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Bone marrow (BM) is commonly used in the pediatric and adult setting as a source of hematopoietic stem cells (HSCs). The standards of the Joint Accreditation Committee of the International Society for Cell & Gene Therapy & European Society for Blood and Marrow Transplantation (JACIE) include specific requirements regarding BM collection, processing and distribution. To run this process, each transplant team develops a series of JACIE-compliant procedures, customizing them with regard to local settings and paths. Moreover, JACIE standards require that transplant teams validate and periodically revise their procedures to keep the entire process under control. In this article, the authors describe the methodology adopted in our center to fulfill the aforementioned JACIE requirements. The authors developed a validation plan based on the failure mode and effect analysis (FMEA) methodology. According to the FMEA approach, the authors carefully revised activities and procedures connected to BM collection, processing and distribution at our institution. The entire process was initially divided into five main phases (assessment of donor eligibility, perioperative autologous blood donation, preparation of BM collection kit, BM harvesting and BM processing and distribution), comprising 17 subphases and 22 activities. For each activity, one or more failure modes were identified, for a total of 28 failure modes, and a risk priority number (RPN) was then assigned to each failure mode. Although many procedures were validated, others were subjected to substantial changes according to the RPN rating. Moreover, specific indicators were identified for subsequent monitoring to contain the risk of failure of steps emerging as critical at FMEA. This is the first study describing use of the FMEA methodology within an HSC transplant program. Shaping the risk analysis based on local experience may be a trustworthy tool for identifying critical issues, directing strict monitoring of critical steps or even amending connected procedures. Overall, the FMEA approach enabled the authors to improve our process, checking its consistency over time. [ABSTRACT FROM AUTHOR]

In the Japan Marrow Donor Program (JMDP), autologous blood is collected from most unrelated bone marrow (BM) donors. We retrospectively evaluated 5772 donors who underwent BM harvest between 2010 and 2015 through the JMDP. Autologous blood was collected in 96.8% of the donors; the wastage rate was 0.6%. Allogeneic blood transfusion was not required. The mean hemoglobin (Hb) levels were 12.1 g/dL after the BM harvest (mean 891 mL) together with autologous blood transfusion (mean 596 mL). Propensity-score matching was used to adjust the backgrounds. Among donors with harvested BM of 100-400 mL, autologous blood transfusion had no impact on Hb levels or complications after BM harvest. Among donors with harvested BM of > 400 mL, more autologous blood transfusion followed by a bleeding volume of ≤ 100 mL did not confer clinical benefit to donors compared with less autologous blood transfusion followed by a bleeding volume of > 300 mL. The findings of the present study suggest that autologous blood transfusion to BM donors is excessive in terms of Hb changes and post-harvest outcomes. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stromal cells (MSCs) are the most prominent cell type used in clinical regenerative medicine and stem cell research. MSCs are commonly harvested from bone marrow that has been aspirated from patients’ iliac crest. However, the ethical challenges of finding consenting patients and obtaining fresh autologous cells via invasive extraction methods remain to be barriers to MSC research. Methods: Techniques of harvesting sternal bone marrow, isolating and culturing MSCs, MSC surface phenotyping, and MSC differentiation are described. Samples from 50 patients undergoing a sternotomy were collected, and the time taken to reach 80% confluency and cell count at the second splitting of MSC were measured. Results: MSC isolated from the sternal bone marrow of patients undergoing cardiac surgery demonstrated successful MSC surface phenotyping and MSC differentiation. The mean cell count at the time of the second split was 1,628,025, and the mean time taken to reach the second split was 24.8 days. Conclusion: Herein, we describe the first reported technique of harvesting sternal bone marrow from patients already undergoing open-chest cardiac surgery to reduce the invasiveness of bone marrow harvesting, as well as the methods of isolating, culturing, and identifying MSCs for the clinical application of constructing autologous MSC-derived biomaterials.

