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Purpose: Studies concerning the scholastic achievement of survivors of childhood leukemia have yielded controversial results. We studied the school marks of childhood leukemia survivors in a register-based study., Patients and Methods: Three hundred seventy-one patients with a diagnosis of leukemia before the age of 16 years who were born between 1974 and 1986 and alive on their 16th birthday were identified from the Finnish Cancer Registry. Five matched controls were sought for each patient from the Population Register Center of Finland. Information on the ninth-grade school report was obtained from Statistics Finland. The overall mark average and the marks (scale 4 to 10) for mother tongue, foreign language, mathematics, and physical education were compared between the patients and controls., Results: The ninth-grade school report was obtained by 97.6% of the patients and 98.5% of the controls. The patients whose treatment included cranial irradiation had a lower overall mark average (mean difference, -0.24; 95% CI, -0.33 to -0.15) and lower marks for all assessed school subjects compared with their controls. Of the patients treated with chemotherapy alone, only the females with leukemia diagnosed before 7 years of age had lower school marks than their controls. The biggest difference was observed in the marks for foreign language among the irradiated females diagnosed at a young age (mean difference, -1.0; 95% CI, -1.25 to -0.74)., Conclusion: Leukemia treatment that includes cranial irradiation impairs scholastic achievement. It is noteworthy that treatment of leukemia with chemotherapy alone impairs school performance only in females diagnosed before school age.

Purpose: The aim of the study was to determine the incidence of and clinical risk factors for radiographic osteonecrosis (ON) in children treated for acute lymphoblastic leukemia (ALL) using the Nordic ALL protocols., Patients and Methods: Ninety-seven consecutive patients with childhood ALL were studied prospectively by magnetic resonance imaging (MRI) of the lower extremities at the end of the treatment., Results: Twenty-three (24%) of the 97 patients had ON. Seven of the patients (30%) were symptomatic, and three patients (13%) required surgical interventions. Multiple logistic regression analysis showed that high body mass index (BMI; P = .04), female sex (P = .01), older age at diagnosis (P < .001), and higher cumulative dexamethasone dose (P = .03) were independent risk factors for radiographic ON. The cumulative prednisone dose did not differ significantly between the patients with and without ON. The incidence of radiographic ON decreased significantly, from 36% to 7%, when the duration of dexamethasone exposure during the delayed-intensification phase was shortened from 3 to 4 weeks to 2 weeks with a taper (P = .001)., Conclusion: ON as determined by MRI was found to be a common complication in children and adolescents after treatment with the Nordic ALL protocols. Revision of the ALL protocols by shortening the single exposure to dexamethasone has diminished the risk for ON remarkably. High BMI was identified as a new significant risk factor for ON.

Unlabelled: Chediak-Higashi syndrome (CHS) is a rare multiorgan disease entity with autosomal recessive inheritance characterized by oculocutaneous albinism, bleeding tendency, recurrent bacterial infections and various neurological symptoms. Intracellular vesicle formation is deficient, resulting in giant granules in many cells, e.g. giant melanosomes in the melanocytes. Diagnosis has been based on morphological examination of peripheral blood and bone marrow, with giant granules seen in cells of the myeloid lineage and in lymphocytes. The ultimate diagnostic test is to look for a mutated LYST gene. Most patients develop an accelerated phase of the disease with deposition of lymphohistiocytes in the liver, spleen, lymph nodes and bone marrow, resulting in hepatosplenomegaly, bone marrow infiltration and haemophagocytosis. Peripheral blood neutropenia becomes more profound as anaemia and thrombocytopenia develop. Most patients succumb before the age of 10 years. Four patients with CHS are described, one of whom is a long-term survivor after successful allogeneic bone marrow transplantation, two succumbed during the accelerated phase and one is living with a chronic form of the disease., Conclusion: Allogeneic bone marrow transplantation from an HLA-matched sibling is the therapy of choice and should be performed early. If there is no matched family donor, an unrelated donor or a placental blood graft is a good alternative. The clinical picture of CHS is heterogeneous and therapeutic decisions need to be made on an individual basis.

