Cytosine arabinoside/cyclophosphamide pulses during continuation therapy for childhood acute lymphoblastic leukemia. Potential selective effect in T-cell leukemia

One hundred seventy-seven children with acute lymphoblastic leukemia (ALL) were admitted to a study designed to determine whether pulses of cytosine arabinoside (ara-C) and cyclophosphamide (cyclo) would improve disease-free survival (DFS). All patients received vincristine, prednisone, and asparaginase for remission induction, CNS prophylaxis with cranial irradiation and intrathecal methotrexate, and continuation therapy with 6-mercaptopurine plus methotrexate. Forty-seven of 101 patients with non-T ALL and 18 of 26 patients with T-cell ALL received ara-C/cyclo pulses every eight weeks during continuation therapy. The age, sex, and initial white cell count distributions were similar in both treatment groups. Patients with non-T-cell ALL had similar DFS with or without ara-C/cyclo pulses (36% versus 48%; P = 0.32). Ara-C/cyclo pulses significantly improved DFS in children with T-cell ALL (36% versus 0%; P = 0.015). Toxicities of the ara-C/cyclo pulses included reversible pancytopenia, drug induced fever, fever associated with neutropenia, and death in one patient from systemic candidiasis while neutropenic. This is the first clinical evidence to indicate that the combination of ara-C/cyclo used during continuation therapy is selectively beneficial in T-cell ALL.     

Economic evaluation of an acute paediatric hospital at home clinical trial.

AIMS: To compare the privately borne and NHS costs of hospital at home (HAH) and conventional inpatient care for children with selected acute conditions. METHODS: Prospective economic evaluation using cost minimisation analysis within a randomised controlled trial, in paediatric wards of a district general hospital, and private homes in the local catchment area in Wirral, Merseyside. Subjects were children who fulfilled the criteria for admission to HAH, suffering from breathing difficulties (n = 202), diarrhoea and vomiting (n = 125), or fever (n = 72). RESULTS: Direct costs borne by families are reduced by 41% for HAH patients ( pound 23.31 v pound 13.76, p = 0.001). There is no evidence that HAH transfers the burden of care to parents, and there is no difference in absence rates from paid employment. Patients and their careers expressed a strong preference for HAH. Comparison of NHS costs is equivocal, depending on how HAH is implemented alongside the conventional hospital service. CONCLUSION: Paediatric HAH schemes are unlikely to reduce NHS costs and do not increase privately borne costs. They will, however, significantly increase patient and career satisfaction with care provision for sick children with appropriate conditions.     

Randomised controlled trial comparing an acute paediatric hospital at home scheme with conventional hospital care.

AIMS: To assess the clinical effectiveness of a paediatric hospital at home service compared to conventional hospital care. METHODS: A total of 399 children suffering from breathing difficulty (n = 202), diarrhoea and vomiting (n = 125), or fever (n = 72) were randomised to Hospital at Home or in-patient paediatric care. Main outcome measures were: comparative clinical effectiveness as measured by readmission rate within three months (used as a proxy for parental coping with illness); and length of stay/care and comparative satisfaction of both patients and carers. RESULTS: Clinical effectiveness of both services was not significantly different. Length of care was one day longer in the Hospital at Home group; however, most parents and children preferred home care. CONCLUSIONS: Hospital at Home is a clinically acceptable form of care for these groups of acute paediatric illness. Readmission rates within three months failed to show any advantage in terms of parental coping. Parents and patients expressed a strong preference for hospital at home.     