• MarrowMiner is a safe, minimally invasive device for the harvest of bone marrow. • MarrowMiner harvests bone marrow without the need for general anesthesia. • MarrowMiner collects rich marrow with a high concentration of stem and progenitor cells. Bone marrow (BM) is a rich source of hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), and other important stem/progenitor cells. It is the traditional source of cells used in hematopoietic cell transplantation, which is a proven curative treatment for many blood and immune diseases. BM-derived cells have also been shown to have other diverse clinical uses and are increasingly being used in orthopedic medicine, regenerative medicine, and gene therapy applications. Traditional methods for harvesting BM are crude, tedious, time-consuming, and expensive, requiring multiple bone punctures under general anesthesia with serial small-volume aspirates often diluted with peripheral blood. The MarrowMiner (MM) is a novel device designed for rapid and minimally invasive BM harvest. Here we show the safety and efficacy of the MM in both preclinical and clinical settings. In a large-animal porcine model, the MM enabled effective BM collection with similar total nucleated cell collection and increased colony formation compared with standard methods. The MM was subsequently evaluated in a clinical study showing effective and complication-free anterior and posterior BM collection of 20 patients under only local anesthesia or light sedation. Increased total nucleated and mononucleated cell collection was achieved with the MM compared with standard methods in the same patients. Importantly, stem cell content was high with trends toward increased HSC, MSC, and endothelial progenitor cells with similar T cell content. Given the MM is a novel device approved by the US Food and Drug Administration, enabling safe, effective, and minimally invasive harvest of BM, we anticipate rapid adoption for various applications. Image, graphical abstract [ABSTRACT FROM AUTHOR]

To avoid risk for allogeneic transfusions in healthy bone marrow (BM) donors, 1–2 preoperative autologous blood donations (PAD) are usually collected before the BM harvest. We analysed the haematological parameters in BM donors before and after the harvest, to assess the efficacy of this practice in limiting the postharvest anaemia. Overall, 102 consecutive donors underwent BM harvest preceded by one (26 cases) or two PAD (76 cases), which were infused during BM collection. We analysed the parameters related to donors, PAD timing and BM graft characteristics. PAD induced a significant decrease in Hb (from 14·6 g/dl, IQ range 13·3–15·5 to12·9 g/dl, IQ range 11·8–13·9; P < 0·0001) in all donors, with a median Hb loss at day −1 of 10·9% (IQ range 6·8–14·2). The PAD‐related Hb decrease was independent of sex or number of PAD, and was inversely related to the time elapsed from first or last PAD. In comparison with values recorded at day‐1, BM harvest produced an additional Hb decrease, accounting for a median Hb loss of 18·9% (IQ range 14·9–24·4). Overall, in comparison with pre‐PAD values, Hb levels at day +1 were reduced of 28·9% (IQ range 23·6–32·2), independently if donors had 1 or 2 PAD reinfused. In conclusion, these data show that two PAD do not carry any advantage over one PAD. An eventual benefit of PAD can be achieved only if an adequate interval between PAD and BM harvest elapses. Prospective randomized studies could be worth to establish if any role for PAD does exist in BM donors. [ABSTRACT FROM AUTHOR]

Supportive care needs for hematopoietic stem cell recipients have been studied. Less is known about the care needs of stem cell donors. Care challenges arise at donor selection, preparation for the donation, the donation procedure and the immediate and long-term after-care. Care needs were analyzed for 1,831 consecutive bone marrow and peripheral stem cell donors at MedStar Georgetown University Hospital between January 2018 and August 2023 in support of a review of the current literature. During the selection, related donors may experience psychological pressures affecting their motivation, while donation centers may be willing to accept co-morbidities in these donors which might preclude donation in unrelated peers. For bone marrow donations, it is important to select donors not only according to optimal genetic matching criteria but also according to suitable donor/recipient weight ratios, to facilitate sufficient stem cell yields. During the donation preparation phase, side effects and complications related to stem cell stimulation must be anticipated and managed for peripheral cell donors, while the pros and cons of autologous blood donation should be evaluated carefully for bone marrow donors. The stem cell donation procedure itself carries potential side effects and complications as well. Peripheral cell donors may require a central line and may encounter hypocalcemia, thrombocytopenia, and anemia. Bone marrow donors face risks associated with anesthesia, blood loss and pain. Post-procedure care focusses on pain management, blood cell recovery and the psychological support necessary to regain a high quality-of-life existence. Hematopoietic stem donors are giving part of themselves to save another's life. They deserve comprehensive supportive care to accompany them throughout the donation process.

