Behavioural assessment of autism spectrum disorders in people with multiple disabilities.

BACKGROUND: It is difficult to diagnose autism spectrum disorder (ASD) in people with a combination of intellectual and sensory disabilities because of overlap in behaviour. The ASD typical behaviours of people with combined intellectual and sensory disabilities are often caused by their disabilities and not by ASD. Current diagnostic tools are inadequate to differentiate between people with and without ASD when they have these combined disabilities, because tools lack norms for this population or are subjective, indirect or unable to adapt to the variety of disabilities that these people may have. Because giving a correct diagnosis is necessary for treatment and support, a new observational tool was developed to diagnose ASD in people with multiple disabilities, observation of autism in people with sensory and intellectual disabilities (OASID). METHOD: Observation of autism in people with sensory and intellectual disabilities was tested on 18 participants with moderate to profound intellectual disabilities, one or dual sensory impairment, with and without ASD. Two independent experts diagnosed these participants as well in order to test the psychometric properties and differentiating abilities of OASID. RESULTS: Observation of autism in people with sensory and intellectual disabilities showed high inter-rater reliability, internal consistency of scales and content and construct validity. OASID could differentiate people with and without ASD without overlap. CONCLUSIONS: Observation of autism in people with sensory and intellectual disabilities could differentiate people with intellectual disabilities combined with sensory impairments, who clearly had or did not have signs of ASD. People with unclear signs of ADS scored in between those two groups with regard to their OASID scores. Psychometric properties of OASID are promising.

Intensive treatment of children with acute lymphoblastic leukemia according to ALL-BFM-86 without cranial radiotherapy: results of Dutch Childhood Leukemia Study Group Protocol ALL-7 (1988-1991).

In The Netherlands from July 1988 to October 1991, children (0 to 16 years of age) with de novo acute lymphoblastic leukemia (ALL) were treated according to protocol ALL-7 of the Dutch Childhood Leukemia Study Group (DCLSG). In this protocol, chemotherapy and treatment stratification were identical to the ALL-BFM-86 protocol (Reiter et al, Blood 84:3122, 1994), but cranial irradiation was restricted to patients with initial central nervous system (CNS) involvement. Patients were stratified into 3 risk groups, based on leukemia cell mass and response to initial treatment: standard-risk group (SRG), risk group (RG), and experimental group (EG). As in ALL-BFM-86, a randomized study on late intensification (protocol S) was performed in RG patients, and during the study (since October 1990), early reinduction treatment (protocol II) was introduced for SRG patients. Treatment duration for all patients was 18 months. Two hundred eighteen children entered the study: 74 SRG, 127 RG, and 17 EG patients. The overall complete remission (CR) rate was 98%. The 5-year event-free survival (EFS) for all DCLSG ALL-7 patients was 65. 3% (standard error [SE] 3.2%), which was significantly different from the 73% (SE 1%) 5-year EFS achieved in the ALL-BFM-86 study (P =.02, Z-test). However, restricting the analysis to SRG patients receiving protocol II with a total duration of treatment of 18 months, the 5-year EFS rates were 64.6% (SE 4.0%) and 67% (SE 4%), respectively, and no significant difference could be established (P =.67, Z-test). The 5-year EFS rates for SRG, RG, and EG patients were 63.5% (SE 5.6%), 66.6% (SE 4.2%), and 63.3% (SE 12.0%), respectively. SRG patients receiving protocol II fared better than patients not receiving protocol II (5-year EFS 76.7% [SE 7.7] and 54. 5% [SE 7.5], respectively). No difference in 5-year EFS was observed in RG patients randomized to receive or not to receive late intensification with protocol S. The overall CNS relapse rate at 5 years was 5.5%. The incidence rate at 5 years was 11.4% in SRG patients not receiving protocol II, whereas no CNS relapses occurred in SRG patients receiving protocol II. Six children died in first complete remission and 2 children developed a second malignancy (thyroid carcinoma and acute nonlymphoblastic leukemia). Systemic high-dose methotrexate (MTX) and intrathecal chemotherapy is a safe and effective method of CNS prophylaxis in the context of BFM-oriented treatment for all children with ALL, regardless of the risk group (with the possible exception of T-ALL patients with high white blood cell counts). The results of the DCLSG ALL-7 study confirm those of the ALL-BFM-86 study showing that early reinduction with protocol II is essential in the treatment of SRG patients and that late intensification with protocol S does not improve the prognosis for RG patients.

