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Edward A Copelan

Publications and source records attributed to Edward A Copelan.

12 recordsLinked to original sources
PubMed2006

Optimization of conditioning for marrow transplantation from unrelated donors for patients with aplastic anemia after failure of immunosuppressive therapy.

In 87 patients with aplastic anemia who failed to respond to immunosuppressive treatment, we determined the minimal dose of total body irradiation (TBI) required when added to antithymocyte globulin (ATG, 30 mg/kg x 3) plus cyclophosphamide (CY, 50 mg/kg x 4) to achieve engraftment of unrelated donor marrow. TBI was started at 3 x 200 cGy, to be escalated or deescalated in steps of 200 cGy depending on graft failure or toxicity. Patients were aged 1.3 to 53.5 years (median, 18.6 years). The interval from diagnosis to transplantation was 3 to 328 months (median, 14.6 months). Donors were HLA-A, -B, -C, -DR, and -DQ identical for 62 patients, and nonidentical for 1 to 3 HLA loci at the antigen or allele level for 25. The dose-limiting toxicity was diffuse pulmonary injury. The optimum TBI dose was 1 x 200 cGy. Nine patients did not tolerate ATG and were prepared with CY + TBI. Graft failure occurred in 5% of patients. With a median follow-up of 7 years, 38 (61%) of 62 HLA-identical, and 10 (40%) of 25 HLA-nonidentical transplant recipients are surviving. The highest survival rate with HLA-identical transplants was observed at 200 cGy TBI. Thus, low-dose TBI + CY + ATG conditioning resulted in excellent outcome of unrelated transplants in patients with aplastic anemia who had received multiple transfusions.

Adolescent↗
PubMed2006

High disease burden is associated with poor outcomes for patients with acute myeloid leukemia not in remission who undergo unrelated donor cell transplantation.

Results were analyzed for 48 consecutive patients with acute myeloid leukemia not in remission who underwent unrelated donor bone marrow or stem cell transplantation between 1991 and February 2003 at 2 transplant centers. Forty-six were adults with a median age of 32 years (range, 4-58 years). Forty-two were HLA-A, -B, and -DR matched with their respective donors, and 6 were mismatched at 1 of these loci. The conditioning regimen was myeloablative in all cases: busulfan/cyclophosphamide/etoposide in 34 patients, busulfan/cyclophosphamide in 10 patients, and total body irradiation based in 4 patients. Median follow-up for survivors was 540 days (range, 145-2716 days). Only patients with <5000 peripheral blood blasts per microliter at the time of transplantation survived 2 years (18% versus 0%; P = .003). Similarly, patients with <20% blasts in the marrow at the time of transplantation had superior 2-year survival compared with those who had > or =20% (33% versus 5%; P = .04). Patients with <20% blasts who had > or =3 prior therapies also fared poorly. Cause of death was more commonly treatment related rather than relapse related. This study confirms that patients with acute myeloid leukemia not in remission can achieve prolonged survival with myeloablative conditioning and unrelated donor cell transplantation. However, sustained survival occurs only in patients with a low disease burden at the time of unrelated donor stem cell transplantation, and patients with a high disease burden may benefit from added counseling regarding the high risk of death due to both treatment-related toxicities and disease relapse.

Acute Disease↗
PubMed2006

A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission.

We compared the outcomes of 298 patients with acute lymphoblastic leukemia in first or second complete remission (CR1 or CR2) receiving HLA-matched sibling allografts after cyclophosphamide and total body irradiation (Cy-TBI) conditioning with 204 patients receiving etoposide and TBI. Consequently, 4 groups were compared: Cy-TBI <13 Gy (n = 217), Cy-TBI > or =13 Gy (n = 81), etoposide-TBI <13 Gy (n = 53), and etoposide-TBI > or =13 Gy (n = 151). Analyses of relapse, leukemia-free survival (LFS), and survival were performed separately for CR1 and CR2 transplantations. Transplant-related mortality did not differ by conditioning regimen. In CR1, there were also no significant differences in relapse, LFS, or survival by conditioning regimen. In CR2, these outcomes differed among conditioning groups. In comparison with Cy-TBI <13 Gy, the risks of relapse, treatment failure (inverse of LFS), and mortality tended to be lower with etoposide (regardless of TBI dose) or with TBI doses > or =13 Gy. For both CR1 and CR2 transplantations, causes of death were similar among the groups; disease recurrence accounted for 47% of deaths. We conclude that for HLA-identical sibling allografts for acute lymphoblastic leukemia in CR2, there is an advantage in substituting etoposide for Cy or, when Cy is used, in increasing the TBI dose to > or =13 Gy.

