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Biomedical subjects

C A Juttner

Publications and source records attributed to C A Juttner.

At least 55 records · Page 3Linked to original sources
PubMed1988

Consolidation therapy without maintenance for acute non-lymphoblastic leukaemia.

The most effective therapy to prolong remission and to increase cure rates in patients with acute non-lymphoblastic leukaemia is uncertain, and approaches vary from one course of consolidation to two years of maintenance and intensification therapy. We report the results of brief intensive therapy with daunorubicin, cytosine arabinoside and thioguanine, and no maintenance therapy, in 72 patients with a minimum follow-up period of two years. The complete remission rate was 67%, the median duration of remission was 11 months, and 23% of patients whose leukaemias went into remission, have remained in remission for three years and longer. These results are equivalent to those that have been reported with long-term chemotherapy.

Actuarial Analysis↗
PubMed1988

Expression of a 150-kD cell surface antigen identified by monoclonal antibody YB5.B8 is associated with poor prognosis in acute non-lymphoblastic leukaemia.

Peripheral blood specimens, obtained from 71 patients with newly-diagnosed acute non-lymphoblastic leukaemia (ANLL) prior to the initiation of therapy, were assayed for the presence of a myeloid leukaemia-associated cell surface antigen identified by monoclonal antibody YB5.B8. The antibody bound to cells from 22 patients, and these patients had a poorer overall survival rate than those whose cells failed to bind the antibody (p less than 0.025). Fifty patients were treated with daunorubicin/cytosine arabinoside/6-thioguanine (DAT) according to a standard protocol and survived at least to the end of the induction phase (7 days). Of the 34 patients whose cells were YB5.B8 negative, 28 obtained a complete remission. In contrast, only four of the 16 patients whose cells expressed YB5.B8 antigen obtained complete remission (p less than 0.001). Expression of the YB5.B8 antigen in ANLL appears to be a strong prognostic indicator which is independent of other known prognostic factors such as patient age, leucocyte count and pre-existing hematopoietic abnormality.

Adolescent↗
PubMed1988

Bone marrow biopsy during induction chemotherapy for acute myeloid leukaemia identifies only 50% of patients with resistant disease.

A study was carried out to determine whether bone marrow biopsy performed on day 6 of induction therapy for acute myeloid leukaemia (AML) can identify those patients with resistant disease who would need an intensification of the first course of induction. Bone marrow biopsies were performed on day 6 of induction chemotherapy in 44 patients with AML treated with daunorubicin, cytosine arabinoside and thioguanine. Biopsies were assessed for blast count, trephine cellularity and leukaemic index. Discrimination between patients who went on to achieve remission and those with resistant disease was best achieved using the reduction in bone marrow cellularity from pretreatment marrow to day-6 marrow. However, this discriminator identified only 50% of the patients with resistant disease and included 13% of patients who achieved remission with the first course of chemotherapy. The other parameters of response were even less effective at discriminating between chemotherapy-resistant and chemotherapy-responsive disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Diffuse histiocytic lymphoma: the 20-year experience of an Australian teaching hospital.

There is a paucity of information regarding the natural history and treatment outcome of diffuse histiocytic lymphoma (DHL) in Australia. Case records from 80 patients treated for DHL at the Royal Adelaide Hospital between 1965 and 1985 were reviewed to determine treatment outcome and prognostic information. Pathological review of biopsy specimens confirmed the correct diagnosis in 78 patients. The Ann Arbor staging criteria were unsatisfactory for prognostic purposes. We identified three prognostic groups: Localised disease (82% five-year survival), Advanced disease marrow negative (36% five-year survival), and Advanced disease marrow positive (11% five-year survival). An elevated plasma lactate dehydrogenase (LDH) and calcium (Ca++) predicted a poorer outcome; no patient with a LDH greater than 500 IU achieved longterm survival (p less than 0.001). Survival was identical for patients reclassified histologically as intermediate grade or high grade (Working Formulation). Localised disease was associated with a good prognosis (82% five-year survival) regardless of treatment modality. The outcome of patients with advanced disease has markedly improved over the last two decades, particularly with the introduction of combination chemotherapy containing doxorubicin in 1974 (p less than 0.005). Using these regimens, complete remission was achieved in 65% of patients, with a 39% five-year survival.

Adult↗
PubMed1988

Recombinant human interleukin-3 stimulation of hematopoiesis in humans: loss of responsiveness with differentiation in the neutrophilic myeloid series.

