Basophil activation test for allergic and febrile non-haemolytic transfusion reactions among paediatric patients with haematological or oncological disease.

BACKGROUND AND OBJECTIVES: Allergic transfusion reactions (ATRs) and febrile non-haemolytic transfusion reactions (FNHTRs) are common, although their mechanisms remain unclear. Immunoglobulin E (IgE)-mediated type I hypersensitivity may be involved in the pathogenesis of ATR. A basophil activation test (BAT) may help elucidate this process. MATERIALS AND METHODS: The BAT was based on peripheral blood samples from paediatric patients with a haematological or oncological disease and on samples of residual blood products transfused in each case. Dasatinib was used to evaluate whether basophil activation was mediated by an IgE-dependent pathway. RESULTS: Twenty-seven patients with and 19 patients without ATR/FNHTR were included in this study, respectively. The median BAT values associated with ATR- (n = 41) and FNHTR-causing (n = 5) blood products were 22.1% (range = 6.1%-77.0%) and 27.8% (range = 15.2%-47.8%), respectively, which were higher than the median value of 8.5% (range = 1.1%-40.9%) observed in blood products without a transfusion reaction. Dasatinib suppressed basophil activity. BAT values were comparable in patients with ATR regardless of severity. Meanwhile, BAT values analysed with blood products non-causal for ATR/FNHTR were higher in patients with ATR/FNHTR than in those without. CONCLUSION: The IgE-mediated type I hypersensitivity may be involved in the pathogenesis of ATR and FNHTR. BAT analyses may help elucidate the underlying mechanisms and identify patients at risk.

Relationship between allergic transfusion reactions and allergic predisposition among pediatric patients with hematological/oncological disease.

BACKGROUND: Allergic transfusion reactions (ATRs) manifest frequently as transfusion reactions, and their onset may be related to a patient's allergic predisposition. Moreover, although pediatric patients with hematological/oncological disease are more susceptible to ATRs, the relationship between allergic predisposition and ATRs remains to be fully clarified. STUDY DESIGN AND METHODS: Patients who were diagnosed with pediatric hematological/oncological disease and received transfusion at the study institutions were included. We determined patient background information related to their allergy history, measured the levels of allergen-specific immunoglobulin E (IgE) using sera obtained on diagnosis, and analyzed their associations with ATR onset. RESULTS: Of the 363 patients analyzed, 144 developed ATRs. Multivariate analysis identified cases with high basophils in the peripheral blood, and Dermatophagoides pteronyssinus- and egg white-specific IgEs were involved in the development of ATR in all age groups. Meanwhile, a history of food allergies, and positivity for Japanese cypress- and D. pteronyssinus-specific IgEs were risk factors for developing ATRs in the <5 years age group. Moreover, patients aged 5-<10 years with a history of asthma, allergic rhinitis, pollinosis, or atopic dermatitis, and those aged ≥10 years with positivity for dog dander-specific IgE were at risk for developing ATRs. CONCLUSION: The allergic constitution of patients plays a role in ATR onset even in pediatric hematological/oncological diseases. Therefore, advance confirmation of a patient's allergic constitution may partly predict the onset of ATRs. However, since multiple allergic predispositions within complex mechanisms may be involved in the onset of ATRs, further verification is required.

Prophylaxis Using a Mixture of Plasma-Derived Activated Factor VII and Factor X (pdFVIIa/FX) in a Patient with Hemophilia B Complicated by Inhibitors and Allergy to Factor IX Concentrates: A Case Report.

Treating patients with hemophilia and inhibitors is often problematic. The presence of inhibitors negatively impacts the effectiveness of treatment to achieve hemostasis especially in patients with hemophilia B, owing mainly to allergic reactions to factor IX (FIX) concentrates and the low success rate of immune tolerance therapy. A 9-month-old boy had intracranial hemorrhage and was diagnosed with hemophilia B. After replacement therapy, he developed inhibitors and an allergic reaction to FIX. Prophylactic therapy was initiated with recombinant activated factor VII (rFVIIa) and later switched to pdFVIIa/factor X (FX; 120 µg/kg as the FVII dose, every other day) because of a recurrence of intracranial hemorrhage. Since then, he remained well without life-threatening bleeding for more than 2 years. Our case suggests that pdFVIIa/FX may be useful for prophylactic therapy in hemophilia B complicated by inhibitors and allergic reaction to FIX concentrates.

