Optimized peripheral blood progenitor cell mobilization for autologous hematopoietic cell transplantation in children with high-risk and refractory malignancies.

BACKGROUND: Autologous hematopoietic stem cell transplantation (aHSCT) using hematopoietic progenitor cells (HPCs) has become an important therapeutic modality for patients with high-risk malignancies. Current literature on standardized method for HPC apheresis in children is sparse and failure rate reported as high as 30%. PATIENTS/METHODS: A retrospective study of 125 pediatric patients with high-risk malignancies undergoing aHSCT in Western Australia between 1997 and 2016 was conducted. RESULTS: Mobilization was achieved by means of chemotherapy and granulocyte colony-stimulating factor (G-CSF). Patients underwent apheresis the day after CD34+ counts reached ≥20/µL and an additional dose of G-CSF. Peripheral arterial and intravenous lines were inserted in pediatric intensive care unit under local anesthetic and/or sedation, omitting the need for general anesthesia as well as facilitating an uninterrupted apheresis flow. Larger apheresis total blood volumes were processed in patients weighing ≤20 kg. The minimal dose of ≥2 × 106 CD34+ cells/kg was successfully collected in 98.4% of all patients. The optimal dose of 3-5 × 106 CD34+ cells/kg was collected in 96% of patients scheduled for a single aHSCT, 87.5% for tandem, and 100% for triple aHSCT. All HPC collections were completed in one apheresis session. Mobilization after ≤3 chemotherapy cycles and cycles including cyclophosphamide resulted in a significantly higher yield of CD34+ cells. CONCLUSION: Our approach to HPC mobilization by means of chemotherapy and single myeloid growth factor combined with optimal collection timing facilitated by continuous apheresis flow resulted in highly effective HPC harvest in children and adolescents with high-risk cancers.

National study of infants hospitalized with pertussis in the acellular vaccine era.

BACKGROUND: In Australia in 1999 acellular pertussis vaccine (DTPa) replaced locally manufactured whole cell vaccine given at 2, 4 and 6 months of age with coverage of about 95% by 12 months of age. Few data are available on pertussis hospitalizations or sources of infection in countries exclusively using DTPa. METHODS: In 2001 national active monthly surveillance of infant hospitalizations for pertussis was conducted through the Australian Pediatric Surveillance Unit, which surveys all child health specialists monthly. A standard questionnaire was completed for notified cases. RESULTS: There were 140 infants reported (median age at diagnosis, 8 weeks). The rate of hospitalization in indigenous infants was significantly higher than in nonindigenous infants (P < 0.01). Of 97 (69%) infants who had not been vaccinated for pertussis, 63 (65%) were <8 weeks old (before the first scheduled dose of DTPa vaccine). Of 76 infants age > or =8 weeks, only 28 (37%) were appropriately immunized for age. Of 68 coughing contacts whose ages were known, 46 (68%) were adults, usually one of the infant's parents. Of 32 child contacts 16 (50%) were siblings. Four infants <6 weeks old died. CONCLUSION: Despite universal vaccination with DTPa in Australia, pertussis remains an important cause of hospitalization, morbidity and death in infants, most of whom were too young to be vaccinated or had missed vaccinations. The most common source of infection was a parent. Strategies to improve pertussis control in countries with high DTPa coverage could include adult-formulated booster pertussis vaccines for adolescents and recent parents and/or accelerated pertussis vaccine schedules for infants.

[Analgesia and sedation in emergency situations and in the pediatric intensive care unit]. / Analgesia e sedação em situações de emergência e unidades de tratamento intensivo pediátrico.

OBJECTIVE: To review the current strategies for use of sedatives and analgesics in emergency rooms and intensive care units. SOURCE OF DATA: Original data from our emergency rooms and intensive care units; Medline literature review focused on sedatives and analgesic drugs; textbooks. SUMMARY OF THE FINDINGS: Despite the advances in understanding pain in children, in many critical care units the misguided treatment of pain and anxiety still results in significant morbidity. Difficulties in communication, invasive procedures and the belief that children do not have sufficient neurologic development to process noxious sensations are still a challenge in intensive care units. CONCLUSIONS: The last decade was marked by significant advances in understanding pediatric pain. Treating intensive care unit-related pain and anxiety has clear benefits which may influence the course of disease.

