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J A Child

Publications and source records attributed to J A Child.

At least 73 records · Page 4Linked to original sources

Combination chemotherapy with cisplatin and methotrexate in advanced transitional cell cancer of the bladder.

We studied 53 patients with bidimensionally measurable metastases of transitional cell cancer of the bladder who were treated with a planned regimen of 70 mg. per m. cisplatin intravenously on day 1, and 40 mg. per m. methotrexate intravenously on days 8 and 15 every 3 weeks. The toxicity of this regimen, with agranulocytosis and mucositis as the most important side effects, was so severe that only 17 per cent of the patients actually received the protocol regimen without modification. Six patients were ineligible and 47 were evaluable for toxicity, including 43 who were evaluable for response. The response to treatment was assessed after each second treatment cycle. A complete response was achieved in 10 patients (23 per cent) and a partial response was achieved in 10 (23 per cent). The median duration of response was 64 weeks for patients with a complete response and 23 weeks for those with a partial response, while the median duration of survival was 81 and 37 weeks, respectively. The aforementioned regimen with allowance of routine leucovorin rescue is tested as preoperative chemotherapy in patients with stages T3 to T4 nonmetastatic bladder cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Ploidy, proliferative activity, cluster differentiation antigen expression and clinical remission in high-grade non-Hodgkin's lymphoma.

Using a large range of monoclonal antibodies to specific cluster differentiation antigens the phenotypes of a series of high-grade non-Hodgkin's lymphomas of B- and T-cell type were investigated. Cell ploidy and proliferative fraction were assessed by fluorescent staining of DNA and flow cytometry and data on the incidence of complete clinical remission were obtained. With the exception of some lymphoblastic lymphomas, high-grade B-cell lymphomas normally expressed the pan B-cell antigens CD19 and CD22 but only immunoblastic lymphomas consistently expressed the pan B marker CD20. Variable, generally weak expression of CD21 was observed whilst CD23 expression was most prevalent in rapidly proliferative cases and in Burkitt's and centroblastic lymphomas. A rapidly proliferative, multilobated B-cell lymphoma displayed phenotypic properties intermediate between centroblastic and immunoblastic lymphomas. The T-cell lymphomas generally showed low proliferative activity and expression of CD4 prevailed over CD8. Most cases also showed CD2 and CD5 positivity with some also showing CD3 and CD7 expression. Patients with rapidly proliferative diploid or DNA aneuploid tumours obtained complete remission more readily than patients with lowly proliferative diploid tumours. An excess of early deaths occurred among T-cell cases.

Adolescent↗

Cell surface expression of beta 2-microglobulin (beta 2m) correlates with stages of differentiation in B cell tumours.

Cell surface beta 2-microglobulin (beta 2m) densities of malignant B cells were determined by enzyme immunoassay in 97 cases of immunologically defined lymphoproliferative disease. Absolute beta 2m densities were found to depend on disease category with the lowest levels found on cells from chronic lymphocytic leukaemia (mean = 5.6 ng/10(6) cells, n = 27); atypical chronic lymphocytic leukaemia (mean = 5.9 ng/10(6) cells, n = 8); and prolymphocytoid chronic lymphocytic leukaemia variant (mean = 6.0 ng/10(6) cells, n = 16). beta 2m densities for B non-Hodgkin's lymphoma (n = 14) and B prolymphocytic leukaemia (n = 17) cases were 8.1 and 10.0 ng/10(6) cells, respectively, and the highest densities were found on cells from "late-B cell" tumours (mean = 14.3 ng/10(6) cells). Plasma cells from cases of Ig secreting tumours expressed unexpectedly low beta 2m densities (mean = 9.3 ng/10(6) cells; n = 6).

B-Lymphocytes↗

Changes in plasma beta 2 microglobulin concentrations after allogeneic bone marrow transplantation.

Plasma concentrations of beta 2 microglobulin (B2M), the light chain of the class I major histocompatibility complex, were measured serially in 26 patients undergoing allogeneic bone marrow transplantation (BMT). The concentrations fell after conditioning treatment, and recovered when the marrow was transplanted. Bacterial infection did not influence B2M concentration, but nine of 22 episodes of acute graft versus host disease were associated with raised concentrations. Increased plasma B2M concentrations were also a feature of eight episodes of chronic graft versus host disease, and these fell after treatment. Reactivation of herpes simplex, varicella zoster, or cytomegalovirus infections were also accompanied by raised B2M concentrations. Three patients with cytomegalovirus pneumonitis had high concentrations of plasma B2M, the rise starting between five and 22 days before onset of symptoms. Although it is non-specific, serial measurement of plasma B2M in patients undergoing BMT may be clinically useful in monitoring chronic graft versus host disease.