Sequential Therapy of Inotuzumab Ozogamicin and Blinatumomab as a Bridge-to Hematopoietic Stem Cell Transplantation in a Pediatric Patient With Primary Refractory Acute Lymphoblastic Leukemia: A Case Report.

For relapsed/refractory (r/r) acute lymphocytic leukemia (ALL), there is a clinical question on how to combine blinatumomab and inotuzumab ozogamicin (InO), which are newly emerging immunotherapeutic agents, with conventional treatment. We report the case of an 11-year-old boy with B-cell ALL, who had a failed primary treatment and achieved molecular complete remission treated with a sequence therapy of InO and blinatumomab. Later, hematopoietic stem cell transplantation could be performed without major complications. Our case may suggest that the sequence therapy of InO and blinatumomab as a bridge-to hematopoietic stem cell transplantation could be effective in the treatment of pediatric r/r ALL.

Transfusion outcome for volume- and plasma-reduced platelet concentrates for pediatric patients.

BACKGROUND AND OBJECTIVES: Plasma reduction in platelet concentrate (PC) products has been reported to prevent large volume load and transfusion-related adverse reactions (TRARs). However, volume reduction might be associated with a poor transfusion response because of a deterioration in platelet (PLT) quality. Because PLT quality control and transfusion responses for recently washed PCs using PLT additive solutions are superior, we investigated the clinical safety and transfusion efficacy of volume-reduced washed PCs in pediatric patients. MATERIALS AND METHODS: We prepared a simplified resuspended PC product (RPC) as a washed PC. Regular RPC (R-RPC) included equivalent volumes of bicarbonate Ringer's solution and anticoagulant citrate dextrose solution A (BRS-A) as the resuspension solution. Half RPC (H-RPC) was prepared by adding a half volume of BRS-A. Twenty-four pediatric patients were scheduled for transfusions with R-RPC and H-RPC up to 4 times. R-RPC was transfused 42 times into 24 patients. H-RPC was transfused 41 times into 23 patients. RESULTS: Neither product was observed to cause TRARs. Although the calculated PLT recovery for H-RPC was significantly reduced, the posttransfusion corrected count increment (24 h) did not differ. Moreover, similar results were observed for vital signs during transfusion. CONCLUSION: Volume-reduced washed PC can be transfused without causing TRARs, differences in vital signs, or inferior transfusion responses. Volume-reduced washed PC also provides the advantages of shortened transfusion times and reduced volume loads. Although a standard technique for stable resuspension is necessary, volume-reduced washed PC may be a beneficial option for children, including neonates, or individuals with cardiovascular or renal problems.

Thyroid tumor surveillance using ultrasound in childhood cancer survivors.

BACKGROUND: The optimal method for thyroid cancer screening in childhood cancer survivors (CCSs) who received radiation involving the thyroid gland is still debated. We describe a case series of ultrasound surveillance for thyroid tumor in CCSs in our institute. METHODS: We conducted thyroid tumor surveillance for CCSs with a history of radiation therapy involving the thyroid. The basic screening method was palpation. Thyroid ultrasound was also performed for patients who agreed after its benefits and risks were explained to them. We surveyed CCSs who visited the long-term follow-up outpatient clinic in our institution between October 2014 and September 2018. RESULTS: Of 82 CCSs who visited our institution during the study period, 44 were eligible for inclusion. None had a mass identified by palpation. Thyroid ultrasound was performed in 39 CCSs, and we identified thyroid nodules in 27. Four patients had a nodule with malignant echo features. Two of these cases received biopsies, and one patient was ultimately diagnosed with an early stage thyroid carcinoma. CONCLUSIONS: Childhood cancer survivors irradiated in the thyroid had a higher prevalence of thyroid nodules than the general population. Ultrasound screening contributed to early detection of impalpable thyroid cancer and enabled us to perform minimal surgery. Thus, ultrasound appears to be a useful option for secondary thyroid cancer screening. The thyroid tumor surveillance modality should be considered according to the individual case, and the patient must receive a clear explanation of the benefits and risks. These results could help doctors consider how to screen for secondary thyroid cancer.

