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J W Sweetenham

Publications and source records attributed to J W Sweetenham.

At least 37 records · Page 2Linked to original sources
PubMed1995

The importance of dose and schedule in cancer chemotherapy: haematological cancer.

Haematological cancers have been the prototype malignant diseases in which dose-intensive strategies have been tested. To date, dose intensification within the conventional dose range has not been shown to result in improved long-term survival in prospective studies. The use of haemopoietic growth factors is important in maintaining adequate doses of chemotherapy, and reducing life-threatening complications, but growth-factor supported dose intensification has yet to be shown to improve outcome in randomised clinical trials. Dose escalation with high-dose therapy and stem cell support has produced encouraging results in several haematological malignancies. Preliminary evidence is also suggesting that it may improve long-term disease-free survival for some patients, but the results of ongoing clinical trials are needed to confirm these encouraging early results.

Antineoplastic Agents↗
PubMed1995

A mononuclear cell dose of 3 x 10(8)/kg predicts early multilineage recovery in patients with malignant lymphoma treated with carmustine, etoposide, Ara-C and melphalan (BEAM) and peripheral blood progenitor cell transplantation.

We have assessed the potential use of the mononuclear cell (MNC) content as the sole assessment of graft quality in 35 patients receiving BEAM (carmustine, etoposide, cytosine arabinoside, melphalan) chemotherapy and autologous peripheral blood progenitor cell (PBPC) transplantation for malignant lymphoma. PBPCs were mobilized with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), and each patient underwent two (n = 20) or three (n = 15) apheresis procedures. Median cell yields were 5.08 x 10(8) MNC/kg (range 1.59-15.70 x 10(8)) and 73.10 x 10(4) CFU-GM/kg (range 0.09-346.72 x 10(4)). All patients achieved hematologic recovery. Median days to neutrophils > or = 0.1 x 10(9)/L, neutrophils > or = 0.5 x 10(9)/L, and platelets > or = 25 x 10(9)/L were 11 (range 8-15), 13 (range 10-37), and 11 (range 7-41), respectively. A close correlation was observed between the MNC and CFU-GM dose (r = 0.79, p < 0.0001). We have previously defined a minimum threshold CFU-GM dose of 20 x 10(4)/kg for patients undergoing high-dose therapy. This corresponds with an MNC dose of 3 x 10(8)/kg. Comparison of engraftment in patients receiving 3 x 10(8) MNC/kg with those receiving lower doses demonstrated significantly longer times to recovery of neutrophils to > or = 0.5 x 10(9)/L and platelets to > or = 25 x 10(9)/L. All patients receiving an MNC dose of > or = 3 x 10(8)/kg achieved neutrophil and platelet recovery by days 12 and 24, respectively. These preliminary data demonstrate that for patients with lymphoma undergoing PBPC mobilization according to this protocol and treatment with BEAM chemotherapy, assessment of MNC dose alone is sufficient to predict early hematologic recovery. Additional assays such as CFU-GM or CD34+ cell counts may not be necessary if this MNC dose is reinfused.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

High-dose therapy and autologous bone marrow transplantation in first complete remission for adult patients with high-grade non-Hodgkin's lymphoma: the EBMT experience. Lymphoma Working Party of the European Group for Bone Marrow Transplantation.

One hundred and eighteen patients presenting with high-grade non-Hodgkin's lymphoma, undergoing autologous bone marrow transplantation (ABMT) in first complete remission (CR), have been reported to the European Group for Bone Marrow Transplantation (EBMT). Of these, 102 were eligible for inclusion in this study following review of registration forms. Patients with lymphoblastic lymphoma were excluded. Remission induction and high-dose regimens varied between contributing centres. A maintained CR was observed in 90% of patients. Early relapse was observed in 6%, and 4% suffered toxic deaths. With a median follow-up of 45 months (3-112 months), the 5-year actuarial overall and progression-free survivals are both 70%. Nineteen (18%) patients relapsed at a median of 3.5 months (0.25-52 months) after ABMT, only 1 achieving a further durable CR. The only factor with prognostic significance was histological subtype, with diffuse small noncleaved-cell lymphoma having a significantly worse outcome. High-dose therapy and ABMT has produced effective consolidation of first remission in this group of patients, even in those with poor prognostic features at presentation.

Adolescent↗
PubMed1994

Isolation and culture of endothelial cells from human bone marrow.

