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Biomedical subjects

J H Scarffe

Publications and source records attributed to J H Scarffe.

At least 55 records · Page 3Linked to original sources
PubMed1994

Acute lymphoblastic leukaemia following Hodgkin's disease is associated with a good prognosis.

Acute leukaemia, both myeloid and lymphoblastic, in patients treated for Hodgkin's disease (HD) is thought to have a poor prognosis. We report four adults who developed secondary acute lymphoblastic leukaemia (ALL) following chemoradiotherapy for HD. The chromosomal translocation t(4;11) (q21;q23) was found in two patients who received a chemotherapeutic regimen containing the DNA topoisomerase II inhibitor etoposide. Three of the four patients are alive and in unmaintained first remission at 3, 5 and 9 years from diagnosis of ALL, two following autologous bone marrow transplantation. These results suggest that ALL following HD may have a good prognosis when treated aggressively.

Adult↗
PubMed1994

Distinctive features of immunoglobulin heavy chain variable region gene rearrangement in multiple myeloma.

We have analysed the rearranged Ig heavy chain (IgH) genes in a series of 28 cases of multiple myeloma (MM), in order to extend the study of Ig heavy chain variable (VH) gene usage in B lymphoid malignancies and to explore the ontogenic compartment from which transformed precursor cells arise in this disease. We were able to amplify 28 rearranged alleles by polymerase chain reaction from 23 of these cases, using a common joining region (JH) amplimer together with a panel of VH family-specific amplimers. The pattern of VH family usage was similar to that reported in normal peripheral blood B cells with infrequent usage of VH5 and VH6 genes. However, nucleotide sequence analysis of 17 IgH alleles revealed rearrangement of other VH family members, closely related to known developmentally regulated VH genes, some of which are known to be associated with autoimmune specificities. In contrast to previous findings on more immature B lineage malignancies, the rearranged genes diverged extensively from consensus germline sequences, consistent with somatic mutation. These findings support the hypothesis that the major proliferating precursor in MM arises at, or following a stage of T cell-dependent germinal centre proliferation in lymphoid follicles.

Base Sequence↗
PubMed1993

Peripheral blood progenitor cell transplantation in lymphoma and leukemia using a single apheresis.

Myeloablative treatment and peripheral blood progenitor cell (PBPC) transplantation are increasingly used for lymphomas and leukemias. We have sought to optimize conditions for priming, collection, and engraftment of the leukapheresis product. Fifty-four consecutive adult patients were eligible, 31 with high-grade non-Hodgkin's lymphoma of poor prognosis, 12 with Hodgkin's disease in chemosensitive relapse, and 11 with poor prognosis acute lymphoblastic leukemia. Filgrastim was administered after routine chemotherapy with VAPEC-B or HiCCOM to mobilize PBPC. A rapidly increasing white blood cell count was used to predict the time of peak PBPC release and plan leukapheresis. Forty-five patients underwent leukapheresis. A median of 14 L of blood was processed at a single apheresis. A median of 2.4 x 10(8)/kg mononuclear cells (MNCs), 1.04 x 10(6)/kg granulocyte-macrophage colony-forming cells (GM-CFCs), and 10.6 x 10(6)/kg CD34+ cells were obtained. Slightly fewer MNCs were obtained from the heavily pretreated Hodgkin's disease group. There were no other significant differences in the size or composition of the leukapheresis harvest in the three patient groups. Forty patients underwent high-dose therapy and PBPC transplantation. Filgrastim was administered by daily subcutaneous injection until the absolute neutrophil count was > or = 1 x 10(9)/L for 2 consecutive days. Rapid and sustained hematopoietic engraftment occurred in all patients. The median time to achieve a neutrophil count > or = 0.5 x 10(9)/L was 9 days (range, 8 to 16 days); to achieve a platelet count > or = 20 x 10(9)/L was 10 days (range, 6 to 88 days); and to achieve a platelet count > or = 50 x 10(9)/L was 15.5 days (range, 10 to 100 days). Neutrophil recovery was faster than that of a historical control group treated with autologous bone marrow transplantation and filgrastim, but platelet recovery times were halved in the PBPC group. There was no secondary engraftment failure. Requirements for blood and platelet transfusions, antibiotic use, and parenteral nutrition were similar in the three patient groups. The median number of days in the hospital was 13 (range, 10 to 55) in the PBPC patients, compared with 19 (range, 14 to 51) in the historical controls. Leukapheresis yields (MNC, GM-CFC, and CD34+ cell numbers) were not useful for predicting the times to engraftment. We have shown that sufficient PBPC for transplantation can be obtained at a single leukapheresis after mobilization with routine chemotherapy and filgrastim in patients with non-Hodgkin's lymphoma, Hodgkin's disease, and acute lymphoblastic leukemia, even those heavily pretreated.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

Cutaneous infection with Rhizopus oryzae and Aspergillus niger following bone marrow transplantation.

