Attentional ability among survivors of leukaemia.

Attentional ability in 19 survivors of acute lymphoblastic leukaemia and 19 sibling controls was assessed using a neuropsychological model of attention. Analysis revealed that children who had received treatment for leukaemia exhibited significantly poorer performance on measures of the "focus encode" and "focus execute" elements of attention and on measures of the ability to respond to external cues and feedback. No significant differences in performance were found for measures of sustained attention and the ability to shift attention. These results indicate that children who have received treatment for leukaemia may experience highly specific attentional deficits that could have an impact on academic performance, particularly mathematical and reading skills. It is suggested that this underlying attentional deficit might be the source of the neuropsychological sequelae associated with the disease. Future attempts at remediation should incorporate activities specifically designed to ameliorate focusing difficulties.

Cerebral candidiasis in a child 1 year after leukaemia.

We describe an unusual case of a late presentation of a fungal brain abscess in a non-neutropenic child 1 year after completing chemotherapy for M5 acute myeloid leukaemia (AML). Biopsy of the mass identified candidal hyphae and the patient was treated with 5 mg/kg of liposomal amphotericin B for 6 weeks. The lesion resolved completely and the child remains well 2 years later. Invasive fungal infection should be included in the differential diagnosis of unexplained symptoms in patients who have previously received intensive chemotherapy.

Validity of the Rotterdam Symptom Checklist in paediatric oncology.

In order to determine the validity of the Rotterdam Symptom Checklist (RSC) for use with paediatric patients, a sample of 47 mothers with a child with acute lymphoblastic leukaemia (ALL) was asked to complete the RSC, the Play Performance Scale for Children PPSC and a measure of daily activity (HDI: Questionnaires were completed during routine outpatient visits. There were no effects of child age on number of symptoms reported. The physical symptom subscale of the RSC distinguished between children in terms of treatment status and number of hospitalisations. However, the psychological symptom subscale did not distinguish between these groups. Limitations of the scale for work with children are considered. These include difficulties experienced by patents in reporting psychological symptoms for their children, and the inappropriateness of a scale developed for adults to assess children. In the absence of other measures, the RSC can be used for children, but a more developmentally appropriate measures is needed.

Whole body protein metabolism in children with cancer.

Whole body protein synthesis and catabolism were measured using the [ring-2H5]phenylalanine and [1-13C]leucine primed constant infusion technique in 32 paediatric patients with cancer at different stages of treatment. Rates of synthesis (S) and catabolism (C) derived from the [ring-2H5]phenylalanine and [1-13C]leucine models were 4.7 (SD 1.3) (S) and 6.0 (1.5) (C) g/d/kg, and 5.5 (0.8) (S) and 6.8 (1.2) (C) g/d/kg, respectively. These results show that these two tracer techniques give similar results in this study population. Comparison of these values with results previously reported for groups of control children using the [ring-2H5]phenylalanine model (S = 3.69 and 3.93; C = 4.09 and 4.28 g/d/kg) and the [1-13C]leucine model (S = 4.32; C = 4.85 g/d/kg) show that rates of synthesis and catabolism were higher in cancer patients than in controls. Thus whole body protein turnover is increased in children under treatment for cancer. Other indices of metabolism such as plasma amino acids and intermediary metabolites were also measured and showed that, although subjects were in isotopic steady state, there were significant metabolic changes during the course of the primed constant infusions used to measure protein turnover.

Ecthyma gangrenosum occurring at sites of iatrogenic trauma in pediatric oncology patients.

We report two cases of ecthyma gangrenosum which occurred at sites of iatrogenic trauma. The first case developed due to metastatic seeding with Pseudomonas aeruginosa during an episode of septicaemia and the second case occurred as a primary skin lesion. Both required prolonged courses of antibiotics and one patient died. The different pathogenic mechanisms and outcomes associated with this condition are discussed.

Primary ocular relapse in acute lymphoblastic leukemia.

Relapse of acute lymphoblastic leukaemia (ALL) occurred in the anterior segment of four children. All cases had been treated according to the Medical Research Council's UK Acute Lymphoblastic Leukaemia trial protocol (UKALL) including 2 years of continuation chemotherapy. In three cases the diagnosis was confirmed by anterior chamber aspirate while in one case the diagnosis was presumed on clinical grounds alone. All four cases experienced isolated leukaemic relapse in the anterior segment within 2 months of stopping therapy. The months immediately following cessation of continuation chemotherapy as part of the UKALL regime appear to represent a 'high-risk' period for primary anterior segment relapse of ALL. Children with ALL presenting with uveitis should be regarded as having leukaemic relapse and anterior chamber taps with or without an iris biopsy should be considered to confirm this diagnosis. Early diagnosis and treatment of ocular leukaemic relapse is likely to give these children the best chance of ultimate cure.

Development of a measure to assess the perceived illness experience after treatment for cancer.