Prophylactic piperacillin administration in pediatric patients with solid tumors following different intensities of chemotherapy.

BACKGROUND: Prophylactic antibiotics decrease mortality and morbidity in patients with hematological malignancies following intensive chemotherapy. However, the efficacy of prophylactic antibiotics for pediatric patients with solid tumors remains unclear. METHODS: We retrospectively assessed 103 neutropenic periods from 26 patients with neuroblastoma or brain tumors following three different intensity chemotherapy regimens (05A3, A, and B). While piperacillin was intravenously administered as prophylaxis (PIPC prophylaxis group), the historical control group received no prophylaxis. As patients exhibited a variable degree of myelosuppression based on the intensity of the chemotherapy regimen, we separately evaluated the frequency and severity of febrile neutropenia (FN) in each regimen. RESULTS: Following intensive chemotherapy, we observed a significantly lower frequency of FN in the PIPC prophylaxis group compared with the historical control group in both regimen 05A3 (20% vs 65%; P = 0.01) and regimen A (56% vs 93%; P = 0.02). We also observed a shorter duration of fever, lower maximum fever, and lower C-reactive protein levels in the PIPC prophylaxis group compared with the historical control group after regimens 05A3 and A. Conversely, the frequency and severity of FN were not different between the two groups after moderate-intensity chemotherapy (regimen B). However, a longitudinal routine surveillance study of Pseudomonas aeruginosa also indicated a reduction in the susceptibility to PIPC throughout the study period. CONCLUSIONS: Although PIPC prophylaxis might provide an advantage for severe neutropenia in pediatric patients with solid tumors, there is concern regarding bacterial resistance to antibiotics. Therefore, further careful examination is necessary for adaptation.

Prevention of transfusion-transmitted cytomegalovirus infection using leukoreduced blood components in patients receiving seronegative umbilical cord blood transplantation.

BACKGROUND: Leukoreduced blood components have been widely implemented to prevent transfusion-transmitted cytomegalovirus (TT-CMV) in transplantation. Recent progress in leukoreduction technology has helped reduce the risk of TT-CMV in hematopoietic stem cell transplantation; however, its efficacy in umbilical cord blood transplantation (CBT) has not been systematically studied. STUDY DESIGN AND METHODS: We retrospectively analyzed the incidence of CMV infection in patients treated with CBT who received prestorage leukoreduced, CMV-unselected blood components between 2007 and 2017 in a single Japanese pediatric center. Patients were monitored for CMV antigenemia at least once weekly. RESULTS: In total, 71 patients treated with CBT were identified. Two patients were excluded because of unknown CMV serostatus or early death after CBT. Of the remaining 69 patients, 24 developed CMV antigenemia. Among them, 3 received granulocyte transfusions (3 of 3; 100%), 2 were infants with severe combined immunodeficiency who had been infected with CMV before CBT (2 of 2; 100%), and 19 were CMV-seropositive patients (19 of 23, 82.6%). Conversely, of the remaining 45 patients in whom CMV antigenemia did not develop, 41 were seronegative (0 of 41; 0%) and were transfused with a total of 925 leukoreduced, CMV-unselected blood components. Among the 41 patients, 9 (22%) received in vivo T-cell depletion with antithymocyte globulin. None of the patients in the seronegative group has subsequently shown evidence of CMV infection or developed CMV disease. CONCLUSION: Using prestorage leukoreduction, no cases of CMV infection were detected in seronegative CBT patients. Our findings showed the safety of leukoreduction in preventing TT-CMV in this patient group.