We describe a case of mixed Rhizopus oryzae and Aspergillus niger infection in a 38 year-old woman who had undergone allogeneic bone marrow transplantation for multiple myeloma. The fungi were isolated from a necrotic ulcer under a plaster cast stabilizing a pathological fracture of the left humerus. We emphasize the necessity for frequent inspection of any covered area of skin and the use of sterile dressings as far as possible in neutropenic patients.

Adult↗
PubMed1993

Future outlook for growth factors.

In the future improvements in the efficacy and safety profiles of the various growth factors in clinical use should be achievable through optimization of dosage schedules. The use of combinations of growth factors to provide hemopoietic support should enable considerable advances to be made in the treatment of hematological and non-hematological malignancies. Growth factors, such as granulocyte-macrophage colony stimulating factor may be used not only to maximize neutrophil recovery after myeloablative therapy, but also to mobilize peripheral blood stem cells prior to harvesting by leukapheresis. Growth inhibitory cytokines such as transforming growth factor-beta and macrophage inflammatory protein-1 alpha may be used to protect normal cells in the bone marrow and other sites where dose-limiting toxicities occur. Therefore, in the next few years, the whole approach to chemoradiotherapy will need to be reconsidered in the light of the dose intensification made possible by improved bone marrow support techniques and advances in other areas of supportive care.

Bone Marrow Transplantation↗
PubMed1992

Recombinant human interleukin 4 (IL-4) given as daily subcutaneous injections--a phase I dose toxicity trial.

Recombinant Interleukin 4 was administered by subcutaneous injection at daily doses of 0.5, 1.0 or 5.0 micrograms kg-1 to nine patients as part of a Phase I Dose Toxicity Study. Dose limiting toxicity was reached at 5 micrograms kg-1 day-1. Symptoms of toxicity included fatigue, 'flu like symptoms and elevated liver enzymes. Modest but significant elevations of neutrophil and platelet counts occurred. No clear evidence of antitumour effects emerged although pain in metastatic lymph nodes and a small fall in myeloma paraprotein levels during dosing were observed. In vitro and murine in vivo studies indicate that patients with lymphoproliferative disease should be selected for Phase II trials.

Bone Marrow↗
PubMed1992

Cyclophosphamide decreases O6-alkylguanine-DNA alkyltransferase activity in peripheral lymphocytes of patients undergoing bone marrow transplantation.

O6-alkylguanine-DNA-alkyltransferase (ATase) levels were measured in extracts of peripheral blood lymphocytes taken at various times during chemotherapy from 19 patients with various haematological malignancies. Seven patients with advanced Hodgkin's disease received preparative treatment consisting of cyclophosphamide (1.5 g m-2, daily) administered on days 1 to 4 and BCNU (600 mg m-2) on day 5 prior to autologous bone marrow rescue (ABMR) delivered on day 7. Treatment in the remaining 12 patients consisted of cyclophosphamide (1.8 g m-2, daily) given on days 1 and 2 followed at day 4 with total body irradiation (TBI) administered in six fractions over the subsequent 3 days to a total dose of 1200 cGy prior to bone marrow transplantation. In the Hodgkin's group, significant decreases in ATase activity were seen during the cyclophosphamide treatment, and the median ATase nadir was 32% (range 0% to 57%) of pretreatment levels following 4 days of cyclophosphamide. In one patient, no ATase activity was detectable following the 4th cyclophosphamide treatment. ATase activities decreased further after BCNU administration to a median of 19% (range 0% to 32%) of pretreatment levels. Extensive cyclophosphamide-induced reduction of lymphocyte ATase levels was also seen in the other group of 12 patients treated with cyclophosphamide/TBI: postcyclophosphamide median ATase nadir was 35% (range 12% to 78%) of the pretreatment levels. No ATase depletion was seen when cyclophosphamide (up to 10 mM) was incubated for 2 h with pure recombinant human ATase in vitro whereas ATase activity was reduced by 90% on preincubation with 100 microns acrolein or with greater than 1 mM phosphoramide mustard. This suggests that a cyclophosphamide-induced decrease in ATase levels in human peripheral lymphocytes in vivo may be due to depletion mediated by the production of intracellular acrolein. Since ATase appears to be a principal mechanism in cellular resistance to the cytotoxic effects of BCNU and related alkylating agents, these observations suggest that a cyclophosphamide-induced reduction in ATase activity may be an additional factor in the effectiveness of the combined sequential therapy.

