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S Mackinnon

Publications and source records attributed to S Mackinnon.

66 records · Page 4Linked to original sources
PubMed1990

Induction of a syngeneic graft-versus-leukemia effect following bone marrow transplantation for chronic myeloid leukemia.

Although clinical data support the concept of a graft-versus-leukemia (GVL) effect following allogeneic bone marrow transplantation (BMT), there are few data to support a similar GVL activity following syngeneic BMT in man. To identify cells with a potential antileukemic activity post-BMT, we monitored the immunological reconstitution in a patient with chronic phase chronic myeloid leukemia (CML) who received a syngeneic BMT from his identical twin brother. Peripheral blood mononuclear cells (PBMC) from the donor prior to the transplant and from the recipient posttransplant were cultured with recombinant interleukin-2 to generate lymphokine activated killer (LAK) cells. LAK cells from both sources lysed the cell line target cells K562 and LCL and also recipient and allogeneic CML target cells in a 51Cr release cytotoxicity assay. Donor-derived LAK cells did not kill normal donor marrow. LAK cells had similar effects on granulocyte-macrophage progenitor cells (CFU-GM): LAK cells from both donor pre-BMT and recipient post-BMT inhibited the proliferation of CFU-GM from the patient's CML cells, but again donor LAK cells did not inhibit the colony growth of normal donor marrow. These results suggest that a syngeneic GVL effect is inducible following BMT in man and that this activity may be truly antileukemic and spare normal marrow progenitors.

Adult↗
PubMed1989

Slow evolution of chronic myeloid leukaemia relapsing after BMT with T-cell depleted donor marrow.

Thirty-three patients with Philadelphia positive (Ph+) chronic myeloid leukaemia (CML) treated in chronic phase by bone marrow transplantation (BMT) with T-cell depleted HLA-identical sibling marrow were evaluable for relapse at a median follow up of 41 months (range 16-59 months). Twenty-six (78%) had Ph+ marrow metaphases demonstrated at some time post BMT. The subsequent pattern of disease was variable. In 15 of these cases haematological relapse occurred within 24 months of BMT. Four patients proceeded to haematological relapse more slowly. Seven patients had only cytogenetic evidence of relapse. Of the 19 patients with haematological relapse, five received second transplants and two survive; 13 of the other 14 survive in chronic phase at median times from allografting and from recognition of haematological relapse of 41 months (range 25-59 months) and 18 months (range 5-36 months) respectively. For these 13 patients disease progression after relapse seems to be relatively indolent. In the four patients we could study, blood lymphocytes were almost all of donor origin. We suggest that even in patients with cytogenetic or haematological evidence of relapse after T-cell depleted BMT, leukaemic cell proliferation may still be restrained to some extent by a graft-versus-leukaemia effect mediated by donor-derived lymphoid cells.

Adult↗
PubMed1989

Prediction of graft versus host disease by frequency analysis of cytotoxic T cells after unrelated donor bone marrow transplantation.

HLA "matched" unrelated donor bone marrow transplants are associated with an increased incidence and severity of graft-versus-host disease in comparison with HLA-identical sibling transplants. This is presumably due to HLA and non-HLA histocompatibility differences between donor and recipient. Using a limiting dilution assay, we have previously demonstrated a relationship between cytotoxic T lymphocyte precursor frequency and HLA disparity. In this study we have compared CTL-p frequencies with clinical GVHD, and demonstrate for the first time a significant correlation (P less than 0.005) between high CTL precursor frequency prior to BMT and severity of acute GVHD after HLA A, B, DR "matched" unrelated donor transplants using T cell depleted marrow. This assay system may be of value in the final selection of HLA "matched" unrelated donors for BMT.

Anemia, Aplastic↗
PubMed1989

Bone marrow transplantation for chronic myeloid leukaemia using matched unrelated donors.

Because the majority of patients with chronic myeloid leukaemia (CML) lack HLA identical siblings, attention has turned in recent years to the possibility of using suitably matched unrelated donors. Tissue typing methods must be refined to help identify the closest possible HLA phenotypic identity. For donor recipient matching the use of the mixed lymphocyte reaction is generally unhelpful and methods that predict for the incidence and severity of graft-versus-host disease, such as assay of cytotoxic T-lymphocyte precursors, may prove especially valuable. Preliminary results from several centres suggest that the probability of survival at two years for patients with CML allografted in chronic phase with matched unrelated donors is 35-40%.

Adolescent↗
PubMed1988

Seronegative blood products prevent primary cytomegalovirus infection after bone marrow transplantation.

