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T J Hamblin

Publications and source records attributed to T J Hamblin.

At least 109 records · Page 6Linked to original sources
PubMed1987

Peripheral blood stem cell autografts in the treatment of lymphoid malignancies: initial experience in three patients.

Large numbers of circulating haemopoietic progenitor cells were collected from three patients with lymphoid neoplasms for the purpose of haemopoietic reconstitution following intensive chemotherapy or chemoradiotherapy. Each patient underwent four to six leukaphereses at a time when the circulating stem cell pool was expanded. 2-3 weeks after the end of myelosuppressive chemotherapy. The peripheral blood mononuclear cells (PBMNC) thus obtained were assayed for granulocyte-macrophage colony-forming cells (CFU-GM) and were cryopreserved in liquid nitrogen. Two patients were autografted with PBMNC containing 60 X 10(4) and 76 X 10(4) CFU-GM/kg body weight respectively. Both these patients showed prompt engraftment which is stable at +10 and +6 months. A third patient who was autografted with PBMNC containing 33 X 10(4) CFU-GM showed only temporary and incomplete engraftment. These observations confirm that the peripheral blood may be used as a source of haemopoietic stem cells for autografting, but criteria for predicting engraftment are at present uncertain.

Adolescent↗
PubMed1987

Monoclonal anti-light chain idiotype as a tumor-specific probe for human neoplastic B lymphocytes.

Tumor cells from patients with B cell neoplasms often secrete small amounts of free monoclonal light chains that can be found in the urine. Such tumor-derived light chains of the lambda type from a patient with typical chronic lymphocytic leukemia have been used to raise mouse monoclonal antibodies (MoAbs). A hybridoma-secreting antibody that recognized the idiotypic lambda chain but not normal lambda chains by a preliminary screen but which also reacted with idiotypic IgM from the patient's tumor cells was selected. This MoAb in fact recognized 1 in 20 X 10(3) molecules of pooled normal lambda chains, thus establishing its specificity for a private idiotypic determinant. It failed to give a detectable reaction with normal IgM, normal serum, or a panel of IgM paraproteins. The antibody bound to the patient's neoplastic B cells but not to normal tonsillar cells. The site of binding of the antibody to idiotypic IgM is clearly separate from that of another MoAb specific for idiotypic determinants on heavy plus light chains, since the two showed additive binding curves. The determinant also appeared to be less available in dimeric lambda chains than in monomeric lambda chains or in idiotypic IgM. Antibodies to idiotypic determinants on light chains show some technical advantages and should be useful for monitoring and possibly treating B cell tumors, either alone or together with the more conventional anti-idiotypic antibodies that usually recognize the heavy and light chain combination.

Antibodies, Anti-Idiotypic↗
PubMed1987

Initial experience in treating human lymphoma with a chimeric univalent derivative of monoclonal anti-idiotype antibody.

Murine monoclonal anti-idiotype antibody was raised against the surface IgM on the neoplastic cells of a patient with widespread follicular lymphoma. For therapy, a chimeric antibody derivative, FabIgG, was constructed by thioether-linking Fab'gamma, from the monoclonal antibody, to human normal IgG. FabIgG is univalent and thereby avoids rapid antigenic modulation. Its human IgG component is intended to optimize recruitment of effectors and metabolic survival while minimizing immunogenicity. Four intravenous (IV) infusions of 380 to 580 mg of anti-idiotype FabIgG were given over a period of 11 weeks. There was no significant toxicity. On each occasion, the antibody disappeared from the plasma with a half-life (t1/2) of less than 24 hours. The brief survival was evidently due to uptake by tumor, as infused control FabIgG, containing Fab'gamma from an irrelevant antibody, yielded a plasma t1/2 of greater than 10 days. With each therapeutic infusion, there was a fall in the number of circulating neoplastic cells over a 24-hour period. The numbers were largely replenished over the next week, but a net fall became discernible over the entire period of treatment. Four days after each infusion, nodal masses were swollen and tender, subsiding over approximately 8 days. At the end of the treatments, the blood lymphocyte count and nodal and splenic swellings continued to subside, so that by 6 weeks a partial remission with removal of greater than 50% of tumor was judged to have occurred. We did not detect any qualitative change in surface idiotype nor any antibody response to the infused Ig.

Animals↗
PubMed1987

Myelodysplasia.

The myelodysplastic syndrome has recently explained obscure anaemias, neutropenias and thrombocytopenias to haematologists, yet the concept remains puzzling to doctors outside the field. This review aims to introduce to non-specialists one of the commonest blood disorders in the elderly.

Bone Marrow Transplantation↗
PubMed1986

Analysis of soluble HLA class II antigenic material in patients with immunological diseases using monoclonal antibodies.

A quantitative assay for soluble human HLA Class II antigenic material is described. The method is a double-determinant ELISA using 2 monoclonal antibodies which recognize different epitopes on the antigen. The first rat monoclonal antibody captures antigen onto the microplate where it is then recognized by a second mouse monoclonal antibody. Bound mouse immunoglobulin is then detected by an enzyme-linked rat polyclonal antibody. The assay has been used to measure soluble HLA Class II antigen in the sera from healthy individuals and patients with leukaemia, and has shown raised levels in acute lymphoblastic but not in chronic lymphocytic leukaemia. Similar material has been identified in synovial fluid of patients with active rheumatoid arthritis. The assay is specific and simple to perform and should be applicable to probing the nature of the soluble material and its mechanism of release.