Therapeutic Plasma Exchange does not Improve Renal Function in Hematopoietic Stem Cell Transplantation–Associated Thrombotic Microangiopathy: An Institutional Experience

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a complication of hematopoietic stem cell transplant (HSCT) that causes severe multiorgan injury. The kidneys are almost universally affected. There is no proven therapy, but therapeutic plasma exchange (TPE) is commonly used to treat TA-TMA at Texas Children's Hospital (TCH). To date, there have been no studies assessing the long-term efficacy of TPE in preventing the development of chronic kidney disease (CKD) in TA-TMA patients. In this study we retrospectively analyzed the incidence of CKD in TA-TMA pediatric patients treated with TPE to determine if this treatment modality improves renal morbidity. We reviewed records between January 2007 and June 2017 of pediatric HSCT patients diagnosed with TA-TMA, identified through an internal database maintained at TCH. To be included patients must have completed a course of TPE per the “TPE in TA-TMA” institutional protocol at TCH. CKD was defined as kidney damage for at least 3 months and stratified into stages 1 through 5 according to estimated glomerular filtration rate. Stages 4 and 5 were considered “severe CKD.” In the 10-year timeframe 15 patients with TA-TMA completed a course of TPE per our institutional protocol and were subsequently followed for a median of 963 days. Fourteen patients developed CKD, and 5 of these 14 patients developed severe CKD. The cumulative incidence of severe CKD development was 33% (95% confidence interval. 11% to 57%). 6 patients required dialysis, and 2 patients received a renal transplant. 5 patients received eculizumab in addition to TPE. In our patients a TPE course of at least 7 weeks (and up to 25 weeks) was not effective in the prevention of CKD. Our data indicate a need for alternative therapeutic measures to prevent the development of CKD in TA-TMA patients.     

Evidence for a multipotential stem cell disease in some childhood Philadelphia chromosome-positive acute lymphoblastic leukemia

Children with Philadelphia chromosome (Ph+) acute lymphoblastic leukemia (ALL) have a poorer prognosis than do most pediatric patients with ALL. Because of this poor prognosis and the presence of the Ph chromosome, we have asked whether or not Ph + ALL involves a multipotential stem cell. We cultured hematopoietic progenitors from two children with Ph+ ALL and examined individual BFU-E and CFU-GM colonies for the Ph chromosome. We studied cells from two patients after 18 to 34 months of first complete clinical remission; direct cytogenetic analyses showed 26% and 13% Ph+ metaphases in these patients' marrow cells. BFU-E colonies were obtained from light density marrow cells cultured in methylcellulose supplemented with erythropoietin and CFU-GM colonies from agar or methylcellulose cultures stimulated with leukocyte feeder layers. Fifty-seven G-banded metaphases were recovered from 33 colonies. Ten metaphases from seven colonies were Ph+. Ph+ metaphases were found in three of 12 and three of five BFU-E colonies from the two patients. One of 16 CFU-GM colonies from one patient had the Ph+ chromosome; analyzable metaphases were not obtained from CFU-GM of the other patient. No colonies contained both Ph+ and Ph- cells. These results indicate that Ph+ ALL with persistence of Ph+ cells in remission involves a multipotential stem cell for erythroid and granulocyte/macrophage as well as lymphoid lineages. Multipotential stem cell involvement in the pathogenesis of some childhood Ph+ ALL suggests similarities to Ph+ chronic myelocytic leukemia and may contribute to the poor prognosis of these patients.     

Transition to Nursing Practice: A Capstone Simulation for the Application of Leadership Skills in Nursing Practice

A large-scale capstone simulation was implemented to fully immerse nursing students into the authentic role of the professional nurse by giving them the autonomy to independently manage the care of multiple complex patients with competing priorities in a realistic hospital environment. This innovative learning experience gave students an opportunity to transfer theory into practice. Overwhelmingly positive feedback from students supports the implementation of a capstone simulation to promote a smoother transition into the nursing workforce.     

Erythrocyte enzymes in experimental lead poisoning

Intravenous administration of 6 mg per kg lead acetate to rabbits resulted in plumbism with elevated erythrocyte lead levels and marked depression of activity of erythrocyte -aminolevulmic acid dehydratase. By comparison other erythrocyte enzymes were insensitive to the effects of lead. Activities of anaerobic glycolysis and of the hexose monophosphate shunt were unaffected by lead administration as were erythrocyte methemoglobin reductase, acid phosphatase, glucose-6-phosphate dehydrogenase, malic dehydrogenase and acetylcholinesterase. The insensitivity of these erythrocyte enzymes to inhibition by lead excludes their usefulness for detection or diagnosis of plumbism.