Intellectual outcome in children and adolescents with acute lymphoblastic leukaemia treated with chemotherapy alone: age- and sex-related differences.

One of the most relevant concerns in long-term survivors of paediatric acute lymphoblastic leukaemia (ALL) is the development of neuropsychological sequelae. The majority of the published studies report on patients treated with chemotherapy and prophylactic central nervous system (CNS) irradiation, little is known about the outcome of patients treated with chemotherapy-only regimens. Using the standardised clinical and neuropsychological instruments of the SPOG Late Effects Study, the intellectual performance of 132 paediatric ALL patients treated with chemotherapy only was compared to that of 100 control patients surviving from diverse non-CNS solid tumours. As a group, ALL and solid tumour survivors showed normal and comparable intellectual performances (mean global IQ 104.6 in both groups). The percentage of patients in the borderline range (global IQ between 70 and 85) was comparable and not higher as expected (10% cases and 13% controls, expected 16%). Only 2 (2%) of the former ALL and 1 (1%) of the solid tumour patients were in the range of mental retardation (global IQ<70). Former known risk factors described in children treated with prophylactic CNS irradiation, like a younger age at diagnosis of ALL and female gender, remained valid in chemotherapy-only treated patients. The abandonment of prophylactic CNS irradiation and its replacement by a more intensive systemic and intrathecal chemotherapy led to a reduction, but not the disappearance of late neuropsychological sequelae.

Brain reorganisation in cerebral palsy: a high-field functional MRI study.

Early brain damage may induce alternative organisation of cortical brain functions. This may happen even if there is no damage to the cortex. We assessed a 15-year-old girl with a perinatal left-sided subcortical lesion without cortical damage by functional MRI at 3 Tesla. The patient had congenital hemiparesis, mirrored limb movements and normal language function. Functional MRI was used to assess language using orthographic-lexical retrieval and noun-verb generation tasks, and demonstrated right-sided language dominance. Functional MRI of motor function was assessed for both hands separately, by squeezing a rubber balloon. Both hand movements induced asymmetric bilateral activation of the motor cortex, with a predominance of contralateral activation. Language-associated activity is usually left-hemispheric, but was found in the undamaged right-sided hemisphere. Motor function was associated with the unusual pattern of bilateral cortical activation. The MR findings explain the clinical features and suggest widespread alternative cortical organisation in the presence of a focal lesion confined to subcortical structures.

Loss of X chromosome in childhood acute lymphoblastic leukemia.

We present six cases of childhood acute lymphoblastic leukemia (ALL) in which an acquired loss of the X chromosome was detected. The cases derive from a consecutive series of 178 childhood ALL, consisting of 80 girls and 98 boys. In five cases the presence of the TEL-AML1, t(12;21), fusion product was detected by FISH. The single negative case had an unusual t(1;19)(p13;q13). In addition, this was the only case that did not have a cytogenetically visible rearrangement involving one of the chromosome regions 6q, 9p, or 12p. The six cases showed the typical presentation features of an ALL of FAB type L1, a common ALL immunophenotype with myeloid marker co-expression, and a median presenting age of 7 years. We, therefore, conclude that loss of chromosome X may be a secondary event in older girls with TEL-AML1-positive ALL.

Constitutional balanced chromosomal rearrangements and neoplasm in children.

A predisposition to tumor development is currently associated with some, but not all, constitutional chromosomal abnormalities. In a series of 578 children, in which conventional cytogenetic investigation was performed on material from various benign and malignant tumors, four boys and one girl were also found to have constitutional balanced chromosomal rearrangements. The figure of 5 in 578 is notable because the reported incidence of balanced rearrangements in newborns is approximately 1 in 450. Thereby suggesting that some, if not all, children with balanced constitutional chromosomal rearrangements have an increased predisposition for neoplasms developing.

[Experiences with the Port-A-Cath system in children]. / Erfahrungen mit dem Port-A-Cath-System bei Kindern.

In a retrospective study (1987-1997) the complications of a totally implantable venous access device (Port-A-Cath, Fa. Pharmacia, Germany) were analysed in 91 children with 99 implants. All but 2 of these children had malignant diseases. Their age ranged from 0.1 to 18.1 (median 6) years. Overall implant time was 171.2 years (62,488 days), averaging 1.63 years (595 days) per device. 11 complications were registered, i.e. infections (6), occlusions (4) and disconnection (1), resulting in an overall infection rate of 0.06 and a total occlusion rate of 0.04. The overall complication rate was thus 0.11, which compares favourably with other studies. With careful handling, the Port-a-Cath device is very reliable and involves few complications.

[Development of formerly preterm infants with a birth weight of below 1500 grams: concept and results of a follow-up program in up to school-aged children in central Switzerland]. / Entwicklung ehemaliger Frühgeborener mit einem Geburtsgewicht unter 1500 Gramm: Konzept und Resultate von Nachkontrollen bis zum Schulalter in der Zentralschweiz.