The development of a scale to measure perceived illness experience in young people with cancer is described. Areas of concern were first identified through semistructured interviews conducted with children and adolescents. As a result, 78 items were generated to cover the main areas identified (physical appearance, interference with activity, peer rejection, integration in school, manipulation, parental behaviour, disclosure, preoccupation with illness, and impact of treatment). These items were rated (on five point scales) by 41 patients (mean age 14.6 years) and 35 of their parents. Measures of physical functioning (symptoms, functional disability, and restrictions) and psychological functioning (symptoms) were included for validation purposes. Test-retest reliability was calculated on the basis of ratings made by a subsample of parents on two separate occasions. A 34 item scale was constructed with four items in each of the areas identified above, except for physical appearance (n = 2). The scale has adequate internal reliability and validity. There were significant correlations between parents and their children on all subscales except for illness disclosure and impact of treatment, suggesting that parents may be less reliable informants for their children in these contexts. The scale has potential use in clinical contexts, in evaluating the psychosocial impact of different treatment regimens, and as an outcome measure in intervention work.

Expression of mu class glutathione S-transferase correlates with event-free survival in childhood acute lymphoblastic leukemia.

Expression of the main classes (pi, mu, and alpha) of glutathione S-transferase (GST) was assessed in the blasts of children presenting with acute lymphoblastic leukemia using an immunohistochemical technique. Bone marrow trephine biopsies obtained at presentation from 71 cases were studied (42 boys, 29 girls; age range, 6 months-14 years; median age, 4 years) and expression was correlated with event-free survival. The period of follow-up was 12-108 months, during which time 21 patients (30%) relapsed. All the samples examined were negative for alpha class GST. Samples from 8 patients, all of whom remained in remission at the time of analysis, were found to be negative for pi class GST at presentation. Samples from 44 (patients were negative for mu class GST (62%); of these, 36 patients (82%) remained in remission. In comparison, of the 27 patients who were positive for mu class GST, only 14 (52%) remained in remission. Analysis of event-free survival demonstrated that expression of mu class GST predicts a 3-fold increased risk of relapse (95% confidence interval, 1.25-7.26). This risk factor appears to be independent of other recognized prognostic factors.

Relapse of acute lymphoblastic leukaemia 14 years after presentation: use of molecular techniques to confirm true re-emergence.

Late relapse after successful treatment of acute lymphoblastic leukaemia (ALL) in children is well-recognized but rare. It is often uncertain whether this represents a true relapse of the original disease or a second malignancy. We present the case of a patient who relapsed 14 years after the original diagnosis of childhood ALL in whom both the original leukaemic cells and those taken at relapse had an identical T cell receptor gamma (TCRG) gene rearrangement. This analysis confirms that this relapse is a true re-emergence of the patient's original disease. The term 'cure' should be used with caution in childhood ALL, even after long periods in continuous remission.

Molecular heterogeneity of variant Philadelphia translocations in childhood acute lymphoblastic leukaemia.

In acute lymphoblastic leukemia (ALL), it is unclear whether variant Philadelphia (Ph) translocations have the same molecular and clinical implications as the classical translocation. Two children with Ph+ ALL with variant translocations are described. One, in whom cytogenetic remission was not achieved, had evidence of translocation of c-abl to chromosome 22, rearrangement of minor breakpoint cluster region (mBCR) and expression of hybrid bcr/abl transcripts. In the other case, no gene rearrangement was found and complete remission was achieved. Variant Ph translocations in childhood ALL are heterogeneous at the molecular level. Molecular studies coupled with observations of clinical outcome are needed in larger numbers of such children to determine whether poor clinical response correlates with bcr/abl involvement and to allow planning of appropriate therapeutic strategies.

Changing causes of septicaemia in paediatric oncology patients: effect of imipenem use.

One hundred and fifty-four episodes of septicaemia occurred in 78 patients on a Paediatric Oncology Unit over 2 years. Septicaemias with Gram-positive bacteria were more common than with Gram-negative organisms, coagulase-negative staphylococci (CNS) being the commonest pathogens. The mortality rate in patients with septicaemia was 1.9%. Azlocillin and gentamicin comprised the first-line of empirical antibiotic therapy for suspected infection for the first 10 months of the study; imipenem with cilastatin, as monotherapy, was used subsequently. More isolates of enterococci, and fewer isolates of Enterobacter, were seen after the introduction of imipenem. The use of imipenem was associated with an increased frequency of resistance to flucloxacillin in CNS. Such strains have been shown to contain sub-populations of cells that are resistant to imipenem. A clinical response was achieved in 82.9% of septicaemic episodes treated with imipenem, compared with 62.7% for azlocillin and gentamicin. However, imipenem as monotherapy may not be appropriate in central venous catheter related infections, owing to the frequent occurrence of imipenem-resistant organisms, CNS and Pseudomonas spp., in this situation.

Serial study of T lymphocytes in childhood leukemia during remission.

Peripheral blood T lymphocyte numbers and function were studied in 22 children on UKALL X maintenance chemotherapy over a 2-year period, and results were compared with 20 healthy children. CD4 and CD8 subsets were enumerated using indirect immunofluorescence, and specific (HSV-1) and polyclonal (Con A, PWM) activation was studied by proliferation and IL-2/IL-4 production in vitro. T lymphocytes were significantly decreased with a greater fall in CD4 than CD8 T lymphocyte numbers. Proliferation responses were slightly but significantly decreased whereas IL-2 and IL-4 production were not significantly different from control values. These findings suggest that decreased numbers of CD4 helper T cells may be the most important factor in clinical immunodeficiency during maintenance chemotherapy for cALL contributing to increased susceptibility to opportunistic infections and argue against the presence of T lymphocytes with defective function.