High cure rate with a moderately intensive treatment regimen in non-high-risk childhood acute lymphoblastic leukemia. Results of protocol ALL VI from the Dutch Childhood Leukemia Study Group.

PURPOSE: Here we report the results of a nationwide cooperative study in the Netherlands on acute lymphoblastic leukemia (ALL) in children. The aim of the study was to improve the cure rate and to minimize side effects in a group of non-high-risk ALL patients, especially with regard to the CNS. A second aim was to study potential prognostic factors. METHODS: Children (age 0 to 15 years) with non-high-risk ALL (WBC count < 50 x 10(9)/L, no mediastinal mass, no B-cell phenotype, and no CNS involvement) were treated with a uniform protocol, ALL VI. The treatment protocol used 6-week induction regimen with three drugs (vincristine, dexamethasone, and asparaginase), three weekly doses of intravenous (IV) medium high-dose methotrexate (2 g/m2), and 2-year maintenance therapy that consisted of alternating 5-week periods of methotrexate and mercaptopurine and 2-week periods of vincristine and dexamethasone. In the first year of maintenance, triple intrathecal therapy was administered every 7 weeks. RESULTS: From December 1, 1984 until July 1, 1988, 291 children with ALL were diagnosed; 206 were categorized as non-high-risk (71%), and 190 were treated according to protocol ALL VI. At 8 years, the event-free survival (EFS) rate was 81% (SE = 3%) and survival rate 85% (SE = 2.9%); the median follow-up time was 7.3 years (range, 36 to 117 months). The CNS relapse rate was 1.1% (two of 184 patients who achieved a complete remission [CR]). The only factor found to be of negative prognostic importance in terms of EFS (P = .05) was a positive acid phosphatase reaction. CONCLUSION: For children with non-high-risk ALL, the combination of IV medium high-dose methotrexate (2 g/m2 times three), triple intrathecal therapy in the first year of maintenance treatment, and the use of dexamethasone for induction and pulses during maintenance treatment has proved to be highly effective, especially in the prevention of CNS relapse. A high cure rate was achieved without the use of anthracyclines, alkylating agents, and cranial irradiation.

CD4 deficiency in myelodysplastic syndrome with monosomy 7.

UNLABELLED: We describe a patient with myelodysplastic syndrome with monosomy 7 presenting with a T-cell defect. He suffered from infections from the age of 10 years, when a CD4 deficiency and impaired lymphoproliferative responses in vitro were found. The only symptom of a myelodysplastic syndrome at that time was thrombocytopenia with giant platelets. Monosomy 7 was found in the bone marrow cells. At the age of 11 years he developed other characteristics of monosomy 7 including splenomegaly and anaemia. Some months later leukaemia was diagnosed. CONCLUSION: In non-HIV CD4 deficiency myelodysplastic syndrome has to be considered.

Noonan's syndrome in association with acute leukemia.

Noonan's syndrome (NS) is a syndrome with multiple congenital anomalies, characterized by craniofacial anomalies, congenital heart disease, skeletal and genital abnormalities, and mild mental retardation. Chromosomal abnormalities have been found in only a few cases. The combination of NS and acute leukemia has been reported in only three cases. Two additional cases are described here.

Late effects among long-term survivors of childhood acute leukemia in The Netherlands: a Dutch Childhood Leukemia Study Group Report.