Adolescent↗
PubMed2005

Unrelated donor marrow transplantation for B-cell chronic lymphocytic leukemia after using myeloablative conditioning: results from the Center for International Blood and Marrow Transplant research.

PURPOSE: To determine the role of myeloablative conditioning and unrelated donor (URD) bone marrow transplantation in the treatment of patients with advanced B-cell chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: A total of 38 CLL patients received a matched URD transplant using bone marrow procured by the National Marrow Donor Program. The median age was 45 years (range, 26 to 57 years), the median time from diagnosis was 51 months, and the median number of prior chemotherapy regimens was three. Fifty-five percent of patients were chemotherapy refractory and 89% had received fludarabine. Conditioning included total-body irradiation in 92% of patients. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate with cyclosporine or tacrolimus for 82% of patients. RESULTS: Twenty-one patients (58%) achieved complete response and six (17%) achieved partial response. Incidences of grades 2 to 4 acute GVHD were 45% at 100 days and incidences of chronic GVHD were 85% at 5 years. Eleven patients are alive and disease free at a median of 6 years (range, 3.0 to 9.0 years). Five-year overall survival, failure-free survival, disease progression rates, and treatment-related mortality (TRM) were 33%, 30%, 32%, and 38% respectively. CONCLUSION: These data demonstrate that lasting remissions can be achieved after URD transplantation in patients with advanced CLL. High TRM suggest that myeloablative conditioning and HLA-mismatched donors should be avoided in future protocols, and it is mandatory to investigate transplant strategies with a lower morbidity and mortality, including the use of nonmyeloablative regimens.

Adult↗
PubMed2004

Dose modification protocol using intravenous busulfan (Busulfex) and cyclophosphamide followed by autologous or allogeneic peripheral blood stem cell transplantation in patients with hematologic malignancies.

We evaluated the safety and toxicity through a 5-cohort dose-modification model of once-daily administration of IV busulfan (Bu) in combination with high-dose cyclophosphamide (Cy) as preparative therapy for stem cell transplantation. Twenty-one adult patients with hematologic malignancies were evaluated. Eleven patients underwent autologous and 10 patients underwent HLA-matched sibling allogeneic transplantation. Patients were sequentially enrolled into 5 cohorts. Cohort 1 received intravenous (IV) Bu 1.6 mg/kg every 12 hours for 2 doses and then 0.8 mg/kg every 6 hours for 12 doses; cohort 2 received IV Bu 1.6 mg/kg every 12 hours for 4 doses and then 0.8 mg/kg every 6 hours for 8 doses; cohort 3 received IV Bu 3.2 mg/kg for 1 dose and then 1.6 mg/kg every 12 hours for 2 doses and 0.8 mg/kg every 6 hours for 8 doses; cohort 4 received IV Bu 3.2 mg/kg every 24 hours for 2 doses and then 0.8 mg/kg every 6 hours for 8 doses; and cohort 5 received IV Bu 3.2 mg/kg every 24 hours for 4 doses. In all groups, Bu was administered on day -7 through day -4 and was followed at least 6 hours after the last Bu dose by Cy 60 mg/kg daily for 2 doses on days -3 and -2. Blood samples were collected for pharmacokinetic analysis on the first and last day of IV Bu administration. All patients were alive and had engrafted at day 30. Five patients developed grade 3 or 4 toxicities. Four patients developed hepatic abnormalities, and 3 exhibited evidence of veno-occlusive disease. Two of 3 patients in cohort 5 with a Bu area under the curve >6000 micromol/min developed autopsy-confirmed veno-occlusive disease. Interpatient variability in AUCs was observed in patients within and between cohorts, but no statistically significant interpatient differences were observed in Bu half-life, volume of distribution, clearance, or dose-adjusted area under the curve. Further, minimal variability in Bu pharmacokinetics was observed between the 2 evaluations performed in each patient, thus reflecting the stability of Bu disposition within individual patients. On the basis of the dosing guidelines and schedule outlined in this study, our data suggest that administration of IV Bu 3.2 mg/kg IV every 24 hours for 4 doses in combination with Cy may result in excessive toxicity.

