History of pediatric hematology and oncology in Finland: a brief review.

The history of Finnish pediatric hematology started in the late 1940s, but this field of pediatrics was not officially acknowledged before 1979. The Children's Hospital, University of Helsinki started hematological services in 1950 but at that time there was no position for a specialist--it was a "spare time" work until 1980 when a hematology/oncology ward was established led by a full time specialist. Since the late 1950s the pediatric department of the Aurora Hospital in Helsinki has made an important contribution to the development of Finnish pediatric hematology. The Blood Transfusion Service of the Finnish Red Cross has also played an important role in Finnish pediatric hematology. The remaining four University Hospitals have now established wards for pediatric Hematology/oncology.

Bone marrow dysfunctions preceding acute leukemia in children: a clinical study.

This is a review of preleukaemic states in children. In a prospective series of 109 children with AML the overt disease was preceded by MDS in 22 cases. Ten of these patients had Down's syndrome. Advanced FAB groups were represented in the series. An important subgroup is the bone marrow monosomy 7 syndrome. Cytogenetic anomalies are common in MDS, and multiple and complicated abnormalities develop in nearly all patients with progressing disease. Some children die before transformation to overt ANLL. Transformation usually occurs, few children survive. With cytostatic treatment the risk of irreversible aplasia is great. The choice of schedule should therefore be carefully considered. Bone marrow transplantation has proved beneficial in a number of cases, but these are still quite few. The dysfunction of the bone marrow preceding ALL is due to transient aplastic anaemia--spontaneous remission--overt ALL, often FAB type L1, immunophenotype CALLA. The ALL reacts to the same treatment as de novo ALL of the same type and the prognosis is the same.

Reproduction following treatment for childhood leukemia: a population-based prospective cohort study of fertility and offspring.

Of all children diagnosed with leukemia in Denmark, Finland, Iceland, Norway, and Sweden, 981 had discontinued therapy before 1985 and had been followed up annually after cessation of therapy. Progeny was registered and fertility evaluated among survivors who passed age 18 years without a relapse (n = 299). By April 1989, 48 offspring were registered, one of whom had congenital anomalies. This was no more than expected from the incidence of birth defects in the general population. No childhood malignancies or genetic diseases have so far been diagnosed in the progeny. In the study group, none of the 19 female and 8 male survivors of myeloid leukemias had become parents, and only 4 fathers were reported among the 131 male survivors of acute lymphoblastic leukemia (ALL). However, 23 of the 149 females treated for ALL had delivered 41 children. Fertility was measured as cumulative rates of first birth by maternal age. In a Cox regression analysis, cases who had received prophylactic radiation of the central nervous system (CNS) had a lower first birth rate than those without radiation (rate ratio 0.39, 95% CI 0.15-1.00), indicating that doses of 18-24 Gy to the brain may possibly be a risk factor. By using the Norwegian birth cohort of 1966 as a control group, matching the median year of birth for the study subjects, the group of female ALL survivors as a whole was as likely as the general female population to have given birth up to the age of 23. The first generation of females successfully treated for childhood ALL seems to have a nearly normal reproductive pattern during young adulthood, without increased risk of congenital anomalies in the offspring. However, cranial radiation as CNS prophylaxis may possibly impair subsequent reproduction.

Preleukemic syndrome in children. Report of four cases and review of literature.

Childhood preleukemia, known as a rare condition, was evaluated in four of the authors' cases and in 24 cases from the literature. The required condition was evolution into overt acute leukemia. The children were 5 months to 15 years of age, and the preleukemia period ranged from 2 to 42 months. The symptoms and physical signs were nonspecific. Different kinds of cytopenia were found in the peripheral blood. Twelve children developed ALL and 16 developed AML. The analysis revealed that in childhood there exist two different types of preleukemia: pre-ALL and pre-AML. The age and sex distribution were different, as were the hematological changes. The marrow was usually hypoplastic in pre-ALL but hyperplastic in pre-AML. True hypoplasia in any of the three cell lines was more common in pre-ALL, whereas ineffective thrombopoiesis and normal or increased myelopoiesis were specific for pre-AML. Ineffective erythropoiesis was characteristic of both types. A typical chromosomal change in marrow, seen in pre-AML only, was a missing group C chromosome. The childhood pre-AML resembled adult preleukemia (also pre-AML) in many aspects, whereas the childhood pre-ALL seemed to be a different entity. It might be assumed that all preleukemic conditions do not evolve to overt malignancy. The incidence and true prognosis therefore remain unknown.