Late events and side effects are reported in 392 children cured of leukemia. They originated from 1193 consecutively newly diagnosed children between 1972 and 1982, in first continuous complete remission for at least 6 y after diagnosis, and were treated according to Dutch Childhood Leukemia Study Group protocols (70%) or institutional protocols (30%), all including cranial irradiation for CNS prophylaxis. Data on late events (relapses, death in complete remission, and second malignancies) were collected prospectively after treatment; late side effects were retrospectively collected by a questionnaire, completed by the responsible pediatrician. The event-free survival of the 6-y survivors at 15 y after diagnosis was 92% (+/- 2%). Eight late relapses and nine second malignancies were diagnosed, two children died in first complete remission of late toxicity of treatment, and one child died in a car accident. The most important long-term side effects reported were learning disabilities (50%), short stature, obesity, and delayed pubertal development. No increase in the incidence of cardiovascular, pulmonary, urogenital, or gastrointestinal tract diseases or an increased vulnerability of the musculoskeletal system was found. However, prolonged follow-up is necessary to study the full-scale late effects of cytostatic treatment and radiotherapy administered during childhood.

Neurocristopathy in mother (ganglioneuroblastoma) and daughter (aganglionosis): incidental or causal?

We report on a mother who had been treated for a ganglioneuroblastoma and her daughter who had a long segment aganglionosis. Review of the relevant literature and recent molecular findings warrant the conclusion that most likely, there is a causal relation between these two neurocristopathies.

Juvenile xanthogranuloma and acute leukemia: a case report.

Juvenile xanthogranuloma (JXG) is a rare benign disease of the skin. It is seen in combination with juvenile chronic myelo-monocytic leukemia (JCML) and/or neurofibromatosis type 1 (NF1). The association with acute lymphoblastic leukemia is hardly mentioned in the literature. A case report of this rare combination is described and a review of the literature is given.

Light chain ratios and concentrations of immunoglobulins G, A, and M in childhood common acute lymphoblastic leukemia.

The light chain ratios and the concentrations of immunoglobulin G (IgG), IgA, and IgM were measured before, during, and after antileukemic therapy in 10 patients with common acute lymphoblastic leukemia. The concentrations of IgG, IgA, and IgM decreased substantially during treatment but recovered slowly after cessation of the therapy. The light chain ratios were not systematically affected, but at diagnosis the kappa/lambda ratios of total serum Igs, IgG, and in particular IgM were somewhat lower in the patient group compared with an age-matched reference group. It is concluded that, despite a decrease in serum Ig concentrations, virtually normal kappa/lambda ratios are preserved, indicating that kappa and lambda syntheses are affected to the same extent. These ratios remained normal for age during the recovery of the serum Ig concentrations; the features as described for the development of the light chain ratios in childhood were not observed.

[Chorea and primary antiphospholipid syndrome]. / Chorea en het primaire antifosfolipidensyndroom.

Primary antiphospholipid syndrome or PAPS is characterised by antiphospholipid antibodies and arterial and/or venous thromboses. Numerous other clinical features have been shown to be related to this syndrome. Chorea is a well known but rare phenomenon in systemic lupus erythematosus; it has been shown to be strongly related to the presence of antiphospholipid antibodies. We describe two patients with chorea that appeared to be caused by the PAPS.

Iatrogenic IgG2 deficiency in a leukaemic child. A case report.

A girl with acute non-lymphoblastic leukaemia was treated with immunosuppressive chemotherapy. After cessation of therapy she had three consecutive episodes of infection due to Streptococcus pneumoniae from which she recovered and was shown to have developed a combined deficiency of both IgG2 and IgG4. The patient eventually relapsed and died 3 years after the initial diagnosis. The importance of measuring IgG subclasses in patients treated with immunosuppressive chemotherapy is discussed.

Prevalence of naevocytic naevi after chemotherapy for childhood cancer.

The frequency of naevocytic naevi (moles) in patients with childhood haematologic malignancies was studied. All patients had received multiple chemotherapy. The majority had also received cranial irradiation as part of their central nervous system leukaemia/lymphoma prophylaxis. Total body mole counts of the patients were compared with those of their healthy brothers and sisters. The median number of moles in the patient group was 20.0 (n = 79), in the healthy sibs 11.0 (n = 88). In two subgroups mole counts of male and female patients were compared with those of their closet brother or sister. There were 19 male and 19 female pairs for comparison. Median numbers of moles were significantly higher in both patient groups than in the controls (P less than 0.05). It is suggested that multiple chemotherapy (and/or cranial irradiation) may induce or activate naevocytic naevi. These findings may have important implications with regard to the aetiology of melanoma.