Use of recombinant tissue plasminogen activator in children with meningococcal purpura fulminans: a retrospective study.

OBJECTIVE: Meningococcal disease causes septic shock with associated disseminated intravascular coagulation and hemorrhagic skin necrosis. In severe cases, widespread vascular thrombosis leads to gangrene of limbs and digits and contributes to morbidity and mortality. Uncontrolled case reports have suggested that thrombolytic therapy may prevent some complications, and the use of tissue plasminogen activator (t-PA) has been widespread. Our aim was to summarize the clinical outcome and adverse effects where systemic t-PA has been used to treat children with fulminant meningococcemia. DESIGN: International, multiple-center, retrospective, observational case note study between January 1992 and June 2000. SETTING: Twenty-four different hospitals in seven European countries and Australia. PATIENTS: A total of 62 consecutive infants and children with severe meningococcal sepsis in whom t-PA was used for the treatment of predicted amputations and/or refractory shock (40 to treat severe ischemia, 12 to treat shock, and ten to treat both). INTERVENTIONS: t-PA was administered with a median dose of 0.3 mg.kg(-1).hr(-1) (range, 0.008-1.13) and a median duration of 9 hrs (range, 1.2-83). MAIN RESULTS: Twenty-nine of 62 patients died (47%; 95% confidence interval, 28-65). Seventeen of 33 survivors had amputations (11 below knee/elbow or greater loss; six less severe). In 12 of 50 patients to whom t-PA was given for imminent amputation, no amputations were observed. Five developed intracerebral hemorrhages (five of 62, 8%; 95% confidence interval, 0.5-16). Of these five, three died, one developed a persistent hemiparesis, and one recovered completely. CONCLUSIONS: The high incidence of intracerebral hemorrhage in our study raises concerns about the safety of t-PA in children with fulminant meningococcemia. However, due to the absence of a control group in such a severe subset of patients, whether t-PA is beneficial or harmful cannot be answered from the unrestricted use of the drug that is described in this report. Our experience highlights the need to avoid strategies that use experimental drugs in an uncontrolled fashion and to participate in multiple-center trials, which are inevitably required to study rare diseases.

Analgesia e sedação em situações de emergência e unidades de tratamento intensivo pediátrico / Analgesia and sedation in emergency situations and in the pediatric intensive care unit

OBJETIVO: Revisar as atuais estratégias de uso de analgésicos e sedativos em salas de emergência e em unidades de tratamento intensivo pediátrico. FONTES DOS DADOS: Revisão de bibliografia realizada na base de dados da Medline, além de capítulos de livros de terapia intensiva pediátrica e da experiência dos serviços dos autores. SíNTESE DOS DADOS: Apesar de todos os avanços e pesquisas no campo da dor, o uso de sedativos e analgésicos em unidades intensivas pediátricas continua deficitário. A dor e o desconforto associados a situações de urgência, procedimentos invasivos e internações prolongadas ainda resultam em significativa morbidade aos pacientes pediátricos criticamente enfermos. A dificuldade de comunicação do paciente pediátrico com a equipe médica, a grande quantidade de procedimentos invasivos necessários à manutenção da vida, aliados à antiga premissa de que os mecanismos de dor não estão bem desenvolvidos nas crianças, fazem desse tema um desafio nas unidades de terapia intensiva pediátrica. Neste estudo, revisamos as drogas mais utilizadas no manejo da dor e sedação, apresentando novas opções terapêuticas mais largamente estudadas recentemente. CONCLUSÕES: Nos últimos dez anos, desenvolveu-se uma consciência mais crítica em relação à necessidade de promover um adequado alívio da dor e da ansiedade inerentes aos ambientes de emergência e de UTI, devendo ser esta uma prioridade no planejamento terapêutico de crianças extremamente doentes.