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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.
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Supervivientes de Cáncer , Neoplasias Hematológicas , Calidad de Vida , Humanos , Niño , Neoplasias Hematológicas/terapia , Factores de RiesgoAsunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Linfohistiocitosis Hemofagocítica , Piebaldismo , Enfermedades de Inmunodeficiencia Primaria , Humanos , Trasplante de Médula Ósea/efectos adversos , Ciclofosfamida/uso terapéutico , Enfermedades de Inmunodeficiencia Primaria/complicaciones , Linfohistiocitosis Hemofagocítica/complicaciones , Acondicionamiento Pretrasplante/efectos adversos , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
Neuroblastoma, a prevalent extracranial solid tumor commonly afflicting pediatric patients, exhibits a diverse spectrum of clinical presentations. Preseptal cellulitis, a childhood infectious ailment, typically demonstrates a favorable response to conservative antibiotic therapy. In this report, we present the case of a two-year-old female child with refractory preseptal cellulitis, ultimately leading to an unforeseen diagnosis of neuroblastoma. Early radiological assessment upon the onset of preseptal cellulitis serves the dual purpose of excluding severe complications and uncovering latent, rare pathologies when the initial antibiotic regimen proves ineffective.
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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.
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Background: Pulmonary veno-occlusive disease (PVOD) is a rare but fatal complication of hematopoietic stem cell transplantation (HSCT). Although literature on PVOD post-HSCT is scarce, a recent study has indicated that this condition may be underestimated. Respiratory syncytial virus (RSV) is a common respiratory pathogen that causes common cold in healthy individuals but may lead to severe lower respiratory infection accompanied by respiratory distress in infants and immunocompromised individuals, such as post-HSCT patients. However, little is known about the relationship between PVOD and RSV infections. Case report: A 4-year-old boy was diagnosed with metastatic neuroblastoma and underwent intensive chemotherapy, autologous HSCT, and allogeneic cord blood transplantation (CBT). He experienced PVOD on day 194 following CBT after displaying upper respiratory symptoms and positive RSV antigen test results approximately one month prior. Pathological examination of a lung biopsy specimen revealed lung injury suspected to be associated with viral infection in addition to PVOD-related findings, suggesting that RSV infection might have contributed to the onset of PVOD. Conclusions: The patient's clinical history and histological findings indicated that RSV could have triggered the development of PVOD under potential endothelial damage caused by HSCT and other prior treatments. Common respiratory viral infections, such as RSV infection, may evoke the development of PVOD.
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BACKGROUND: Leiomyosarcoma is classified as a soft tissue sarcoma. In adults, leiomyosarcoma is the most common malignancy affecting the vascular system; however, vascular leiomyosarcoma in children is extremely rare as most pediatric soft tissue tumors are rhabdomyosarcomas. The survival rate is very low, and incomplete resection is a poor prognostic factor. There is also a high rate of distant recurrence, with the lungs and liver being the most common sites of metastasis. There is no established effective chemotherapy, and complete surgical resection is the only potentially curative treatment for leiomyosarcoma. CASE PRESENTATION: A 15-year-old female patient with no significant medical history presented with severe upper abdominal pain and was admitted. Abdominal contrast-enhanced computed tomography and magnetic resonance imaging showed a large retroperitoneal tumor protruding into the lumen of the inferior vena cava behind the liver and multiple small nodules, and metastasis to the liver was suspected. The tumor was 6 × 4 × 5 cm in diameter, located just behind the hepatic hilar structures, and was suspected to infiltrate into the right portal vein. The tumor was diagnosed as a leiomyosarcoma through an open tumor biopsy. As the multiple liver metastases were located only in the right lobe of the liver on imaging, we performed tumor resection with right hepatectomy and replacement of the inferior vena cava (IVC). The postoperative course was uneventful; however, on postoperative day 51, distant metastatic recurrences were found in the remaining liver and right lung. The patient was immediately started on chemotherapy and trabectedin proved to be the most effective drug in the treatment regimen; however, severe side effects, such as hepatotoxicity, prevented timely administration, and the patient passed away 19 months after surgery. CONCLUSIONS: IVC resection and reconstruction combined with right hepatectomy were able to be safely performed even in a pediatric case. To improve the prognosis of leiomyosarcoma with multiple metastases, an effective treatment strategy combining surgical treatment and chemotherapy, including molecularly targeted drugs, should be established as early as possible.
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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.
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Hipersensibilidad Inmediata , Hipersensibilidad , Reacción a la Transfusión , Humanos , Niño , Prueba de Desgranulación de los Basófilos , Dasatinib , Hipersensibilidad/complicaciones , Reacción a la Transfusión/etiología , Hipersensibilidad Inmediata/complicaciones , Basófilos , Inmunoglobulina ERESUMEN
Histiocytic sarcoma (HS) is a rare disease with a poor prognosis. The efficacy of immune checkpoint inhibitors for this disease has not been established. A 13-year-old boy with HS refractory to conventional chemotherapy was treated with pembrolizumab, an immune checkpoint inhibitor. After treatment, the primary lesion and the bone metastases showed improvement; however, new metastatic lesions also occurred. This case suggests that the effect of immune checkpoint inhibitors might depend not only on programmed death ligand-1 expression and the ratio of tumor mutational burden, but also on other factors, such as the tumor microenvironment. Evaluation of more cases is required to identify biomarkers that define the efficacy of immune checkpoint inhibitors.
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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.
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Hipersensibilidad , Reacción a la Transfusión , Animales , Basófilos , Niño , Susceptibilidad a Enfermedades/complicaciones , Perros , Humanos , Hipersensibilidad/etiología , Inmunoglobulina E/análisis , Factores de Riesgo , Reacción a la Transfusión/complicacionesRESUMEN
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.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Anticuerpos Biespecíficos/administración & dosificación , Niño , Terapia Combinada , Humanos , Inotuzumab Ozogamicina/administración & dosificación , Masculino , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , PronósticoRESUMEN
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.
