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J D Buckley

Publications and source records attributed to J D Buckley.

At least 19 recordsLinked to original sources
PubMed1992

Expression of lymphoid-associated cell surface antigens by childhood acute myeloid leukemia cells lacks prognostic significance.

The prognostic significance of cell surface antigens associated with lymphoid and myeloid lineage differentiation on the blasts of children with acute myeloid leukemia (AML) was evaluated. Leukemic blasts from 176 patients enrolled on Childrens Cancer Study Group Protocol 213 determined to have AML by standard morphologic and cytochemical criteria were immunophenotyped. Cell surface antigens associated with myeloid differentiation were found on blasts from 88.1% of patients (CD15, 44%; CD33, 65%; CD36, 53%; glycoprotein Ib, 9.3%). However, blasts from 30.7% of patients expressed surface antigens thought to be specific for lymphoid lineage differentiation (CD2, 9.4%; CD5, 2.7%; CD19, 34.5%; CD20, 0.8%). In addition, CD34, a glycoprotein found on immature cells of both myeloid and lymphoid lineages, was expressed on the blast cells of 48.2% of patients. With the exception of the lymphoid lineage nonspecific antigen CD4, no correlation was found between white blood cell count at diagnosis, age, and French-American-British morphology, and the expression of any of the lymphoid- or myeloid-associated cell surface antigens studied. Nor was the expression of these antigens prognostically significant with respect to response to induction therapy, death during induction, survival, event-free survival, or survival/event-free survival following remission induction. Multivariate analysis showed that CD4 expression was not an independent predictor of outcome. Thus, this prospective study suggests that expression of lymphoid-associated cell surface antigens as well as myeloid-associated antigens by childhood AML blasts lacks prognostic significance.

Adolescent↗
PubMed1992

Expression of myeloid differentiation antigens in acute nonlymphocytic leukemia: increased concentration of CD33 antigen predicts poor outcome--a report from the Childrens Cancer Study Group.

Ninety-eight cryopreserved specimens of acute nonlymphocytic leukemia (ANLL) cells obtained at initial diagnosis of children enrolled on the Childrens Cancer Study Group 251 protocol (CCG 251) were examined by indirect immunofluorescence using four monoclonal antibodies to myeloid differentiation antigens. The relationship between the level of differentiation of ANLL cells as determined by their antigen phenotype and the clinical outcome of treatment, including complete remission (CR) rate, survival, and event-free survival, was evaluated. Most leukemic specimens were determined to express the CD33 antigen (L4F3), a 67-kD protein. Because the level of differentiation of normal myeloid cells is reflected by the concentration of the CD33 antigen expressed, samples were categorized as CD33-bright (immature) versus CD33-dull (mature). Patients with CD33-bright leukemic blasts had a marginally inferior CR rate to those with CD33-dull blasts (P = 0.08). With respect to survival and event-free survival, there was a significantly inferior outcome in the CD33-bright patients (P = 0.04 and P = 0.06, respectively). Reactions of ANLL with anti-CD15 antibody (1G10), anti-CD36 antibody (5F1), or anti-CD17 antibody (T5A7) did not predict clinical outcome. This study indicates that patients whose ANLL blasts displayed the CD33 antigen in an amount associated with immature myeloid cells experienced a worse outcome than patients with ANLL blasts that expressed a phenotype associated with more mature cells.

Antibodies, Monoclonal↗
PubMed1992

The CCSG prospective study of venous access devices: an analysis of insertions and causes for removal.

This is an interval analysis of the 2-year prospective multicenter Childrens Cancer Study Group study of 1,141 chronic venous access devices in 1,019 children with cancer. Device type was external catheter (EC) 72%, totally implantable (TID) 28%, and did not differ for diagnosis or age except more double-lumen devices in bone marrow transplant protocols (77%) and more TIDs in children less than 1 year old (17.7%). Insertion characteristics evaluated in 1,078 (95%) were: operating room placement 99%; general anesthesia 98%; cutdown 67%; percutaneous 33%; atrial position 50%, caval position 50%; and perioperative antibiotics 48%. Vein entry was the external jugular 33%, internal jugular 22%, subclavian 35%, cephalic 7%, and saphenous 3%. Insertion was difficult or very difficult in only 10% and operative complications occurred in only 0.7%. Degree of difficulty bore no relationship to device type or patient age. The reasons for removal in 736 devices (67%) were due to complications in 39%, of which infections were the most frequent. There was some variance between centers ranging from 8.5% to 31% for infection; 2.8% to 24% for dislodgment; and 0% to 13% for occlusion. ECs had a higher risk of dislodgment; elective removals were more frequent in TIDs; there was no difference in infection as a cause for removal between ECs and TIDs. Dislodgment was associated with the shortest distance of the cuff to the skin exit (mean, 4 cm): less than or equal to 2 cm, 49%; greater than 2 cm, 28% (P = .009) and occurred most frequently in the younger patient (18.9%, 0 to 1 years; 0.5%, greater than 8 years.

