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Biomedical subjects

Y Takaue

Publications and source records attributed to Y Takaue.

At least 145 records · Page 8Linked to original sources
PubMed1991

[Peripheral blood stem cell autografts (PBSCT) in the treatment of 30 children with acute leukemias and lymphoma].

Thirty children (1-16 y.o.; median, 10 y.o.) with acute leukemia or non-Hodgkin's lymphoma (NHL) associated with high-risk features underwent high-dose chemotherapy without total body irradiation and peripheral blood stem cell autografts (PBSCT). Eighteen patients had acute lymphoblastic leukemia (ALL), 6 had acute non-lymphoblastic leukemia (ANLL), 2 had mixed-lineage leukemia and 4 had NHL. Twelve patients with two or more high-risk features (WBC greater than 10 x 10(4)/microliter, T- or B-phenotypes, infancy, massive organ infiltration, or induction failure) underwent PBSCT in 1st CR. Twelve patients underwent PBSCT in 2nd CR, and 4 in the subsequent remission greater than or equal to 3rd CR). Two patients were treated at refractory relapse. After PBSCT the number of days required to achieve a granulocyte count of 0.5 x 10(9)/l and a platelet count of 50 x 10(9)/l was 6.39 (median, 13) and 9-427 (median, 16), respectively. The disease-free survival rate was 6/12 in 1st CR group (6-41 mo) and 6/16 in the patients who underwent PBSCT in 2nd or subsequent remission (2-35 mo). The data justify the incorporation of PBSCT in the design of salvage protocol for children with leukemias or NHL. However, the application of the procedure as part of initial therapy in patients still remaining in 1st CR should be regarded as highly experimental and deserve further clarification.

Acute Disease↗
PubMed1991

Retrospective analysis of late intensification therapy with high-dose methotrexate for standard-risk acute lymphoblastic leukemia in childhood (CCLSG-S811 study). The Children's Cancer and Leukemia Study Group.

Using the CCLSG-S811 protocol for children with standard-risk acute lymphoblastic leukemia (ALL), late intensification therapy (LIT) with high-dose methotrexate (HD-MTX) was conducted without randomization. Of 118 eligible patients, 114 attained complete remission and 82 maintained continuous complete remission (CCR) for at least 3 years, completing the entire S811 regimen. Among the latter, 74 patients received LIT with HD-MTX between 2-3 years after CCR onset. MTX (2,000 mg/m2 per dose per week) was administered by 24 h infusion and three doses were given every 12 weeks. Leucovorin rescue (15 mg/m2 i.v.) every 6 h was initiated 12 h after the end of MTX infusion for seven doses. As regular maintenance chemotherapy, intermittent (Regimen A) or continuous (Regimen B) MTX plus 6-mercaptopurine (6MP) combined with pulses of prednisolone and vincristine was administered (Koizumi S, Fujimoto T, Takeda T, et al. Cancer 1988; 61: 1292-1300). Retrospective analysis revealed that patients on Regimen A who started LIT earlier (within 2 years of CCR onset (n = 23)) showed a higher rate of event-free survival (EFS) at 8 years (95.5% +/- 4.4%, mean +/- S.E.) than patients who started LIT later (2.5 years after CCR onset (n = 18, 66.2% +/- 11.3%, p less than 0.01)). In addition, the superiority of four or five courses of the LIT (n = 39) as compared to 2 or 3 courses (n = 35) was noted for both regimens. The data suggest that early and aggressive LIT with HD-MTX may improve the long-term survival of childhood ALL patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Suppression of hematopoiesis by activated T-cells in infectious mononucleosis associated with pancytopenia.

