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Biomedical subjects

J Treleaven

Publications and source records attributed to J Treleaven.

141 records · Page 8Linked to original sources

Colony stimulating activity in the serum of patients with multiple myeloma is enhanced by interleukin 3: a possible role for interleukin 3 after high dose melphalan and autologous bone marrow transplantation for multiple myeloma.

Sera from 36/37 multiple myeloma patients and 19/21 sera from patients with other solid or liquid tumours had granulocyte-macrophage colony stimulating activity (CSA) towards normal human donor bone marrow whereas 1/16 sera from normal donors had this activity. Unlike human rhGM-CSF and GM-CSF from 5637 (human bladder cell line) conditioned medium which is heat stable, CSA from serum is heat labile (56 degrees C/30 min). In multiple myeloma patients, CSA was detectable more than 2 years after treatment with 'high dose melphalan. Although multiple myeloma patients, at relapse, have sufficient CSA in their serum to produce maximal stimulation of GM-CFUc from normal donor bone marrow in vitro, their own GM population responds poorly. The results suggest that the failure of patients own bone marrow to respond to endogenous CSA may be due to damage to the stem cells of the marrow or the failure of precursor cells to respond to CSA. Addition of rhIL-3 to myelomatous serum increased the number of GM-CFUc from both normal and myelomatous bone marrow but did not stimulate the growth of MY-CFUc significantly. The results suggest that rhIL-3 may assist bone marrow recovery in multiple myeloma patients after intensive chemotherapy.

Bone Marrow↗

Cyclosporine-induced graft-versus-host disease following autologous bone marrow transplantation in acute myeloid leukaemia.

Cyclosporine was used to induce graft-versus-host disease (GVHD) in patients with acute myeloid leukaemia (AML) receiving autologous bone marrow transplantation (ABMT). Nine consecutive patients with AML in remission were conditioned with either busulphan and cyclophosphamide or melphalan and total body irradiation (TBI) followed by ABMT. Cyclosporine, 1 mg/kg daily from days 1-28 was administered intravenously in four patients and orally in five. Acute GVHD of the skin, confirmed by histological and immunological criteria occurred in three patients, 4-28 days after ABMT and lasted 8-18 days. Incidence and severity of GVHD were independent of cyclosporine levels. Three patients subsequently relapsed, of whom two had had evidence of GVHD. All of these patients were in second remission at time of graft, and therefore poor risk. The potential of cyclosporine to induce GVHD in the AML autograft setting is demonstrated, although the significance of this observation in terms of an antileukaemia effect needs clarification.

Adult↗

Drugs and the bone marrow.

Some drugs have a predictable suppressive effect upon the bone marrow and are used in the treatment of malignant disease. Others are unpredictable and may cause unanticipated side effects to bone marrow during the treatment of non-malignant pathologies. In this article, bone marrow maturation is discussed and both the defined and potential effects of drugs upon the bone marrow are considered.

Agranulocytosis↗

Delayed engraftment associated with splenomegaly in patients undergoing bone marrow transplantation for chronic myeloid leukaemia.

There is no general agreement about the effect of an enlarged spleen on the outcome after bone marrow transplantation (BMT) for chronic myeloid leukaemia (CML). In this retrospective analysis, we compared rate of engraftment, haematological recovery and survival in 42 CML BMT recipients, 19 with splenomegaly and 23 without. Other variables analysed included interval from diagnosis to BMT, disease status at BMT, conditioning regimen, additional splenic irradiation, marrow cell dose, donor recipient ABO match and graft-versus-host disease. In multivariate analysis, the only significant variable was the presence or absence of splenomegaly. Splenomegaly was significantly correlated with delayed engraftment and graft failure. Patients with delayed engraftment experienced higher mortality, largely due to sepsis. These results emphasize the adverse impact of splenomegaly upon BMT survival in CML, and suggest that splenic irradiation does not favourably affect the early outcome after BMT.

Adolescent↗

Treatment of relapsed and refractory acute leukaemia with high-dose cytosine arabinoside and etoposide.

A total of 65 patients under the age of 55 with acute leukaemia received high-dose cytosine arabinoside (Ara-C) in combination with high-dose etoposide without an anthracycline. Complete remission rates for patients with relapsed or refractory acute myelogenous leukaemia (AML) were 15/25 (60%) and 11/16 (69%), respectively. The complete remission rate for patients with refractory or relapsed acute lymphoblastic leukaemia (ALL) was 10/18 (56%). The treatment-related mortality was 17%. Nine patients whose leukaemia relapsed after matched allogeneic, sibling bone-marrow transplantation (BMT) were also treated in this way; the treatment-related mortality in this group was high (7/9) and the duration of remission in the two patients who responded, too short to justify this intensive treatment in such patients. Similarly, patients who underwent BMT after achieving a complete remission with high-dose Ara-C and etoposide did very poorly, only one patient surviving well and disease-free at 8 months. The important finding in this study was the high complete remission rate rapidly obtained in patients with relapsed or refractory AML without using an anthracycline.