Adolescent↗
PubMed1992

The aetiology of cancer in the very young.

Epidemiological studies of cancer in young children have implicated a number of environmental factors, which need to be studied in more detail, but it is probably fair to say that the main benefit of these studies has come from the negative findings, which have served to exclude (or at least place an upper limit on the role of) potential risk factors. Our inability to identify environmental causes could mean either that the environment does not substantially affect cancer incidence in young children, or that we are simply not looking in the right places. Most attention has naturally been focused on the known and suspected environmental carcinogens and mutagens. Based on the data summarised in this paper, one possibility is that the most important mutagen is endogenous: 5-methyl-cytosine. If so, factors increasing cancer risk could be those which increase the rate of spontaneous deamination, or impair the efficiency of the excision repair enzymes, or regulate the processes of CpG methylation and demethylation. These factors could still be classed as mutagens in their own right, since they would lead to an increase in uncorrected point mutations, but they would be distinctive in a number of ways. Firstly, since the role of methylation in bacteria is very different from that in eukaryotic cells the Ames mutagenicity assay could not be relied upon to detect methylation-mediated mutagens. Furthermore the risk may be highly age dependent, reflecting changes in methylation patterns with growth and cellular differentiation. Agents which disrupted the imprinting process in the testis would not be detectable by animal carcinogenicity tests unless specifically looked for.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1991

From gene to carcinogen: a rapidly evolving field in molecular epidemiology.

Chemical and physical carcinogens leave footprints of their activities on DNA because of the patterns of base changes they induce. Additionally, the conversion of 5-methylcytosine to thymine in CpG sequences leads to a characteristic mutation which can be used to estimate the contribution of endogenous processes to human mutations. Knowledge of the pattern mutations found in genes commonly mutated in human cancer, such as the p53 tumor suppressor gene, allows for predictions to be made on the likelihood of an exogenous DNA-damaging agent being involved. Working from gene to carcinogen is likely to have a profound impact on our understanding of the origins of human cancer.

Carcinogens↗
PubMed1991

Successful reinduction therapy with amsacrine and cyclocytidine in acute nonlymphoblastic leukemia in children. A report from the Childrens Cancer Study Group.

Amsacrine (AMSA) and cyclocytidine were studied as retrieval therapy in 122 pediatric patients with acute nonlymphoblastic leukemia (ANLL). Patients either failed to achieve sustained initial remissions or were in relapse. Induction therapy consisted of intravenous (IV) AMSA (75 mg/m2) from days 1 to 5 and subcutaneous cyclocytidine (600 mg/m2) from days 1 to 7. Maintenance therapy consisted of IV etoposide (VP-16) (100 mg/m2) for 5 days and IV AMSA (100 mg/m2) on day 1. Of 122 patients, 109 were evaluable. There were 13 early deaths. Ninety-six patients received adequate therapy defined as completion of two courses of therapy. Of these 96 patients, 52 achieved complete remission. Fifteen of 33 patients who failed initial induction achieved complete remission. Eighteen of 39 patients who were resistant to anthracyclines had complete responses. There was no direct evidence of AMSA-induced cardiotoxicity. Remission duration was 28 days to 3 or more years (median, 98 days). AMSA and cyclocytidine were effective retrieval therapy for patients who were in relapse or unresponsive to frontline therapy. Duration of remission was short (median, 98 days).

Adolescent↗
PubMed1991

High-resolution linkage mapping for susceptibility genes in human polygenic disease: insulin-dependent diabetes mellitus and chromosome 11q.

