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Lot number and expiry not available at this time.Article citation: knapp, s.,brosig, a.,troeger, a.,kleinschmidt, k.,offner, r.,corbacioglu, s.,burkhardt, r.,foell, j.,ahrens, n.2022.Granulocyte transfusions made with modified fluid gelatin in pediatric and adolescent patients with prolonged neutropenia.Transfusion.62:306-315.Investigation is in process.A follow up report will be provided.
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This report is being filed to provide additional information in h.6 and h.10.Investigation: since this was a journal publication presenting data of a retrospective study on the safety and efficacy of transfusing granulocytes collected with modified fluid gelatin (mfg) from (b)(6) 2013 to (b)(6) 2019, the lot numbers were not requested; therefore, a disposable lot history search could not be conducted.An investigation was conducted for a journal publication presenting data of a retrospective study on the safety and efficacy of transfusing granulocytes collected with modified fluid gelatin (mfg) instead of hydroxyethyl starch (hes) to pediatric patients from (b)(6) 2013 to (b)(6) 2019 using cobe spectra and spectra optia.Forty-six pediatric and adolescent patients with prolonged febrile neutropenia who received granulocyte transfusions were included in this retrospective single-center analysis.Patients received prophylactic gt to prevent infection and bridge the time until engraftment or marrow recovery after intensive radiotherapy/ chemoradiotherapy, or therapeutic gt to treat severe disseminated or local infection, as appropriate.The intent of granulocyte transfusion was therapeutic in 35 cases (76%) and prophylactic in 11 cases (24%).In the therapeutic subgroup, two deaths occurred on the day of the last transfusion, and one on the day after the last transfusion; the cause of death was cardiovascular failure as a complication of severe cytomegalovirus pneumonia in association with absolute neutropenia after allogeneic stem cell transplantation in one case, and septic shock with multiple organ-system failure (mof) in the other two.In these, no bacterial or fungal infection was found by microbiological examinations.The two deaths in the prophylactic treatment group occurred 1 or 2 days, respectively, after the last granulocyte transfusion; the cause of death was multiple organ system failure (mof) in each case.Patients were observed for 24 days following the first gt (median; range five for one diseased patient up to 636 days).Of the 41 survivors who lived at least 21 days after their last granulocyte transfusion, seven (17%) succumbed to their underlying disease before the end of the observation period ((b)(6) 2019).Adverse events (aes) occurring up to 2 days after granulocyte transfusion were recorded as part of their hemovigilance system.Fever occurred in six cases (13%) and allergic reactions (exanthema) in two (4%), which were classified as possible adverse reactions to the granulocyte transfusions.Fungal pneumonia occurred due to underlying diseases in two cases and therefore, was not considered to be related to granulocyte transfusion.There were no severe pulmonary adverse events and three patients with mild pulmonary side effects (coughing or transient oxygen supply).The authors did not attribute the adverse reactions to a specific platform so all are documented under the newer platform, spectra optia.Adverse events (aes) occurring up to 2 days after granulocyte transfusion were recorded as part of their hemovigilance system.Fever occurred in six cases (13%) and allergic reactions (exanthema) in two (4%), which were classified as possible adverse reactions to the granulocyte transfusions.Fungal pneumonia occurred due to underlying diseases in two cases and therefore, was not considered to be related to granulocyte transfusion.There were no severe pulmonary adverse events and three patients with mild pulmonary side effects (coughing or transient oxygen supply).The authors stated that ¿adverse event reporting in granulocyte transfusion is inherently difficult to standardize because of the variety in clinical conditions and partly immunosuppressive treatments.