In most cases of hematopoietic cell transplantation (HSCT) in pediatric recipient, the priority is given to bone marrow as a hematopoietic cell (HSC) source. The same expectations should be given to pediatric sibling donor. Bone marrow (BM) harvest is a standard method of HSC collection in pediatric siblings, however peripheral blood HSC (PBSC) collection is safe in healthy pediatric donors, and target hematopoietic cell yields can be achieved. Bone marrow or peripheral blood cell collection, both hematopoietic cells and lymphocytes, in pediatric sibling donors is safe, however there is a small risk of severe adverse events (SAE); still the risk of SAE is lower in children than in adults. The early adverse effects (AE) both after BM and PBSC collection are mild, short-term and easy to prevent or control, however they can occur in a relatively large proportion of donors. The risk of mild AE is lower in children than in adults, except PBSC collection in children <20 kg, who might be at risk of various complications. Short-term G-CSF administration and PBSC collection in pediatric donors is safe. No data exist on long-term adverse effects of short-term G-CSF course. Pediatric donors and their parents must be informed about the risk of possible complications. [ABSTRACT FROM AUTHOR]

Objectives Bone marrow harvesting is one of the essential sources of stem cells for hematopoietic stem cell transplantation. We describe here the current 'up-to-date' standard of the bone marrow harvest in unrelated stem cell donors. Methods We analyzed medical data of 187 unrelated hematopoietic stem cell donors who underwent bone marrow harvest without previous peripheral blood stem collection at the center between 2011 and 2015. The methodology of marrow collection includes multiple cells aimed at safety of the procedure, for example, educational movie, modified skin disinfection protocol, cell enumeration during the procedure, reduction of the contamination surfaces, and ongoing monitoring of the quality of work of the doctors. Results The total nucleated cell count over 2×108 per kg of recipient has been reached in 93.6% of harvests. All of the donors harvested more than 1×108 per kg of the recipient. There were no donors who required transfusions or had serious adverse events during and after the harvest. Conclusion We describe here the current up-to-date standard of bone marrow harvest, which leads to excellent results in majority of donors without causing significant complications during the donation. [ABSTRACT FROM AUTHOR]