Adult↗

Circulating lymphoma cells in patients with B & T non-Hodgkin's lymphoma detected by immunoglobulin and T-cell receptor gene rearrangement.

We studied peripheral blood mononuclear cells from 50 patients with active B- and T-cell non-Hodgkin's lymphoma by DNA hybridisation. Nineteen patients (38%) had circulating clones of cells detected by immunoglobulin gene rearrangement (17 patients) or T-cell receptor gene rearrangement (2 patients) with JH and J beta 2 probes. Lymphoma tissue and peripheral blood were studied simultaneously in 22 patients, 9 of which had a circulating clone of cells in peripheral blood. In 7 patients the gene rearrangement in lymphoma tissue and peripheral blood mononuclear cells was identical. However, in 2 patients both heavy chain and light chain gene rearrangements were different in tissue and peripheral blood. The incidence of peripheral blood involvement was commonest in advanced CSIII & IV disease (54%) compared to CSI & II disease (18%) (P less than 0.05), and in low grade (45%) compared to intermediate and high grade lymphoma (31%) (difference not statistically significant). Only 4 patients had definite lymphoma cells seen on peripheral blood smear. The presence of circulating lymphoma cells correlated with conventional assessment of bone marrow involvement although circulating clones were detected in 30% (12/40) of patients with apparently normal bone marrow.

B-Lymphocytes↗

Monoclonal antibodies and magnetic microspheres for the depletion of leukaemic cells from bone marrow harvested for autologous transplantation.

The use of a panel of monoclonal antibodies and anti-mouse immunoglobulin-coated microspheres is described for the depletion of leukaemic blasts from bone marrow. Marrow treated in this way rapidly reconstitutes haemopoietic function after high-dose consolidation chemoradiotherapy. The recovery of cells from bone marrow is similar but not identical to results obtained on removal of neuroblasts from marrow to be used for autologous transplant. This is probably a reflection of the cross-reactivity of 'anti-leukaemic' antibodies with a variety of haemopoietic progenitor cells. The study described here demonstrates the feasibility of using this method to purge leukaemic cells from bone marrow. A much larger randomised study between patients receiving either purged or non-purged bone marrow would be necessary to validate the need to remove small numbers of tumour cells from bone marrow.

Antibodies, Monoclonal↗

Magnetic microspheres and monoclonal antibodies for the depletion of neuroblastoma cells from bone marrow: experiences, improvements and observations.

Improvements to the original procedure of using a panel of monoclonal antibodies and magnetic microspheres for the depletion of tumour cells from bone marrow are described. These include a completely disposable system for the magnetic depletion of tumour cells coated with magnetic microspheres. Properties of a new series of microspheres are compared with the old M330 beads in their ability to deplete neuroblasts from both model systems and 50 bone marrows harvested from Stage IV neuroblastoma patients. Using human neuroblastoma cell lines labelled with the DNA intercalating, Hoechst dye 33342 a 5% tumour contamination can routinely be removed from 5 X 10(6) - 5 X 10(7) nucleated cells. Analysis of the 50 purged marrows revealed that 10 were visibly contaminated with tumour (by conventional cytology and immunological procedures). In all but one case, tumour cells were removed. In this instance the tumour:bead ratio fell to 1:4 indicating the importance of maintaining a sufficient number of beads in the system. Red cell contamination of marrow was also kept extremely low so preventing possible physical blockade of bead:tumour cell interaction. Marrow engraftment was rapid in this group, apart from patients who had been exposed to high doses of alkylating agents prior to autografting.

Antibodies, Monoclonal↗

Decrease in clonogenic tumour cells in bone marrow aspirates from multiple myeloma patients due to the incorporation of cyclophosphamide into treatment with vincristine, adriamycin and methyl prednisolone.

A study of 32 patients receiving cyclophosphamide (CY) and verapamil (VER) in addition to the drug combination vincristine, adriamycin and methyl prednisolone (VAMP) was made in which the clinical response and growth of clonogenic myeloma cells (MY-CFUc) from bone marrow aspirates were compared. At presentation, MY-CFUc were grown from 72 per cent (23/32) of the patients. After treatment with CY-VAMP or VERCY-VAMP, MY-CFUc were grown from 25 per cent (8/32) of patients of whom only 50 per cent responded clinically. The overall clinical response rate for patients receiving CY-VAMP and VERCY-VAMP was 64 per cent (9/14) and 72 per cent (13/18) respectively of whom 14 per cent in each group achieved complete remission. There was no concomitant increase in normal tissue toxicity as measured by granulocyte-macrophage colony (GM-CFUc) formation. Comparison of these data with our previous study of patients receiving VAMP alone, suggests that the addition of CY to the regimen may increase the tumour cell kill. Further clinical studies will determine whether there is a significant increase in the complete remission rate.

Antineoplastic Combined Chemotherapy Protocols↗