Our purpose was to assess the risk of developing a second malignant neoplasm (SMN) after cancer in childhood and adolescence associated with different treatment modalities. Our investigation was performed as a nested case-control study within a Nordic cohort of 25,120 patients younger than 20 years old at first malignant neoplasm (FMN) diagnosed in 1960 through 1987. SMNs were diagnosed in 1960 through 1991. For each case of SMN, 3 controls were sampled, matched by sex, age, calendar year of diagnosis and length of follow-up. For the final analysis, there were 234 cases and 678 controls. Relative risks (RRs) of various exposures were estimated by means of conditional logistic regression, with non-exposed as the reference. The RR of developing SMN in the radiated volume was 4.3 (95% confidence interval 3.0-6.2). The risk was highest in children diagnosed before the age of 5 years; it increased with the dose of radiation and with increasing follow-up time after FMN. Chemotherapy alone was not associated with an increased RR, but it significantly potentiated the effect of radiotherapy. RRs were unchanged between the periods 1960-1973 and 1974-1987, and since the use of chemotherapy increased in the latter period, the number of SMNs may increase. Hereditary factors were important for the occurrence of SMN independently of therapy. We conclude that radiation was the most important treatment-related risk factor for the development of SMN. Chemotherapy appeared to play only an accessory role during the study period, potentiating the carcinogenic effect of radiotherapy., (Copyright 2000 Wiley-Liss, Inc.)

Background: The objective of this study was to assess the eligibility for and the course of compulsory military service of childhood cancer survivors., Methods: The medical, military recruitment, conscription, and military service data of male Finnish childhood cancer survivors were collected from manually filed records. Inclusion criteria were: survivors born 1977 or earlier, treated for a malignancy between birth and age 15 years, and followed by a pediatrician until at least age 18 years. The documents of 207 survivors from the Pediatric Clinics of Finnish University Hospitals were examined, and 130 of these survivors were considered eligible for military service. Demographic factors, the predictors of fitness for military service, factors associated with service interruption, the attained level of military training, and the health status of conscripts during service were evaluated. Comparisons were made with the Finnish male population of the same age and with conscripts serving at the corresponding time., Results: Approximately 60% of studied survivors were enlisted. Positive predictors of fitness for service were year of birth of 1973 or later (odds ratio [OR], 3.2), height at call-up age of 170-174.9 cm (OR, 3.6), and the man's own positive opinion of his fitness for service (OR, 62.3). Negative predictors were age at diagnosis > or = 11 years (OR, 0.5), central nervous system radiotherapy (OR, 0.3), limb defects (OR, 0.02), and the group of sequelae concerning neurologic, cardiopulmonary, and gastrointestinal systems, or secondary malignancies (OR, 0.3). Survivors interrupted their service more often (20%) (P < 0.001). Leukemia survivors were less likely to interrupt their service (7%) compared with other survivors (P = 0.04). Factors associated with service interruption were: diagnosis (P = 0.04), the man's own opinion of his fitness for service (P = 0.013), surgery (P = 0.003), and height (P = 0.049), weight (P = 0.019), and body mass index (P = 0.035) at the beginning of military service. The attained level of military training was equal to that of controls. The survivors visited the garrison physician less frequently in total (mean, 5.9 times) (P < 0.001), visited because of infections as much as controls, and were off duty more (mean, 11.9 days) (P = 0.012) than controls., Conclusions: The current study found that childhood cancer survivors were less likely to meet the requirements set for military service in Finland. The causes of rejection usually were obvious, but approximately 30% were rejected merely on the basis of a former cancer diagnosis. However, enlisted survivors coped well with military service if their treatment sequelae were taken into consideration carefully at the time of enlistment. Vocational opportunities within the armed forces might be an appropriate career option even for survivors of childhood malignancies.

Background: Increasing numbers of children with cancer survive and reach reproductive age. However, the risk of cancer (other than retinoblastoma) in the offspring of survivors of childhood and adolescent cancer is uncertain., Methods: Using data from national cancer and birth registries, we assessed the risk of cancer among 5847 offspring of 14,652 survivors of cancer in childhood or adolescence diagnosed since the 1940s and 1950s in Denmark, Finland, Iceland, Norway, and Sweden. The offspring were followed up for a diagnosis of cancer for 86,780 person-years, and standardized incidence ratios were calculated., Results: Among the 5847 offspring, 44 malignant neoplasms were diagnosed (standardized incidence ratio, 2.6; 95 percent confidence interval, 1.9 to 3.5). There were 17 retinoblastomas, yielding a standardized incidence ratio of 37. There were 27 neoplasms other than retinoblastoma (standardized incidence ratio, 1.6; 95 percent confidence interval, 1.1 to 2.4). The second most common primary site of cancer among the offspring was the brain and nervous system, in which eight tumors were observed (standardized incidence ratio, 2.0; 95 percent confidence interval, 0.9 to 3.9.) There were between zero and four apparently sporadic cases of cancer in other primary sites among the offspring. Excluding 4 likely cases of hereditary cancer and 2 subsequent cancers among the offspring with hereditary retinoblastoma, there were 22 sporadic cancers, for a standardized incidence ratio of 1.3 (95 percent confidence interval, 0.8 to 2.0)., Conclusions: There is no evidence of a significantly increased risk of nonhereditary cancer among the offspring of survivors of cancer in childhood.