Adhesive interactions between haemopoietic progenitor cells and bone marrow sinusoidal endothelium are potentially important in the homing of these cells back to the extravascular compartment of the marrow to re-establish haemopoiesis following stem cell transplantation. A simple method for the isolation and culture of human bone marrow endothelial cells is described using bone marrow aspirates obtained from patients undergoing bone marrow harvests for autologous or syngeneic bone marrow transplantation. The method is based on the selective binding of the lectin Ulex europaeus agglutinin-1 (UEA-1) to endothelial cells. Magnetic Dynabeads coupled with UEA-1 were incubated with single cell suspensions of bone marrow following red cell lysis, and bound cells were isolated with a magnet. The isolated cells demonstrated positive immunofluorescence staining for von Willebrand factor. Cells were plated onto tissue culture flasks coated with extracellular matrix derived from human umbilical vein endothelial cells in an endothelial serum-free medium together with 5% fetal calf serum for 24 h. Cells were then cultured in endothelial serum-free growth medium supplemented with 5% fetal calf serum, endothelial cell growth supplement and heparin. After 2-4 weeks in culture, two morphologically different cell populations can be identified. One has a polygonal spindle-shaped morphology with a rapid growth rate, the other a rounded morphology and a slow growth rate. Both populations have a vesiculated cytoplasm. Positive immunostaining of the cells was demonstrated with a number of endothelial cell markers including von Willebrand factor, and antibodies to ICAM-1, VCAM-1, E-selectin, CD31 and BMA120. Weibel-Palade bodies were observed by electron microscopy. Culture of these cells will allow detailed in vitro studies of adhesion mechanisms in the homing of haemopoietic progenitor cells.

Bone Marrow↗
PubMed1994

High-dose therapy and autologous bone marrow transplantation for adult patients with lymphoblastic lymphoma: results of the European Group for Bone Marrow Transplantation.

PURPOSE: To investigate the results of treatment and factors that affect prognosis in adult patients undergoing high-dose therapy and autologous bone marrow transplantation (ABMT) for lymphoblastic lymphoma (LBL). PATIENTS AND METHODS: The study was a retrospective analysis of 214 patients reported to the Lymphoma Registry of the European Group for Bone Marrow Transplantation (EBMT) between January 1981 and December 1992, including 105 patients undergoing marrow transplantation in first complete remission (CR). Data on all patients were reviewed, and analysis of prognostic factors conducted. RESULTS: The actuarial overall survival rate at 6 years for the entire group is 42%. Disease status at ABMT was the major determinant of outcome: 6-year actuarial overall survival was 63% for patients transplanted in first CR, compared with 15% for those with resistant disease at the time of transplantation. Transplantation in second CR resulted in a 31% rate of actuarial overall survival at 6 years. For patients transplanted in first CR, univariate analysis failed to identify any factors at presentation that predicted for outcome after transplantation. CONCLUSION: These results suggest that ABMT is effective therapy for adults with LBL, even in patients with disease that is resistant to conventional-dose therapy. Results for patients transplanted in second CR are superior to those reported for conventional-dose salvage regimens. The results in first CR require verification in a prospective randomized clinical study.

Actuarial Analysis↗
PubMed1994

High-dose therapy and autologous bone marrow transplantation for intermediate and high grade non-Hodgkin's lymphoma in patients aged 55 years and over: results from the European Group for Bone Marrow Transplantation. The EBMT Lymphoma Working Party.

The results of high-dose therapy and autologous BMT for patients with intermediate/high grade NHL were analysed in 82 patients aged > or = 55 years, identified from the EBMT lymphoma database. These were compared with the results for 82 patients aged < 55 years who were matched on the basis of disease status at transplantation, presence of bone marrow or CNS involvement and closest date of transplantation. The 5 year actuarial progression-free survival (PFS) for patients aged < 55 years was 33% compared with 37% for the > or = 55 year group (p = 0.08). Corresponding figures for overall survival (OS) were 39% and 38%, respectively (p = 0.19). No difference in outcome was observed according to histological subtype. Although the number of patients receiving total body irradiation (TBI) is small, a significantly lower PFS was observed in patients > or = 55 years receiving TBI-based high-dose regimens compared with younger patients. This difference was due to a higher toxic death rate in the older patient group. In this retrospective matched analysis, age > or = 55 years was not associated with lower PFS or OS following high-dose therapy and autologous BMT. The increased toxic death rate in patients receiving TBI suggests that this should be avoided in older patients, who should receive chemotherapy only high-dose regimens.

Adolescent↗
PubMed1994

Immuno-, lectin-, and enzyme-histochemical characterization of human bone marrow endothelium.

