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.

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.

Myeloproliferative disease in children: a demographic study.

Over eight years, eight cases of childhood myeloproliferative disease were recognised in the northern region of England (population 3.1 million). Five were classic chronic myeloid leukaemia (CML) and the three others, forms of myeloproliferative disease. No case of juvenile CML was recognised. With the exception of CML, "adult" type myeloproliferative disease of children is underrepresented in the literature and its natural history remains unknown.

Virus infections in bone marrow transplant recipients: a three year prospective study.

Over three years 81 consecutive bone marrow transplant recipients (32 allogeneic and 49 autologous) who received prophylaxis with acyclovir, were studied for symptomatic virus infection. Thirty nine infections were documented in a total of 28 patients. Thirty two infections were mild, five were moderately severe, and two were severe. Cytomegalovirus infection occurred in only six allogeneic recipients. Herpes simplex virus and varicella zoster virus infections occurred infrequently. Seven patients who were considered at the time of death to have died due to an infectious cause were studied virologically at necropsy. In only one patient was a virus infection thought to have been the cause of death. Prophylaxis with acyclovir may have influenced the rate and clinical prominence of herpes virus infections. In this study viruses were considered to have had a relatively minor role in causing morbidity and mortality.

Translocation t (8;21) associated with marked granulocytic hyperplasia.

A 16-year-old boy with leukemia had a marked leucocytosis (165 x 10(9)/L) at presentation. The large number of neutrophils, myelocytes, and metamyelocytes and negative leucocyte alkaline phosphatase reaction raised the possibility of chronic myeloid leukemia. Cytogenetic analysis showed a deletion of chromosome 7, a t (8;21), a missing Y chromosome, and, in some cells, duplication of the der(21). The Philadelphia chromosome was not detected, nor was the breakpoint cluster region of chromosome 22 found to be rearranged. Myeloid leukemia with t (8;21) can therefore be associated with a greater degree of granulocytic hyperplasia than has so far been apparent, and cytogenetic analysis in this case has been crucial in distinguishing leukemia types.

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.

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.

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.

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.

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.

Measles in children who have malignant disease.

A review study examined the clinical course of measles diagnosed in children being treated for malignant disease in Newcastle upon Tyne during 1973-86. Of the 17 cases diagnosed, five were fatal. Factors associated with a favourable outcome were a typical rash and Koplik's spots, which were accompanied by a detectable serum antibody response and the disappearance of measles giant cells from nasopharyngeal secretions. Pneumonitis severe enough to require assisted ventilation was invariably fatal. Pneumonitis and encephalitis were the main complications. Treatment included immunoglobulin, interferon, and ribavirin, but none could clearly be shown to be effective. The comparatively low mortality in this series may have been due to the extensive use of the fluorescent antibody technique in Newcastle during the study period and therefore detection of less severe cases as compared with other reports.

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.

Dental caries and dental anomalies in children treated by chemotherapy for malignant disease: a study in the north of England.

Fifty-two children in remission from childhood cancer and 41 siblings underwent a full clinical and radiographic dental examination. All the children had received chemotherapy. The leukaemic patients had received radiotherapy also, but not involving the jaws. There was no significant difference in dental caries experience between the treated children and the siblings, but significantly more dental anomalies were detected radiographically in the treated group.

Cognitive function after two doses of cranial irradiation for acute lymphoblastic leukaemia.

The cognitive function of 23 children given cranial irradiation in a dose of 24 Gy was compared with that of 41 given 18 Gy. No significant differences were found in intellectual function or in mean number of intelligence quotient points lost between patients in the two treatment groups. A reduction in the dose of cranial irradiation does not seem to alleviate long term neuropsychological deficits.

Nasal interferon responses in leukaemia.

Nasal concentrations of leucocyte interferon measured immunoradiometrically were appreciably higher in children infected with influenza viruses than those infected with paramyxoviruses. Regardless of the infecting virus, leukaemic children produced normal amounts of interferon, but this appeared to have little effect on the duration of excretion of virus.

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.

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.