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S Garwicz

Publications and source records attributed to S Garwicz.

At least 37 records · Page 2Linked to original sources
PubMed1996

No FISH evidence for trisomy 7 in normal or leukemic bone marrow.

Trisomy 7 has been found as the sole chromosomal anomaly in both benign and malignant tumors, as well as in nonneoplastic lesions. It has been reported that +7 may occur in tumor-infiltrating as well as in peripheral T cell and in the thymus. The precursor cells, which mature in the thymus to T lymphocytes, originate in the bone marrow and the present study was undertaken to investigate whether cells carrying an extra chromosome 7 can be detected there. Bone marrow samples from five hematologically normal individuals and 12 children with acute lymphoblastic leukemia (ALL) were analyzed by interphase fluorescence in situ hybridization (FISH) using a chromosome 7 centromere-specific probe. Half of the ALLs were karyotypically normal, whereas the other half displayed clonal abnormalities (one pseudodiploid and five hyperdiploid karyotypes, none of which had +7). The FISH analysis showed no evidence of cells with trisomy 7 in the bone marrow samples from the controls or ALLs. This suggests that the gain of a chromosome 7 by T lymphocytes does not occur before the bone marrow precursor cells are conditioned in the thymus.

Adolescent↗
PubMed1996

t(3;21)(q26;q22) with AML1 rearrangement in a de novo childhood acute monoblastic leukaemia.

t(3;21)(q26;q22) is a recurrent chromosomal abnormality in Philadelphia-positive chronic myeloid leukaemia in blast crisis and in treatment-related myelodysplastic syndrome and acute myeloid leukaemia. The molecular consequences of the t(3;21) are presently being unravelled; various transcripts between the AML1 gene in 21q22 and several unrelated genes, i.e. EAP, EVI1 and MDS1, in 3q26 are generated, resulting in the formation of a chimaeric transcription factor. The t(3;21) has only rarely been described in de novo leukaemias and never before in an acute leukaemia in a child. We here present the clinical, cytogenetic and molecular genetic findings in a boy with a de novo acute monoblastic leukaemia with t(3;21)(q26;q22) and AML1 rearrangement.

Blotting, Southern↗
PubMed1996

Risk of subsequent malignant neoplasms among 1,641 Hodgkin's disease patients diagnosed in childhood and adolescence: a population-based cohort study in the five Nordic countries. Association of the Nordic Cancer Registries and the Nordic Society of Pediatric Hematology and Oncology.

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.

Adolescent↗
PubMed1995

Outcome after first relapse in children with acute lymphoblastic leukemia: a population-based study of 315 patients from the Nordic Society of Pediatric Hematology and Oncology (NOPHO).

UNLABELLED: This study reports the outcome after relapse of acute lymphoblastic leukemia (ALL) in a population-based study of 809 children over 1 year of age diagnosed July 1981 through June 1986 and with non-B acute lymphoblastic leukemia in the five Nordic countries. By January 1994, 315 children had suffered at least one relapse. The bone marrow was involved in 216 cases. There were 69 isolated CNS relapses, 25 isolated testicular recurrences and five relapses in other extramedullary sites. Of the 315 children with relapse, 94 are still in a second complete remission 12-138 (median: 78) months after relapse. The overall probability of a second event free survival (P-2.EFS) and survival after relapse was 0.28 and 0.33 respectively. The probability of remaining in second remission at 11 years was significantly correlated to the duration of first remission (P < 0.001), the site of relapse (P < 0.001) and gender (P = 0.004). The P-2.EFS for early, intermediate, and late bone marrow involved relapses were 0.08, 0.19, and 0.50 respectively. For early, intermediate and late isolated CNS relapses the P-2.EFS were 0.21, 0.38 and 0.61, respectively. The P-2.EFS for boys with isolated testicular relapses was 0.69. Girls with isolated CNS relapse (P < 0.001) and with bone marrow involved relapse (P = 0.04) had a significantly better prognosis than boys. Children with initial high risk criteria, especially T-ALL and mediastinal mass who relapsed, had a very poor prognosis. CONCLUSION: In this population-based study, about 30% of children with ALL obtained a long second remission and possible cure.

Adolescent↗
PubMed1995

High-dose methotrexate causes short-term suppression of growth in rabbits.

Bone growth in rabbits was measured using roentgen stereophotogrammetric analysis (RSA), a method for accurate measurement of the distance between metallic markers inserted into long bones. Injections of methotrexate (Mtx) were given to five rabbits and tibial growth was measured daily for 5 days. Im injections of Mtx 100 mg/kg body weight, followed by folinic acid "rescue" 48 h later, had no influence on growth. Intraperitoneal injection of Mtx 1000 mg/kg body weight resulted in a clear reduction in daily growth during the study period. The rabbits were given folinic acid "rescue" 24, 36 and 48 h after Mtx injection and showed no symptoms or signs of Mtx toxicity. Serum levels of Mtx, 3 days after the high-dose injection, declined successively but were still measurable after 72 h. Using RSA, the short-term influence of cytostatic drugs can be evaluated in an experimental setting. The effect of Mtx on growth in rabbits was discernible only at very high doses. Suppression of growth was moderate, appeared soon after injection of Mtx and was of moderate duration.

