Summary:Retrospective analysis of 206 patients undergoing 215 consecutive bone marrow transplants (BMT) at St Jude Children's Research Hospital between November 1990 and December 1994 identified 6% (seven male, six female) with adenovirus infection. The affected patients had a median age of 7.9 years (range 3-24 years) at time of transplantation. Although transplants were performed for hematologic malignancies, solid tumors or nonmalignant conditions, only patients with hematologic malignancies had adenoviral infections. Adenovirus was first detected at a median of 54 days (range ؊4 to ؉333) after BMT. Adenovirus developed in eight of 69 (11.6%) patients receiving grafts from matched unrelated or mismatched related donors, in four of 52 (7.7%) receiving grafts from HLA-matched siblings, and in one of 93 (1.1%) receiving autografts. The most common manifestation of adenovirus infection was hemorrhagic cystitis, followed by gastroenteritis, pneumonitis and liver failure. The incidence of adenovirus infection in pediatric BMT patients at our institution is similar to that reported in adult patients. Using univariate analysis, use of total body irradiation and type of bone marrow graft were significant risk factors for adenovirus infection. Only use of total body irradiation remained as a factor on multiple logistic regression analysis.

Little is known about the factors that affect treatment outcome in very young children with acute myeloid leukemia (AML). We therefore analyzed the prognostic impact of various presenting clinical and laboratory features by discrete age group in 299 children with AML treated in four consecutive clinical trials between 1980 and 1997. Differences in presenting features, as well as treatment outcome, were compared between children aged 12 months or less (n = 28) or 13 to 24 months (n = 28) and those more than 24 months of age (n = 243). Children in the two youngest groups (24 months of age or less) had similar presenting features and treatment outcome. Collectively, these 56 children were significantly more likely than the 243 older patients to have M4 or M5 leukemia (70% vs 30%), CNS leukemia (33% vs 22%), the t(9;11) (p22;q23) (18% vs 6%) or other 11q23 translocations (23% vs 3%), and less likely to have Auer rods (2% vs 54%) or the t(8;21) (q22;q22) (0% vs 17%). Among patients aged 24 months or less, two factors independently predicted a favorable prognosis: FAB M4 or M5 leukemia (relative risk of relapse, 0.4; 95% confidence interval, 0.2-0.9) and the t(9;11) (relative risk, 0.3; 95% confidence interval , 0.1-1.0). Leukocyte count and 11q23 translocations other than the t(9;11) lacked prognostic significance. Among older patients, a leukocyte count Ͻ50 × 10 9 /l and the presence of the t(9;11) conferred a favorable prognosis. Leukemia (2000) 14, 684-687.

We offer a large scale purification procedure for the recombinant human liver medium-chain acyl-CoA dehydrogenase (HMCAD). This procedure routinely yield 100-150 mg of homogeneous preparation of the enzyme from 80 L of the Escherichia coli host cells. A comparative investigation of kinetic properties of the human liver and pig kidney enzymes revealed that, except for a few minor differences, both of these enzymes are nearly identical. We undertook detailed kinetic and thermodynamic investigations for the interaction of HMCAD-FAD with three C8-CoA molecules (viz., octanoyl-CoA, 2-octenoyl-CoA, and 2-octynoyl-CoA), which differ with respect to the extent of unsaturation of the alpha-beta carbon center; octanoyl-CoA and 2-octenoyl-CoA serve as the substrate and product of the enzyme, respectively, whereas 2-octynoyl-CoA is known to inactivate the enzyme. Our experimental results demonstrate that all three C8-CoA molecules first interact with HMCAD-FAD to form corresponding Michaelis complexes, followed by two subsequent isomerization reactions. The latter accompany either subtle changes in the electronic structures of the individual components (in case of 2-octenoyl-CoA and 2-octynoyl-CoA ligands), or a near-complete reduction of the enzyme-bound flavin (in case of octanoyl-CoA). The rate and equilibrium constants intrinsic to the above microscopic steps exhibit marked similarity with different C8-CoA molecules. However, the electronic structural changes accompanying the 2-octynoyl-CoA-dependent inactivation of enzyme is 3-4 orders of magnitude slower than the above isomerization reactions. Hence, the octanoyl-CoA-dependent reductive half-reaction and the 2-octynoyl-CoA-dependent covalent modification of the enzyme occur during entirely different microscopic steps. Arguments are presented that the origin of the above difference lies in the protein conformation-dependent orientation of Glu-376 in the vicinity of the C8-CoA binding site.