¿ according to the aabb circular of information for the use of human blood components (revised 2017), febrile nonhemolytic reactions are typically manifested by a temperature elevation of >1c or 2f occurring during or within 4 hours after a transfusion and in the absence of any other pyrexic stimulus or active warming.Febrile nonhemolytic reactions are frequently noted in patients receiving granulocyte transfusions.Fever and chills in patients receiving granulocyte components may be avoided or mitigated by slow administration and recipient premedication.According to the aabb circular of information for the use of human blood components (revised 2017), allergic reactions frequently occur (ie, 1-3% of plasma-containing components) as mild or self-limiting urticaria or wheezing that usually respond to antihistamines.More severe manifestations, including respiratory and cardiovascular symptoms, are more consistent with anaphylactoid/anaphylactic reactions and may require more aggressive therapy.No laboratory procedures are available to predict these reactions.Anaphylactic reactions, characterized by hypotension, tachycardia, nausea, vomiting and/or diarrhea, abdominal pain, severe dyspnea, pulmonary and/or laryngeal edema, and bronchospasm and/or laryngospasm, are rare (<10/100,000 transfused units) but dangerous complications requiring immediate treatment with epinephrine.While these reactions have been reported in iga-deficient patients with anti-iga antibodies and patients with haptoglobin deficiency, most reactions are idiosyncratic and not associated with a specific serum protein deficiency, polymorphism, or identifiable cause.According to the aabb circular of information for the use of human blood components (revised 2017), transfusion-related acute lung injury (trali) is characterized by the acute onset of hypoxemia and noncardiogenic pulmonary edema within 6 hours of a blood or blood component transfusion in the absence of other causes of acute lung injury or circulatory overload.Various stimuli in blood components, most commonly white blood cell (wbc) antibodies from donors sensitized during pregnancy or prior transfusion or transplantation, or proinflammatory molecules that accumulate in stored blood components may cause trali.These mechanisms may not be mutually exclusive and may act synergistically with underlying patient factors to lead to a final common pathway of acute lung injury.These stimuli may trigger an inflammatory response, granulocyte activation and degranulation, and injury to the alveolar capillary membrane and the development of permeability pulmonary edema.Although most trali cases are associated with donor antileukocyte antibodies, rare cases have implicated recipient antileukocyte antibodies that reacted with donor leukocytes.Root cause: a root cause assessment was performed for the fever.Based on the available information a definitive root cause could not be determined but it is likely due to one or a combination of the possible causes listed below: * febrile reactions occur more frequently in patients previously alloimunized by transfusion or pregnancy.It is likely the reactions were caused by the presence of recipient antibodies (raised as a result of previous transfusions) reacting to donor human leucocyte antigens (hla) or other antigens.It is also widely known that febrile reactions are caused by passively transfused cytokines or recipient antibodies reacting with leukocytes in the blood product.* leak in the disposable set.A root cause assessment was performed for the allergic reactions.Based on the available information a definitive root cause could not be determined but it is likely due to one or a combination of the possible causes listed below: * anaphylactic reactions have been reported in iga-deficient patients with anti-iga antibodies and patients with haptoglobin deficiency, most reactions are idiosyncratic and not associated with a specific serum protein deficiency, polymorphism, or identifiable cause.* immediate hypersensitivity reaction (production of ige antibodies in response to allergens in plasma proteins.* passive sensitization (passive transfer of donor allergens or donor antibodies (e.G.Allergen-specific ige); transient allergic sensitivity to allergens.A definitive root cause of the mild pulmonary side effects could not be determined.Possible reasons include various stimuli in blood components, most commonly white blood cell (wbc) antibodies from donors sensitized during pregnancy or prior transfusion or transplantation or proinflammatory molecules that accumulate in stored blood components.These mechanisms may not be mutually exclusive and may act synergistically with underlying patient factors to lead to a final common pathway of acute lung injury.These stimuli may trigger an inflammatory response, granulocyte activation and degranulation, and injury to the alveolar capillary membrane and the development of permeability pulmonary edema.Although most trali cases are associated with donor antileukocyte antibodies, rare cases have implicated recipient antileukocyte antibodies that reacted with donor leukocytes.Article citation: knapp, s.,brosig, a.,troeger, a.,kleinschmidt, k.,offner, r.,corbacioglu, s.,burkhardt, r.,foell, j.,ahrens, n.2022.Granulocyte transfusions made with modified fluid gelatin in pediatric and adolescent patients with prolonged neutropenia.Transfusion.62:306-315.
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