We report our experience of collecting stem cells in patients who failed to mobilize sufficient hematopoietic stem cell (HSC) using plerixafor (P) in the initial mobilization attempt. Twenty four patients were identified who failed a first mobilization attempt using P. Of these, 22 patients received granulocyte colony stimulating factor (G-CSF) and two patients received cyclophosphamide (CY) + G-CSF in combination with P for the initial attempt. The agents used for second collection attempt were granulocyte macrophage colony stimulating factor (GM-CSF) + G-CSF (19 patients), G-CSF + P (three patients), CY + G-CSF (one patient), and bone marrow harvest (one patient). A median of 0.6 × 106 CD34+ cells/kg (range 0-1.97) were collected in the initial attempt. A second collection was attempted at a median of 22 days (range 15-127) after the first failed mobilization. The median CD34+ cell dose collected with the second attempt was 1.1 × 106 CD34+ cells/kg (range 0-7.2). A third collection was attempted in six patients at median of 51 days (range 34-163) after the first failed mobilization. These patients collected a median of 1.1 × 106 CD34+ cells/kg (range 0-6.5). Total of 16 patients (67%) collected sufficient cells to undergo autologous stem cell transplant and eight patients (33%) were able to collect ≥2 × 106 CD34+ cells/kg in a single subsequent attempt. Our experience suggests that a majority of patients who fail primary mobilization despite use of P can collect sufficient HSC with a subsequent attempt using combination of G-CSF with either P or GM-CSF. J. Clin. Apheresis 29:293-298 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background aims. Bone marrow (BM)-derived mononuclear cell (MNC) preparations are increasingly used in experimental studies exploring the potential effect of progenitor cell-derived therapies in cardiocirculatory diseases. We analyzed the cellular BM composition, side-effects and other process-related variables of BM harvest and BM-MNC preparation in 80 patients with cardiovascular disease. Methods. BM (median 828 mL, range 223-1038 mL) was collected from the iliac crest. After BM harvest the MNC fraction was enriched by semi-automatic apheresis to reduce the total volume of the transplant. Autologous red blood cells (RBC) were salvaged from the initial BM harvest and autotransfused to the patients. Results. There were no serious side-effects related to BM collection, particularly no serious bleeding complications. Twenty- five of 80 (31%) patients developed mild pain. BM harvest resulted in the collection of a median of 2.8 × 109 MNC, containing a median of 66.5 × 106 CD34/45 cells, 39.5 × 106 CD133/45 cells and 50.3 × 106 CD34/CD133 cells. Apheresis technology-based MNC enrichment of harvested BM resulted in a progenitor cell recovery of 69-75.3% of total cells. Additional salvage of RBC from the initial BM harvest resulted in the recovery of a median of 175.0 mL autologous RBC mass. Transfusion of salvaged RBC was well tolerated and resulted in a significant increase in hemoglobin levels. Conclusions. Collection of BM of up to 1 L in combination with in vitro processing using a semi-automated apheresis device is a safe and feasible approach to increasing the number of progenitor cells necessary for cellular therapies, particularly when combined with RBC salvage. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Unrelated hematopoietic stem cell donors may donate twice. We studied donors’ preference for peripheral blood stem cell (PBSC) collection or bone marrow (BM) harvest and compared the yields of and side effects associated with two BM harvests. Materials and Methods: The psychosocial and physical experience of 13 donors who underwent two different stem cell collection procedures and their preferences were collected via a self-reported questionnaire. Among four donors who underwent two BM harvests, we compared the yields of and the side effects associated with the first and second harvest via chart review and self-reported questionnaire, respectively. Results: The median recovery time associated with PBSC (1 day) was significantly shorter than that associated with BM harvest (7 days) (p <0.01). Although most of the donors who underwent both procedures felt that BM harvest was more physically demanding, caused more preprocedural anxiety, was more time consuming, and was more inconvenient than PBSC collection, 63.6% of them preferred BM donation. This preference for BM harvest over PBSC collection is different from previous studies. There was no significant difference in the yields of marrow nucleated cells (p =0.25) and no significant differences in the incidence of side effects and recovery time between the first and second BM donations. Conclusion: Further understanding of donors’ preferences and reducing side effects associated with stem cell harvesting procedures will help the registry improve its work. [Copyright &y& Elsevier]

Background After large volume bone marrow (BM) harvest, donors and patients can develop severe anaemia, because collected BM can contain up to 20% of their red cell mass. In a prospective analysis, we investigated the feasibility to recover red blood cells (RBCs) from the harvested BM and investigated whether these RBC units meet the quality requirements of the European Council. Patients and Methods From 19 patients (median age 51 yrs, range 31–77) with acute myocardial infarction, who participated in the MYSTAR study, a median volume of 1299 ml (range, 700–1870 ml) BM was collected. During BM processing, mononuclear cells (MNC) were separated using the Cobe Spectra™ apheresis system and the residual RBCs were collected in a separate bag. The quality of the collected RBCs was assessed by measuring LDH, free haemoglobin, potassium and lactate. Haemolysis was calculated and the intracellular concentration of ATP, ADP, AMP was determined by HPLC. Results RBC units recovered from BM after MNC separation had a mean volume of 312 ± 95 ml with a haematocrit of 47 ± 8·9%, a haemoglobin content of 51 ± 15 g per unit, a haemolysis of 0·15 ± 0·005%, a pH of 6·8 ± 0·007 and an intracellular ATP concentration of 135 pmol/106 RBC ± 41, which is comparable with freshly collected packed red blood cells (PRBCs). Conclusion RBCs, collected from bone marrow harvests, can be used for autologous blood support to minimize allogeneic blood transfusions in donors and patients after large volume BM donation. [ABSTRACT FROM AUTHOR]