Two patients with primary Epstein-Barr virus (EBV) infection followed by pancytopenia were studied. They showed increased numbers of DR-positive, activated T-cells and serological evidence of persistent EBV infection over a 12 and 18 week period. Bone marrow granulocyte-macrophage colony formation (CFU-GM) was investigated by limiting dilution assay (LDA) and methylcellulose assay. CFU-GM of bone marrow mononuclear cells (BMMNC) was markedly suppressed in both patients during the pancytopenic phase. Removal of bone marrow T-cells by E-rosetting resulted in a significant increase of CFU-GM to normal levels in BMMNC of both patients, while no significant increase was observed in the BMMNC of normal subjects. CFU-GM in BMMNC from Patient 1 in the recovery phase was normal when DR-positive T-cells were within normal levels, irrespective of the presence or absence of T-cells. These results suggest that pancytopenia due to infectious mononucleosis in these patients was due to bone marrow suppression by activated T-cells. In vitro studies with Con A activated T-cells and their culture medium showed that suppression of CFU-GM by T-cells was mediated by a lymphokine.

Adult↗
PubMed1990

Effects of recombinant human G-CSF, GM-CSF, IL-3, and IL-1 alpha on the growth of purified human peripheral blood progenitors.

The effects of recombinant products of granulocyte colony-stimulating factors (G-CSF), granulocyte/macrophage CSF (GM-CSF), human interleukin-3 (IL-3), and interleukin-1 (IL-1) were studied using purified target cell populations from patients undergoing peripheral blood stem cell transplantation after myeloablative therapy. Cells were subjected to combined purification procedures including negative selection with a panel of monoclonal antibodies (CD2, 3, 5, 10, and 20). The purified cells were enriched for HLA-DR+ (51% to 71%) and My-10+ (CD34; 37% to 54%) and had a plating efficiency of up to 20%. In the liquid-suspension limiting dilution clonal assay (LDA), purified progenitors responded directly to IL-3 by proliferation with single-hit kinetics. The ability of GM-CSF to support progenitor growth was inferior to that of IL-3, and the cells were virtually unresponsive when cultured with G-CSF, supporting the notion that these blood-derived progenitors belong to a primitive population of hematopoietic progenitor cells. The results obtained in simultaneous methycellulose cultures (MC) showed the same trend and provided additional information on the ability of GM-CSF and IL-3 to support erythroid progenitor growth. The combination of IL-3 plus G-CSF, but not IL-3 plus GM-CSF, resulted in a synergistic increase in colony number. IL-1 alpha increased both the size and number of colonies when added to IL-3 or G-CSF. Study of this enriched progenitor cell population in MC and LDA represents an excellent model for the investigation of myeloid and erythroid differentiation and for evaluating the influence of various cytokines on human hematopoiesis.

Antigens, CD↗
PubMed1990

Circulating hematopoietic progenitors in patients with primary lung cancer.

The levels of circulating hematopoietic progenitors were measured in 28 patients with primary lung cancer. The average numbers of progenitors per milliliter of blood were 33 (range 0-360) for colony-forming unit-granulocyte macrophage (CFU-GM), 23 (range 0-140) for burst-forming unit-erythrocyte (BFU-E), and 4 (range 0-50) for colony-forming unit-mixed lineages (CFU-mix). No significant influence of age, sex, histological type, or clinical stage of the tumor on the progenitor levels was detected. After cytoreductive chemotherapy of the patients by treatment with cisplatin plus etoposide, the cells showed 6- to 50-fold rebound overshoots, but no rebound was observed after treatment with cisplatin alone, cisplatin plus mitomycin C or cisplatin plus vindesine plus mitomycin C, or in 4 of 5 patients treated with cyclophosphamide plus adriamycin plus vincristine. Peripheral blood hematopoietic progenitors should be useful as an alternative source of stem cells for lung cancer patients treated with marrow ablative chemotherapy.

Adult↗
PubMed1990

[Optimal methods for peripheral blood progenitor assay and its relevance in the blood cell autotransplantation].