Acrolein↗
PubMed1992

A phase II study of sulofenur (LY186641) in gastric cancer.

Sulofenur is a novel diarylsulfonylurea with proven anti-tumor activity in murine tumor models. In this phase II study in patients with advanced gastric or gastroesophageal adenocarcinoma, 17 patients were treated with sulofenur orally at 700 mg/m2 for 14 days every 3 weeks. No tumor responses were seen. The main toxicities were anemia, methemoglobinemia and abnormalities in liver function tests. These toxicities precluded dose escalation. However, plasma levels of sulofenur, and its hydroxy and keto metabolites were probably insufficient to exert anti-tumor effect in comparison with data from murine studies. Further structure-activity studies are warranted.

Adenocarcinoma↗
PubMed1992

Failure of balloon dilatation of the pulmonary valve in carcinoid pulmonary stenosis.

BACKGROUND: Carcinoid heart disease typically results in pulmonary stenosis and tricuspid incompetence. Percutaneous balloon dilatation is an effective treatment for congenital pulmonary stenosis and has been applied successfully to tricuspid stenosis caused by carcinoid heart disease. The value of balloon dilatation of the pulmonary valve in carcinoid pulmonary stenosis was assessed. METHODS: Two patients with severe congestive heart failure secondary to carcinoid heart disease and with documented pulmonary stenosis had balloon dilatation of the pulmonary valve. In both cases tricuspid regurgitation was also present together with reduced cardiac output. RESULTS: The procedure was technically successful in both patients. One patient experienced symptomatic benefit for two months and the other experienced no improvement. Both patients subsequently required combined tricuspid and pulmonary valve replacement from which good results and symptomatic improvement were obtained. CONCLUSION: Though balloon dilatation of the pulmonary valve is technically feasible it is unlikely to provide useful palliation in carcinoid heart disease. Valve surgery should be considered in patients in whom the malignancy is controlled but carcinoid heart disease is producing drug resistant congestive heart failure.

Carcinoid Heart Disease↗
PubMed1991

Recombinant human GM-CSF in small cell lung cancer: a phase I/II study.

Seventeen patients with small cell lung cancer were entered into a dose ranging phase I-II study using rhGM-CSF (Glaxo). In the phase I study patients received 50, 150, 300 or 500 micrograms/m2 GM-CSF for 10 days by daily subcutaneous injection. Full blood counts were performed thrice weekly. After 4 days off all therapy patients then received chemotherapy with doxorubicin 50 mg/m2 i.v. bolus, day 1, ifosfamide 5 g/m2 with mesna 5 g/m2 over 24 h by continuous infusion followed by mesna 3 g/m2, and etoposide 120 mg/m2 i.v. on days 1-3. A total of six courses of chemotherapy were given. In the phase II study patients received the same dose of GM-CSF as in the phase I. GM-CSF was given 24 h after the last dose of chemotherapy for 14 days. Full blood counts were checked thrice weekly and the incidence of infections noted. Patients were randomised to receive GM-CSF with either odd or even courses of chemotherapy. The leucocyte count rose from a mean of 8.7 to 21.6 x 10(9)/l at the 50 micrograms/m2 GM-CSF dosage and from 11.4 to 39.4 x 10(9)/l at the 500 micrograms/m2 dosage during the phase I study. Phase I toxicity was: bone pain in 65% of patients, rash in 47%, fever in 24%, lethargy in 12% and diarrhoea in 12%. In the phase II study the duration of neutropenia was less during the chemotherapy courses with GM-CSF (p = 0.04) but the number of infections was similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Upper humeral cortical thickness as an indicator of osteopenia: diagnostic significance in solitary myeloma of bone.

