Search PubMed⌕ Search

Biomedical subjects

D N Haylock

Publications and source records attributed to D N Haylock.

43 records · Page 3Linked to original sources
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↗
PubMed1985

Circulating autologous stem cells collected in very early remission from acute non-lymphoblastic leukaemia produce prompt but incomplete haemopoietic reconstitution after high dose melphalan or supralethal chemoradiotherapy.

Haemopoietic reconstitution (HR) using autologous peripheral blood stem cells (PBSC) was attempted after intensive chemotherapy or chemoradiotherapy in two patients with relapsed acute non-lymphoblastic leukaemia (ANLL). The PBSC were collected by leukapheresis very early in first remission and cryopreserved in liquid nitrogen. Both patients demonstrated early evidence of trilineage engraftment. The first patient received melphalan 200 mg/m2 followed by rescue with 1.3 X 10(8) mononuclear cells/kg body weight containing 29 X 10(4) granulocyte-macrophage progenitor cells (CFU-GM)/kg, and HR was evident by Day 14. The second patient was treated with supralethal chemoradiotherapy followed by rescue with 3.0 X 10(8) mononuclear cells/kg containing 23 X 10(4) CFU-GM/kg. He demonstrated early engraftment with near normal peripheral blood counts by Day 16. There was a subsequent fall in both bone marrow cellularity and peripheral blood counts to a level of low but persistent activity. There was a further phase of haematological recovery from 8 weeks following transplantation with an increase in peripheral blood counts and bone marrow cellularity until final relapse at 13 weeks. This study demonstrates that circulating stem cells have haemopoietic reconstitutive capacity, previously only shown with buffy coat cells from chronic granulocytic leukaemia. The minimum number of PBSC required for satisfactory engraftment remains unknown, although it seems probable that the ratio of pluripotent stem cells to committed progenitor cells is lower in very early remission peripheral blood than in either allogeneic normal bone marrow or autologous bone marrow collected later in stable remission. The question of leukaemic contamination of the PBSC remains to be answered.

Acute Disease↗
PubMed1984

High levels of circulating haemopoietic stem cells in very early remission from acute non-lymphoblastic leukaemia and their collection and cryopreservation.

Circulating myeloid progenitor cells (PB CFU-GM) were measured in the peripheral blood of 13 patients with acute non-lymphoblastic leukaemia (ANLL) as they entered first remission. The mean of the recorded peak levels was 2796 X 10(3) CFU-GM/l, representing a 25-fold increase above the mean value in normal subjects. These elevated levels of PB CFU-GM occurred regularly during the very early remission phase when platelet counts rose rapidly. Five of the patients had PB mononuclear cells collected by continuous-flow leukapheresis during this early recovery phase. CFU-GM were assayed as a measure of the number of haemopoietic stem cells in each collection. The cells were concentrated and then cryopreserved in liquid nitrogen. Leukapheresis was also performed on five normal subjects for comparison. Low numbers of CFU-GM were harvested from normal subjects, mean 0.33 +/- 0.06 X 10(4) CFU-GM/kg body weight for each leukapheresis. In ANLL patients entering remission, however, very large numbers of CFU-GM were regularly harvested. A mean of 11 +/- 2 X 10(4) CFU-GM/kg body weight were cryopreserved after each leukapheresis, representing 5 times the number of CFU-GM considered necessary for successful autologous haemopoietic reconstitution. Haemopoietic stem cell viability was assessed after varying periods of cryopreservation. There was no significant stem cell loss after up to 24 months storage. Thus, it is possible to collect and cryopreserve large numbers of CFU-GM and by inference pluripotent haemopoietic stem cells from the peripheral blood of patients with ANLL during very early remission. The possible biological and therapeutic implications are discussed.

Acute Disease↗
PubMed1983

The effect of monocytes in the peripheral blood CFU-C assay system.

The effect of cellular interactions in the in vitro assay of myeloid progenitor cells in peripheral blood (PB CFU-C) was investigated. Ficoll-Paque-separated peripheral blood mononuclear cells (PB MNC) from 7 healthy subjects were cultured at cell concentrations from 10 to 0.625 X 10(5) MNC/plate in doubling dilutions. The number of colonies per 10(6) lymphocytes plated (corrected colony count, CC) was significantly higher when 2.5 X 10(5) or less PB MNC were cultured than when 5 or 10 X 10(5) cells were cultured. This decrease in CC when large numbers of cells were cultured was not present when the nonadherent cells only were cultured. The inhibition was reproduced when adherent cells were added back to the nonadherent cells. The inhibition appeared to be proportional to the number of monocytes present. A model depicting the role of monocytes in the PB CFU-C assay system is presented. The increased understanding of cellular interaction represents an important step towards the standardization of the PB CFU-C assay.

Cell Adhesion↗