RESUMEN
We established a transition program from hospital to home administration of blinatumomab using the CADD-Legacy® pump and evaluated its safety and feasibility in 2 pediatric patients. The program recommended that repeated overnight stays with continued hospitalization would help patients safely transition to home administration of blinatumomab. Pediatric patients who do not attend school, such as preschoolers, or who return to their original school, can be transited to an outpatient setting if people caring for pediatric patients, including teachers in the school, are educated.
Asunto(s)
Anticuerpos Biespecíficos , Niño , Preescolar , Femenino , Humanos , Masculino , Anticuerpos Biespecíficos/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Servicios de Atención de Salud a DomicilioRESUMEN
BACKGROUND: Preventing infection and managing febrile neutropenia (FN) is mandatory for children with cancer undergoing chemotherapy. However, the current situation in Japan is unknown. METHODS: We conducted a nationwide web-based questionnaire survey in 153 institutions treating childhood cancer in Japan. We asked about the type prophylaxis used to prevent infectious disease and manage FN. If patients with childhood cancer were managed by both pediatricians and surgeons at the same institution, we asked both to reply. RESULTS: We received replies from 117 departments at 111 centers: of these, 108 were from pediatricians. Laminar air flow for neutropenic patients, and frequent hand sanitization with ethanol, were widespread. Twenty-eight percent and forty percent of departments performed active surveillance by taking cultures from patients and the environment, respectively, before initiation of chemotherapy. Forty-four percent of departments administered prophylactic intravenous antibiotics according to patient status. Many departments measured serum (1,3)-ß-D glucan, procalcitonin, and aspergillus galactomannan at the onset of FN. Twenty-eight percent of departments used carbapenem as empirical therapy for FN. Some departments used prophylactic granulocyte-colony stimulating factor for acute leukemia. Seventy-two percent of departments used prophylactic immunoglobulin for hypogammaglobinemia caused by chemotherapy. Palivizumab was administered widely for respiratory syncytial virus prophylaxis in immunocompromised infants. CONCLUSION: As a whole, intensive care for infectious prophylaxis or FN is applied in Japan; however, the methods vary among centers, and some are excessive or inadequate. Therefore, it is desirable to conduct clinical trials and establish adequate care protocols for infection in children with cancer in Japan.
Asunto(s)
Antineoplásicos , Neutropenia Febril , Control de Infecciones , Infecciones , Neoplasias , Niño , Humanos , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Enfermedades Transmisibles/complicaciones , Neutropenia Febril/inducido químicamente , Neutropenia Febril/etiología , Neutropenia Febril/prevención & control , Fiebre/inducido químicamente , Fiebre/etiología , Fiebre/prevención & control , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Control de Infecciones/métodos , Infecciones/etiología , Internet , Japón , Leucemia Mieloide Aguda/tratamiento farmacológico , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Encuestas y CuestionariosRESUMEN
The MLL-10 trial (UMIN000004801) modified a Children's Oncology Group (COG) AALL0631 therapy for infants with KMT2A-rearranged acute lymphoblastic leukemia (ALL). In 2016, one registered case developed secondary immunodeficiency during maintenance therapy and eventually died due to cytomegalovirus infection. Around the same time, fatal secondary immunodeficiencies were reported in five infants with ALL in North America who had received COG-based chemotherapy between 1996 and 2015. Given these cases, we decided to conduct a retrospective study on the postchemotherapy immune status of infants with ALL. A questionnaire collected data on posttreatment immune function, frequency of infections, and supportive care for the 34 infants in the MLL-10 trial. Patients receiving allogeneic hematopoietic stem cell transplantation in first remission were excluded. Responses to the survey were obtained in 28 cases (85%). Most patients were immunocompetent after the completion of chemotherapy (median follow-up duration from the day of chemotherapy completion was 431 days), except for the aforementioned case. There were seven patients with nonsevere viral infection, all of whom recovered. In conclusion, severe chemotherapy-induced immunodeficiency in infants with ALL appears to be rare, but prospective data collection of immune function is necessary to clarify this finding.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Lactante , Proteína de la Leucemia Mieloide-Linfoide/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
BACKGROUND: We encountered 7 Japanese patients with bile acid synthesis disorders (BASD) including 3ß-hydroxy-Δ5-C27-steroid dehydrogenase/isomerase (3ß-HSD) deficiency (n = 3), Δ4-3-oxosteroid 5ß-reductase (5ß-reductase) deficiency (n = 3), and oxysterol 7α-hydroxylase deficiency (n = 1) over 21 years between 1996 and 2017. AIM: We aimed to clarify long-term outcome in the 7 patients with BASD as well as long-term efficacy of chenodeoxycholic acid (CDCA) treatment in the 5 patients with 3ß-HSD deficiency or 5ß-reductase deficiency. METHODS: Diagnoses were made from bile acid and genetic analyses. Bile acid analysis in serum and urine was performed using gas chromatography-mass spectrometry. Clinical and laboratory findings and bile acid profiles at diagnosis and most recent visit were retrospectively obtained from medical records. Long-term outcome included follow-up duration, treatments, growth, education/employment, complications of treatment, and other problems. RESULTS: Medians with ranges of current patient ages and duration of CDCA treatment are 10 years (8 to 43) and 10 years (8 to 21), respectively. All 7 patients, who had homozygous or compound heterozygous mutations in the HSD3B7, SRD5B1, or CYP7B1 gene, are currently in good health without liver dysfunction. In the 5 patients with CDCA treatment, hepatic function gradually improved following initiation. No adverse effects were noted. CONCLUSIONS: We concluded that CDCA treatment is effective in 3ß-HSD deficiency and 5ß-reductase deficiency, as cholic acid has been in other countries. BASD carry a good prognosis following early diagnosis and initiation of long-term CDCA treatment.