Methylcellulose culture study revealed that the potency of recombinant granulocyte-colony stimulating factor (G-CSF) or granulocyte/macrophage (GM)-CSF to support the growth of purified target cell populations from peripheral blood of patients undergoing peripheral blood stem cell (PBSC) autotransplantation was inferior to that of PHA-stimulated lymphocyte conditioned medium (PHA-LCM) or interleukin-3 (IL-3). In liquid-suspension limiting dilution assay the cells responded directly to IL-3 by proliferation with single-hit kinetics. Hence, optimal culture for PBSC should include the use of PHA-LCM or IL-3. Further study disclosed a linear relationship between the number of CFU-GM infused into the patients and days required to achieve a granulocyte count above 0.5 x 10(9)/l.

Adolescent↗
PubMed1990

[Autografts with peripheral blood stem cells].

This paper reports a clinical and laboratory experience of peripheral blood stem cell (PBSC) autografts at a single institute. Twenty-eight children with various types of cancer underwent a total of 90 leukaphereses to collect PBSC and 17 of them subsequently received marrow-ablative therapy and PBSC autografts. We found that frozen-thawed progenitor dose is important in determining the rate of hematopoietic recovery after transplantation; in 11 patients who received more than 1 x 10(5) CFU-GM/kg, the granulocyte count reached to 0.5 x 10(9)/L in two weeks. With conditioning chemotherapy without total body irradiation, 6 of 14 patients with high-risk acute leukemia or non-Hodgkin's lymphoma have survived disease-free 3 to 25 months posttransplant. This approach may have a potential to induce prolonged remission-interval and ultimate cure.

Adolescent↗
PubMed1990

[Peripheral blood stem cell autografts in pediatric cancer].

Harvest of peripheral blood stem cells (PBSC) for autografts is a safe, reliable procedure with low morbidity in children with cancer, and cryopreserved PBSC are useful in reducing cytopenia following marrow-ablative chemotherapy. The colony forming unit granulocyte/macrophage (CFU-GM) content of the thawed grafts is an important determinant of hematopoietic recovery after PBSC autografts. The possible value of high-dose chemotherapy without total body irradiation and PBSCT compared to intensified chemotherapy in the treatment of children with very high-risk lymphoid malignant disorders was reported.

Adolescent↗
PubMed1990

[Evaluation of BPA secretory ability from blood mono-nuclear cells in uremic patients after renal transplantation or rEpo treatment].

Conditioned media (CM) of phyto-hemagglutinin-stimulated lymphocytes from chronic uremic patients were studied for burst promoting activity (BPA), using methylcellulose cultures with cord blood cells as a target population. Renal transplantation procedure was followed by a prompt rise of BPA, as well as the number of blood burst-forming unit erythroid (BFU-E) and hemoglobin levels, while no change in BPA and blood BFU-E number was observed in patients receiving rEpo and recovering from anemia. Thus, low BPA secretion from blood cells may have a role in the development of anemia in uremic patients.

Adult↗
PubMed1989

Cell-mediated suppression of human hematopoiesis: evaluation by limiting-dilution analysis of hematopoietic progenitors.

We have used limiting-dilution clonal analysis (LDA) in microwells to study the inhibitory effects of T lymphocytes (T-cells) or natural killer (NK) cells on human marrow progenitor cell growth. In four subjects with normal hematopoiesis, the growth of progenitors showed single-hit kinetics both before and after T-cell removal, indicating that, in the presence of colony-stimulating activity, T-cell have no effect on progenitor growth. In a patient with marrow hypoplasia associated with thymoma, hypogammaglobulinemia, and an increased number of suppressor T-cells (Good's syndrome), the progenitor growth deviated from linearity, demonstrating the presence of cells with suppressor activity. After T-cells were removed from this sample, the progenitor growth showed single-hit kinetics. The suppressive action of E-rosette-positive cells with NK or cytotoxic activities was also suggested in a patient with severe combined immune deficiency and in a patient with T gamma lymphocytosis. Poor progenitor-cell growth in three other patients with aplastic anemia was not significantly altered by T-cell removal. Thus, LDA of human hematopoietic progenitors is useful for evaluating cell-mediated interactions affecting hematopoiesis. This method may facilitate elucidation of mechanisms of myelosuppression in clinical settings.