Sixty-four children with malignant brain tumours diagnosed at less than 3 years of age were reported to the Finnish Cancer Registry from 1975 to 1993. The survival rate has improved significantly: the 5-year survival rate was 26% for all children, 13% for children diagnosed during 1975-85 (n = 30) and 40% for those diagnosed during 1986-93 (n = 34). Of the surviving children in 1986-93, 43% were categorized in Bloom's group I or II and could lead active lives without major disabilities. The remaining children had severe neurologic late complications, such as hemiplegia, intractable seizures, and mental retardation.

Purpose: To assess the risk of subsequent malignant neoplasms among Hodgkin's disease patients diagnosed before 20 years of age in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden)., Patients and Methods: There were 1,641 Hodgkin's disease patients identified through the national cancer registries since the 1940s or 1950s. The patients were monitored for 17,000 person-years until the end of 1991. Expected figures were derived from the age-specific incidence rates in each country and standardized incidence ratios (SIR) were calculated., Results: A total of 62 subsequent neoplasms were diagnosed (SIR, 7.7; 95% confidence interval [CI], 5.9 to 9.9). The overall cumulative risk of subsequent neoplasms was 1.9% at the 10-year follow-up point, 6.9% at 20 years, and 18% at 30 years. There were 26 subsequent neoplasms among males (SIR, 6.5; 95% CI, 4.3 to 9.6) and 36 among females (SIR, 8.9; 95% CI, 6.2 to 12), of which 16 were breast cancers (SIR, 17; 95% CI, 9.9 to 28). High risks were seen for thyroid cancer (SIR, 33; 95% CI, 15 to 62), for secondary leukemia (SIR, 17; 95% CI, 6.9 to 35), and for non-Hodgkin's lymphoma (SIR, 15; 95% CI, 4.9 to 35). The relative risk increased from 3.3 (95% CI, 1.2 to 7.1) for Hodgkin's disease patients diagnosed in the 1940s and 1950s to 15 (95% CI, 7.4 to 27) in the 1980s. The highest risk of secondary leukemia (SIR, 68; 95% CI, 18 to 174) was seen among those diagnosed with Hodgkin's disease in the 1980s., Conclusion: Patients who survive Hodgkin's disease at a young age are at very high relative risk of subsequent malignant neoplasms throughout their lives. In particular, the high relative risk of breast cancer following Hodgkin's disease in the teenage years calls for enhanced activity for early diagnosis.

We evaluated the outcome of 68 children with malignant brain tumors treated with the "8 in 1" chemotherapy protocol in Finland from 1986 to 1993, comparing 5-year survival rates with those for a historical control group (from 1975 to 1985). For all malignant brain tumors, overall survival was 43% (vs 28% in the control group; P <0.05), and progression-free survival (PFS) was 43% (vs 23%; P <0.05). For medulloblastoma and primitive neuroectodermal tumor, survival was 63% (vs 35%; P <0.05), and the corresponding PFS was 59% (vs 35%; P = 0.15). For high-grade glioma, both the survival rate and the PFS were 27% (vs 17%; P = NS). Thus the outcome was significantly better for our "8 in 1" -treated patients than for the historical controls, especially among the children with primitive neuroectodermal tumor and medulloblastoma. In contrast, those with high-grade gliomas and brain stem tumors seem to have received little benefit; different, more effective treatments are needed for these patients.