Antibodies, Monoclonal↗
PubMed1986

Immunological abnormalities in myelodysplastic syndromes. I. Serum immunoglobulins and autoantibodies.

The immunoglobulin levels and autoantibody profiles of 104 patients with primary myelodysplastic syndromes (MDS), classified according to the FAB criteria, were analysed. Eight patients, four with coexistent non-Hodgkin's lymphomas, three with chronic lymphocytic leukaemia and one with a lymphoplasmacytoma, were excluded from the final analysis of immunoglobulin levels. Serum protein electrophoresis and immunoelectrophoresis revealed the presence of monoclonal gammopathy in 12 patients (12.5%). Of the remaining 84 patients, a polyclonal rise in serum immunoglobulins was present in 27 (32%) while a further 16 (19%) had low immunoglobulin levels. The direct antiglobulin test was positive in eight out of 98 patients tested (8.1%), and organ and non-organ specific autoantibodies were present in 15 out of 67 patients tested (22.3%). Two patients had associated pernicious anaemia (PA), two hypothyroidism, and one PA with hypothyroidism. Three patients had sero-negative rheumatoid arthritis. These results demonstrate that there is a high incidence of immunological abnormalities in MDS.

Aged↗
PubMed1986

Immunological abnormalities in myelodysplastic syndromes. II. Coexistent lymphoid or plasma cell neoplasms: a report of 20 cases unrelated to chemotherapy.

We report a series of 20 patients with the myelodysplastic syndrome (MDS) each with a coexistent lymphoid or plasmacytic neoplasm. In none of the patients did chemotherapy play a part in the pathogenesis. The possible reasons for the coincidence of these conditions are discussed. The frequency and variety of associated neoplasms reinforces the idea that in MDS there are genetically unstable progenitor cells liable to clonal differentiation along a variety of pathways given appropriate stimuli.

Aged↗
PubMed1986

Monocytic skin infiltration in chronic myelomonocytic leukaemia.

Although leukaemic infiltration of the skin commonly occurs in acute monoblastic leukaemia, the association with chronic myelomonocytic leukaemia (CMML) has only been described recently. We confirm the association and report histologically proven monocytic infiltration of the skin in four patients with CMML. This did not herald a more aggressive phase of the disease as previously suggested. Treatment of the rash with low dose cytarabine or etoposide was effective but razoxane produced no benefit. Superficial radiotherapy was useful to control pruritus in one patient.

Aged↗
PubMed1986

Reduced survival of isotope-labelled Rh(D)-negative donor red cells in a patient with anti-LWab.

The serum of an 85-year-old Caucasian male with no history of blood transfusion contained an IgG3 antibody with anti-LWab specificity. The antibody failed to react with dithiothreitol-treated red cells, and there was a marked reduction in titre of the antibody with pronase-treated cells, findings consistent with an antibody having this specificity. High association values were obtained in a mononuclear phagocyte assay when LW-positive red cells, sensitised in vitro with the patient's serum antibody, were incubated with peripheral blood monocytes from the patient. In vivo red cell survival studies demonstrated that 99mTc-labelled rhesus-negative (rr), LW-positive red cells had 53% survival at 1 h. The IgG subclass of the antibody, mononuclear phagocyte assay results and in vivo survival studies predicted a significant reduction in the posttransfusion survival of therapeutic volumes of rhesus-negative (rr), LW-positive red cells.

Aged↗
PubMed1986

Evolution of a terminal deoxynucleotidyl transferase-positive lymphoma from a chronic T cell lymphocytosis.

A 56-yr-old Caucasian man presented with a generalised scaly rash and a peripheral blood lymphocytosis of 5.6 X 10(9)/l. 5 yr later he developed cutaneous nodules, lymphadenopathy and hepatosplenomegaly. Cells with convoluted nuclei and prominent nucleoli were seen in the peripheral blood. He underwent splenectomy and received intensive chemotherapy but died 6 months later with CNS infiltration. At presentation the peripheral blood lymphocytes were E-ve, UCHT1 + ve, and OKT8 + ve. Following transformation, cells in blood, spleen and CSF were E-ve, OKT11 + ve, DR + ve and Tdt + ve. A proportion of these cells had a Sézary-like appearance at E/M. The splenic cells showed functional suppressor activity. This is the first reported case of the evolution of a Tdt + ve lymphoma from a post-thymic T cell lymphocytosis.

DNA Nucleotidylexotransferase↗
PubMed1986

Autoimmunity in chronic lymphocytic leukaemia.

The prevalence of autoantibodies in B cell chronic lymphocytic leukaemia (B-CLL) was investigated. A lower prevalence of autoimmune haemolytic anaemia than that found in other series was found: large numbers of non-progressive stage A disease cases were included, in which the prevalence of autoimmune haemolytic anaemia is low. Non-haematological autoantibodies were no commoner than in age matched controls. Whatever explanation is offered for autoimmune phenomena in B-CLL it must take account of the fact that those phenomena are virtually confined to autoantibodies against the formed elements of the blood.

Aged↗