Several approaches to perform assessment in training simulators based on virtual reality have been proposed. There are two kinds of assessment methods: offline and online. The main requirements related to online training assessment methodologies applied to virtual reality systems are the low computational complexity and the high accuracy. In the literature it can be found several approaches for general cases which can satisfy such requirements. An inconvenient about those approaches is related to an unsatisfactory solution for specific cases, as in some medical procedures, where there are quantitative and qualitative information available to perform the assessment. In this paper, we present an approach to online training assessment based on a Modified Naive Bayes which can manipulate qualitative and quantitative variables simultaneously. A special medical case was simulated in a bone marrow harvest simulator. The results obtained were satisfactory and evidenced the applicability of the method. [ABSTRACT FROM AUTHOR]

Predeposit autologous blood donation (PAD) is frequently offered to bone marrow donors, but its cost-effectiveness is dubious. We assessed the impact of PAD and bone marrow donation on transfusion requirements; and the use of donated blood units in a retrospective study of 61 bone marrow donors. The mean haemoglobin (Hb) concentration fell from 12·9 to 11·8 g dL−1 in women who predonated one unit and from 13·2 to 10·9 g dL−1 in those who predonated two units. In men who donated two units of blood, the Hb concentration decreased to 12·9 g dL−1. Bone marrow harvest led to a further decline in Hb concentration by 2·3 g dL−1 in women and by 2·4 g dL−1 in men. The postharvest Hb fell to ≤9·0 g dL−1 in 39% of female and in 6% of the male donors; all but one of them had predonated blood. The utilization rate of autologous units was 45·6%, with 55% of women and 24% of men receiving autologous blood. In females, 59% of transfused autologous units were given with the donor's Hb of ≥ 9·0 g dL−1; overtransfusion was even more apparent in men: 71% units were given with a Hb ≥ 10·0 g dL−1. PAD in bone marrow donors is associated with high wastage and increases the likelihood of requiring a transfusion. We recommend that PAD should not be routinely offered to bone marrow donors. [ABSTRACT FROM AUTHOR]

Summary:A total of 50 unrelated marrow donors were examined by pelvic magnetic resonance imaging (MRI) to investigate the morphological sequelae of bone marrow harvesting (BMH). Signal increase in T2-weighted sequences and contrast media enhancement in T1 sequences at the operative sites were found as typical MRI morphology 4 weeks after harvest (group A, n=16), corresponding to edema, hyperemia and proliferative activity. Although tissue repair was completed in the majority of donors 1 year after BMH, about 36%of donors in group B (n=16) had abnormal findings. These included a persistence of the‘acute injury’signal pattern (2/16, 12%), and signal alterations due to fatty marrow conversion (4/16, 24%). The proportion of MRI abnormalities increased to over 70%in two-time donors (group C, n=11), which might indicate a cumulation of tissue damage after repetitive harvests. If donors had experienced prolonged discomfort after BMH (group D, n=7), MRI revealed pathological signals in 86%. In conclusion, the MRI morphology reflects the pathophysiological reactions after BMH, including inflammation and tissue repair. A further prospective evaluation in a larger number of donors is necessary to confirm these results and to identify the factors which influence the extent and duration of tissue damage.Bone Marrow Transplantation (2005) 35, 667-673. doi:10.1038/sj.bmt.1704873 Published online 21 February 2005 [ABSTRACT FROM AUTHOR]

