This prospective study describes chemotherapy-induced nausea and vomiting (CINV) in children (4-18 years) receiving their first hematopoietic stem cell transplant. Emetic episodes, nausea severity (assessed using a validated, self-report nausea severity assessment tool) and antiemetic administration were documented from the start of conditioning until 24 h after the last conditioning agent was administered (acute) and for a further 7 days (delayed). Relationships between CINV control and parenteral nutrition (PN) use and acute gut GvHD (aGvHD) were explored. Fifty-nine children (4.6-17.4 years) were evaluable. Complete chemotherapy-induced vomiting (CIV; acute: 24%; delayed 22%) and chemotherapy-induced nausea (CIN; acute 7%; delayed 12%) control rates were low. Few children experienced complete CINV control (no vomiting/retching and no nausea) during the acute (5%) or delayed phases (12%). Children experiencing complete acute or delayed CIN control or complete delayed CIV control were more likely to have received: a lower proportion of their total energy requirement as PN at the end of the delayed phase (P<0.036) and PN for a shorter time (P<0.044). Low patient numbers did not permit evaluation of the association between gut aGvHD and CINV control. Effective and safe interventions aimed at improving CINV control in children are required.
BACKGROUND:The manufacturing of cellular products for immunotherapy, such as chimeric antigen receptor T cells, requires successful collection of mononuclear cells. Collections from children with high-risk leukemia present a challenge, especially because the established COBE Spectra apheresis device is being replaced by the novel Spectra Optia device (Optia) in many institutions. Published experience for mononuclear cell collections in children with Optia is lacking. Our aim was to compare the two collection devices and describe modified settings on the Optia to optimize mononuclear cell collections. STUDY DESIGN AND METHODS:As a quality initiative, we retrospectively collected and compared data from mononuclear cell collections on both devices. Collected data included patient's clinical characteristics; collection parameters, including precollection lymphocyte/ CD3 counts, total blood volumes processed, runtimes, and side effects (including complete blood count and electrolyte changes); and product characteristics, including volumes and cell counts. Collection efficiencies and collection ratios were calculated. RESULTS:Twenty-six mononuclear cell collections were performed on 20 pediatric patients: 11 with COBE and 15 with Optia. Adequate mononuclear cell products were successfully collected with a single procedure from all patients except one, with mean calculated mononuclear cell collection efficiency that was significantly higher from Optia collections compared with COBE collections (57.9 6 4.6% vs 40.3 6 6.2%, respectively; p 5 0.04). CD3-positive yields were comparable on both machines (p 5 0.34) with significantly smaller blood volumes processed on Optia. Collected products had larger volumes on Optia. No significant side effects attributed to the procedure were noted. CONCLUSION:Mononuclear cell apheresis using the Optia device in children is more efficient and is as safe as that with the COBE device.T reating patients who have therapy-resistant or high-risk, relapsed acute lymphoblastic leukemia (ALL) is challenging.1,2 Cellular therapies using chimeric antigen receptor (CAR)-transfected T cells is currently being investigated as a promising new immunotherapeutic treatment modality.3 To manufacture CAR T cells, mononuclear cells (MNCs) from the patient need to be collected beforehand. 4 Recently, manufacturer support for the commonly used COBE Spectra (COBE) apheresis device has been discontinued, and many centers are replacing the COBE device with the new Spectra Optia (Optia) device (both from Terumo BCT). Both devices use centrifugation for blood separation, but they have different operating systems and collection techniques. The COBE device operates on manual color coordination, which requires intermittent manual interface control and repositioning by the operator based on the product color and aspect of the product aspired through the collect port. The Optia device, on the other hand, automates this process through an advanced automated interface management system, which provides constant feedback ...
Major ABO incompatible BM transplantation carries a risk of acute haemolysis. Red cell depletion reduces this risk but not all incompatible RBC (iRBCs) are removed and in children the residual volume can be significant relative to body weight. We sought to determine the volume of iRBCs that can be safely given to children. All patients receiving fresh BM from a donor with a major ABO blood group mismatch between January 2000 and July 2013 at the Hospital for Sick Children, Toronto, were included. Seventy-eight patients were identified. The median volume of iRBCs transfused was 1.6 mL/kg (range 0.1-10.6 mL/kg). Thirty-five patients had minor haemolytic events and five patients had clinically significant adverse events. Two patients, who received 3.66 and 3.9 mL iRBCs/kg, developed renal impairment and in one case hypoxia and hyperbilirubinaemia. One patient had mild hypotension that resolved with i.v. fluid. Two patients developed hypotension secondary to sepsis and unrelated to BM infusion. Although signs of haemolysis occur, with appropriate hydration and monitoring of renal function, clinically significant adverse events related to the infusion of ABO incompatible BM are rare, and, in this study, were only seen in patients receiving 43 mL/kg of iRBCs per kg.Bone Marrow Transplantation (2015) 50, 536-539; doi:10.1038/bmt.2014.309; published online 26 January 2015 INTRODUCTION ABO incompatibility between donor and recipient is not a contraindication to allogeneic haematopoietic SCT (HSCT). However, a number of immunohaematological issues must be carefully considered and appropriately managed. 1 Major ABO mismatch is characterised by preformed recipient isoagglutinins to donor red cell antigens, and minor ABO mismatch occurs when the graft contains isoagglutinins directed against recipient red cells. Bidirectional mismatch occurs when both situations are present. 1 The risks of major ABO incompatibility include acute haemolysis at the time of graft infusion, delayed engraftment and pure red cell aplasia. 2 The literature suggests that 20-30 mL of incompatible RBCs (iRBCs) can be safely infused into an adult 2 and this has been extrapolated to 0.2-0.4 mL/kg, but there is no evidence about safe volumes in children. In the case of major ABO incompatibility, most centres will red cell deplete donor BM using centrifugation or sedimentation techniques. 2 Even with the best available technology it is not possible to remove all iRBCs and in small children this can result in a volume of red cells per kilogram of wt that is significantly higher than would routinely be transfused into an adult. In our experience we are rarely able to red cell deplete BM such that 40.4 mL/kg of iRBCs remain, without significantly reducing the total nucleated cell dose and thus jeopardising engraftment. Therefore, we sought to determine what volume of iRBCs can safely be given to children in the context of allogeneic HSCT using fresh BM.
Recent advances in genetic diagnosis have identified mutations in gene encoding interleukin-10 (IL-10) and IL-10 receptor (IL-10R) proteins as a cause for early-onset enterocolitis leading to hyperinflammatory immune response. Allogeneic HSCT offers a potential cure; however, it was only performed in a few infants and mainly from family-related donors. We report a case of a girl who presented very early in life with severe infantile enterocolitis. Gene sequencing confirmed IL-10R defect. Her older sister died at 13 months of age from severe undiagnosed enterocolitis. There was no family donor. An unrelated search identified a potential 10/10 high-resolution HLA-matched donor. There was some delay in donor activation because IL-10R defect was not on the standard list of indications for unrelated HSCT. Our patient received the unrelated HSCT at seven months of age, and she is currently nine months after transplant and doing very well. Because HSCT is the curative option of choice for this disorder, we encourage adding IL-10 and IL-10R protein defects to the list of HSCT indications for unrelated donor procurement.
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