| Catalog Number |
10110 |
| Medical Device Problem Codes |
Adverse Event Without Identified Device or Use Problem (2993); Insufficient Device Problem Information (3190)
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| Health Effect - Clinical Codes |
Low Blood Pressure/ Hypotension (1914); Appropriate Clinical Signs, Symptoms and Conditions Term/Code Not Available (4581)
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| Date of Event |
09/19/2019
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Type of Reportable Event
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Serious Injury
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Event or Problem Description
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Per journal article, "optimized peripheral blood progenitor cell mobilization for autologous hematopoietic cell transplantation in children with high-risk and refractory malignancies", by furlong, e., jensen, j., woodard, m., griffiths, k., knight, g., sturm, m., kerr, f., gough, h., bear, n., carter, t.L., cole, c.H., kotecha, r.S., & ramachandran, s., a retrospective study of 125 pediatric patients with high-risk malignancies undergoing ahsct in western australia between 1997 and 2016 was conducted.Mobilization was achieved by means of chemotherapy and granulocyte colony-stimulating factor (g-csf).Patients underwent apheresis the day after cd34+ counts reached =20/l and an additional dose of g-csf.Peripheral arterial and intravenous lines were inserted in pediatric intensive care unit under local anesthetic and/or sedation, omitting the need for general anesthesia as well as facilitating an uninterrupted apheresis flow.Larger apheresis total blood volumes were processed in patients weighing =20 kg.The minimal dose of =2 × 106 cd34+ cells/kg was successfully collected in 98.4% of all patients.The optimal dose of 3-5 × 106 cd34+ cells/kg was collected in 96% of patients scheduled for a single ahsct, 87.5% for tandem, and 100% for triple ahsct.All hpc collections were completed in one apheresis session.Mobilization after =3 chemotherapy cycles and cycles including cyclophosphamide resulted in a significantly higher yield of cd34+ cells.Our approach to hpc mobilization by means of chemotherapy and single myeloid growth factor combined with optimal collection timing facilitated by continuous apheresis flow resulted in highly effective hpc harvest in children and adolescents with high-risk cancers.The hpc collection procedures were well tolerated with no significant adverse effects.Between september 2006 and december 2016, five out of 81 patients (6.2%) required a calcium infusion to correct hypocalcemia (ctcae v5.0 grade 1 or 2) and one patient was given 4% human albumin solution for hypotension (ctcae v5.0 grade 3).There were no vascular, ischemic, or infectious complications associated with percutaneous arterial or venous cannulation.Specific details, such as patient information and outcome, were not included in the article for these events, therefore this report is being provided as a summary of the events.The collection set is not available for return because it was discarded by the customer.
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Additional Manufacturer Narrative
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Investigation: lot number, manufacture and expiry date are not available at this time.Investigation is in process, a follow-up report will be provided.Furlong, e., jensen, j., woodard, m., griffiths, k., knight, g., sturm, m., kerr, f., gough, h., bear, n., carter, t.L., cole, c.H., kotecha, r.S., & ramachandran, s.(2019b).Optimized peripheral blood progenitor cell mobilization for autologous hematopoietic cell transplantation in children with high-risk and refractory malignancies.Pediatric transplantation, 24(1).Https://doi.Org/10.1111/petr.13602.