Adolescent↗

Downgrading of non-Hodgkin's lymphoma following chemotherapy.

A case of high-grade non-Hodgkin's lymphoma (malignant lymphoma centroblastic) is presented which, following chemotherapy, manifested low-grade histology. The importance of repeated biopsies in cases of persistent or recurrent disease following therapy for lymphoma is emphasized.

Aged↗

Cluster differentiation antigen expression, proliferative activity and clinical stage in centroblastic centrocytic lymphomas.

Using a panel of B-cell antibodies recognizing clusters of leucocyte differentiation antigens, immunostaining patterns of eight reactive lymph nodes and 28 centroblastic/centrocytic and centrocytic lymphomas have been studied. Centroblastic/centrocytic and centrocytic lymphomas retained many of the B-cell differentiation antigens and neoplastic follicles partially recapitulated the staining patterns observed in reactive follicles. Centrocytic lymphomas usually expressed a heavy chain mantle zone-like phenotype. Nearly one-half of follicular lymphomas showed extension of neoplastic cells into interfollicular areas as evidenced by positivity for CD10 (common acute lymphoblastic leukaemia) and/or CD9 (immature B-cell) and CD23 (B-blast cell) antigens. Cases showing interfollicular involvement also manifested considerable phenotypic heterogeneity. Light chain restriction could not be used to determine interfollicular involvement because of the presence of many non-neoplastic cells. Most follicular lymphomas retained a polyclonal mantle around at least some neoplastic follicles and in no case was a monoclonal mantle seen. Most lymphomas (16/21) were diploid when examined by flow cytometry. Diploid tumours exhibiting interfollicular lymphomatous involvement had high proliferation (S + G2) fractions and these lymph nodes were usually derived from patients with widespread disease. Tumours containing a high percentage of cells in the G0/G1 phases displayed fewer B-cell differentiation antigens than tumours with low G0/G1 fractions.

Antigens, Neoplasm↗

DNA content and prognosis of non-Hodgkin's lymphoma.

Ninety cases of non-Hodgkin's lymphoma diagnosed prior to the use of modern therapeutic regimens (1963-67) and 88 cases treated with such chemotherapy (1980-85) were studied using conventional morphology and flow cytometry. DNA aneuploidy as determined by flow cytometry was more common among high grade (38%) than low grade (19%) tumours (P less than 0.01). Measurements of proliferative index (S + G2 phase cells) revealed significantly increased values for high grade as compared with low grade lymphomas (P less than 0.001). In the first group of cases (1963-67) the relationship between histological grade and survival just failed to reach statistical significance over the long term (20 yr) (P = 0.1) but proved significant over 3 yr (P = 0.012). Differences in ploidy and proliferative index status were not associated with survival. In the second patient group (1980-85) attainment of complete remission following chemotherapy was associated with the presence of DNA aneuploidy in high grade tumours (P less than 0.05). The limited follow up of this group precluded assessment of survival in relation to ploidy.

Adolescent↗

Surface membrane phenotypic expression and treatment response of malignant lymphomas.

Cryopreserved lymphoid tissue has been used from 113 patients for an analysis of cell surface membrane phenotypes using a panel of monoclonal antibodies. Dual heavy chain expression was common in many B-cell malignant lymphomas and in the B-cell lymphomas as a whole there was a predominance of lambda light chains. The expression of lambda light chain was associated with a poorer response to treatment and there was a tendency for such tumours to fall into the high grade lymphoma category. Surface membrane heavy chain expression, as assessed by staining intensity, was greatest in the lymphomas composed mostly of centrocytes and IgD expression was reduced in high grade lymphomas. The ratio of helper to suppressor T-cells was reduced in centroblastic and immunoblastic lymphomas. In Hodgkin's disease a predominance of T-cells was found in most instances although the series included a large proportion of nodular sclerosis cases.

Adult↗

Concurrent T-cell lymphocytic lymphoma and malignant histiocytosis.

A case in which both malignant histiocytosis and T-cell lymphocytic lymphoma occurred together is presented. Examples of malignant histiocytosis-like syndromes associated with lymphoreticular malignancies have been previously reported. Many of these represent reactive haemophagocytic syndromes, probably virally induced. The considerable degree of cytological atypia and frequent mitotic figures seen in the histiocytes in this case were indicative of a true malignant histiocytosis.

Adult↗

Prednisolone levels in plasma and leukemia cells during therapy of chronic lymphocytic leukemia.