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Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Hiperplasia Suprarrenal Congénita/genética , Ácidos y Sales Biliares/biosíntesis , Ácido Quenodesoxicólico/uso terapéutico , Familia 7 del Citocromo P450/metabolismo , Oxidorreductasas/genética , Esteroide Hidroxilasas/metabolismo , Adolescente , Adulto , Niño , Familia 7 del Citocromo P450/genética , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Predisposición Genética a la Enfermedad , Humanos , Japón , Mutación , Esteroide Hidroxilasas/genética , Adulto JovenAsunto(s)
Trasplante de Células Madre Hematopoyéticas , Enfermedades Autoinflamatorias Hereditarias/terapia , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/genética , Adolescente , Productos Biológicos/uso terapéutico , Niño , Haploinsuficiencia , Enfermedades Autoinflamatorias Hereditarias/genética , Humanos , Inmunosupresores/uso terapéutico , MasculinoRESUMEN
Autoimmune lymphoproliferative syndrome (ALPS) is classically defined as a disease with defective FAS-mediated apoptosis (type I-III). Germline NRAS mutation was recently identified in type IV ALPS. We report 2 cases with ALPS-like disease with somatic KRAS mutation. Both cases were characterized by prominent autoimmune cytopenia and lymphoadenopathy/splenomegaly. These patients did not satisfy the diagnostic criteria for ALPS or juvenile myelomonocytic leukemia and are probably defined as a new disease entity of RAS-associated ALPS-like disease (RALD).
Asunto(s)
Enfermedades Autoinmunes/genética , Síndrome Linfoproliferativo Autoinmune/genética , Mutación , Proteínas Proto-Oncogénicas/genética , Proteínas ras/genética , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Síndrome Linfoproliferativo Autoinmune/inmunología , Síndrome Linfoproliferativo Autoinmune/patología , Femenino , Humanos , Lactante , Masculino , Proteínas Proto-Oncogénicas p21(ras)RESUMEN
Optimal supportive care for disseminated intravascular coagulation (DIC) and hemostatic complications by asparaginase is indispensable for the successful treatment of pediatric leukemia. However, the situation regarding this type of care in Japan is unclear. We conducted a questionnaire-based survey at 155 institutions treating childhood leukemia in Japan. The questionnaire asked about the supportive care provided by each institution to acute leukemia patients with DIC and asparaginase-induced hemostatic alterations. Ninety-eight institutions responded. The most common diagnostic criteria for DIC were those established by the Japanese Ministry of Health and Welfare. Regardless of the etiology underlying DIC, recombinant human thrombomodulin and synthetic protease inhibitors were used as anticoagulation therapy by around 70% and 40% of institutions, respectively. Additionally, 92%, 93%, and 73% of institutions measured plasma antithrombin, fibrinogen, and D-dimer/fibrin degradation products, respectively, more than twice per week during induction therapy for acute lymphoblastic leukemia. Survey responses indicate that 95% and 24% of the institutions used antithrombin replacement and fresh-frozen plasma, respectively. Supportive care for DIC and/or asparaginase-induced hemostatic alterations at Japanese pediatric centers was intensive and differs markedly from protocols in other countries. The efficacy of supportive care should be evaluated prospectively in the setting of pediatric leukemia.