Objective: To evaluate trunk muscle strength and performance in long-term survivors of childhood malignancies relative to age and sex-matched controls, and to relate the muscle strength observations to the therapeutic agents used and possible hormonal disturbances., Design: Age and sex-matched cohort study., Setting: Referral center in the northern part of Finland., Patients: Forty-six long-term survivors of childhood cancer. Mean age at examination 19.1 years and median off-therapy time 9.4 years., Intervention: Isokinetic dynamometer testing., Main Outcome Measures: Measurements of trunk muscle peak torque (PT) and total work done (TWD) were performed at angle speeds of 50 degrees/sec and 200 degrees/sec. The results were normalized relative to body fat-free weight (FFW)., Results: PT in the trunk muscles was lower in the patients at both angle speeds (mean normalized PT = 5.7Nm/kgFFW vs 7.6Nm/kgFFW for controls at 50 degrees/sec), as also was TWD except for extension TWD at the higher angle speed (mean normalized TWD = 59.9J/kgFFW vs 84.6J/kgFFW for controls at 200 degrees/sec). The normalized PT at 50 degrees/sec and TWD at 200 degrees/sec were lower in the males with testicular damage; also, low age at diagnosis correlated positively with muscle strength and performance. There were no differences in normalized PTs or TWDs between cranial radiation and non-radiation cases, or between growth-hormone-deficient and non-deficient cases, and the patients without cranial radiation or with normal growth hormone secretion still had lower normalized PTs and TWDs than the controls., Conclusions: Survivors of childhood malignancies have decreased maximal trunk muscle strength and performance. The etiology of this effect remains unclear, but young age at diagnosis, as well as serum testosterone levels in male survivors, evidently influence muscle strength and performance.

Objective: To assess the relative risk of developing a second malignant neoplasm in people with a diagnosis of cancer in childhood and adolescence., Design: Register based follow up study., Setting: Populations of Nordic countries., Subjects: 30,880 people under the age of 20 with a first malignant neoplasm diagnosed during the period 1943-87., Main Outcome Measures: Relative and attributable risks of second malignant neoplasms by type of first cancer, age at first diagnosis, calendar period, sex, and country. Expected figures were based on the appropriate national incidence rates for cancer., Results: 247 cases of second malignant neoplasms were observed in 238 patients, yielding a relative risk for cancer of 3.6 (95% confidence interval 3.1 to 4.1). The risk changed significantly from 2.6 in people first diagnosed during the 1940s and 1950s to 6.9 among cohort members included in the late 1970s and 1980s. Increases were observed for most types of cancer. Highest levels of the relative risk were seen during the 10 years immediately after first malignant diagnosis. The incidence of second malignant neoplasms attributable to the first cancer and associated treatments, however, showed a consistent rise throughout the 45 years of follow up., Conclusion: The estimated risks for a second malignant neoplasm were significantly lower than those found in most large hospital based studies but compatible with the results from a similar population based study in the United Kingdom. Extent of risk and cancer pattern were similar among the Nordic countries and are believed to be representative for a large part of the European population.

111 febrile episodes in 98 neutropenic children were randomly treated with either ceftazidime (CAZ) 150 mg/kg/day or with piperacillin (PIP) 200 mg/kg/day, both combined with flucloxacillin (FLUC) 50 mg/kg/day. A total of 37/47 (79%) eligible episodes in the CAZ group and 41/53 (77%) in the PIP group were cured without needing to stop the initial therapy. The success without modification of the treatment in the verified septicaemias in the CAZ group was 8/18 (44%) and in the PIP group 5/18 (28%). Of the bacteriologically documented infections, 13/24 (54%) in the CAZ group and 11/24 (46%) in the PIP group were cured without modification of the therapy. Similarly, 17/31 (55%) of all the isolated bacteria in the CAZ group and 14/33 (42%) in the PIP group were eradicated with the initial therapy. Overall there were 13 deaths of which 4 in the CAZ group and 5 in the PIP group occurred during the infection. An increasing granulocyte count exceeding 0.25 x 10(9)/l at the end of the therapy was a good prognostic sign for the outcome of the infection. This study indicates that CAZ is as effective as PIP in the treatment of infections in neutropenic children.

Ultrasonic features of the kidneys of seven infants with congenital nephrotic syndrome of the Finnish type under active conservative treatment are described. In all cases the kidney were enlarged an the cortex more echogenic than the liver and spleen parenchyma. The pyramids were small with hazy borders resulting in an indistinct or lost corticomedullary border. At follow-in the echogenity of the renal cortex increased still further in four infants and the pyramids became invisible. The differential diagnosis is discussed.

The prevalence and location of enamel opacities was recorded in 37 subjects from low-fluoride areas who had received anti-neoplastic therapy and was compared with an equal number of healthy controls. All the patients had received combination chemotherapy for a malignant disease for at least 2 yr early on in their lives. These cases, and especially those with leukemia, had more opacities than the controls, although these opacities were mild in form. The results show that childhood cancer and/or the therapy provided for this can affect the developing dentition, involving all teeth in leukemia cases and the permanent teeth of the mixed dentition period in other cancer diseases.