Benign congenital erythropenia.

Normochromic anaemia was diagnosed in two brothers in early infancy. At the time of this report they were aged 10 (M.H.) and 12 (T.H.) years. A defect of the atrial septum was found in both patients. They had slight skeletal malformations. Their haemoglobin values have remained constantly at the level of about 100 g/l and the RBC count at about 3.5 x 10(12)/l. At repeated examinations, both the patients and their parents had low or borderline low erythrocyte enolase levels. Erythropoietin levels were normal and so were numerous other laboratory tests, including analysis for abnormal haemoglobins. The condition could represent a mild form of chronic congenital hypoplastic anaemia.

Change in cellular phenotype from lymphoid to erythroid in a case of ALL.

Acute leukaemia was diagnosed in a 3-month-old boy. Initial blood leucocyte count was 97 x 10(9)/1, 92% of the cells were morphologically small lymphoblasts which according to surface marker analysis were of the common ALL (non-T non-B) type. Remission was achieved with initial treatment. During relapse 5 months later a morphologically different leukaemic cell appeared in the bone marrow, blood and liquor. This cell type which dominated during the terminal stage of the disease was larger and had an abundant bosophilic cytoplasm which contained PAS-positive granulae. Sudan, myeloperoxidase and benzidine staining gave negative results. Neither T nor B lymphocyte markers were seen but a strong surface expression of glycophorin A was found by indirect immunofluorescence with specific rabbit anti-glycophorin A antiserum. The cells showed a unique surface glycoprotein pattern. Bone marrow karyotype analysis gave in about 80%: 47,XY,+8,t(4:11) indicating that this blast cell represented a malignant clone. As glycophorin A is expressed exclusively on erythroid cells and their precursors, this finding indicates a change from a 'lymphoid' to an erythroid phenotype of the leukaemic cells during the course of the disease.

Progeny of survivors of acute lymphocytic leukemia.

Eight successful pregnancies and one spontaneous abortion have been observed in 5 women belonging to a group of 212 Nordic children who had their antileukemic therapy discontinued before January 1, 1978. Furthermore a young leukemic man was the father of a healthy child after 4 years of intensive cytostatic therapy. No malformations have been observed in the progeny of these treated individuals.

A case of pure monocytic leukaemia in a child - characterization of cellular morphology, membrane markers, surface glycoproteins and karyotype.

A case of pure monocytic, 'Schilling-Type' leukaemia in a 9-year-old boy is described. The leukaemic cells resembled monocytes and were abundantly present in blood and bone marrow. They were strongly alpha-naphthyl-acetate-esterase positive, contained fine PAS-positive granules and did not stain by Sudan B. They were negative for surface bound and intracytoplasmic IgG, but had a high density of membrane Fc-receptors and showed phagocytosis. The surface glycoprotein pattern resembled that of monocytes, but was clearly different from those of lymphocytic and myelocytic cells or those of acute lymphocytic leukaemia cells. The karyotype of bone marrow cells was 44,X, -15, -21, +mar,del(2)(p11), with the missing Y-chromosome located in the marker chromosome. Especially the surface glycoprotein and membrane receptor analyses aided in the accurate classification of the monocytic origin of the leukaemic cells.

Transient erythroblastopenia in childhood. A study of 15 cases.

A survey is presented of 15 patients from the Aurora Hospital and 35 patients reported in the literature with transient erythroblastopenia of childhood (TEC). The children were hospitalized because of pallor and tiredness, some of them having signs of mild infection. They displayed normochromic anaemia, reticulocytopenia and erythroblastopenia during the severe stage of the disease. In addition, they had moderately high values for serum iron and iron-binding saturation. No other haematological, chemical or cytogenetic abnormalities could be demonstrated. 80% of the children were between 6 and 48 months old and the sexes were equally affected. In the 15 patients from the Aurora Hospital a barely significant (p=0.02-0.05) association with blood group A was recorded. Remission, indicated by a rise in the reticulocyte count, begins within a week after the diagnosis is made, even without treatment. The aetiology of the disease is unknown. Analysis of the red blood cell population at the time of diagnosis indicates that damage to the red cell precursors has occurred 2-3 months before the child is brought for examination.