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Event or Problem Description
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Per journal article, "optimized peripheral blood progenitor cell mobilization for autologous hematopoietic cell transplantation in children with high-risk and refractory malignancies", by furlong, e., jensen, j., woodard, m., griffiths, k., knight, g., sturm, m., kerr, f., gough, h., bear, n., carter, t.L., cole, c.H., kotecha, r.S., & ramachandran, s., a retrospective study of 125 pediatric patients with high-risk malignancies undergoing ahsct in western australia between 1997 and 2016 was conducted.Mobilization was achieved by means of chemotherapy and granulocyte colony stimulating factor (gcsf).Patients underwent apheresis the day after cd34+ counts reached 20/l and an additional dose of gcsf.Peripheral arterial and intravenous lines were inserted in pediatric intensive care unit under local anesthetic and/or sedation, omitting the need for general anesthesia as well as facilitating an uninterrupted apheresis flow.Larger apheresis total blood volumes were processed in patients weighing 20 kg.The minimal dose of 2106 cd34+ cells/kg was successfully collected in 98.4% of all patients.The optimal dose of 35106 cd34+ cells/kg was collected in 96% of patients scheduled for a single ahsct, 87.5% for tandem, and 100% for triple ahsct.All hpc collections were completed in one apheresis session.Mobilization after 3 chemotherapy cycles and cycles including cyclophosphamide resulted in a significantly higher yield of cd34+ cells.Our approach to hpc mobilization by means of chemotherapy and single myeloid growth factor combined with optimal collection timing facilitated by continuous apheresis flow resulted in highly effective hpc harvest in children and adolescents with high-risk cancers.The hpc collection procedures were well tolerated with no significant adverse effects.Between september 2006 and december 2016, five out of 81 patients (6.2%) required a calcium infusion to correct hypocalcemia (ctcae v5.0 grade 1 or 2) and one patient was given 4% human albumin solution for hypotension (ctcae v5.0 grade 3).There were no vascular, ischemic, or infectious complications associated with percutaneous arterial or venous cannulation.Specific details, such as patient information and outcome, were not included in the article for these events, therefore this report is being provided as a summary of the events.The collection set is not available for return because it was discarded by the customer.
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Additional Manufacturer Narrative
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This report is being filed to provide additional information in h.6 and h.11.Investigation: an investigation was conducted for a journal article that references terumo bct product.Journal article, titled optimized peripheral blood progenitor cell mobilization for autologous hematopoietic cell transplantation in children with highrisk and refractory malignancies by furlong et al was reviewed with primary purpose of screening for allegations of terumo bct device causing or contributing to death/injury or device malfunctions.Since this was a journal publication to evaluate the efficacy and safety of pediatric patients with highrisk malignancies undergoing ahsct in western australia between july 1997 and december 2016, the lot numbers were not requested; therefore, a dhr search could not be conducted for this specific incident.All lots must meet acceptance criteria for release.Background: autologous hematopoietic stem cell transplantation (ahsct) using hematopoietic progenitor cells (hpcs) has become an important therapeutic modality for patients with highrisk malignancies.Current literature on standardized method for hpc apheresis in children is sparse and failure rate reported as high as 30%.Patients/methods: a retrospective study of 125 pediatric patients with highrisk malignancies undergoing ahsct in western australia between 1997 and 2016 was conducted.Results: mobilization was achieved by means of chemotherapy and granulocyte colony stimulating factor (gcsf).Patients underwent apheresis the day after cd34+ counts reached 20/l and an additional dose of gcsf.Peripheral arterial and intravenous lines were inserted in pediatric intensive care unit under local anesthetic and/or sedation, omitting the need for general anesthesia as well as facilitating an uninterrupted apheresis flow.Larger apheresis total blood volumes were processed in patients weighing 20 kg.The minimal dose of 2 106 cd34+ cells/kg was successfully collected in 98.4% of all patients.The optimal dose of 35 106 cd34+ cells/kg was collected in 96% of patients scheduled for a single ahsct, 87.5% for tandem, and 100% for triple ahsct.All hpc collections were completed in one apheresis session.Mobilization after 3 