Animals↗
PubMed1994

[Second cancer. Risk of a second malignant neoplasm in persons with cancer in childhood and adolescence].

Cancer treatments in early life have in previous studies been associated in with high risks of developing a second malignant neoplasm. This study reports on the relative and attributable risks of second malignant neoplasms among 30,880 people under the age of 20, who had been identified in the files of any of the five Nordic cancer registers, 1943-1987. Overall, 247 cases of second malignant neoplasms were observed in 238 patients, yielding a relative risk for cancer of 3.6 (95% confidence interval 3.1-4.1). 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. Highest levels of the relative risk were seen during the ten 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. It was concluded that the estimated risks for second malignant neoplasms 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.

Adolescent↗
PubMed1994

Cerebral irradiation causes blunted pubertal growth in girls treated for acute leukemia.

The improved treatment of childhood leukemia is a major achievement. The late effects of the treatment need further investigation. Growth inhibition has been demonstrated in earlier studies. Growth and the timing of puberty were studied in 179 girls who had been treated for acute lymphoblastic leukemia (ALL) in Denmark, Finland, Norway, and Sweden. The patients were divided into two groups according to mode of CNS prophylaxis: with or without cerebral irradiation. Longitudinal analysis of 103 patients showed no difference in prepubertal growth in irradiated and nonirradiated girls. Growth during puberty was normal in girls without irradiation and below normal in irradiated girls. There was no difference in growth between girls after 24 Gy or 20 Gy of cerebral irradiation. Irradiated girls had a final height which was one SD less than expected before puberty and menarche occurred one year earlier than in the nonirradiated girls. Prophylactic cerebral irradiation is the most important factor for subnormal growth after treatment for ALL. There is no short-term influence on growth but the effects of irradiation become apparent several years after therapy when girls enter puberty somewhat early and have a subnormal pubertal growth. Growth and growth hormone (GH) levels should be evaluated several years after CNS irradiation, and treatment with GH and/or luteinizing hormone releasing hormone (LHRH) analogues may be considered.

Adolescent↗
PubMed1993

Second malignant neoplasms after cancer in childhood or adolescence. Nordic Society of Paediatric Haematology and Oncology Association of the Nordic Cancer Registries.

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.

Adolescent↗
PubMed1992

Hepatocellular carcinoma associated with arteriohepatic dysplasia in a 4-year-old girl.

Hepatocellular carcinoma and obliterated hepatic bile duct were found at postmortem examination in a 4-year-old girl with arteriohepatic dysplasia (Alagille's syndrome). AFP level was extremely high. Liver cirrhosis was present on percutaneous needle biopsy 9 months before she succumbed in progressive liver failure. Episodes of repeated gastrointestinal, life-threatening hemorrhages occurred during the last 6 months of her life. Histopathologic findings of the eyes were documented at autopsy.

Alagille Syndrome↗
PubMed1992

Superior treatment results in females with high-risk acute lymphoblastic leukemia in childhood.

In this population-based study, 808 children aged 1-15 years from Denmark, Finland, Iceland, Norway and Sweden, were diagnosed between July 1981 and June 1986 as suffering from non-B-cell acute lymphoblastic leukemia (ALL). The total population was 4.5 million children. Remission was achieved in 770/808 of the patients (95%). No sex difference in the remission rate was observed. The event free survival (EFS) at 102 months was 0.47 for males and 0.62 for females (p less than 0.001). There was no difference in EFS between males and females with standard-risk (0.58 and 0.60) or intermediate-risk (0.47 and 0.60) ALL, respectively. The EFS for females with high-risk ALL (0.68) was superior to that of males with high-risk ALL (0.31). Cox multivariant analysis showed that white blood cell count, sex, age and thrombocyte count were significant prognostic factors in all children. The intensified treatment according to the prognostic factors used in this study led to equal EFS for females with ALL from all risk groups. Males with high-risk ALL, however, did not benefit from the intensified treatment.

Age Factors↗
PubMed1992

Molecular analysis of Philadelphia-positive childhood chronic myeloid leukemia.

The breakpoints in chromosome 22 were determined in five children with Philadelphia-positive chronic myeloid leukemia. All had rearrangements within the major breakpoint cluster region (M-bcr). Four patients had breakpoints in the 5' region of M-bcr (zones 1-3), whereas one had a rearrangement in the 3' region (zone 4). The patient with the 3' rearrangement was the only one to develop a lymphoid blast crisis; he also had a substantially longer survival (102 months) than the others (11-54 months).

Child↗
PubMed1991

Second malignant neoplasms in patients treated for childhood leukemia. A population-based cohort study from the Nordic countries. The Nordic Society of Pediatric Oncology and Hematology (NOPHO).