Insulin-dependent diabetes mellitus (IDDM) has a complex pattern of genetic inheritance. In addition to genes mapping to the major histocompatibility complex (MHC), several lines of evidence point to the existence of other genetic susceptibility factors. Recent studies of the nonobese diabetic mouse (NOD) model of IDDM have suggested the presence, on mouse chromosome 9, of a susceptibility gene linked to the locus encoding the T-cell antigen, Thy-1. A region on human chromosome 11q is syntenic to this region on mouse chromosome 9. We have used a set of polymorphic DNA markers from chromosome 11q to investigate this region for linkage to a susceptibility gene in 81 multiplex diabetic pedigrees. The data were investigated by maximization of lod scores over genetic models and by multiple-locus affected-sib-pair analysis. We were able to exclude the presence of a susceptibility gene (location scores less than -2) throughout greater than 90% of the chromosome 11q homology region, under the assumption that the susceptibility factor would cause greater than 50% of affected sib pairs to share two alleles identical by descent. Theoretical estimates of the power to map susceptibility genes with a high-resolution map of linked markers in a candidate region were made, using HLA as a model locus. This result illustrates the feasibility that IDDM linkage studies using mapped sets of polymorphic DNA markers have, both for other areas of the genome in IDDM and for other polygenic diseases. The analytic approaches introduced here will be useful for affected-sib-pair studies of other complex phenotypes.

Chromosome Mapping↗
PubMed1990

Occupations of parents of children with retinoblastoma: a report from the Children's Cancer Study Group.

A matched case-control study was conducted by the Children's Cancer Study Group to investigate the role of parental occupation in the etiology of sporadic heritable and nonheritable retinoblastoma. Eligible cases were those patients with retinoblastoma diagnosed in 1982-1985 at any of the Children's Cancer Study Group member hospitals. Telephone interviews of 201 parents of cases and their pair-matched controls selected by random digit dialing were completed. Of the 201 cases, 19 were familial, 67 were sporadic heritable, and 115 were nonheritable. The 19 familial cases were excluded from the analysis. Paternal employment in the military [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.1-8.8, P = 0.04] and in the metal industry (OR infinity, 95% CI 1.4-infinity, P = 0.02) was associated with sporadic heritable retinoblastoma (N = 67). For nonheritable retinoblastoma (N = 115), a significant association was observed for a job cluster consisting mostly of welders and machinists (OR 4.0, 95% CI 1.1-22.1, P = 0.04). Occupations of maternal grandparents were also studied and an association was observed with farming and nonheritable retinoblastoma (OR 10.0, 95% CI 1.4-433, P = 0.02). Many comparisons were made and the number of significant findings did not exceed that expected by chance. Thus, the results need to be interpreted very cautiously. However, the findings related to metal exposure corroborate observations on other childhood cancers.

Case-Control Studies↗
PubMed1990

The role of timing of high-dose cytosine arabinoside intensification and of maintenance therapy in the treatment of children with acute nonlymphocytic leukemia.

The Children's Cancer Study Group instituted a pilot study to investigate the use of high doses of cytosine arabinoside (AraC) in the intensification phase of treatment for acute nonlymphocytic leukemia (ANLL). Patients achieving remission and not eligible for allogeneic bone marrow transplantation were treated with four doses of high-dose AraC and L-asparaginase. These drugs were repeated either on or after 28 days (q28 days), after recovery of hematologic parameters (for the first 49 patients entered onto this trial); or after 7 days (q7 days), despite dropping blood counts (for the last 53 patients enrolled). After completing an additional 3 months of intensification therapy, patients were then allocated by physician choice to either discontinue therapy or receive 18 28-day cycles of maintenance therapy, including the daily administration of 6-thioguanine. Despite three deaths associated with the toxicity of the aggressive (q7 days) AraC timing, patients receiving this approach demonstrated equal or better disease-free survival from the end of induction (55% versus 42% actuarially at 3 years [P = 0.52]). Maintenance therapy appeared to play no role in improving outcome for people who received the aggressive timing of AraC cycles. Fifty-nine percent were alive disease free actuarially at 3 years from the decision to not give maintenance therapy (n = 27) compared with 62% for those receiving maintenance therapy (n = 16; P = 0.49). On the other hand, patients who received the less aggressive AraC intensification timing (q28 days) had an improved survival rate if maintenance therapy was administered (n = 17) (65% versus 39% for patients not receiving maintenance therapy [n = 24] at 3 years [P = 0.07]). Maintenance therapy therefore may not improve outcome in patients receiving aggressive timing of high-dose AraC but may be important in less intensive postremission regimens in childhood ANLL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Acute monoblastic leukemia: a unique subtype--a review from the Childrens Cancer Study Group.