The capacity of chronic lymphocytic leukemia cells to concentrate prednisolone has been evaluated in vivo and in vitro employing a radioimmunoassay for prednisolone. No evidence to suggest that leukemia cells are capable of selectively concentrating glucocorticoid was found. The relative uptake of glucocorticoid by leukemia cells was found to be greater in vitro than in vivo. This may be attributable to differences in steroid bioavailability to cells. Substantially lower levels than previously reported of free prednisolone were found in plasma of patients receiving oral treatment with prednisolone. This may result from the failure in previous studies to remove derivatives of prednisolone and other steroids prior to assay for hormones.

Humans↗

Pulmonary infiltrates and adult acute leukaemia: empirical treatment and survival related to the extent of pulmonary radiological disease.

In a retrospective review of 141 consecutive adult patients with acute leukaemia there were 33 local and eight diffuse parenchymal pulmonary abnormalities noted on the first abnormal chest radiograph. Empirical treatment was given without any invasive diagnostic procedures. Twenty of the 41 patients (49%) with radiographic abnormalities died--10 of 31 patients (32%) in the "local" group (excluding two who were not actively treated) and all eight patients in the "diffuse" group. One patient in the local group and six in the diffuse group died within 48 hours of the first abnormal chest radiograph. The results in the local group suggest that failure to respond to the initial treatment prescribed would allow time to perform an invasive procedure in most patients that may lead to a change in management. In the diffuse group, however, an early invasive procedure would be required if the result were to have a chance to influence the outcome.

Adolescent↗

A pilot study of cyclical chemotherapy with high-dose methotrexate and CHOP (MTX-CHOP) in poor-prognosis non-Hodgkin's lymphoma (NHL).

In a pilot study of cyclical chemotherapy in patients with poor-prognosis non-Hodgkin's lymphoma (NHL), high-dose methotrexate (MTX) 1 g/m2 with folinic acid rescue was given as initial treatment and then between cycles of a single-arm CHOP combination administered every 4 weeks. Of 21 patients with previously untreated or minimally treated grade 2 (high-grade) histology stage II/III/IV NHL, 13 (62%) achieved complete remission (CR); the CR rate for stage III/IV patients was 56%. Of all 25 patients with grade 2 stage II/III/IV NHL, including previously treated patients, 16 (64%) achieved CR. The median follow-up of patients who completed treatment is currently 22 months and only 1 relapse has been recorded in the CR group. Only five of 24 grade 2 patients given the initial 'test' MTX failed to show any response, and eight patients achieved partial remission (PR) as a result of this single treatment. The response to MTX-CHOP in nine patients with grade 1 (low-grade) histology NHL was poor; only two achieved CR. These findings lend support to other data which indicate a useful role for MTX in the induction chemotherapy of advanced high-grade NHL, though the optimum dosage and drug sequence have yet to be determined.

Adolescent↗

Evaluation of serum beta 2-microglobulin as a prognostic indicator in myelomatosis.

Serum beta 2-microglobulin (beta 2-m) is frequently increased in patients with myelomatosis. The possibility that it could provide a biochemical indicator of prognosis was tested in a group of 129 patients from 3 centres, all serum analyses being carried out in one laboratory by radioimmunoassay. A strong association between the pretreatment serum beta 2-m level and survival was demonstrated, the data for the 2 main subgroups being very similar. In further detailed analyses of 64 patients, serum beta 2-m proved to be a stronger indicator of prognosis than current "standard" clinical and laboratory data, including stage determined by the method of Durie and Salmon and the combination of haemoglobin level and blood urea. The association between serum beta 2-m and survival remained close after treatment as indicated by the findings at one year. The serum beta 2-m in myeloma reflects the tumour mass and also reduced glomerular filtration when renal failure supervenes. It is concluded that the serum beta 2-m is a powerful prognostic indicator in myelomatosis and of considerable value in the investigation of patients with the disease.

Beta-Globulins↗

Plasma fibronectin in myeloproliferative disorders and chronic granulocytic leukaemia.

A significant reduction of plasma fibronectin levels was found in polycythaemia vera and myelofibrosis, the lowest levels being found in patients with marked splenomegaly. Plasma fibronectin concentration was normal in essential thrombocythaemia, and only modest reduction was seen in chronic granulocytic leukaemia in either controlled chronic phase or blast cell crisis. In a patient with myelofibrosis, the plasma fibronectin rose from less than 100 mg/l to 177 mg/l after splenectomy. Possible explanations include increased consumption of plasma fibronectin in the expanded mononuclear phagocyte system present in the liver and spleen, reduced hepatic synthesis, and the clearance of circulating immune complexes. Low plasma fibronectin concentrations may increase susceptibility to infection.

Adult↗