Anemia, Aplastic↗
PubMed1989

Sustained cytopenia after leukapheresis for collection of peripheral blood stem cells in small children.

Marked and persistent cytopenia was observed in two 3-year-old children with cancer, after lymphopheresis to collect peripheral blood stem cells (PBSC) for autotransplantation after high-dose chemotherapy. This finding suggests that PBSC are a major component of the hematopoietic cells in small children and, hence, that special care is necessary in the construction of a protocol for collection of stem cells from young children.

Child, Preschool↗
PubMed1989

In vivo dose-response effect of recombinant human granulocyte colony-stimulating factor on increase in granulocytes after peripheral blood stem cell autotransplantation.

The in vivo dose-response potential of recombinant human granulocyte colony-stimulating factor (rG-CSF) in facilitating reconstitution of granulopoiesis was evaluated in an 11-year-old girl who received autotransplantation of peripheral blood stem cells (PBSC) after marrow-ablative therapy for relapsing acute lymphoblastic leukemia. The recovery of hematopoiesis was slow when a small number of progenitors were collected and reinfused into the patient, but administration of rG-CSF led to significant dose-dependent increase in peripheral blood granulocytes.

Blood Transfusion, Autologous↗
PubMed1989

Quantitative analysis of the effect of colony-stimulating factors on human marrow progenitor growth in liquid-suspension cultures: application of limiting dilution assay.

Proliferation of human marrow progenitors in liquid cultures can be quantitated by limiting dilution clonal analysis (LDA) of progenitors in microwells. In this study, we have used LDA to study the effect of purified native or recombinant granulocyte colony-stimulating factors (G-CSFs) and recombinant granulocyte-macrophage CSF (GM-CSF) on progenitor growth. These results were compared to those of simultaneous cultures in methylcellulose. In LDA, single-hit kinetics were obtained with up to 500 U/ml of the recombinant preparation. In LDA with recombinant GM-CSF, progenitor growth conformed to single-hit kinetics from 100 to 2000 U/ml with maximum progenitor frequency at 500 U/ml. In simultaneous methylcellulose cultures with recombinant GM-CSF, colony formation reached a plateau at 100 U/ml. In LDA, purified native G-CSF was shown to support progenitor growth with single-hit kinetics at 100 U/ml, but at greater concentrations (greater than 150 U/ml), it suppressed progenitor growth with almost complete inhibition at a concentration of 200 U/ml. However, this dose-response effect was not observed in either simultaneous methylcellulose culture with G-CSF or in LDA with a purified recombinant preparation of the corresponding G-CSF. In methylcellulose cultures, colony formation reached a maximum at 100 U/ml and maintained a plateau up to 1000 U/ml. Hence, liquid culture allowed detection of contaminating suppressive activity in the G-CSF preparation that was not detected by methylcellulose assay. LDA may be more sensitive than methylcellulose culture for screening factors regulating human hematopoietic cell growth.

Bone Marrow↗
PubMed1989

[Recovery kinetics of hematopoiesis after peripheral blood stem cell autotransplantation].

Hematopoietic recovery kinetics was evaluated in five children with therapy-refractory cancers who received peripheral blood stem cell autotransplantation (PBSCT) following marrow-ablative chemotherapy. Four children received graft containing more than 1.5 X 10(4) CFU-GM/kg and days required to achieve granulocyte counts of greater than 0.5 X 10(9)/l were 6, 10, 13, and 18, respectively. One patient received 0.9 X 10(4) CFU-GM/kg, but, recovery of granulopoiesis was retarded (greater than 30 days). The days required to achieve platelet count of greater than 50 X 10(9)/l were 12, 15, 16, 195, and greater than 240, respectively. Transient decrease of blood cell counts developed 3 to 5 weeks after transplantation and thereafter, the recovery of hematopoiesis became stable. With the use of a large number of progenitors, PBSCT seems to be safe and effective new type of stem cell rescue operation as an alternative to bone marrow transplantation.

Acute Disease↗