The acute non-lymphocytic leukemias (ANLL) are generally treated as a homogeneous group. However, the literature is replete with articles alluding to distinctive features of acute monoblastic leukemia (AMoL). This review addresses the unique clinical, laboratory, epidemiological, and therapeutic features of AMoL. Leukemic monoblasts are distinguished from other cells in the myelocytic series by physical properties such as greater adhesiveness, deformability, and motility. Patients with AMoL often exhibit hyperleukocytosis, disseminated intravascular coagulation, and extramedullary involvement, particularly in the skin, gingiva, and central nervous system (CNS). AMoL occurs predominantly in adults over 40 and children under 10, fifty percent of whom are under 2 years of age at diagnosis. Its relatively common occurrence in infants parallels the high rate of proliferation of monocytes in that age group. Additionally, its occurrence in young children appears to be associated with in utero exposure to marijuana and parental exposure to pesticides and solvents. Therapeutic results are generally poor due to high rates of fatal complications during induction, induction failures, and frequent extramedullary and medullary relapses. This poor outcome is particularly noted in infants. Higher remission induction rates attained with epipodophyllotoxins and incorporation of bone marrow transplantation have not yet resulted in substantial improvement of long-term outcome. Recurrence of disease in the CNS is minimized by the use of intensive CNS presymptomatic treatment, usually incorporating irradiation. Our review suggests that unique and innovative treatment strategies are needed to improve outcome for patients with AMoL.

Adult↗
PubMed1990

Preferential retention of paternal alleles in human retinoblastoma: evidence for genomic imprinting.

The origins of the initial mutations in sporadic retinoblastoma were explored using polymorphic markers from chromosome 13q. The paternal chromosome was maintained in 3 of 3 informative bilateral tumors which had undergone reduction to homozygosity for regions of this chromosome. The paternal chromosome was maintained in 7 of 8 informative unilateral tumors which likewise demonstrated a reduction of homozygosity. These data are in contrast to previously published studies of chromosome retention in unilateral retinoblastoma [Dryja, T. P., Mukai, S., Petersen, R., Rapaport, J. M., Walton, D., and Yandel, D. W. Nature (Lond.), 339: 556-558, 1989; Zhu, Z., Dunn, J. M., Phillips, R. A., Goddard, A. D., Paton, K. E., Becker, A., and Gallie, B. L. Nature (Lond.), 340: 312-313, 1989] and provide the first evidence that genomic imprinting may play a role in this disease.

Alleles↗
PubMed1989

Pre- and postconception factors associated with sporadic heritable and nonheritable retinoblastoma.

A matched case-control study of retinoblastoma was conducted by the Children's Cancer Study Group (CCSG) to investigate the hypotheses that postconception exposures affect the risk of the nonheritable (post-zygotic origin) form of this disease and that preconception exposures affect the risk of the sporadic heritable (prezygotic origin) form. Eligible cases were those patients with retinoblastoma diagnosed in 1982-1985 at any of the CCSG member hospitals. Cases were classified as familial heritable, sporadic heritable, or nonheritable based on family history, tumor laterality, and cytogenetic analysis. Telephone interviews of parents of 201 cases and their pair-matched controls selected by random digit dialing were completed. Analysis of possible risk factors for the 67 sporadic heritable cases and the 115 nonheritable cases was performed. (The 19 familial cases were excluded). For the nonheritable group, gestational exposure to X-ray [odds ratio (OR) = 2.3, P = 0.08] and morning sickness medication (OR = 2.8, P = 0.02) and low maternal educational level (OR = 5.5, P = 0.03) were associated with increased risk; anemia (OR = 0.3, P = 0.02) and multivitamin use (OR = 0.4, P = 0.03) during pregnancy and periconceptional use of barrier contraceptive (OR = 0.1, P = 0.02) or spermicide (OR = 0.2, P = 0.02) were associated with decreased risk. In the sporadic heritable group, observations included a negative association with multivitamins during pregnancy (OR = 0.2, P = 0.02) and nonsignificant positive associations with preconception gonadal X-ray (maternal, OR = 2.0, P = 0.30; paternal, OR = 1.8, P = 0.42) and older parental age (case-control difference 1.0-1.2 years, P = 0.24-0.27). Many of the associations support study hypotheses, although the possibility of recall bias and chance findings suggest cautious interpretation.