Seventy one patients underwent bone marrow transplantation for aplastic anaemia or haematological malignancy, 39 as allografts and 32 as autografts. All patients who were seronegative to cytomegalovirus received blood product support exclusively from seronegative community blood donors; seropositive patients received unscreened products. In no patients was there any attempt to reduce cytomegalovirus (CMV) infection by giving prophylaxis with immunoglobulin, and granulocyte transfusions were not given. The incidence of cytomegalovirus infection in the seronegative recipients (22 allograft, 15 autograft) was 0%; in the seropositive recipients 16 (63%) in allografts and 17 (18%) in autografts. These results suggest that provision of exclusively seronegative blood products is an important contribution for seronegative transplant recipients, but make little impact in autologous transplantation where the incidence of infection is low.

Adolescent↗
PubMed1988

Bone marrow transplantation for patients with chronic myeloid leukaemia.

Patients with chronic myeloid leukaemia may be rendered asymptomatic with conventional chemotherapy but this does not increase their life expectancy. Bone marrow transplantation provides not only the chance of increased survival but also an opportunity to cure the leukaemia.

Bone Marrow Transplantation↗
PubMed1988

Prevention of graft-versus-host disease by ex vivo T cell depletion: reduction in graft failure with augmented total body irradiation.

Graft-versus-host disease prevention was attempted in 35 consecutive patients with hematological malignancy who received bone marrow from an HLA match sibling donor who was depleted of T cells ex vivo. Five of the first 8 patients who received cyclophosphamide 60 mg/kg on 2 consecutive days followed by fractionated total body irradiation (TBI) (6 x 2 Gy) had graft failure. The subsequent 27 patients had received an extra fraction of TBI (7 x 2 Gy), and only one failed to have stable engraftment. There were no differences in nucleated cell dose, granulocyte-macrophage colony-forming units, or T cell numbers given to the two groups. Neutrophil but not platelet regeneration of those patients who successfully grafted was slower than in a group of historical controls receiving unmanipulated marrow. Significant graft-versus-host disease was prevented with no increase in relapse rate. We suggest that engraftment can be reliably achieved by augmenting the TBI conditioning in recipients of T cell-depleted matched allogeneic bone marrow.

Adolescent↗
PubMed1987

Plasma fibrinolysis during and after normal childbirth.

A detailed sequential study of plasma fibrinolytic components in 42 healthy women during and after childbirth showed that striking changes occurred within minutes of placental separation. Significant increases in overall fibrinolytic activity were detected 15 min after delivery. During this period statistically significant increases in tissue plasminogen activator levels were noted but were overshadowed by a dramatic decrease in the level of plasminogen activator inhibitor (PAI). A 10-fold fall in PAI was noted by days 3-5 post-partum, suggesting that the placenta is the major source of PAI detectable at the end of pregnancy and during labour. Persisting slightly elevated levels of PAI were detected for the first few days post partum. This may be due to increased production of normal 'endothelial' PAI in response to the vascular trauma incurred by placental separation, and in response to uterine vascular changes immediately post-partum.

Antigens↗
PubMed1986

A blood bank audit of elective gynaecological surgery: a case for group and antibody screen.

A blood bank audit was carried out in a Glasgow teaching hospital to assess the utilization of blood in elective gynaecological surgery. The audit was facilitated by use of the blood bank microcomputer system. Routine cross-matching for the gynaecological procedures studied was found to be wasteful of blood bank resources. The study has underlined the value of local audit and supports the general experience of other centres which have adopted group and antibody screen policies to reduce blood wastage and allow for more effective utilization of blood.

Antibodies↗
PubMed1982

Nerve allograft response: a quantitative immunological study.

The nerve allograft response between closely and distantly related inbred strains of rats was investigated. Lewis rats (RTl1) and Fischer rats (RTl1) have only minor histocompatibility differences, whereas Buffalo rats (RTlb) and ACI rats (RTla) differ from Lewis rats at the major histocompatibility locus. Lewis rats served as the recipient animals; the other three strains of rats provided donor nerves. The 51 Cr release cytotoxicity assay was used to asses antigen recognition. The results showed sensitization with ACI and Buffalo nerves as early as Day 8. When the donor and recipient were matched (Lewis/Fischer), sensitization occurred very late (Day 80). By contrast, with skin allografts, sensitization occurred early with all strains (Day 10), even when the animals differed only at the minor histocompatibility loci. Histological changes were similar in all three donor strains (Fischer, Buffalo, ACI). The strain of origin of the nerve could not be deduced by an unbiased examiner.

Animals↗