AIM: To document the psychomotor development and general health of former very low birthweight infants born between 1980 and 1986 from birth up to school age. We wished to evaluate the quality of neonatal intensive care in Central Switzerland over this time period and test the reliability of a patient-oriented follow-up programme. If successful, the latter could perhaps serve as a model for a national follow-up programme in Switzerland. METHODS: Information regarding three different developmental periods was collected. The medical records of the perinatal period were used to abstract details of labour and delivery and the neonatal period. The records of the infant follow-up programme were used to describe psychomotor development between 0 and 24 months of age. The current health status and school performance were evaluated using a questionnaire sent to parents and teachers. RESULTS: Of 139 infants born with a birthweight of < or = 1500 g, 102 were discharged home (mortality rate 26.6%). One third was not screened for hearing deficits or retinopathy of prematurity. Eighty-two were seen in the infant follow-up programme between 0 and 24 months of age. Seventy-seven percent of these infants were judged to be normal and discharged from the infant follow-up programme; 1/5 of these infants had had transient motor problems treated by physical therapy. Twenty-three percent of the infants seen in infant follow-up had persistent but mainly minor motor handicaps, and only two infants (2%) had multiple handicaps. At school age, data from 99 of the 102 surviving infants was collected. Ninety-six percent attended regular school, but almost half of them had significant school problems and required professional help. These problems correlated poorly with the results of examinations during early childhood (positive predictive value 67%). CONCLUSIONS: These long-term results of a population of preterm infants born in Central Switzerland in the 1980s are encouraging. To ensure completeness of early ophthalmological and audiological examinations of all former small preterm infants, neonatal follow-up programmes should adhere to uniform guidelines.

Treatment of relapsing acute lymphoblastic leukemia in childhood. III. Experiences with 54 first bone marrow, nine isolated testicular, and eight isolated central nervous system relapses observed 1985-1989.

Of 54 children with acute lymphoblastic leukemia (ALL) and first hematological recurrence observed between 1985 and 1989, 31 relapsed while still on treatment and 23 after cessation of therapy. Of the former, only one survived. Of the latter, 11 children survived after a minimum follow-up of 25 months. During the same period, a first isolated testicular relapse was observed in nine boys, of whom six survived, and an isolated CNS relapse in eight patients, of whom three survived. As a rule, survivors of a bone marrow or testicular relapse were doing well while those surviving a CNS relapse had considerable neuropsychological sequelae. These results, compared with those of two preceding studies, suggest that with intensification of front-line treatments, it becomes more difficult to rescue children who relapse, particularly those with a bone marrow relapse while on therapy.

Isolated central nervous system relapse in acute lymphocytic leukemia (ALL) in children. Experiences of the Swiss Pediatric Oncology Group (SPOG/SAKK) 1976-1986.

The incidence of isolated CNS-relapse in the SPOG ALL studies 1976-1986 was analyzed and the prophylaxis of meningosis leucaemica of the different studies was compared. In the SPOG ALL high-risk study 1979-1983, the incidence of isolated CNS-relapse was significantly higher (17/71, 24%) than in the other studies. In this period, radiotherapy was omitted and the prophylactic treatment consisted only of moderately high doses of intravenous methotrexate and intrathecal methotrexate. In other studies, it was shown that the prophylactic combination of CNS-radiotherapy and intrathecal methotrexate, or the periodic administration of combined intrathecal chemotherapy alone, during the whole therapy of 2 1/2 years, produced comparably good results. The prophylaxis with the combined intrathecal chemotherapy was less neurotoxic and allowed the use of a curative radiotherapy in case of a CNS-relapse.

Treatment of relapsing acute lymphoblastic leukemia in childhood. I. Experiences with 82 first bone marrow and 17 isolated central nervous system relapses observed 1968-1980.

Of 99 patients with acute lymphoblastic leukemia in first bone marrow or isolated CNS relapse seen between 1968 and 1980, 48 were treated without standardized protocol and 51 according to a relapse protocol. Of 16 patients with bone marrow relapse after cessation of the initial treatment 6 survived 8 1/2 years or more, of 66 with bone marrow relapse while on therapy only 4 survived. All of the latter were low risk patients with an initial WBC of less than 20 x 10(9)/l and no enlargement of the mediastinum. All of the 17 patients with isolated CNS relapse died. The relapse protocols used probably improved the chances of children with first bone marrow but not of those with isolated CNS relapse.

Treatment of relapsing acute lymphoblastic leukemia in childhood. II. Experiences with 45 first bone marrow and 24 isolated central nervous system relapses observed 1981-1984.