Case-Control Studies↗
PubMed1989

A case-control study of risk factors for hepatoblastoma. A report from the Childrens Cancer Study Group.

Parents of 75 children with hepatoblastoma, registered with the Childrens Cancer Study Group, and 75 age-matched controls, who had been identified through random digit dialing were interviewed. No evidence was found to support the primary study hypotheses relating to hepatitis infection, maternal estrogen exposure, alcohol consumption, smoking, or potential sources of nitrosamines. Case mothers were more likely to report occupational exposure to metals (odds ratio [OR] = 8.0, P = 0.01), petroleum products (OR = 3.7, P = 0.03), and paints or pigments (OR = 3.7, P = 0.05). Metal exposures were commonly to welding or soldering fumes, and most occurred daily, before and during the index pregnancy. Petroleum product exposures were predominantly to lubricating oils or protective greases. The only significant paternal exposure was to metals (OR = 3.0, P = 0.01) and the risk with exposure to petroleum products was marginally significant (OR = 1.9, P = 0.06). These findings provide further evidence that occupational exposures may increase the risk of cancer in offspring.

Adult↗
PubMed1989

Occupational exposures of parents of children with acute nonlymphocytic leukemia: a report from the Childrens Cancer Study Group.

The Childrens Cancer Study Group conducted a case-control study of occupational exposures of parents of 204 children (under 18 yr of age) with acute nonlymphoblastic leukemia. The most consistent finding was an association of acute nonlymphoblastic leukemia risk with pesticide exposure. Controls matched by date of birth and race were obtained through random digit dialing. Odds ratio (OR) for paternal pesticide exposure in jobs held for longer than 1000 days was 2.7 (95% confidence interval, 1.0 to 7.0; trend, P = 0.06), and seven case mothers and no control mothers had prolonged exposure (trend, P = 0.008). Risk estimates for parental pesticide exposure were substantially increased for children under age 6 at diagnosis (OR for prolonged exposure to either parent = 11.4; trend, P = 0.003) and for those with myelomonocytic and monocytic subtypes (OR, 13.6; trend, P = 0.007). Moreover, there were significantly elevated risks for direct exposure of the child to pesticides in the household (OR for exposure most days = 3.5; trend, P = 0.04) and for maternal exposure to household pesticides at the time of pregnancy (eight case mothers versus no controls for exposure most days; trend, P = 0.05). Paternal exposures to solvents (OR, 2.1; P = 0.003) and petroleum products (OR, 2.4; P = 0.002) were reported more commonly for cases than controls. Other occupational exposures reported significantly more often by case parents were paternal exposure to plastics or lead and maternal exposure to paints and pigments, metal dusts, and sawdust. These data provide further evidence for a role of occupational risk factors in the etiology of childhood cancer.

Adolescent↗
PubMed1989

Maternal drug use and risk of childhood nonlymphoblastic leukemia among offspring. An epidemiologic investigation implicating marijuana (a report from the Childrens Cancer Study Group).

The Childrens Cancer Study Group conducted a case-control study designed to assess in utero and postnatal exposures in children with acute nonlymphoblastic leukemia (ANLL). Analyses were performed for reported maternal use of medications and drugs in the year preceding and during the index pregnancy of the 204 case-control pairs. An 11-fold risk (P = 0.003) was found for maternal use of mind-altering drugs just prior to or during the index pregnancy. Compared with ANLL cases not exposed to marijuana, exposed cases were significantly younger at diagnosis of ANLL (P less than 0.01) and were more often of the myelomonocytic and monocytic subtypes (P less than 0.01). Use of antinausea medication for more than 11 weeks was also associated with a significantly elevated relative risk of 2.81 and a dose-response relationship was noted (P = 0.05 for trend). These results suggest that maternal drug use of marijuana may have an etiologic role in childhood ANLL and may be specific for morphologically defined subgroups.

Adolescent↗