Historical metal concentrations in lacustrine food webs revealed using fossil ephippia from Daphnia.

Metal contamination of freshwater ecosystems is increasingly prevalent due to anthropogenic activities such as metal smelting and fossil fuel combustion. While toxicological studies focus on aqueous metal concentrations that result in lethal or sublethal responses, currently the only method for reconstructing a lake's metal contamination history is through an examination of the sedimentary deposits. In this paper, we suggest that cladoceran diapausing eggs (ephippia), which are abundant in nature and accumulate maternally derived metals, can be used to measure historical variations in biologically relevant metals that derive from the water column (water, diet). Linear regressions of total metal content against ephippia density or mass were strong (R2 > 0.80, P < 0.04) and revealed that metals were incorporated into ephippia with little contamination from the sediment matrix. Comparison of metal concentrations in ephippia and bulk sediments from three lakes demonstrated that some metals associated with urban sources (Cd, Cr, Mo) were preferentially concentrated in ephippia, whereas concentrations of other metals indicating landscape erosion (Al, Ca, Fe, Mn) exhibited greater concentrations in bulk sediments than in diapausing eggs. Because historical changes in metals within fossils and bulk sediments were uncorrelated in most instances, past variation in the metal content of ephippia provided a unique history of food web exposure to metals in the water column.

Prognostic significance of early response to a single dose of asparaginase in childhood acute lymphoblastic leukemia.

PURPOSE: The in vitro and in vivo efficacy of a single dose of asparaginase in children with newly diagnosed acute lymphoblastic leukemia and the correlation between in vitro and in vivo antileukemic response and long-term outcome were prospectively evaluated. PATIENTS AND METHODS: Two hundred fifty-one patients were randomized to receive 1 of 3 asparaginase preparations (Escherichia coli, Erwinia chrysanthemi [Erwinia], or pegaspargase). In vitro assessment of efficacy was expressed as the percent total cell kill (TCK), based on the number of viable cells found after 5 days of culture in the presence of asparaginase. In vivo leukemia cell kill (LCK) was calculated by comparing bone marrow cellularity and percent leukemic blasts in marrow obtained before and 5 days after treatment with a single dose of asparaginase. Acute toxicity was determined by clinical and laboratory assessment. RESULTS: There was equivalent cell kill with all three types of asparaginase. The mean in vitro TCKs for E. coli, Erwinia, and pegaspargase were 31%, 39%, and 36%, respectively (P = 0.63). The mean LCKs in marrow of patients exposed to E. coli, Erwinia, and pegaspargase were 69%, 74%, and 65%, respectively (P = 0.88). The lack of response to asparaginase in vitro predicted a higher risk for clinical relapse regardless of risk assignment (12 leukemic events among 21 in vitro nonresponders; 57%, P < 0.001). There was no difference in acute toxicity among the three asparaginase preparations. CONCLUSIONS: All three asparaginase preparations produced equivalent LCKs in in vitro and in vivo analyses. In vitro response to asparaginase provided a risk group-independent prognostic factor.

Autologous and allogeneic bone marrow transplantation for poor prognosis patients with B-cell chronic lymphocytic leukemia.

Twenty patients with poor prognosis B-cell chronic lymphocytic leukemia (B-CLL) underwent uniform high-dose chemoradiotherapy followed by rescue with multiple monoclonal antibody-purged autologous bone marrow (BM) (12 patients) or T-cell-depleted allogeneic BM from HLA-identical siblings (8 patients) in a pilot study to assess the feasibility of BM transplantation (BMT) in this disease. All had poor prognosis disease by either staging, BM pattern, tumor doubling time criteria, or cytogenetics. All patients achieved remission criteria (defined as < or = 2 adenopathy, absence of splenomegaly, < or = 20% of the intertrabecular space involved on BM biopsy) before BMT. Despite the use of fludarabine, a median of three treatment regimens were required to achieve BMT eligibility. After BMT, all patients achieved complete hematologic engraftment. Toxicities were not significantly different between autologous versus allogeneic BMT. Two toxic deaths were observed. Of 19 evaluable patients, 17 clinical complete clinical remissions (89%) were observed, with 2 patients (1 allogeneic and 1 autologous) exhibiting persistent BM disease. Complete clinical remissions were documented at the phenotypic and molecular level for the majority of patients in whom dual fluorescence for CD5 and CD20 (15 of 15; 100%) and Ig gene rearrangements (11 of 14; 79%) were performed. Although long-term follow-up is needed to assess any potential impact on the disease-free and overall survival of these patients, this study shows the feasibility of using high-dose chemoradiotherapy and BMT in patients with poor prognosis B-CLL.

Prognostic factors in childhood acute myelogenous leukemia.

The prognostic significance of initial clinical and laboratory parameters was evaluated in 125 children with acute myelogenous leukemia (AML) treated on two consecutive protocols (VAPA and 80-035). Both protocols used an anthracycline with cytosine arabinoside (ara-C) for induction therapy followed by 12 to 14 months of intensive sequential postremission chemotherapy. Results are similar for the two treatment regimens. Seventy-two percent of patients achieved a complete remission, with 42% projected 5-year disease-free survival for the complete responders. Monocytic or myelomonocytic leukemic subtype (French-American-British [FAB] types M4 and M5), WBC count less than 100,000/microL, and age less than 2 years at diagnosis all predicted increased risk of relapse and decreased overall survival in univariate analyses. FAB subtype and high white count continued to predict for an increased risk of relapse in multivariate analyses and only M5 leukemic subtype independently predicted for poor survival. Patients with M4 or M5 leukemic subtype had a higher incidence of initial relapses in the CNS. The addition of intrathecal cytosine arabinoside in the second protocol, 80-035, decreased the percentage of patients with initial failure in the CNS, but did not improve overall survival. Improved CNS prophylaxis, better systemic therapy, and/or different treatment strategies are needed to improve therapy in these high-risk patients.

A pericentric inversion of chromosome 16 is associated with dysplastic marrow eosinophils in acute myelomonocytic leukemia.

Cytogenetic studies were performed in 18 consecutive children with acute nonlymphocytic leukemia (ANLL) between 1981 and 1983. Three children with acute myelomonocytic leukemia (AMMoL; M4, FAB classification) had the following unique bone marrow morphology and cytogenetic abnormality: eosinophilic precursors with dysplastic violaceous granules and a pericentric inversion of chromosome 16. Surface marker analysis of leukemic cells from these patients, using a panel of monoclonal antibodies, revealed the expression of a series of monocyte markers. The association of an inversion of chromosome 16 with abnormal eosinophil morphology in the M4 subtype of ANLL appears to represent a unique subgroup of patients.

Immunological and cytogenetic studies in two cases of B-cell acute lymphoblastic leukemia (Burkitt's type).

Immunological and cytogenetic studies were performed on two patients who presented with L-3 acute lymphocytic leukemia (Burkitt-type). Surface marker studies showed that both had B-cell leukemias. The blast cells in Case 1 expressed monoclonal IgM kappa surface immunoglobulin and in Case 2, IgG kappa. In the first case, cytogenetic analysis of bone marrow revealed the presence of a rare variant translocation involving the short arm of chromosome 2 and the long arm of chromosome 8 in all the metaphases examined. This is the second report of such a translocation in Burkitt's leukemia. The 8;14 translocation reported in classical Burkitt's lymphoma and other B-cell lymphomas was present in all the bone marrow metaphases in the second case.