We assessed autologous bone marrow (BM) harvest and hematologic recovery after high-dose chemotherapy (HDCT) in patients who failed to achieve peripheral blood stem cell (PBSC) mobilization. One hundred and ninety-three patients with germ cell tumor, malignant lymphoma, sarcoma or medulloblastoma were scheduled for HDCT. In 123 patients, PBSC were mobilized by disease-specific chemotherapy plus granulocyte colony-stimulating factor (G-CSF). In 110/ 123 patients (89%) with circulating CD34+ cell counts 2 > or = 10/microl, sufficient hematopoietic autografts were collected (group A). In 13/123 patients (11%) with peripheral CD34 + cell counts < 10/microl, PBSC harvesting was not performed (group B). These latter patients were classified as "poor mobilizers" and underwent second-line BM harvest at a median of 46 (range 10-99) days after mobilization failure. Seventy patients with first-line BM harvest (group C) acted as historical controls. Ten patients from group B proceeded to HDCT and nine were evaluable for hematopoietic reconstitution. Recovery to neutrophils >0.5 x 10(9)/l was comparable with group C patients: 16 (range 9-34) days vs 13 (range 8-98) days. However, platelet (PLT) reconstitution >20 x 10(9)/l was significantly slower, with a median of 35 (range 13-50) days as compared with 19 (range 9-148) days (P = 0.0106) for control patients. Supportive care requirements, febrile days and length of hospital stay were not significantly different between the two groups of patients. We conclude that patients who fail to mobilize PBSC should be evaluated for second-line BM harvest. This approach may preserve the therapeutic option of HDCT for these patients. [ABSTRACT FROM AUTHOR]

Purpose: Bone marrow harvesting is associated with significant postoperative pain that may have potential negative consequences for the patient and health care system. In the current absence of uniform guidelines, there exists considerable variability amongst providers with respect to perioperative analgesia, especially opioid administration. In this initiative, we explored the potential for preoperative bilateral quadratus lumborum blocks in combination with a standardized perioperative analgesic protocol to manage pain with the goal of reducing perioperative narcotic usage and thereby improving opioid stewardship., Methods: Adults who underwent bone marrow donation from 2018 to 2020 were included in this analysis ( n = 32). The pre-implementation group ( n = 19) was reviewed retrospectively while the implementation group ( n = 13) was evaluated prospectively. Patient demographics, pain scores, and opioid consumption were evaluated., Results: Patient characteristics were equivalent except for anesthesia type with an increased number of patients in the implementation group undergoing spinal anesthesia. The implementation group showed significantly reduced median intraoperative (20.0 mg vs. 0.0 mg; p < 0.001) and total opioid consumption (20.5 mg vs. 0.0 mg; p < 0.001). The number of patients who received any opioids decreased from 84.2% (16/19) before implementation to 23.1% (3/13) after implementation., Conclusion: This change in practice suggests that implementation of a standardized perioperative protocol, including bilateral quadratus lumborum blocks, for bone marrow harvest patients leads to reduced perioperative opioid administration without compromising immediate perioperative pain control., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 McCoy, Hay, Romeo, Doty, Wolf and Hudspeth.)

Background: Mesenchymal stromal cells (MSCs) are the most prominent cell type used in clinical regenerative medicine and stem cell research. MSCs are commonly harvested from bone marrow that has been aspirated from patients' iliac crest. However, the ethical challenges of finding consenting patients and obtaining fresh autologous cells via invasive extraction methods remain to be barriers to MSC research. Methods: Techniques of harvesting sternal bone marrow, isolating and culturing MSCs, MSC surface phenotyping, and MSC differentiation are described. Samples from 50 patients undergoing a sternotomy were collected, and the time taken to reach 80% confluency and cell count at the second splitting of MSC were measured. Results: MSC isolated from the sternal bone marrow of patients undergoing cardiac surgery demonstrated successful MSC surface phenotyping and MSC differentiation. The mean cell count at the time of the second split was 1,628,025, and the mean time taken to reach the second split was 24.8 days. Conclusion: Herein, we describe the first reported technique of harvesting sternal bone marrow from patients already undergoing open-chest cardiac surgery to reduce the invasiveness of bone marrow harvesting, as well as the methods of isolating, culturing, and identifying MSCs for the clinical application of constructing autologous MSC-derived biomaterials. [ABSTRACT FROM AUTHOR]