Solitary myeloma of bone is a form of plasma cell tumor, histologically indistinguishable from multiple myeloma but characterised by a single bony focus of disease. Most patients respond to local radiotherapy (median survival 10-12 years); however, many (greater than 30%) rapidly develop multiple myeloma (median survival 2-4 years). Currently, no criteria exist for identifying these high-risk patients at the time of diagnosis. We have assessed the prognostic value of clinical features at presentation in 32 patients with solitary myeloma of bone. Only osteopenia at presentation (P less than 0.000003) and immunoparesis (P less than 0.00002) proved to be independent, significant prognosticators of decreased survival. Exclusion of patients with osteopenia or immunoparesis at presentation identified a group with an 80%-90% chance of surviving 10 years. Patients with either risk factor had a median survival of only 27 months. Osteopenia was assessed using measurements of combined cortical thickness in the upper humerus. This site has not previously been used, and normal values are presented for a control group (n = 413).

Adult↗
PubMed1991

MMAF for advanced gastric cancer.

65 patients with metastatic gastric carcinoma were treated with a combination of methotrexate 1.5 g/m2 with 5-fluorouracil 1.5 g/m2 on day 1 and doxorubicin 30 mg/m2 with mitomycin 4 mg/m2 on day 14. Cycles of chemotherapy were repeated every 4 weeks. The overall response rate was 29% with 6% complete responses and 23% partial responses. Prognostic factors that individually affected response were Karnofsky performance (P less than 0.002), and site of the primary tumour (P less than 0.007). Multivariate analysis showed that only increasing Karnofsky performance (P = 0.01) and disease status (P less than 0.02) (patients with recurrent tumours responding better than patients with postoperative residual disease and those with inoperable disease) were important in predicting response to therapy. The overall median survival was 7 months. All 4 patients with a complete response are alive in remission at 13, 28, 48 and 52 months from the date of starting chemotherapy. Univariate analysis identified increasing Karnofsky performance (P less than 0.0001), response to chemotherapy (P less than 0.02) and higher serum albumin (P less than 0.03) as prognostic indicators for survival. Multivariate analysis, of pretreatment factors and day 14 full blood count showed that only Karnofsky performance (P less than 0.0001) and day 14 platelet count (P less than 0.03) were shown to predict survival, higher platelet values being associated with decreased survival.

Adenocarcinoma↗
PubMed1991

Viridans streptococcal bacteraemia in patients with haematological and solid malignancies.

Thirty-three episodes of septicaemia caused by viridans streptococci are reported in 32 adults under treatment for malignant diseases. The underlying diseases were acute leukaemia (17), lymphoma (4), myeloma (1), small cell carcinoma of the bronchus (6), carcinoma of the breast (2) and carcinoma of the stomach (2). Important predisposing factors included severe neutropenia and oral mucositis due to intensive chemotherapeutic regimens. There was a poor response to standard empirical antibiotics and a mortality of 12%. A role for prophylactic penicillin in high risk groups is suggested.

Adolescent↗
PubMed1991

Post consolidation therapy for adult patients with acute myeloid leukaemia.

One hundred and sixteen adult patients aged 14-73 with previously untreated acute myeloid leukaemia received induction and consolidation chemotherapy with daunorubicin, cytosine arabinoside and thioguanine. Two novel approaches to post consolidation therapy have been investigated. Patients aged 50 years or less who had no suitable matched allogeneic donor were considered for autologous bone marrow transplantation (BMT) using bone marrow which had been cultured in vitro for 14 d. Patients over the age of 50 years with normal bone marrow cellularity and peripheral blood count were treated with a single oral dose of busulphan 100 mg/m2 (without BMT rescue) 3 months following the completion of consolidation therapy. Eighty-seven patients (75%) achieved a complete remission. Of 70 patients who completed consolidation therapy, 40 were aged less than or equal to 50 years and 30 were greater than 50 years. Forty-three patients went on to receive post consolidation therapy in first CR (autologous BMT 12, allogeneic BMT 7, busulphan therapy 24). The event-free survival at 4 years was 47% for autologous BMT, 34% for allogeneic BMT and 45% for busulphan-treated patients. The survival for the older cohort of patients who received post consolidation therapy with single dose busulphan therapy was encouraging, and this agent should be considered for future post consolidation strategies.

Acute Disease↗