chemotherapy cycles and cycles including cyclophosphamide resulted in a significantly higher yield of cd34+ cells.Conclusion: our approach to hpc mobilization by means of chemotherapy and single myeloid growth factor combined with optimal collection timing facilitated by continuous apheresis flow resulted in highly effective hpc harvest in children and adolescents with highrisk cancers.Summary of terumo bct product in relation to the journal article: 2.3 | collection procedures and apheresis the hpc collection is performed in the pediatric intensive care unit where the cell separator is housed.Peripheral venous and percutaneous arterial access are obtained under local anesthesia and/or deep sedation.The largest possible intravenous catheter is inserted for both the venous and arterial access, ranging between 24 and 18 gauge depending on the patient's size and feasibility of the cannulation.Three different continuous blood flow apheresis systems were used over the 20year period: cs3000 blood cell separator (between july 1997 and july 2006), cobe spectra (between august 2006 and june 2012), and spectra optia (between july 2012 and december 2016).The whole blood volume for processing is calculated as per the following formula: patient weight (kg) desired cd34+ yield (106/kg)/patient cd34+ (106/l) preapheresis 0.4, based on an estimated collection efficacy of 40%.The collection efficacy is calculated as ce% = total cd34+ collected/ (total processed volume (ml)/cd34+ pre-apheresis/l 1000) 100.Patients who weigh 20 kg have a machine custom primed with packed red blood cells.A platelet and/or packed red blood cell transfusion is given before or after the procedure based upon clinical need.The platelet loss during apheresis is calculated as plt loss% = (platelets preapheresis platelets post apheresis)/platelets pre-apheresis 100.All patients have 50 ml of plasma collected at the time of apheresis, used for hpca reconstitution and preservation.Close monitoring of electrolytes and coagulation parameters are performed as per institutional guidelines.3.2 | peripheral blood progenitor cell yield the median cd34+ cell count on the day prior to the hpc collection (day 1) was 122/l (range, 21764/l) with a corresponding wbc of 6.95 103/l (range, 1.336.2 103/l).The median cd34+ cell count the following day immediately pre-apheresis (day 0) was 188/l (range, 171990/l) with a corresponding median wbc of 18.6 103/l (range, 3.666.2 103/l) (figure 1).Only one patient during the study period failed to mobilize their cd34+ cell count to 20/l by the apheresis day, after 13 days of 5 g/kg/day gcsf and four preceding chemotherapy cycles.The minimum progenitor cell collection dose of 2 106 cd34+ cells/kg per scheduled ahsct (2 106 cd34+ cells/kg for a single ahsct, 4 106 cd34+ cells/kg for tandem ahsct, and 6 106 cd34+ cells/kg for triple ahsct) was achieved in 122 out of 124 patients (98.4%).One patient, a 16.8-year-old female with primary pnet after two cycles of cyclophosphamide containing chemotherapy and 13 days of gcsf at 5 g/kg, underwent apheresis on the day her cd34+ count reached 20/l (cd34+ count 21/l), resulting in a harvest of 1.5 106 cd34+ cells/kg.Another patient, a 9.9-year-old male with primary rhabdomyosarcoma after two cycles of cyclophosphamide based chemotherapy and 8 days of gcsf at 5 g/kg, achieved favorable cd34+ counts of 192/l by day 1 and 204/l by day 0 but had a poor hpc harvest of 1.7 106/kg, attributable to the apheresis system hard drive failure during the hpc collection.The optimal cd34+ dose of 35 106 cd34+ cells/kg per scheduled ahsct was obtained in 95 out of 99 patients (96%) planned for a single ahsct (range, 3.2194.0 106 cells/kg) and 14 out of 16 patients (87.5%) planned for tandem ahsct (range, 6.736.6 106 cells/kg).All nine patients planned for triple ahsct underwent a successful collection of 9 106 cd34+ cells/kg (range, 9.6194 106 cd34+ cells/kg; table 2).All patients had their hpcs collected in one apheresis session after initial mobilization with chemotherapy and gcsf, with the majority of patients (n = 122, 97.6%) having apheresis performed on day 0.Three patients underwent apheresis on day + 1 due to issues with obtaining arterial access, apheresis system failure, and a late arrival for the procedure, respectively.The subsequent hpc collection for these patients resulted in an optimal harvest of 35 106 cd34+ cells/kg for a single ahsct in two patients and a minimum hpc collection of 4 106 cd34+ cells/kg for tandem ahsct in one patient.3.4 | apheresis parameters a closed apheresis circuit was obtained between a peripheral artery and vein during the study period.Documentation on details of the procedure was available for 67 out of 81 patients who underwent hpc collection after august 2006 (table 4).The radial artery was accessed in 60 patients (89.6%), who had a median weight of 19 kg (range, 8109 kg).The