Biomedical subjects

Edward J Lee

Publications and source records attributed to Edward J Lee.

4 recordsLinked to original sources

PubMed2004

Intensive chemotherapy with and without cranial radiation for Burkitt leukemia and lymphoma: final results of Cancer and Leukemia Group B Study 9251.

BACKGROUND: The objective of the current study was to evaluate the efficacy of intensive chemotherapy with and without cranial radiation for central nervous system (CNS) prophylaxis in adults with Burkitt leukemia or lymphoma. METHODS: Patients received 18 weeks of therapy. Prophylactic cranial radiation (2400 centigrays) and 12 doses of triple intrathecal chemotherapy were administered to the first cohort of patients. A subsequent cohort received the same therapy, with the exceptions that intrathecal therapy was reduced to six doses and radiotherapy was administered only to high-risk individuals. RESULTS: The median follow-up durations were 6.8 years in Cohort 1 and 4.1 years in Cohort 2. Three occurrences of transverse myelitis, 2 severe neuropathies, 3 cases of aphasia, and 1 case of blindness were documented in the first cohort of 52 patients (Cohort 1). In the subsequent cohort of 40 patients (Cohort 2), none of these occurrences were observed, and patients experienced less neurologic toxicity overall (61% vs. 26%; P=0.001). Responses were similar, and the 3-year event-free survival rate was 0.52 (95% confidence interval, 0.38-0.65) for Cohort 1 and 0.45 (0.29-0.60) for Cohort 2. CONCLUSIONS: Intensive, short-duration chemotherapy with less intensive CNS prophylaxis led to control at this sanctuary site with little neurotoxicity and may be curative for adults with Burkitt leukemia or lymphoma.

Adolescent↗

PubMed2004

Differences in prognostic factors and outcomes in African Americans and whites with acute myeloid leukemia.

Whites have a more favorable prognosis than African Americans for a number of cancers. The relationship between race and outcome is less clear in acute myeloid leukemia (AML). Using data from 7 Cancer and Leukemia Group B studies initiated from 1985 to 1997, we conducted a retrospective cross-sectional analysis of 2570 patients (270 African American and 2300 white) with de novo AML who received induction chemotherapy. African Americans were younger than whites (48 versus 54 years, P <.001). African Americans also had different cytogenetic risk group distributions than whites (P <.001): they were more commonly classified in the favorable (23% versus 14%) and unfavorable (31% versus 23%) groups, and less commonly classified in the intermediate group (47% versus 63%). African American men had a lower complete remission (CR) rate (54%, compared with 64% for white men, 65% for white women, and 70% for African American women, P =.001) and a worse overall survival compared with all other patients (P =.004), when known risk factors are taken into account. African Americans and whites with AML differ with respect to important prognostic factors. African American men have worse CR rates and overall survival than whites and African American women, and should be considered a poor-risk group.

Acute Disease↗

PubMed2002

A cyclophilin functions in pre-mRNA splicing.

We report that the cyclophilin USA-CyP is part of distinct complexes with two spliceosomal proteins and is involved in both steps of pre-mRNA splicing. The splicing factors hPrp18 and hPrp4 have a short region of homology that defines a high affinity binding site for USA-CyP in each protein. USA-CyP forms separate, stable complexes with hPrp18 and hPrp4 in which the active site of the cyclophilin is exposed. The cyclophilin inhibitor cyclosporin A slows pre-mRNA splicing in vitro, and we show that its inhibition of the second step of splicing is caused by blocking the action of USA-CyP within its complex with hPrp18. Cyclosporin A also slows splicing in vivo, and we show that this slowing results specifically from inhibition of USA-CyP. Our results lead to a model in which USA-CyP is carried into the spliceosome in complexes with hPrp4 and hPrp18, and USA-CyP acts during splicing within these complexes. These results provide an example of the function of a cyclophilin in a complex process and provide insight into the mechanisms of action of cyclophilins.

Amino Acid Sequence↗

PubMed2002

Postremission therapy with low-dose interleukin 2 with or without intermediate pulse dose interleukin 2 therapy is well tolerated in elderly patients with acute myeloid leukemia: Cancer and Leukemia Group B study 9420.

PURPOSE: The purpose of the study is to investigate the tolerability of interleukin 2 (IL-2) after intensive chemotherapy in elderly acute myeloid leukemia (AML) patients in first complete remission (CR). EXPERIMENTAL DESIGN: AML patients > or =60 years in CR after induction and consolidation chemotherapy on Cancer and Leukemia Group B study 9420 were eligible if they had neutrophils > or =1 x 10(9)/liters and platelets > or =75 x 10(9)/liters. Patients received low-dose IL-2 (1 x 10(6) IU/m(2)/day s.c. for 90 days) or low-dose IL-2 with intermediate pulse doses (6-12 x 10(6) IU/m(2)/day s.c. for 3 days) every 14 days (maximum five pulses). In a subset of patients, we investigated the expression of NKG2D ligands by leukemic cells because they are likely important mediators of natural killer cytotoxicity. RESULTS: Of 35 CR patients receiving IL-2, 34 were evaluable for toxicity. Median age was 67 (range, 60-76) years. Thirteen of 16 patients receiving low-dose IL-2 completed the planned therapy, and 11 of 18 who also received intermediate pulse dose IL-2 therapy completed all five pulses. The spectrum of toxicity in both groups was similar, with predominantly grade 1-2 fatigue, fever, injection site reactions, nausea, anemia, and thrombocytopenia. Grade 3-4 hematological and nonhematological toxicity were more frequent in patients also receiving intermediate pulse dose IL-2 therapy. Grade 3-4 fatigue and hematological toxicity, although uncommon, were the major causes for discontinuing or attenuating therapy. In 8 cases, mRNA for one or more NKG2D ligands was detected in leukemic cells obtained at diagnosis before treatment. CONCLUSIONS: Low-dose IL-2, with or without intermediate pulse dose therapy, given immediately after chemotherapy in first CR to elderly AML patients is well tolerated. Expression of NKG2D ligands by leukemic cells was detected in the majority of cases tested and should be assessed for correlation with response to IL-2 in future studies.

Acute Disease↗