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.

Flow cytometric determination of intracellular calcium changes in human peripheral blood mononuclear cells during conjugation to tumour cell lines.

Using a flow cytometric assay, conjugate formation between human peripheral blood mononuclear cells (PBMC) and three different human tumour cell lines has been analysed. Changes in the intracellular calcium levels of PBMC were monitored using the calcium sensitive dye Fluo-3. Target cell populations were distinguished by forward scatter or following loading with the fluorescent dye, SNARF-1. Intracellular calcium was expressed as a ratio of fluorescence of conjugated to unconjugated PBMC and followed for ten minutes after initiation of conjugation. The results demonstrate an apparent increase in intracellular calcium in PBMC conjugated to the NK-sensitive cell line K562, and that the kinetics and magnitude of this response varied considerably between individuals. Tumour cells which were resistant to lysis (as determined in a 4 h chromium release assay) were also capable of eliciting a calcium response from PBMC. Although the induction of a rise in intracellular calcium was therefore not correlated with cytotoxicity, it was greater in IL-2-activated PBMC upon exposure to the same target cell lines as PBMC.

ELISA determination of IgG antibodies to pneumococcal capsular polysaccharides in a group of children.

An enzyme-linked immunosorbent assay (ELISA) was developed to measure specific IgG antibody levels to pneumococcal polysaccharide antigens in 300 children attending various hospital departments. By expressing the results as a specific binding index (SBI) of given high and low controls, good reproducibility was obtained. Serum levels of the antibodies were found to fall rapidly during the 1st year of life, plateau during the 2nd and then rise steadily, reaching adult levels by the 7th year.

Posttransplantation B lymphoblastic leukemia with Burkitt-like features.

BACKGROUND: Posttransplantation Epstein-Barr virus-associated lymphoproliferative disease (PTLPD) occurs as a spectrum of disease ranging from benign, polyclonal, localized lymphoid hyperplasia to malignant, monoclonal, disseminated lymphoma, sometimes involving the bone marrow. To our knowledge, PTLPD has not been previously reported to present as acute lymphoblastic leukemia. METHODS: We report the case of a boy who developed PTLPD in the form of acute lymphoblastic leukemia 6 years after cardiac transplantation. He had greater than 90% bone marrow invasion by Epstein-Barr virus-positive B lymphoblasts with Burkitt-like features and a t(8;14) translocation. RESULTS: He was successfully treated with combination chemotherapy but unfortunately died, 6 months after completing treatment, from ischemic heart disease. CONCLUSIONS: B lymphoblastic leukemia may occur as a manifestation of PTLPD and should be included in the classification of these diseases. Bone marrow examination should be an essential part of the investigation of patients suspected of having PTLPD.

Acute megakaryocytic leukemia (M7) in children.

We analyzed the clinical and laboratory features of eight children (median age, 20 months; range, 13 months to 11 years) with acute megakaryocytic leukemia (M7) and compared the findings with those reported in the literature. The diagnosis was supported by ultrastructural examination for platelet peroxidase or immunophenotyping for glycoprotein IIb/IIIa or the von Willebrand factor protein. Two patients had Down's syndrome. Initial findings included anemia (in all patients), thrombocytopenia (in six), myelofibrosis (in three), lytic bone lesions (in two), and pronounced leukocytosis (in one). Stem cell culture studies of peripheral blood specimens revealed an aberrant phenotype of the megakaryocytes in one patient and reversal to a normal pattern after successful therapy. Remission was achieved in seven of the eight patients after aggressive chemotherapy, and four patients remained in remission 27 to 57 months after diagnosis. Three of these four patients underwent allogeneic bone marrow transplantation. M7 leukemia is not infrequent in children younger than 3 years of age, especially in those with Down's syndrome. The availability of monoclonal antibodies specific to restricted antigens of the megakaryocytic lineage has made the diagnosis of M7 leukemia both possible and practical.

CD30 expression by peripheral blood monocytes and hepatic macrophages in a child with miliary tuberculosis.

The peripheral blood of a 3 month old boy with disseminated tuberculosis showed CD30 positive monocytes on flow cytometric analysis. His liver contained CD30 positive staining macrophages and giant cells. CD30 is an activation antigen which has not been previously found on peripheral blood monocytes.

Demographic study of leukaemia presenting within the first 3 months of life in the Northern Health Region of England.

AIMS: To determine the incidence and outcome of congenital leukaemia. METHODS: Retrospective population based study of putative leukaemia arising during the first 3 months of life over an 18 year period within the Northern Health Region of England. RESULTS: Nine infants with putative leukaemia were identified. Five had acute leukaemia and four had transient myeloproliferative disorder (TMD). Trisomy 21, either as Down's syndrome or perhaps restricted to proliferating marrow cells, was present in all four infants with TMD. The incidence of congenital acute leukaemia was 8.6/10(6) live births/year, but would be less than half this value if only patients presenting within 4 weeks of birth were counted. Remission was induced in three of the five patients with acute leukaemia. One patient, who presented at birth, remains well five years after diagnosis. All four patients with TMD survive. CONCLUSIONS: Congenital leukaemia is very rare but is not inevitably fatal. Finding trisomy 21 in spontaneously dividing blood or bone marrow cells of an infant with putative acute leukaemia, particularly within 3 months of birth, should encourage a cautious clinical approach and suggests that the diagnosis might be TMD.