Recombinant human (rh) interleukin-3 (IL-3) stimulated the proliferation and differentiation of erythroid, granulocyte, macrophage, eosinophil (Eo), and mixed colonies as well as megakaryocytes from human bone marrow cells. rh IL-3 was a weaker stimulus than rh granulocyte-macrophage colony-stimulating factor (GM-CSF) for day 14 myeloid cell colonies. At day 7 of incubation, rh IL-3 stimulated a few G, M, and Eo clusters but no colonies. This loss of responsiveness of myeloid cells to rh IL-3 was accentuated with further differentiation of the cells. rh IL-3 stimulated very few or no clones after five-day incubation with enriched promyelocytes and myelocytes, whereas rh GM-CSF was an efficient stimulus. Responsiveness to rh IL-3 was completely lost in postmitotic mature neutrophils. Incubation of these cells with rh IL-3 did not result in enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) of tumor cells or superoxide anion production after stimulation with formyl-methyl-leucyl-phenylalanine (FMLP), although they could be stimulated by rh GM-CSF. In addition, preincubation of neutrophils with different concentrations of rh IL-3 failed to increase or decrease their response to rh GM-CSF. In contrast to neutrophils, mature Eos could be stimulated by rh IL-3 to kill antibody-coated tumor cells. These results show that cells of the neutrophilic myeloid series lose their responsiveness to h IL-3 as they differentiate and suggest that although h IL-3 may be an important therapeutic agent to use for hematopoietic regeneration in vivo, the lack of stimulation of mature neutrophil function makes it an unlikely sole candidate as adjunct therapy for treatment of infectious diseases.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1987

Successful peripheral blood stem-cell autograft with a near-critical dose of myeloid progenitor cells in acute non-lymphoblastic leukaemia in relapse.

Rapid, complete and sustained haemopoietic reconstitution was achieved in a 69-year-old man with acute non-lymphoblastic leukaemia in relapse who received an autograft of peripheral blood cells that were collected during very early remission. The patient received 1.7 X 10(8) nucleated cells/kg bodyweight containing 63 X 10(4) myeloid progenitor cells (CFU-GM)/kg bodyweight. Trilineage engraftment was evident in the bone marrow seven days after the graft. Normal neutrophil and platelet counts were attained by day 17, on which day the patient was discharged from hospital. He remained in complete remission three months after the graft with normal blood counts and bone-marrow cellularity. The rapid and sustained haemopoietic activity in this patient, in conjunction with our previous experience of four other patients who received autografts with peripheral blood stem cells, supports the concept we have proposed that a minimum CFU-GM dose of 50 X 10(4)/kg bodyweight produces complete and sustained engraftment. The rapid recovery minimizes aplasia-related risks and suggests that such autografting can be carried out safely in first remission even in older patients. This technique should be considered as a new therapeutic option for patients with acute non-lymphoblastic leukaemia.

Acute Disease↗
PubMed1987

Residual leukemia cannot be detected in very early remission peripheral blood stem cell collections in acute non-lymphoblastic leukemia.

We have used a combined cell culture and cytogenetic approach to study the level of residual leukemia during the very early remission (VER) phase of acute non-lymphoblastic leukemia. Clonogenic leukemic cells were induced to proliferate by phytohemagglutinin-stimulated leucocyte conditioned medium and identified by a leukemia-associated karyotype t(8;21) and a morphological marker (Auer rod). When leukemic blasts were cultured, the leukemic karyotype and Auer rods were most readily detected after 3-9 days. When VER blood cells were cultured, no leukemia-associated karyotype or Auer rods could be detected. Based on the number of VER blood cell derived metaphases analysed, the incidence of leukemic blasts among dividing cells is less than 2%.

Cells, Cultured↗
PubMed1987

Immunological competence of patients in remission from acute leukaemia: apparently normal T cell function but defective pokeweed mitogen-driven immunoglobulin synthesis.

Immunological function of 62 patients in remission from acute leukaemia has been evaluated using peripheral blood mononuclear cells in vitro assays. T cell function, as indicated by proliferation in response to polyclonal activation (by phytohaemagglutinin) and antigen-specific stimulation (allogeneic cells), was normal in these patients. In contrast, pokeweed mitogen-driven Ig synthesis was significantly decreased for all immunoglobulin classes measured (IgM, IgG and IgA) in the case of adult and childhood acute lymphocytic leukaemia patients, and for IgA in the case of adult acute non-lymphocytic leukaemia patients. The defects in humoral immunological responses may contribute to the increased susceptibility to infection of these patients.