brachial artery was accessed in four patients weighing 13.6, 15.7, 41, and 59 kg each and the femoral artery in three patients weighing 7.3, 8.7, and 9.7 kg each.An existing double lumen central venous line was used in one patient weighing 8.3 kg due to difficulty obtaining percutaneous arterial access.The average apheresis flow rate was 24.8 ml/min when using cobe spectra and 27.9 ml/min when spectra optia was used.A median of 2.6 blood volumes (range, 0.67.6) was processed during this period in patients weighing 20 kg.Patients of a low weight (1020 kg) and very low weight (10 kg) had a median of 3.3 (range, 1.27.6) and 3.5 (range, 2.07.1) blood volumes processed, respectively.The average duration of the hpc collection was 163 minutes (range, 57373 minutes).We compared the effectiveness of the different apheresis systems used over the study period: cs3000 blood separator, cobe spectra, and spectra optia, by analyzing data of collection efficacy, platelet loss, and adverse events (table 5).We observed an increase in the collection efficacy (ce%) over time, with a median ce% of 38.7% (range, 13.073.9) when using the cs3000 blood separator to 44.8% (range, 9.7104.4) whilst using the cobe spectra, and up to 49% (range, 11.980.1) when using the spectra optia.The platelet loss fell significantly over the study period from a median platelet loss of 65.3% (range, 31.191.3) when using the cs3000 blood separator, to 31.9% (range, 2.373.3) when using cobe spectra, and 26.1% (range, 056.1) when spectra optia was used.The hpc collection procedures were well tolerated with no significant adverse effects.Between september 2006 and december 2016, five out of 81 patients (6.2%) required a calcium infusion to correct hypocalcemia (ctcae v5.0 grade 1 or 2) and one patient was given 4% human albumin solution for hypotension (ctcae v5.0 grade 3).There were no vascular, ischemic, or infectious complications associated with percutaneous arterial or venous cannulation.4 | discussion the optimal timing of the hpc collection has been the subject of numerous studies.Most apheresis centers start monitoring cd34+ cell counts when the total wbc reaches 2000/l and proceed to apheresis when the cd34 + count reaches 20/l to achieve a target collection of at least 2 106 cd34+ cells/kg.39-41 at our institution, we opt to harvest hpcs the day after cd34+ cells reach the optimal number of 20/l as we observe a significant rise of cd34+ cells between the pre apheresis day (day 1) and the day of apheresis (day 0), further increasing the chance of a successful hpc collection.42-45 furthermore, based on the fact that cd34+ cell counts rise 46 hours post administration of gcsf,46 we routinely proceed to an hpc collection after an additional dose of 10 g/kg of gcsf administered early in the morning of the apheresis procedure.Continuous apheresis flow was facilitated by creating a closed circuit between a peripheral artery and vein in the majority of our patients, preferably using the radial artery and anterior cubital vein as previously described but not widely adopted.47,48 where possible, we avoided using the femoral artery to minimize complications resulting from possible thrombosis and/or infection.In order to achieve an optimal uninterrupted inlet flow and ultimately a single hpca collection, we also avoided using existing central venous lines for access due to inherent issues related to line resistance resulting in flow restrictions.Larger total blood volumes, a median of 3.33.5 blood volumes in patients weighing 20 kg compared to 2.6 in patients of 20 kg, were processed when collecting progenitor cells from very small children as previously described.49,50 the minimal progenitor cell dose of 2 106 cd34+ cells/kg was collected for 122 out of 124 patients (98.4%), and the optimal dose of 35 106 cd34+ cells/kg was achieved in 118 out of 124 patients (95.2%).All patients required a single apheresis session to achieve the required target.During the 20 year study period, only one patient failed to mobilize stem cells to the desired cd34+ cell count of 20/l by the time of apheresis, likely due to the intensity of prior chemotherapy received.Failure to collect the minimal required stem cell dose occurred in two patients, possibly due to the apheresis taking place on the day the cd34+ count reached 20/l in one patient and due to the hard drive apheresis system failure in the other.Significantly improved platelet loss over the study period allowed patients with a platelet count as low as 20 109/l to undergo apheresis at our institution.There were no serious adverse events in relation to the apheresis procedure, highlighting the safety of our approach.Since this was a journal publication to evaluate the efficacy and safety of pediatric patients with highrisk malignancies undergoing ahsct in western australia between july 1997 and december 2016, the lot numbers were not