Ovarian function after allogeneic hematopoietic stem cell transplantation in children and young adults given 8-Gy total body irradiation-based reduced-toxicity myeloablative conditioning.

BACKGROUND: The spectrum of late sequelae after hematopoietic stem cell transplantation (HSCT) includes infertility, which is the most frequent complication. Some reports suggested that ovarian function may be better preserved in females undergoing HSCT with reduced-intensity conditioning (RIC) than with conventional myeloablative conditioning (MAC). However, the impact of HSCT after 8-Gy TBI-based reduced-toxicity MAC (RTMAC), whose efficacy is between those of conventional MAC and RIC, on ovarian function remains unclear. PROCEDURE: A single-center retrospective analysis of data derived from patient information for all the children who underwent transplantation at the Shinshu University Hospital was carried out. Patients who underwent 8-Gy total body irradiation (TBI)-based RTMAC before HSCT were analyzed. RESULTS: A total of 36% (five of 14) of the patients developed primary ovarian insufficiency (POI) during the observation period, but serum follicle-stimulating hormone levels reduced to normal range with spontaneous menstruation in two, implying the reversal of POI. Furthermore, only one (10%) of the 10 prepubertal patients (71%; 10/14) at the time of HSCT suffered from POI at the last observation, but all three post-pubertal patients developed POI (100%), and two (67%) continued to suffer from POI at the last observation. CONCLUSIONS: Taken together, 8-Gy TBI-based RTMAC before HSCT may decrease the possibility of POI compared with conventional MAC, especially in prepubertal patients. A longer follow-up will be required to ascertain whether a normal pregnancy and delivery can occur in such patients.

Significance of Molecular Monitoring of T Cells for the Decision of Treatment Strategy for Epstein-Barr Virus-associated Hemophagocytic Lymphohistiocytosis.

A 17-year-old patient with Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis achieved first remission after immunochemotherapy (ICT). However, he had fever with an increase in soluble interleukin-2 receptor, but not in ferritin. Molecular analysis revealed augmented plasma and T-cell EBV loads and reappearance of clonal T cells. Despite achieving second remission, the T-cell EBV load at week 8 after second ICT was almost similar to that at week 8 after first ICT. Hence, cyclosporine was decreased over a 9-month period, with molecular monitoring of plasma and T cells. In this article, we describe how useful molecular monitoring was for detecting relapse and resuming ICT.

Transfusion-associated hypoxemia in pediatric patients with solid tumors after autologous peripheral blood stem cell transplantation.

BACKGROUND: Although several types of transfusion-related adverse reactions (TRARs) have been reported, one of the most important involves respiratory features during and after blood transfusion. Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are the most severe adverse events following blood transfusion, whereas transfusion-associated dyspnea　(TAD) is a less severe respiratory distress. However, there exists little evidence of these factors in pediatric populations. CASE REPORT: Here, two cases of atypical TRARs with respiratory features, in pediatric patients with solid tumors, appearing after transfusion of platelet concentrate following autologous peripheral blood stem cell transplantation are reported. Both patients developed mild hypoxemia during PC transfusion, which continued for approximately 2 weeks. Chest radiography in either patient did not reveal any abnormalities that are included in the criteria of either TRALI or TACO. Both patients recovered following oxygen administration. CONCLUSION: This complication of TRARs with respiratory features may occur more frequently in pediatric populations than realized because it may be under-recognized or under-reported. Accumulation of additional cases, including non-typical cases, is necessary to fully understand the pathology of TRARs, correctly classify these reactions, and improve care of patients receiving blood transfusions.

Transfusion-associated circulatory overload in a pediatric patient with neuroblastoma.

There have been few reports on pediatric transfusion-associated circulatory overload (TACO). A 5-year-old boy with neuroblastoma underwent resection of the residual tumor. Because anemia progressed at the end of the operation, transfusion of red cell component was initiated. Ten minutes later, he suddenly developed hypoxemia, tachypnea, and tachycardia. Although elevated blood pressure and bilateral infiltrative shadows on chest X-rays were not observed, TACO was diagnosed based on positive balance during operation and N-terminal pro-brain natriuretic peptide elevation. He had no cardiac or renal disorder; however, mild cardiac and/or renal damage due to a long history of chemotherapy and bias toward his primary hematological and malignant disease may have affected the development of TACO.

