transfusion safety. Conclusions: The proposal themes not only represent inquiries about the indications for transfusion, but also epitomize the lack of consensus when clinical practice lacks a strong evidence base. Ultimately, the purpose of this publication is to provide a “blueprint” of ideas for further development rather than endorse any one specific clinical trial design.
Background
Alloantibodies are a clinically significant sequelae of platelet transfusion, potentially rendering patients refractory to ongoing platelet transfusion support. These antibodies are often IgG class switched, suggesting the involvement of CD4+ T cell help; however, platelet specific CD4+ T cells have not been visualized in vivo and specifics of their stimulation are not completely understood.
Study Design and Methods
A murine model of alloimmunization to transfused platelets was developed to allow in vivo assessment and characterization of CD4+ T cells specific for platelet MHC alloantigen. Platelets were harvested from BALB/c mice, filter leukoreduced, and transfused into C57BL/6 recipients. Platelet specific CD4+ T cell responses were visualized by using a TCR transgenic mouse that detects peptide from donor MHC I presented on recipient MHC II. Antibody responses were determined by indirect immunofluorescence using BALB/c donor targets.
Results
C57BL/6 recipients of BALB/c leukoreduced platelet transfusions produced anti-BALB/c antibodies, with proliferation of antigen specific CD4+ T cells seen in the spleen but not lymph nodes or liver. Depletion of recipient CD4+ cells or splenectomy independently abrogated the alloantibody response.
Conclusion
We report a novel model to study antigen-specific CD4+ T cells during alloimmunization to platelet transfusion. The presented data support a critical role for CD4+ T cell help in the humoral response to platelet transfusion and establish the spleen as a required microenvironment for effective CD4+ T cell priming against donor platelet derived MHC I.
Background The association of blood donation-related iron deficiency with pica or restless legs syndrome (RLS) remains poorly elucidated. This study evaluated the prevalence of RLS and pica in blood donors completing the REDS-II Iron Status Evaluation (RISE) study. Study Design and Methods RISE enrolled 2425 blood donors in a prospective cohort study; 1334 donors provided blood samples to characterize iron status and answered a questionnaire inquiring into symptoms of RLS and pica at a final visit after 15 to 24 months of follow-up. Associations between both conditions and iron status were evaluated. Results There were 9 and 20% of donors reporting symptoms of probable or probable/possible RLS, respectively. Iron depletion and donation intensity were not predictive of RLS. Pica was reported by 65 donors (5.5%), half of whom reported daily cravings. Prevalence of pica increased with degree of iron depletion in women (2% in iron-replete females, 13% in those with ferritin < 12 ng/mL), but not in men. Probable RLS and pica coexpressed in eight individuals, but no more frequently than expected by chance. Conclusion RLS and pica have been associated with iron deficiency in nondonor populations. This study indicates a potentially high prevalence of RLS in frequent blood donors but shows no association with iron status or donation intensity. Low iron stores were associated with higher prevalence of pica, but only in females. Furthermore, the results are incompatible with RLS and pica sharing a common pathophysiology.