High dose ifosfamide in combination with etoposide and epirubicin followed by autologous stem cell transplantation in the treatment of relapsed/refractory Hodgkin's disease: a report on toxicity and efficacy.

Patients with Hodgkin's disease (HD) refractory to first line chemotherapy and those who have rapid or multiple relapses have a very poor prognosis. With the increasing use of hybrid chemotherapy these patients will have been exposed to many of the drugs active in HD so it is important to develop salvage regimens that are novel and demonstrate activity in this group of patients. We report the use of a continuous high dose infusion of ïfosfamide at a dose of 9g/m(2) over 3 days in combination with etoposide and epirubicin followed by autologous stem cell transplant with either BEAM or Melphalan/VP16 conditioning in this difficult group. Forty six patients (28M:18F) with a median age of 28 years (range 13-45) were treated. Overall 39 out of 46 (85%) patients responded to treatment, with 17 achieving complete remission and 11 a good partial remission; 28 proceeded to autologous bone marrow/stem cell transplantation. In total, 23 patients are alive and in continuous remission with a follow up of between 12 and 61 months. Median overall survival for the whole group is 36 months. Haematological toxicity, particularly neutropenia (WHO grade IV), was observed in all cases but improved over the 3 courses of treatment in all patients. Non-haematological toxicity was not a major problem; no significant cardiac, hepatic, renal, pulmonary or neuro toxicity was observed and there were no deaths on treatment. This regime shows promise in patients with difficult Hodgkin's disease and warrants further study.

Chemotherapy and marrow transplantation for congenital leukaemia.

The optimum approach to congenital leukaemia is unclear. Results of treatment are generally discouraging and palliation is offered to many. The successful treatment of an infant with congenital leukaemia is reported.

Childhood lymphoma.

Lymphoma accounts for some 10% of childhood malignancy. Hodgkins disease is slightly less common than Non Hodgkins lymphoma, of which lymphoblastic, Burkitts and large cell anaplastic are the common subtypes. Accurate subtyping and staging are critical to ensure correct therapy is initiated. With current therapeutic strategies, almost all cases of Hodgkins and in excess of 70% of Non Hodgkins lymphomas can be cured.

Langerhans cell histiocytosis: a multisystem disorder.

Langerhans cell histiocytosis can involve single or multiple organ/tissue systems and may go undiagnosed for years until it enters the clinician's differential diagnosis framework. We report on a young patient who initially presented with diabetes insipidus and subsequently with pyrexia of unknown origin. She progressed from single system Langerhans cell histiocytosis to multisystem involvement and remains in long-term remission following chemotherapy.

Langerhans cell histiocytosis.

Langerhans cell histiocytosis is a rare disease. Depending on which organs are involved, the disease may prove rapidly fatal, develop a chronic reactivating but therapy-responsive pattern or resolve spontaneously. Understanding of the pathology of the disease is progressing rapidly, and while clinical trials of standard chemotherapy agents continue, it is likely that novel targeted therapy will become feasible in the next decade. Permanent consequences of the disease are more commoner than generally realised.

Incidence and clinical features of Langerhans cell histiocytosis in the UK and Ireland.

OBJECTIVES: There are few published studies on the epidemiology of Langerhans cell histiocytosis (LCH). We undertook a survey to ascertain all newly diagnosed cases aged 0-16 years in the UK and Republic of Ireland. DESIGN: Three methods of ascertainment were used: the British Paediatric Surveillance Unit (BPSU) system, a survey by Newcastle University, and the Children's Cancer and Leukaemia Group (CCLG) registry. Deaths data were obtained from the UK Office for National Statistics and the Central Statistics Office in Ireland. Clinicians who reported cases were sent a questionnaire to obtain demographic and clinical details. RESULTS: Over the 2-year period, 94 cases were identified. The age-standardised incidence rate of LCH in children aged 0-14 years was 4.1 per million per year. The sex ratio (M:F) was 1.5:1 and the median age at diagnosis was 5.9 years. Single system disease (predominantly bony involvement) accounted for 73% of cases and 27% had multisystem disease of whom 7% had involvement of "risk organs" (liver, lung, spleen and bone marrow). Three children died, two of whom were diagnosed after death. CONCLUSIONS: This is the first study of LCH to use an active surveillance method with additional sources of ascertainment. Our incidence is comparable with those in other national reports, although it is likely to be an underestimate as each method may have missed some cases, either diagnosed or undiagnosed.

Outcome of a risk-related therapeutic strategy used prospectively in a population-based study of Hodgkin's lymphoma in adolescents.