Preoperative Treatment With Pazopanib in a Case of Chemotherapy-Resistant Infantile Fibrosarcoma.

Clinical and radiological diagnosis of infantile fibrosarcoma (IFS) is challenging because of its similarity to vascular origin tumors. Treatment involves complete resection. Although chemotherapy may allow more conservative resection, treatment guidelines are not strictly defined. One IFS patient with an unresectable tumor had disease progression during chemotherapy. A primary tumor sample showed high VEGFR-1/2/3 and PDGFR-α/ß expression. After pazopanib therapy, most tumor showed necrosis within 29 days and could be removed completely, with no relapse in 8 months post-resection. When IFS features hypervascularity, VEGFR and PDGFR expression may be high, thus allowing consideration of VEGFR inhibitors such as pazopanib.

Temozolomide Treatment for Pediatric Refractory Anaplastic Ependymoma with Low MGMT Protein Expression.

The benefit of postoperative chemotherapy for anaplastic ependymoma remains unknown. We report two pediatric patients with refractory anaplastic ependymoma treated with temozolomide (TMZ). We did not detect O(6) -methylguanine-DNA methyltransferase (MGMT) promoter methylation in tumor samples; however, MGMT protein expression was low. With TMZ treatment, one patient had a 7-month complete remission; the other, stable disease for 15 months. Three other patients did not respond to TMZ; two had high and one low MGMT expression, and two showed no MGMT promoter methylation. These findings suggest that TMZ may be effective for pediatric refractory anaplastic ependymoma with low MGMT protein expression.

Extraosseous Ewing sarcoma in the mesentery: the first report of cases in children.

Extraosseous ewing sarcoma (EES) is a rare soft-tissue tumor usually found in the extremities or paraspinal region. We describe the case of a 4-year-old boy with a large cystic mass in the mesentery diagnosed as mesenteric lymphangioma preoperatively and as EES after partial resection and histopathological examination. EES in the mesentery is extremely rare, with only 2 reports described in the English literature. This represents the first report of EES in a child.

Screening and interventional strategies for the late effects and toxicities of hematological malignancy treatments in pediatric survivors.

INTRODUCTION: Advancements in pediatric cancer treatment have increased patient survival rates; however, childhood cancer survivors may face long-term health challenges due to treatment-related effects on organs. Regular post-treatment surveillance and early intervention are crucial for improving the survivors' quality of life and long-term health outcomes. The present paper highlights the significance of late effects in childhood cancer survivors, particularly those with hematologic malignancies, stressing the importance of a vigilant follow-up approach to ensure better overall well-being. AREAS COVERED: This article provides an overview of the treatment history of childhood leukemia and lymphoma as well as outlines the emerging late effects of treatments. We discuss the various types of these complications and their corresponding risk factors. EXPERT OPINION: Standardizing survivorship care in pediatric cancer aims to improve patient well-being by optimizing their health outcomes and quality of life. This involves early identification and intervention of late effects, requiring collaboration among specialists, nurses, and advocates, and emphasizing data sharing and international cooperation.

Ifosfamide-Induced Encephalopathy Successfully Prevented by Methylene Blue: A Pediatric Case Report and Review of the Literature.

Ifosfamide, which is widely used as a chemotherapeutic agent in various kinds of malignancies, sometimes causes neurotoxicity known as ifosfamide-induced encephalopathy (IIE). Herein, we report the case of a three-year-old girl who developed IIE during chemotherapy for Ewing's sarcoma and was treated with methylene blue as a prophylactic agent for IIE, after which she continued with ifosfamide and completed treatment without IIE recurrence. This case suggests that methylene blue may be effective in preventing the recurrence of IIE in pediatric patients. Further studies, including clinical trials, are needed to confirm the efficacy and safety of methylene blue in pediatric patients.