Acute Disease↗
PubMed1987

Stimulation of proliferation, differentiation, and function of human cells by primate interleukin 3.

Cloned gibbon interleukin 3 (gIL-3) was found to stimulate the proliferation and differentiation of human bone marrow cells to produce day-14 granulocyte, macrophage, granulocyte-macrophage, and eosinophil colonies in semisolid agar. In the presence of normal human plasma, gIL-3 stimulated megakaryocytes. In methylcellulose cultures, it stimulated erythroid colonies in the presence, but not in the absence, of erythropoietin. When mature human leukocytes were used, gIL-3 stimulated the function of purified mature eosinophils as measured by the capacity to kill antibody-coated target cells, to produce superoxide anions, and to phagocytize opsonized yeast particles in a manner similar to recombinant human granulocyte-macrophage colony-stimulating factor. In contrast, gIL-3 did not significantly stimulate any of the neutrophil functions tested, whereas human recombinant granulocyte-macrophage colony-stimulating factor was active in these assays. Among cytokines that are active on human hematopoietic cells, gIL-3 thus has a distinct set of functions and may predict the range of actions of the human molecule.

Animals↗
PubMed1987

CFU-mix are no better than CFU-GM in predicting hemopoietic reconstitutive capacity of peripheral blood stem cells collected in the very early remission phase of acute nonlymphoblastic leukemia.

High levels of circulating myeloid progenitor cells (CFU-GM) occur during the very early remission phase of acute nonlymphoblastic leukemia (ANLL). Autologous stem cell rescue using blood cells collected during this phase has shown that successful hemopoietic reconstitution can be achieved, but a higher CFU-GM dose appears to be required than when bone marrow cells are used. This suggests that during very early remission, the level of marrow repopulating pluripotent stem cells (PSC) in blood does not undergo the same amount of increase as does the CFU-GM. This study set out to determine whether the levels of the multilineage progenitor cell (CFU-Mix) would be better indicators of the PSC in these cells than the CFU-GM. Serial peripheral blood CFU-Mix and CFU-GM measurements were carried out in six ANLL patients during very early remission. The levels of peripheral blood CFU-Mix showed a mean 12-fold increase, as compared to a mean 20-fold increase in the CFU-GM. The timing of the increase in the CFU-Mix paralleled that of the CFU-GM. These findings suggest that the CFU-Mix is no better than the CFU-GM in predicting PSC levels during very early remission of ANLL, and is closer to the CFU-GM than to the PSC in ontogeny.

Acute Disease↗
PubMed1987

Peripheral blood stem cells collected in very early remission produce rapid and sustained autologous haemopoietic reconstitution in acute non-lymphoblastic leukaemia.

Haemopoietic reconstitution was achieved in a patient with acute non-lymphoblastic leukaemia (ANLL) in relapse who was autografted with blood-derived stem cells collected during very early remission. The patient received a myeloid progenitor cell dose of 230 x 10(4) CFU-GM/kg body weight. Engraftment was evident in the bone marrow 7 days post-graft. Normal neutrophil and platelet counts were attained by day 14 and blood counts remained normal thereafter. An overshoot in peripheral blood haemopoietic progenitor levels occurred at the end of the second week, presumably the progeny of a family of early progenitor cells. The completeness of haemopoietic reconstitution is further illustrated by the satisfactory nucleated cell and myeloid progenitor cell yield when a bone marrow harvest was performed 4 1/2 months post-graft. Seven months post-graft, the patient remained in complete remission with normal blood counts and bone marrow cellularity, although haemopoietic progenitor levels were slightly reduced. The rapid recovery minimises aplasia-related risks and suggests that such autografting can be carried out safely in first remission. We propose that autografting using very early remission blood cells is a new therapeutic option for patients with acute ANLL.

Adolescent↗
PubMed1987

Evaluation of a monoclonal IgM antibody for purging of bone marrow for autologous transplantation.

A monoclonal antibody of the IgM class, reacting with the CD9 (p24) antigen is described. The antibody (FMC27) is cytotoxic against cells of the common type of acute lymphoblastic leukaemia (c-ALL), giving killing at higher dilutions than an IgG antibody (FMC8) against the same antigen. FMC27 and FMC8 recognise different epitopes, and FMC27 may thus be used in a cocktail together with FMC8 and an antibody against the c-ALL antigen, WM21. Furthermore, the IgM antibody can be coated directly onto magnetic microparticles for magnetic purging, unlike the IgG antibody which must be used in a two-layer procedure.

Antibodies, Monoclonal↗