"Homing" of hematopoietic progenitor cells to the bone marrow occurs during the clinical practice of bone marrow transplantation. Its mechanism is unknown, although adhesive interactions between hematopoietic cells and sinusoidal endothelium in the bone marrow may be implicated. Studies of human bone marrow endothelial cells have previously been limited by the lack of markers for these cells. In this report, we describe positive staining of bone marrow endothelial cells from human bone marrow trephine biopsies with antibody to factor VIII-related antigen (FVIIIR-Ag) (Dako, High Wycombe, UK), the plant lectin Ulex europaeus agglutinin-I (UEA-I), and two mouse monoclonal antibodies, BMA120 and QBEND/10. In addition, alkaline phosphatase could be demonstrated in the majority of marrow endothelial cells using a novel enzyme histochemical technique. These studies defined the marker profile of human marrow endothelium. The results of this study will facilitate the isolation and culture of human marrow endothelial cells for in vitro studies of their roles in hematopoietic stem cell homing.

Alkaline Phosphatase↗
PubMed1993

Prednisolone, cytosine arabinoside, lomustine (CCNU), etoposide and thioguanine (PACET) combination chemotherapy for relapsed or refractory non-Hodgkin lymphoma.

27 patients with relapsed/refractory non-Hodgkin lymphoma (NHL) received combination chemotherapy with prednisolone, cytosine arabinoside, lomustine (CCNU), etoposide and thioguanine (PACET). 25 patients are evaluable for response. 7 (26%) obtained a complete response and one (4%) a partial response. The median survival for the entire group was 6 months. 2 patients are currently alive without disease, 1 of whom has received further therapy. The regimen was intensely myelosuppressive, but was well tolerated. The complete response rate and median survival figures are comparable to previous studies of salvage therapy confirming the poor prognosis for relapsed NHL and emphasising the need for prospective randomised studies.

Adult↗
PubMed1993

E-SHAP: inadequate treatment for poor-prognosis recurrent lymphoma.

BACKGROUND: The treatment of refractory and recurrent lymphomas remains problematic, with the majority of patients showing no response to 'salvage' therapies. One regimen which has been suggested as showing particular efficacy is etoposide (40 mg/m2 daily x 4), cytosine arabinoside (2.0 g/m2 one dose), cisplatin (25 mg/m2/day infused over 4 days) and methylprednisolone (500 mg daily x 4) (E-SHAP). This study attempted to reproduce the encouraging results seen with this regimen in North America. PATIENTS AND METHODS: Twenty-eight patients with recurrent or refractory lymphoma were treated with E-SHAP given 3 to 4 weekly. Thirteen patients were treated at first recurrence and twenty-two had previously received etoposide. RESULTS: No objective responses were seen although five patients had a transient reduction in tumour before regrowth despite continued treatment. Sixteen patients received further chemotherapy after failure of E-SHAP of whom four had responses. The principal toxicity was myelosuppression with over half the patients requiring hospital admission for neutropenia-associated fever. Median time to treatment failure was 2.5 months and median survival 7 months from the start of E-SHAP. CONCLUSIONS: These results are in marked contrast to those reported from North America, possibly due to differing patient selection. E-SHAP shows strictly limited efficacy but marked toxicity in the treatment of recurrent or refractory lymphomas with poor prognostic features.

Adult↗
PubMed1993

CAPE/PALE salvage chemotherapy for Hodgkin's disease patients relapsing within 1 year of ChlVPP chemotherapy.

BACKGROUND: Patients with advanced Hodgkin's disease failing to achieve complete remission with chemotherapy or developing disease progression within 1 year have a poor prognosis with salvage chemotherapy. PATIENTS AND METHODS: Twenty-five patients fulfilling the above criteria after failing treatment with ChlVPP (chlorambucil, vinblastine, procarbazine and prednisolone) or its variant were treated with a new salvage regimen CAPE/PALE (cyclophosphamide, adriamycin, prednisolone, etoposide and lomustine), given for 6 courses at three weekly intervals. RESULTS: Thirteen of the 25 patients (52%) achieved complete remission. After a minimum follow-up period of 38 months five of these patients remained free from disease progression. This regimen was very well tolerated. CONCLUSIONS: CAPE/PALE produces results comparable to other salvage regimens in Hodgkin's disease. New strategies are however required for this patient group.

Adult↗
PubMed1992

Adult lymphoblastic lymphoma: high incidence of central nervous system relapse in patients treated with the Stanford University protocol.

Twelve adult patients with non-leukaemic lymphoblastic lymphoma were treated with combination chemotherapy and central nervous system prophylaxis according to the protocol developed at Stanford University. Despite strict adherence to the Stanford protocol, 4 of 12 patients relapsed in the CNS, all with meningeal disease. Only four of the 12 patients are in continuing complete remission 6 to 88 months from the completion of induction therapy. These results are inferior to those previously reported for this regimen, and fail to confirm the high rate of control of CNS disease.