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Inhibidores de Factor de Coagulación Sanguínea/sangre , Factor VIIa/uso terapéutico , Factor X/uso terapéutico , Hemofilia B/tratamiento farmacológico , Hipersensibilidad/diagnóstico , Factor IX/efectos adversos , Factor IX/genética , Factor IX/uso terapéutico , Hemorragia , Humanos , Hipersensibilidad/etiología , Lactante , Masculino , Polimorfismo de Nucleótido Simple , Tomografía Computarizada por Rayos XRESUMEN
Post-transplant early immune disorders and engraftment failure/delay are major issues in unrelated umbilical cord blood transplantation (UCBT). We evaluated graft-versus-host disease (GVHD) prophylaxis approaches after UCBT by comparing UCBT outcomes with GVHD prophylaxis using tacrolimus plus methylprednisolone (Tac/mPSL, n = 32) to that with Tac plus methotrexate (Tac/MTX, n = 31) at a single pediatric transplantation center. The 30-day cumulative incidence rates of neutrophil engraftment and median neutrophil engraftment times in the Tac/mPSL and Tac/MTX groups were 70.1% and 90.3% and 19 and 17 days, respectively (p = 0.09). Pre-engraftment immune reactions (PIR) and acute GVHD were improved with Tac/MTX; PIR incidence (p = 0.020) and cumulative incidence of 100-day acute GVHD (grade II-IV, 38.7% vs 68.8%, p = 0.045; grade III-IV, 9.7% vs 34.4%, p = 0.021) were significantly lower in the Tac/MTX group than in the Tac/mPSL group. However, the incidence rates of relapse (p = 0.921) and cytomegalovirus reactivation (p = 0.908), and the estimated overall (p = 0.87) and event-free survival (p = 0.88) were comparable between the two groups. These data indicate that GVHD prophylaxis with Tac/MTX is associated with favorable results, including reduced PIR and acute GVHD incidence after UCBT, without adverse effects.
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Sangre Fetal/trasplante , Enfermedad Injerto contra Huésped/prevención & control , Inmunosupresores/administración & dosificación , Metilprednisolona/administración & dosificación , Tacrolimus/administración & dosificación , HumanosRESUMEN
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.
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Antibacterianos/uso terapéutico , Fiebre/prevención & control , Neutropenia/prevención & control , Piperacilina/uso terapéutico , Profilaxis Antibiótica , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Carboplatino/uso terapéutico , Niño , Preescolar , Farmacorresistencia Microbiana , Femenino , Fluorouracilo/uso terapéutico , Humanos , Lactante , Leucovorina/uso terapéutico , Masculino , Metotrexato/uso terapéutico , Neuroblastoma/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
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.
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Trasplante de Células Madre de Sangre del Cordón Umbilical , Infecciones por Citomegalovirus/prevención & control , Citomegalovirus , Isoanticuerpos/administración & dosificación , Depleción Linfocítica , Adolescente , Adulto , Niño , Preescolar , Infecciones por Citomegalovirus/epidemiología , Femenino , Humanos , Incidencia , Lactante , Masculino , Estudios RetrospectivosRESUMEN
We established mutated and non-mutated induced pluripotent stem cell (iPSC) clones from a patient with PTPN11 (c.226G>A)-mutated juvenile myelomonocytic leukaemia (JMML). Both types of iPSCs fulfilled the quality criteria. Mutated iPSC colonies generated significantly more CD34+ and CD34+ CD45+ cells compared to non-mutated iPSC colonies in a culture coated with irradiated AGM-S3 cells to which four growth factors were added sequentially or simultaneously. The haematopoietic differentiation potential of non-mutated JMML iPSC colonies was similar to or lower than that of iPSC colonies from a healthy individual. The PTPN11 mutation coexisted with the OSBP2 c.389C>T mutation. Zinc-finger nuclease-mediated homologous recombination revealed that correction of PTPN11 mutation in iPSCs with PTPN11 and OSBP2 mutations resulted in reduced CD34+ cell generation to a level similar to that obtained with JMML iPSC colonies with the wild-type of both genes, and interestingly, to that obtained with normal iPSC colonies. Transduction of the PTPN11 mutation into JMML iPSCs with the wild-type of both genes increased CD34+ cell production to a level comparable to that obtained with JMML iPSC colonies harbouring the two genetic mutations. Thus, PTPN11 mutation may be the most essential abnormality to confer an aberrant haematopoietic differentiation potential in this disorder.
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Diferenciación Celular/genética , Células Madre Hematopoyéticas/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Leucemia Mielomonocítica Juvenil , Células Madre Neoplásicas/metabolismo , Mutación Puntual , Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Animales , Células Madre Hematopoyéticas/patología , Humanos , Células Madre Pluripotentes Inducidas/patología , Leucemia Mielomonocítica Juvenil/genética , Leucemia Mielomonocítica Juvenil/metabolismo , Leucemia Mielomonocítica Juvenil/patología , Masculino , Ratones SCID , Células Madre Neoplásicas/patología , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismoAsunto(s)
Neoplasias Encefálicas/terapia , Quimioradioterapia/métodos , Linfoma no Hodgkin/terapia , Terapia de Protones , Planificación de la Radioterapia Asistida por Computador , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de la radiación , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Relación Dosis-Respuesta en la Radiación , Humanos , Linfoma no Hodgkin/diagnóstico por imagen , Linfoma no Hodgkin/patología , Imagen por Resonancia Magnética , Masculino , Neoplasia Residual , Resultado del TratamientoRESUMEN
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.