T cell function in children with acute lymphoblastic leukaemia.

Modern intensive chemotherapy has dramatically improved the prognosis of acute lymphoblastic leukaemia (ALL) in children. However, once remission has been established, quality of life and even survival may be threatened by exacerbation of viral infections in the prolonged period of continuation therapy necessary to prevent relapse. Often the viruses involved in the most severe infections are from the herpesvirus and paramyxovirus groups, suggesting that patients suffer from a defect in the cellular immunity thought essential to control such cell-associated infections. This may result from a T cell defect and, in this study, T cell responsiveness of patients under therapy for leukaemia has been investigated. In vitro proliferative responses of peripheral blood leucocytes (PBL) to the T cell mitogen phytohaemagglutinin (PHA) were impaired in children with ALL before treatment and in the induction of remission. Impairment was attributable to reduced T cell numbers, the presence of inhibitors in the patient's serum and direct damage to lymphocytes. On achieving remission, proliferative responses to PHA of both CD4+ and CD8+ T cell subsets quickly returned to normal levels with the switch to continuation chemotherapy. Proliferative responses to Herpes simplex virus antigens were also apparently normal in the majority of patients tested in remission. Further investigations, however, have suggested a persisting defect in CD8+ lymphocyte function. Gamma interferon secretion by PHA-stimulated PBLs was severely reduced for children with ALL in remission when compared with control children of similar age. Further, cytotoxic T lymphocyte responses to allogeneic cells could only be induced in PBL isolated from two of 13 children in remission from ALL whilst all control children of similar age and adults produced anti-allogeneic responses.

Low dose continuous infusion doxorubicin in children and young adults.

Ten patients (age range 3.2-26.3 yrs) with relapsed or resistant malignancies received a total of 20 courses of low dose continuous infusion doxorubicin (3 mg/m2/day for 28 days) delivered by portable Graseby infusion pumps via central venous catheters. Each patient received a median dose of 144 mg/m2 (range 87-261). Four patients responded to treatment (1 complete response (CR) and 3 partial response (PR)) and performance status improved in seven patients. Overall toxicity was minimal: WHO Grade 4 anaemia in 2/18 courses, Grade 4 neutropenia in 1/18, Grade 3-4 thrombocytopenia in 3/18, nausea and vomiting of Grades 2 and 4 in 4/20 and 1/20 respectively, and mucositis of Grades 2 and 4 in 2/20 courses each. Cardiac toxicity was assessed using echocardiography, and fractional shortening remained within normal limits in all patients. Low dose continuous infusion doxorubicin is a feasible, well tolerated, ambulatory therapy in children and may be an effective way of delivering doxorubicin with less toxicity, thus enabling the development of more dose intensive regimens.

Chronic myelomonocytic leukemia with t(13;14) in a child.

Bone marrow cells from a child with chronic myelomonocytic leukemia showed an acquired, non-Robertsonian translocation between chromosomes 13 and 14, t(13;14)(q12.?2;q32.?3). This rearrangement has not previously been reported in childhood myeloproliferative or myelodysplastic disorders.

Philadelphia positive acute leukaemia with minor breakpoint cluster rearrangement may be a stem cell disease.

The biology of Philadelphia chromosome positive (Ph+) acute lymphoblastic leukaemia (ALL) is the subject of much interest. We present a case of Ph+ ALL with a minor breakpoint cluster (mBCR) rearrangement who subsequently relapsed with Ph+ mBCR+ acute myeloid leukaemia and later with Ph+ mBCR+ acute stem cell leukaemia. This case provides further evidence that Ph+ ALL with a mBCR rearrangement may arise from a pluripotent stem cell with similar potential to that of chronic granulocytic leukaemia to undergo blastic crises with differing lineage characteristics.

Comparison of saphenous versus jugular veins for central venous access in children with malignancy.

A retrospective analysis was carried out to compare the performance and complications of central catheters inserted into either the saphenous (27) or jugular (52) veins. The saphenous route may be preferred in certain circumstances including extensive mediastinal pathology, prior neck surgery, previous catheter(s), and cosmetic reasons. There was no difference in complications (local or systemic catheter-related infections, catheter occlusions, or venous thrombosis). The incidence of catheter removal due to complications was also not different between sites. Hence, the saphenous route can provide an additional portal of vascular access in selected patients.

Memory after treatment for acute lymphoblastic leukaemia.

Long term survivors of acute lymphoblastic leukaemia (ALL) often experience cognitive difficulties, which may be related to impairment of memory function. Memory ability has been studied in a group of survivors of ALL along with sibling controls and in children who have received treatment for other forms of cancer. Children in the ALL group were found to have significant deficits in memory function in tasks which required the application of strategic planning behaviour. These deficits are potentially remediable by educational strategies.