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Biomedical subjects

C A Juttner

Publications and source records attributed to C A Juttner.

65 records · Page 4Linked to original sources

Autologous responses to human leukaemic cells in mixed leucocyte culture.

Cryopreserved leukaemic blasts and remission non-T cells from 22 patients with acute leukaemia (15 lymphocytic, 7 non-lymphocytic) were tested as stimulators of autologous remission T cells and normal allogeneic T cells in primary and secondary MLC. In most cases the autologous response elicited by leukaemic cells was less than or equal to that elicited by remission non-T cells. However, T cells from 2 patients in long-standing first remission from ANLL displayed greater proliferation in response to leukaemic blasts than to remission non-T cells in both primary and secondary MLC. The results are suggestive of sensitization of these 2 patients to leukaemia-specific antigens, but other possible explanations are discussed.

Acute Disease↗

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↗

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↗

Central nervous system relapse after bone marrow transplantation for acute myeloid leukemia.

Central nervous system (CNS) relapse with meningeal leukaemia occurred 6 months after allogeneic bone marrow transplantation (BMT) for acute myeloid leukaemia, without systemic relapse. Despite intrathecal chemotherapy a severe progressive proprioceptive impairment of the lower limbs developed. Autopsy revealed selective ascending tract degeneration of the gracile fasciculi of the posterior columns of the spinal cord and residual endoneurial deposits were found in lumbosacral dorsal nerve roots and ganglia. While CNS relapse may occur in acute leukaemia after chemotherapy, it has rarely been reported following BMT.

Antineoplastic Agents↗

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↗

Primary gastrointestinal tract lymphoma--a clinico-pathological study of 28 cases.

A retrospective study of 28 patients with primary gastrointestinal tract lymphoma is presented. There were 27 cases of non-Hodgkin's lymphoma and one case of Hodgkin's disease. The patients with non Hodgkin's lymphoma of the gastrointestinal tract represented 10% of all non-Hodgkin's lymphoma cases seen at the Royal Adelaide Hospital/Institute of Medical and Veterinary Science complex over the six year survey period, 1972-1977. Of the patients with non-Hodgkin's lymphoma, 26 cases were diffuse type, and one case was nodular type. There was a M/F sex preponderance of 2 . 8/1, and 70% of cases were aged between 40 and 69 years. The commonest site was the stomach (19 cases), followed by small intestine (7 cases), and one case involved large intestine. At initial presentation, the disease was confined to the affected viscus (Stage IE) in seven patients (25%), and in 12 patients (43%) the disease involved viscus and regional lymph nodes (State IIE). The one patient with Hodgkin's disease had involvement of the large intestine, abdominal lymph nodes and bone marrow (Stage IV). This study was retrospective, and a management protocol was not employed. However, of the seven patients presenting with Stage IE disease, six cases had diffuse poorly differentiated lymphocytic lymphoma. Five of these patients were treated by surgical resection alone, and were in complete remission at follow-up of 66 to 103 months. In order to compare realistically the survival of different groups of patients with primary gastrointestinal lymphoma, we consider that a prospective multicentre clinical trial with comprehensive staging procedures, uniform histological classification and accepted management protocol is warranted.

Adult↗

Marrow autotransplantation accelerates haematological recovery in patients with malignant melanoma treated with high-dose melphalan.

In a Phase I study, melphalan 140 mg/m2 was administered to 8 patients with disseminated malignant melanoma. Marrow was removed from the patients immediately before melphalan administration and returned i.v. 8 h later. Studies on marrow culture and melphalan pharmacokinetics predicted that this was a safe time to administer non-cryopreserved marrow. Four patients received lower doses of i.v. melphalan without autologous marrow. In the group receiving autologous marrow the time for recovery of peripheral-blood granulocytes to 800/mm2 or greater was significantly less (P = 0.01) than in those not receiving marrow. In 7 patients the tumour showed evidence of response to the drug and there was 1 complete remission. This treatment deserves investigation in patients with tumours more sensitive to drugs than melanoma.

Adult↗

Three years' experience with Ch1VPP (a combination of drugs of low toxicity) for the treatment of Hodgkin's disease.

In 3 years, 118 patients with Hodgkin's disease have completed chemotherapy with chlorambucil, vinblastine, procarbazine and prednisolone (Ch1VPP). The complete remission rates were 90% for 29 patients previously treated with radiotherapy, 67% for 73 patients previously untreated and 44% for 16 patients with prior chemotherapy. The 3-year survival rates for the first 70 patients in the series were 83% for previously irradiated patients, 84% for previously untreated patients and 67% for those with prior chemotherapy. Forty-seven previously untreated or previously irradiated patients in this group achieved complete remission. The 3-year disease-free survival rates for these patients were 71% and 67% respectively. This regimen gives complete remission and survival rates comparable with results obtained with combinations including nitrogen mustard, while producing fewer side-effects.

Adolescent↗