Of 45 children with ALL who had a first hematological recurrence between 1981 and 1984, 33 relapsed while still on treatment and 12 after cessation of therapy. Of the former 1 of 16 high risk (initial WBC greater than or equal to 20 x 10(9)/l and/or enlargement of the mediastinum) and 5 of 17 low risk patients (initial WBC less than 20 x 10(9)/l and no enlargement of the mediastinum), of the latter 6 patients survived after a minimum follow-up of 20 months. During the same time period, a first isolated CNS relapse was observed in 24 children of whom 16 survived. These results suggest that at the time of evaluation 1. the prognosis of children with ALL in first hematological relapse during the years 1981-1984 was not significantly different from that of similar children treated earlier; and 2. the prognosis of children with isolated CNS relapse had improved.

Terminal deletion of the short arm of chromosome 3, del(3pter-p25): a recognizable syndrome.

The 3p- syndrome (terminal deletion of the short arm of chromosome 3 with breakpoint at 3p25) was found in the G-banded karyotypes from an undergrown and developmentally retarded 13-month-old girl with a distinct pattern of congenital abnormalities. Features present in the patient and characteristic of the 3p- syndrome included low birthweight, brachy-trigonocephaly, a high and narrow forehead with a prominent metopic suture, epicanthic folds, upslanting palpebral fissures, ptosis, depressed nasal bridge, anteverted nares and a small mandible. She lacked postaxial polydactyly of fingers and toes which is present in about half of the so far reported about one dozen 3p- cases, but she showed an anteriorly placed anus. The deletion was overlooked at a first routine cytogenetic examination. At a later clinical evaluation of the patient, the suspicion of the 3p- syndrome was raised and the aberration found at revision of the old karyotypes. The importance of a good information flow between clinicians and cytogeneticists is stressed.

[Disease (Lyme disease) in pediatric patients in Switzerland caused by spirochetes (Borrelia burgdorferi) of Ixodes ricinus]. / Durch Ixodes-ricinus-Spirochäten (Borrelia burgdorferi) verursachte Krankheitsbilder (Lyme-Krankheit) bei pädiatrischen Patienten in der Schweiz.

Lyme disease in children is studied in the light of questionnaires sent out twice to departments and divisions of pediatrics in Switzerland. Thirty-six serologically proven cases were collected. The 48 clinical signs attributed to Lyme disease involved the skin in 40%, the nervous system in 40%, and the joints in 20%. They were erythema chronicum migrans (13), lymphocytoma (4), acrodermatitis chronica atrophicans (2), peripheral facial palsy (14), sensomotor radiculoneuritis (2), meningoencephalitis (3) and arthritis (10, 7 of which were monoarthritic). Only half the patients had a history of tick-bite. Antibiotic therapy, usually with penicillin, reduced both the duration of symptoms and frequency of secondary disease. Cardiac involvement and chronic stages with residua were not observed in this series.

[Tick-borne meningoradiculitis--a form of spirochetosis]. / Die Zecken-Meningoradikulitis - eine Spirochätose.

Three pediatric cases of tick-borne meningoradiculitis are presented. This disease is characterized by a distinct sequence of symptoms: erythema chronicum migrans, localized pain, and eventually radicular asymmetric neurologic involvement (in particular facial palsy) associated with findings of aseptic meningitis. On the basis of specific serologic data in these three patients, it is suggested that the etiology of tick-borne meningoradiculitis is also spirochetal , as recently shown for the tick-associated Lyme disease. Analogue positive spirochetal antibody titers were found in additional patients with erythema chronicum migrans and in a child with B afverstedt cutaneous lymphadenosis (see addendum). 20% of tick specimens collected in the area of Lucerne (Ixodes ricinus) were infected by these spirochetes.

[Hemangio-endothelioma of the liver (case report) (author's transl)]. / Das infantile Hämangio-Endotheliom (Fallbeschreibung).

The infantile hemangio-endothelioma (IHE) of the liver, a rare neoplasm, may lead the clinician and the surgeon to suspect the presence of a malignant tumor, whereas histologic examination often reveals a benign condition; our case report illustrates this discrepancy in a 3 1/2-month-old girl suffering from multiple nodules in the liver. Conservative steroid treatment resulted in a marked reduction in tumor size; the girl is in good health more than two years after diagnosis. More than 80% of hepatic IHE are diagnosed during the first six months of life. Hepatomegaly, congestive heart failure and hemangiomas of the skin combine to the classic symptomatic triad. Since the mortality is high in untreated cases, early diagnosis is of importance. IHE may regress spontaneously. Therefore, conservative therapy, such as steroid medication and treatment of the secondary, tumor-induced complications appear indicated. Alternatively, embolization and/or resection of the tumor may be considered. Signs of cardiac or hepatic insufficiency at diagnosis and a low degree of histologic differentiation are of unfavorable prognostic significance.