To determine the clinical significance of central nervous system (CNS) involvement at the time of diagnosis of pediatric acute myeloid leukemia (AML), we analyzed clinical features and outcomes of 290 patients treated consecutively on four institutional trials (AML80, AML83, AML87, and AML91). CNS status was classified as CNS1 (no blast cells in CSF; n ¼ 205), CNS2 (o5 WBC/ll CSF with blast cells; n ¼ 37), or CNS3 (X5 WBC/ll CSF with blast cells, or signs of CNS involvement; n ¼ 48). Patients with CNS3 status were significantly younger than others (P ¼ 0.016) and significantly more likely to have the favorable cytogenetic features t(9;11), t(8;21), or inv(16) (Po0.001). The CNS3 group had a significantly greater probability (7s.e.) of 5-year event-free survival (43.777.0%) than did the CNS1 (27.873.2%, P ¼ 0.015) and CNS2 (24.377.5%, P ¼ 0.032) groups. However, after adjustment for favorable genetic features, there was no significant difference in EFS between the CNS3 and the combined CNS1 þ CNS2 groups (P ¼ 0.075). In all, 10 of 151 patients treated on AML80 and AML83, but none of 139 treated on AML87 and AML91, had primary CNS relapse. CNS involvement had no adverse prognostic significance, and patients with CNS2 status had similar outcome to CNS1 patients in this large group of pediatric patients with AML, treated at a single institution.

Our study provides strong evidence that germline genetics outside high-risk syndromes could modify the effect of radiation exposure on breast cancer risk after childhood cancer.

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The purpose of this study was to assess the feasibility and efficacy of a treatment regimen for pediatric acute myelogenous leukemia (AML) that uses four rotating drug pairs and adjusts dosages of etoposide and cytarabine to target specific plasma concentrations. Thirty-one girls and 27 boys (median age, 9.7 years) with de novo AML were treated on the protocol. Six cycles of chemotherapy were planned. Cycles 1 to 4 comprised the drug combinations cytarabine plus etoposide, cytarabine plus daunomycin, etoposide plus amsacrine, and etoposide plus azacitidine, respectively. For cycles 5 and 6, the first two combinations were repeated. Dosages were adjusted to achieve plasma concentrations of

Summary:Our purpose was to describe the types and frequencies of altered dental development in pediatric patients following bone marrow transplantation (BMT). A retrospective review of the medical records and panoramic radiographs of all patients who underwent BMT at St Jude Children's Research Hospital between 1990 and 2000, for whom pre-BMT and post-BMT dental examination and panoramic radiography records were available, is presented. All patients were treated on institutional protocols. We recorded patient demographics and radiographic evidence of microdontia, hypodontia, taurodontia, root stunting, caries, enamel pearls, dental restorations/extractions and pulpal calcification. The 99 patients identified (52 males, 47 females) had a median age of 13.5 years (range, 3.4-25.9 years) at the time of BMT. In all, 73 were Caucasian, 15 were African-American, and 11 were of other races. The frequency of radiographically evident root stunting in permanent teeth was significantly increased after BMT (Po0.001), but there was no significant change in the frequency of other dental abnormalities after BMT. Dental abnormalities are prevalent in survivors of childhood BMT, but only root stunting appeared to progress with BMT. Bone Marrow Transplantation (2005) 36, 725-729.