Adolescent↗
PubMed2003

Autologous stem cell transplantation for non-Hodgkin's lymphoma.

Autologous stem cell transplantation (ASCT) is the only curative option for many patients with relapsed or refractory non-Hodgkin's lymphoma. ASCT achieves long-term survival in up to 50% of patients with chemotherapy-sensitive relapsed diffuse large cell lymphoma (DLCL), and prospective randomized studies have documented the superiority of ASCT over salvage chemotherapy in patients with relapsed DLCL However, the role of ASCT as an upfront therapy for patients with high-risk DLCL remains unclear, and prospective randomized studies have yielded mixed results. In addition, ASCT may not be curative in follicle center or mantle cell lymphoma, although longer follow-up may identify a subset of patients with prolonged survival. Ongoing clinical trials are studying the use of monoclonal antibodies, such as rituximab and iodine 131I-tositumomab, in ASCT regimens to purge tumor cells in vivo and improve long-term outcome in follicle center and mantle cell lymphoma.

Antibodies, Monoclonal↗
PubMed2002

Comparison of outcome following allogeneic bone marrow transplantation with cyclophosphamide-total body irradiation versus busulphan-cyclophosphamide conditioning regimens for acute myelogenous leukaemia in first remission.

We evaluated transplant-related mortality (TRM), leukaemia relapse, leukaemia-free survival (LFS) and overall survival (OS) in patients receiving busulphan and cyclophosphamide (BuCy) or cyclophosphamide and total body irradiation (CyTBI) prior to allogeneic bone marrow transplantation (BMT) for acute myelogenous leukaemia (AML) in first remission. Outcomes of 381 human leucocyte antigen (HLA)-matched sibling transplants using BuCy were compared with 200 transplants using CyTBI performed between 1988 and 1996. The incidence of hepatic veno-occlusive disease was higher with BuCy (13%) than with CyTBI (6%) (P = 0.009). Risks of acute and chronic GVHD were similar. In multivariate analysis, relapse risk was higher in the BuCy group [relative risk (RR) = 1.72; 95% confidence interval (CI), 1.05-2.81; P = 0.031]. Eleven of 373 evaluable patients in the BuCy group had a central nervous system relapse in contrast to none of 194 evaluable patients in the CyTBI group (P = 0.016). There were no differences in TRM, LFS and OS. CyTBI conditioning may lower relapse risk but produces comparable TRM, LFS and OS to BuCy for HLA-matched sibling transplantation in first remission AML.

Adult↗
PubMed2002

Breast cancer cell contamination of blood stem cell products in patients with metastatic breast cancer: predictors and clinical relevance.

The incidence and clinical relevance of tumor cells contaminating the stem cell products of patients with advanced breast cancer treated with high-dose chemotherapy is uncertain because prior studies used small sample sizes and lacked standardization of the immunocytochemistry (ICC) detection method used. We evaluated blood stem cell and bone marrow samples obtained from 535 women with metastatic breast cancer who received high-dose chemotherapy and unmanipulated mobilized blood stem cell support. Of the patients tested, 20.6% and 26.3% had blood stem cell and bone marrow contamination, respectively. Blood stem cell contamination was significantly more frequent in patients with marrow involvement than in patients without marrow involvement (35% versus 18.4%, respectively; P = .009). In fact, according to multivariate analysis results, marrow involvement was the only significant predictor for blood stem cell product contamination. Patients without marrow involvement who had fewer apheresis procedures were also observed to have a significantly lower incidence rate of blood stem cell contamination than patients who had more procedures (P < or = .008), and patients who received combined chemotherapy and cytokine mobilization therapy had less contamination than patients who received cytokine alone (P = .0001). Combined mobilization therapy appears to be associated with a lower incidence of contamination as a result of fewer apheresis procedures rather than through an antitumor effect of chemotherapy (P < or = .001). Patients with ICC-negative blood stem cell products had significantly longer progression-free survival (PFS) and overall survival (OS) than did patients with ICC-positive blood stem cell products (median PFS, 401 versus 291 days, respectively, P = .007; median OS, 1060 versus 697 days, P = .009) . However, multivariate analysis did not reveal any significant independent predictors of survival outcomes. Thus, further study is needed to determine if contaminating tumor cells in the stem cell products of breast cancer patients ever directly impact survival outcomes or are only indicative of residual in vivo disease in high-dose chemotherapy recipients.

Adult↗