Adolescent↗
PubMed1991

Intensive weekly combination chemotherapy for patients with intermediate-grade and high-grade non-Hodgkin's lymphoma.

High response and overall survival rates have been reported for second- and third-generation combination chemotherapy regimens used in the treatment of advanced intermediate- and high-grade non-Hodgkin's lymphoma (NHL). Results with methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) chemotherapy have been particularly impressive, although this regimen produces considerable toxicity. We have devised a similar regimen, which differs from previously reported weekly regimens in that it includes etoposide given at 14-day intervals. The doses of methotrexate and prednisolone were lower in our regimen than those used in MACOP-B. Alternating cycles of cyclophosphamide, doxorubicin, and etoposide (week 1) and methotrexate, bleomycin, and vincristine (week 2) were given for a total of 12 weeks, with continuous oral prednisolone and prophylactic antibiotics. We report here the first 61 patients entered onto this study. The overall response rate is 84% (57% complete remission [CR], 27% partial remission [PR]). With a median follow-up of 32 months for surviving patients, the actuarial overall survival at 3 years is 47%, and the failure-free survival is 45%. The dose-limiting toxicity of this regimen was mucositis. Five deaths occurred during chemotherapy, two of which were due to sepsis. The dose intensities of cyclophosphamide and doxorubicin in this regimen are considerably lower than those in MACOP-B. However, because of the inclusion of etoposide, the projected average relative dose intensity for our regimen is higher than that for MACOP-B. Our regimen has produced inferior results to those reported for MACOP-B. This may be because the addition of etoposide has failed to compensate for the lower doses of doxorubicin and cyclophosphamide. Alternatively, it may reflect differences in the presenting features of the patient populations.

Adult↗
PubMed1990

Urinary epidermal growth factor (hEGF) levels in patients with carcinomas of the breast, colon and rectum.

A specific two-site ELISA for human epidermal growth factor (hEGF) has been used to measure urinary hEGF/creatinine ratios in 30 normal subjects, 30 hospital in-patients with breast cancer and 30 hospital in-patients with colonic or rectal cancer. There was no significant difference between patients with breast cancer and controls. Although a statistically significant difference between patients with colorectal cancer and controls was observed, the biological significance of this observation is doubtful. No clear effect of the presence of breast or colorectal carcinoma on the urinary excretion of hEGF has been observed.

Adult↗
PubMed1990

High dose intensity combination chemotherapy for advanced epithelial ovarian carcinoma: results of a pilot study.

Retrospective studies have recently demonstrated a significant correlation between dose intensity of chemotherapy and response rates and survival in various diseases including epithelial ovarian carcinoma. As part of a proposed randomised trial to assess the effect of dose intensity on outcome in ovarian carcinoma, a pilot study has been undertaken to determine the toxicity and efficacy of the high intensity therapy. Nineteen patients with advanced ovarian carcinoma received initial treatment with cisplatin 120 mg m-2 i.v. day 1, and cyclophosphamide 1,000 mg-2 i.v. day 1, given at 21-day intervals for six cycles. The average relative dose intensity of this therapy is 1.14 when compared with the CHAP regimen. Severe toxicity was experienced by most patients. The median received average relative dose intensity was 0.90, with only one patient receiving treatment to the proposed intensity. Randomised studies of the effect of dose intensity in ovarian carcinoma are essential, but an initial step must be to assess whether the proposed high dose treatment can be delivered.

Adult↗
PubMed1989

Involvement of the ileocaecal region by non-Hodgkin's lymphoma in adults: clinical features and results of treatment.

Between January 1977 and January 1988, 19 patients with non-Hodgkin's lymphoma (NHL) involving the ileocaecal region were cared for by the CRC Wessex Medical Oncology Unit. Fifteen of these patients had primary ileocaecal NHL (stages IE or IIE) and four had secondary involvement of this region (stage IV). The commonest clinical presentation was with abdominal pain and a palpable mass in the right iliac fossa. Bulky (greater than 10 cm) disease was a particularly common feature, and complete surgical removal was possible in only seven patients. All patients had intermediate (18) or high grade (one) NHL using the Working Formulation. The commonest histological subtype was diffuse large cell. Seventeen patients received postoperative therapy, comprising local radiotherapy in one and combination chemotherapy in the remaining 16. Eleven of the 19 patients remain disease-free 6-60 months from diagnosis. Because of the high incidence of bulky disease at this site, postoperative therapy may be indicated, even for patients with apparently completely excised stage I disease.

Adult↗