Mild course of mumps in patients with acute lymphoblastic leukaemia.

Few details exist on the course of mumps during cytostatic treatment. We therefore describe our observations on the course of mumps seen between 1974 and 1988 in eight children suffering from acute lymphocytic leukaemia (ALL). Our data suggest that in malignant disease the course is rarely severe and that the infection often remains subclinical, as in healthy children. Mumps was accidentally diagnosed by routine lumbar puncture in four of the eight patients. Literature data suggest that the intrinsic low cytopathological effect of the virus, together with a parallelism between T cell response and clinical severity, may explain the usual mild course in immunodepressed patients, contrasting with the severe course of measles and Varicella zoster.

Pyoderma gangrenosum in acute myeloid leukaemia during immunosuppression.

We describe a patient who developed pyoderma gangrenosum during the remission phase of acute myeloid leukaemia whilst receiving maintenance therapy with methotrexate and 6-mercaptopurine. The spontaneous resolution of these skin lesions following discontinuation of chemotherapy suggests that these drugs may be of major significance in the aetiology of pyoderma gangrenosum. Nevertheless, 27 months later, a relapse of the leukaemia followed. Although pyoderma gangrenosum occurred during clinical remission, we cannot rule out a synergism of leukaemia and chemotherapy in its pathogenesis.

[Biochemical and clinico-pharmacological aspects of antimetabolites in the treatment of leukemia]. / Biochemisch- en klinisch-farmacologische aspecten van antimetabolieten bij de behandeling van leukemie.

Methotrexate (MTX) and 6-mercaptopurine (6MP) have been used since 30 years in the maintenance treatment of acute lymphoblastic leukemia (ALL) of childhood. A synergistic effect of this combination was demonstrated in mouse and childhood leukemia. In this article an overview is given of our investigations, concerning the biochemical basis of this synergism. This synergism is caused by a selective inhibition of the purine de novo synthesis in malignant lymphoblasts by MTX, associated with an enhanced intracellular uptake of 6MP. Pharmacokinetic studies of MTX in various schemes of prophylactic central nervous system treatment in ALL are discussed. Treatment with 24-hr infusions of MTX in a dosage of 5 g/m2, as recommended in the new BFM-86/SNWLK ALL VII protocol, seems to be optimal. Pharmacokinetic studies of intravenous 6MP infusions demonstrated a good cerebral fluid penetration. Exploiting the synergistic action of the combination of MTX and 6MP may offer an improvement of the prophylactic central nervous systems treatment in ALL in the future, using intravenous administration of both MTX and 6MP.

Effect of thymectomy on myasthenia gravis and autoimmune thrombocytopenic purpura in a 13-year-old girl.

We report the association of myasthenia gravis (MG) and autoimmune thrombocytopenic purpura (AITP) in a 13-year-old girl. The co-existence of these autoimmune diseases is rare in adults and, to our knowledge, never described in children. In our patient thymectomy had a therapeutic effect on both MG and AITP, suggesting a altered T-cell function as a pathogenic factor of major importance in both affections.

Prognostic implication of hyperdiploidy as based on DNA flow cytometric measurement in childhood acute lymphocytic leukemia--a multicenter study.

The pretreatment distribution of DNA content was determined in the leukemic blasts of 114 children with standard risk acute lymphocytic leukemia. The patients were admitted to four different centers for pediatric oncology, participating in a national study ALL-V. In 39 of 107 evaluable patients (36.4%), a single aneuploid leukemic line was detected with a median DNA Index of 1.22 (range 1.10-1.40). These hyperdiploid patients did not differ from those with diploid disease for the presenting features of age, sex, FAB classification, immunophenotype, or white blood cell count. However, patients with hyperdiploid acute lymphocytic leukemia had a significantly longer (p = 0.021) disease-free survival after a median observation period of 52 months. These observations indicate that routinely applied flow cytometry of DNA content can identify a fairly large subgroup of children with standard risk acute lymphocytic leukemia who have a low probability of relapse. It may be considered to exempt these patients from more intensive treatment regimens.