Among a cohort of 981 children who were followed up 4.3-26.5 years after cessation of antileukemic therapy, eight patients in remission of acute lymphoblastic leukemia (ALL) developed a distinctively new malignant disease. The second malignant neoplasms (SMN) included brain tumors, basal cell carcinomas, thyroid cancer, leiomyosarcoma and finally rhabdomyosarcoma in a patient who also had suffered from Hodgkin's disease while still on antileukemic treatment. Cranial radiation had been given to 58.4% of the patients in the study group, which consisted of 895 ALL patients who had completed various chemotherapy protocols. With one exception, the SMN appeared after 7.5-16.5 years at a location previously exposed to radiotherapy (RT). The estimated cumulative risk of SMN appearing within 20 years after diagnosis was 2.9%, and the corresponding risk for cases with RT was 8.1% compared to 0.3% for those without (p = 0.05). In a Cox regression analysis, the incidence rate ratio of SMN between patients with and without RT was 6.7 (95% CI = 0.8, 57.7). Based on age-, year- and sex-specific cancer incidence figures for Norway, the overall standardized incidence rate ratio (SIR) of SMN after treatment for ALL was 5.9 (95% CI = 2.2, 12.9). The number of brain tumors among patients who had received cranial radiation was nearly 27 times greater than expected, whereas no such tumors were seen after chemotherapy. Individuals treated for childhood ALL are at increased risk of a new malignancy, and this seems mainly to be associated with previous irradiation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Pharmacokinetics of cytosine arabinoside in cerebrospinal fluid and of its metabolite in leukemic cells.

Concentrations of ara-CTP in leukemic cells isolated from CSF and of ara-C in lumbar CSF were measured following intraventricular ara-C administration in two girls with refractory meningeal leukemia. CSF samples were collected with a permanent intrathecal-lumbar catheter. In contrast to the comparatively short retention of ara-C in the CSF (t1/2 1.8 to 2.9 hours), there was a high accumulation and an extremely long retention of ara-CTP in the leukemic cells (t1/2 8.1 to 36 hours). The patients included in this study had an ara-C-resistant disease. No obvious relationship was seen between concentrations of ara-C in the CSF and of ara-CTP in the leukemic cells. Similar studies were performed after simultaneous intraventricular administration of hydrocortison and ara-C. Hydrocortison did not increase ara-CTP retention in the leukemic cells, nor did it effect CSF pleocytosis.

Arabinofuranosylcytosine Triphosphate↗
PubMed1990

Bone marrow karyotypes in 94 children with acute leukemia.

During the last 10 years, we have cytogenetically analyzed at diagnosis bone marrow cells from a total of 94 children with acute leukemia. Of the 78 children with acute lymphatic leukemia (ALL), 53 (68%) had clonal acquired chromosome abnormalities; in the group with acute nonlymphatic leukemia (ANLL), the corresponding proportion was 13 out of 16 (81%). Among the cytogenetically abnormal ALL patients, the most numerous subset was the hyperdiploid cases with stemlines containing 51 or more chromosomes (26 of 53 abnormal cases; 49%). This is a clearly higher proportion than has been reported in large series from other centers. Deletions of 6q were present in 8 cases and rearrangements of 12p in 5. Of the 7 T-cell ALLs, 3 had translocations of the distal part of 7q, i.e., of the region where the beta T-cell receptor is encoded. Only 2 of 26 (8%) patients with leukemic stemlines with more than 50 chromosomes have relapsed; the remainder are still in first remission (mean observation time 42 months). This may be contrasted with 6 of 25 (24%) relapses among the cytogenetically normal (observation time 41 months), and 8 of 27 (30%) relapses among ALL patients with aberrations but with less than 51 chromosomes (observation time 26 months). Our results support the conclusion that the finding of a markedly hyperdiploid leukemia karyotype is indicative of good prognosis in ALL.

Adolescent↗
PubMed1990

Platelet surface-bound IgG and platelet-specific IgG in plasma in childhood thrombocytopenia.

Quantification of platelet-bound immunoglobulin is widely used in the evaluation of thrombocytopenia. Several methods have been devised among which labelled ligand-binding assays seem to be most appropriate. In series of adult patients such assays have been shown to be superior in separating immune-thrombocytopenia from thrombocytopenia of non-immune causes. We studied 62 children with thrombocytopenia of various causes, using radiolabelled protein A as a ligand to measure platelet-surface bound IgG. The test was highly sensitive (93%) in detecting immune-thrombocytopenia. The specificity, however, was only 57%, which is less than in published studies of adults. In a number of cases presumed to be non-immune-thrombocytopenia, notably a few patients with leukaemia and bone marrow aplasia, we found increased amounts of platelet surface-bound IgG. The significance of this finding is not clear. An indirect assay measuring platelet-specific IgG in plasma was less sensitive (46%) but highly specific for immune-thrombocytopenia (89%). The measurements of platelet-surface-bound IgG and platelet-specific IgG in plasma are of limited diagnostic value in childhood thrombocytopenia but are useful in following the treatment in chronic ITP.

Antigens, Surface↗