requested; therefore, a disposable lot history search could not be conducted.According to therapeutic apheresis: a physician's handbook, adverse events occur during therapeutic procedures with a frequency of 4.8%.Some of the most common reactions include fever, urticaria, hypocalcemic symptoms, pruritus, dyspnea, tachycardia, and mild hypotension.Vasovagal incidents occur around 0.5% of procedures.The reactions generally manifest as pallor and diaphoresis.In a full blown attack, the reaction progresses from pallor and sweating to pulse slowing and blood pressure decreasing.More severe vasovagal reactions may include nausea, vomiting, and/or convulsions according to therapeutic apheresis: a physician's handbook, adverse events occur during therapeutic procedures with a frequency of 4.8%.Some of the most common reactions include fever, urticaria, hypocalcemic symptoms, pruritus, dyspnea, tachycardia, and mild hypotension.Transient hypocalcemia associated with apheresis is usually well tolerated.Symptoms often show as paresthesia (tingling) but patients may also experience unusual taste, nausea, lightheadedness, shivering, and tremors.Severe hypocalcemia may also cause muscle contractions and can progress to tetany and seizures if hypocalcemia escalates and is not corrected root cause: a root cause assessment was performed for the reported low yield.A definitive root cause could not be determined.Potential causes for the low mnc or low cd34 stem cell collection efficiency include but are not limited to: - patient's blood physiology interferes with separation of cellular components and chamber triggering (i.E.Abnormal rbcs, hyperviscous plasma) - not processing enough blood to optimize the collection of target cells - poor mobilization of target cells due to patient's physiology and mobilization regimen - accumulation of buffy coat resulting in filling chamber with non-target cells.- incorrect setting of collection preference - entry of incorrect wbc and/or platelet counts - poor access, which resulted in pump pauses and caused the system to repeatedly re-establish the interface - platelet clumping which can interfere with proper separation of cells in the connector and/or chamber and can also cause system to repeatedly re-establish the interface.- changes to the inlet pump flow rate of more than 5% during accumulation phase - lighting is too bright and is not within the appropriate range - dirty aperture plate and/or reference block - calculation of collection efficiency is based on the initial target cell concentration (ce2) instead of the average of the initial and final cell concentrations (ce1) to account for the decrease in target cells over the course of the procedure.-chamber harvests were initiated by the operator or inlet volume processed that overfilled the chamber.-insufficient harvest volume and/or chase volume was configured by the operator to harvest the chamber.- improper temperature during product transportation or storage.- improper sampling technique.- cell counter out of calibration.- incorrect calculation of manual volume.Factors that impact the calculated volume for the yield equation include improper tare weight, scale out of calibration, and/or neglect of division by the correct specific gravity (weight to volume conversion).- partial or full occlusion of the collection line tubing - insufficient weld of the skimmer dam to the collect connector - rbc port height is too high - improper loading of the channel into the filler a root cause assessment was performed for the reported hypotension reactions.Based on the available information a definitive root cause could not be determined.Vasovagal are common side effects of therapeutic apheresis procedures.They are typically caused by the patient's disease state, the rate of ac infusion, the length of the procedure, the patient's sensitivity to the procedure and/or the hemodynamic stress of the procedure.A root cause assessment was performed for the reported citrate reactions.These reactions occur due to decreased ionized calcium in circulation as a result of exogenous citrate administered during the apheresis procedure and are influenced by patient physiology, the patient's disease state, the rate of ac infusion, the citrate contents in the replacement fluid, and/or the length of the procedure.These symptoms may be treated with oral or intravenous calcium supplements or by adjusting the ac infusion rate.Citation: furlong, e., jensen, j., woodard, m., griffiths, k., knight, g., sturm, m., kerr, f., gough, h., bear, n., carter, t.L., cole, c.H., kotecha, r.S., & ramachandran, s.(2019b).Optimized peripheral blood progenitor cell mobilization for autologous hematopoietic cell transplantation in children with high risk and refractory malignancies.Pediatric transplantation, 24(1).Https://doi.Org/10.1111/petr.13602.
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