The aim was to assess outcome in a population-based cohort of adolescents with Hodgkin's lymphoma (HL) diagnosed in the UK's northern region over a 10-year period. Among a population of 3.09 million, 55 of 676 patients (8%) diagnosed with HL were aged 13-19. Seven had nodular lymphocyte-predominant HL, 48 classical HL (cHL). Of the latter, 36 were >or=16 years. Application of the Scottish and Newcastle Lymphoma Group (SNLG) prognostic index meant 21 patients were considered high risk (index >or=0.5). They received PVACEBOP multi-agent chemotherapy as primary therapy. Standard risk patients (SNLG index <0.5) were treated with standard ChlVPP or ABVD chemotherapy+/-radiotherapy. Scottish and Newcastle Lymphoma Group indexing is not valid for patients under 16. Twelve patients therefore received UKCCSG protocols (n=8), ABVD plus radiotherapy (n=2), or PVACEBOP (n=2). Forty-six patients with cHL (96%) achieved complete remission. Seven patients relapsed but all entered complete remission after salvage therapy. Five patients died: three of HL, one in an accident and one of disseminated varicella complicating cystic fibrosis. Five- and 10-year overall survival was 93 and 86%, respectively; disease-specific survival was 95 and 92%. The data suggest that older adolescents with high-risk HL require intensive protocols as primary therapy to secure optimal outcome.

Follicular dendritic cell tumour in a 9-year-old child.

Follicular dendritic cell tumour (FDCT) or sarcoma is a rare tumour first described in 1986. Some 80 cases have been reported, the youngest being in teenagers. Our patient first presented at 9 years of age with a cervical mass that was removed and revealed an apparently benign, but florid reactive process. At age 14 the lump recurred and biopsy was diagnostic of FDCT. Radical block dissection showed disease to level III and 6 weeks of radiotherapy was followed by 6 months adjuvant chemotherapy. Three years after completing his final treatment he shows no signs of recurrent disease.

A comparison of self-reported satisfaction between adolescents treated in a "teenage" unit with those treated in adult or paediatric units.

BACKGROUND: Despite recommendations that adolescents should have in-patient management amongst their peers, there is little literature to support this. The study aim was to evaluate and contrast patient satisfaction for teenage cancer patients treated in two settings. The first is a split site unit (a paediatric ward and adult cancer centre in different locations within one city) and the second, a dedicated adolescent unit for patients aged 13-20. PROCEDURE: Eligible patients aged 13-20 years received treatment from September 1997 to June 2000 and totalled sixty-five adolescents. The patients were identified at both centres from departmental databases. Postal questionnaires (the Youth Satisfaction Questionnaire) were sent to those eligible. RESULTS: Patients receiving treatment in the teenage cancer unit (TCU) were not significantly more satisfied overall than those receiving treatment in adult or paediatric units. However, significant differences were noted in: recreational and relaxation facilities (P < 0.005, P < 0.0002), studying space (P < 0.004), ward noise (P < 0.02), and company of the same age (P < 0.0001). The Grade Point Average (a score of all specific items) was higher in favour of the TCU (P < 0.03). Patients at both centres were dissatisfied with hospital food and menus offered. CONCLUSIONS: Adolescents with cancer are satisfied with the overall care they receive independent of whether it is a TCU or a split site unit. Teenagers are significantly more satisfied with environmental aspects of care in the TCU. More research is required to establish the correct provision for teenagers with cancer. This is the first study that contrasts satisfaction between different centres and thus adding to an understanding of the needs of teenagers with cancer.

Attentional ability among survivors of leukaemia treated without cranial irradiation.

BACKGROUND: Previous research has indicated that children who have received treatment for leukaemia which includes cranial irradiation exhibit deficits in their ability to focus attention. It has been suggested that the use of cranial irradiation may have a role to play in long term sequelae. AIMS: To investigate neuropsychological functioning among children treated for leukaemia without cranial irradiation. METHODS: In a cross sectional study, 17 leukaemic patients and their sibling controls were assessed using a neuropsychological model of attention. All were treated on the UKALL XI protocol and none had received cranial irradiation. Participants completed the Arithmetic subtest and Digit Span subtest of the Weschler Intelligence Scale for Children-Revised to assess focus-encode elements of attention; the Coding subtest and the Speed of Information subtest of the BAS to assess focus-execute aspects of attention; the VIGIL computerised battery to assess sustain elements of attention; and the Wisconsin Card Sorting test to assess the ability to shift attention. RESULTS: These children did not exhibit the deficits witnessed in previous cohorts, and were performing at comparable levels to their controls on all measures of attention CONCLUSIONS: These findings suggest that children who have received treatment for leukaemia without the use of cranial irradiation do not show the neuropsychological insult found in earlier treatment groups.

Recurrent pneumomediastinum and pneumothorax in Langerhans cell histiocytosis.

Pneumothorax is an unusual complication of pulmonary Langerhans cell histiocytosis. We report three children who developed recurrent intrathoracic air leaks. In one case, bilateral pneumothoraces may have been precipated by intermittent positive pressure ventilation during general anaesthesia. Chemical pleurodesis was unsuccessful in preventing recurrence of pneumothoraces in two children. The use of extracorporeal membrane oxygenation as an alternative to intermittent positive pressure ventilation in children with respiratory failure from Langerhans cell histiocytosis is discussed.