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Biomedical subjects

Y Takaue

Publications and source records attributed to Y Takaue.

At least 163 records · Page 9Linked to original sources
PubMed1989

[Rapid and complete hematopoietic reconstitution following peripheral blood stem cell autotransplantation in a child with T cell acute lymphoblastic leukemia].

Rapid and complete hematopoietic reconstitution was achieved in a child with T cell acute lymphoblastic leukemia who was autografted with peripheral blood stem cells (PBSC). A large number of PBSC was collected by two courses of 3-4 hour-lasting lymphopheresis during early remission induced by the second-line chemotherapy and then cryopreserved in liquid nitrogen. A myeloid progenitor cell dose of 203 X 10(4) CFU-GM/kg body weight was reinfused to the patient following marrow-ablative chemotherapy (MCNU 600 mg/m2, cytosine arabinoside 6 g/m2, etoposide 300 mg/m2, cyclophosphamide 160 mg/kg). Neutrophil count reached 0.5 X 10(9)/l by day + 7 and platelet count reached 20 X 10(9)/l by day + 9. Thereafter, white blood cell count continued to increase and reached a maximum of 38 X 10(9)/l on day + 14. Thus, the rapid recovery of hematopoiesis minimised marrow aplasia-related risks. This approach of stem cell rescue operation can be applied to the treatment of children with cancer, who otherwise have no hope to be cured, as an alternative to bone marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Peripheral blood stem cell autotransplantation in treatment of childhood cancer.

The levels of circulating hematopoietic progenitor cells were measured sequentially in eight children receiving chemotherapy for acute leukemia or neuroblastoma. Significant increases in the progenitor levels (up to 50-fold in CFU-GM numbers) were observed during post-chemotherapy cytopenia in all cases, but differences among individuals in the kinetics of recovery of less committed progenitors (CFU-mix) contrasted with the synchronized-mode of expansion of committed progenitors (CFU-GM). Peripheral blood cells were collected by repeated continuous-flow leukaphereses from three of the children during post-chemotherapy expansion of the progenitor pool and were cryopreserved after fractionation procedures. Infusion of these stored cells into the patients after marrow-ablative chemotherapy established trilineage hematopoiesis. This use of stem cell rescue should be useful as an alternative to bone marrow transplantation and extends the application of cure-oriented salvage therapy to childhood cancers.

Blood Cell Count↗
PubMed1989

Isolation and storage of peripheral blood hematopoietic stem cells for autotransplantation into children with cancer.

Peripheral blood stem cells (PBSC) were collected for autotransplantation by a total of 46 continuous-flow leukaphereses in 17 children with various types of cancer in whom the stem-cell pool had been expanded by chemotherapy. As the cells collected by leukapheresis were contaminated with many visible cell clumps, platelets, and erythrocytes, they were separated from the platelet-rich plasma (PRP) by slow-speed centrifugation and fractionated on a discontinuous gradient of Percoll. All the hematopoietic progenitors (CFU-GM, CFU-GEMM) in the starting samples were recovered at the interface of 40% and 60% Percoll solutions largely free of other cellular components and with a substantial reduction in volume. The separation and freezing procedures could be completed within three hours after obtaining cells by leukapheresis. After their fractionation and storage, these PBSC were shown to be able to reconstitute normal hematopoiesis in ten children with poor prognosis leukemia or neuroblastoma for whom no HLA-compatible marrow donors were available and who had been subjected to marrow-ablative therapy. This separation procedure is simple, efficient, and readily available and can be used for children as a routine procedure for PBSC autotransplantation.

Adolescent↗
PubMed1989

[Interstitial pneumonitis following high-dose MCNU].

We describe a 11-year-old boy with NHL, who developed interstitial pneumonitis following high-dose MCNU with autologous peripheral stem cell transfusion. Non-productive cough, malaise and progressive dyspnea on exertion were noticed 7 weeks after high-dose MCNU (600 mg/kg) treatment, and chest X-ray revealed a bibasilar reticular pattern. Arterial blood was hypoxemic and pulmonary function showed the development of a restrictive ventilatory effect and a reduced diffusing capacity for carbon monoxide (DLCO). Clinical Symptoms were resolved after 3 courses of m-PSL pulse therapy and 6 months prednisolone, but an isolated reduction in DLCO has been present. This case suggests that pulmonary toxicity is a dose limiting factor for MCNU treatment.

Antineoplastic Agents↗
PubMed1989

[Comparative study on in vitro lymphocytotoxicity and mitogenicity of different antilymphocyte globulin (ALG) preparations].

The lymphocytotoxicity and mitogenicity between six different ALG preparations on the clinical use world wide were compared. No significant difference in the lympholytic activity was observed between preparations and 100% cell lysis was achieved at a concentration of 50 micrograms/ml in the presence of complement. On the other hand, four preparations now in use in European countries and USA showed variable mitogenic activities on lymphocytes in the absence of complement, whereas two ALGs used in Japan did not. As the stimulatory effects of ALG on lymphocytes may contribute to the clinical outcome in the treatment of severe aplastic anemia (Kawano et al, 1988), these date can explain the poor clinical results of ALG therapy with those two preparations in Japan. Careful measures should be paid in the construction of treatment protocol and selection of ALG preparations to yield the best results.

Antilymphocyte Serum↗
PubMed1989

[Studies of children with acute lymphoblastic leukemia (ALL) who relapsed. Relationship of site of relapse, time and prognosis].

One hundred and forty patients out of 511 children with ALL who were entered in the study of the Children's Cancer & Leukemia Study Group from 1981 through March 1988 had relapsed by August 1988. The sites of relapse were BM (including concurrent CNS relapse) in 96 cases (70%), CNS in 36 cases (25%), and testicles in 8 cases (5%). A second complete remission was induced in 57 of the 75 patients (76%) with ALL in the first BM relapse. The projected disease-free survival (DFS) for those in the second BM remission was 26.0% at 2 years and the length of the first remission was correlated with the outcome. In the patients in early marrow relapse within 12 months after diagnosis, the probability of maintaining a second remission at 2 years was 6.7% compared to 29.8% in those in intermediate marrow relapse. All patients in late relapse after more than 48 months from diagnosis are surviving with no evidence of disease. The outcome of the patients with isolated extra-marrow relapse was so favorable that the probability of maintaining a second remission for those in CNS relapse was 41.4% at 3 years, and 57.1% in patients in testicular relapse. These data suggest that 20-30% of patients relapsing after more than 12 months from diagnosis may be salvaged, but those who relapsed during active therapy within the first 12 months after diagnosis, other types of treatment should by considered.

Bone Marrow↗
PubMed1988

[Attempted marrow rescue with cryopreserved circulating stem cells following high-dose chemotherapy].

Circulating hematopoietic stem cells were collected by three consecutive leukaphereses during post-chemotherapy expansion of the stem cell pool in a 3-year-old boy with advanced and therapy-resistant neuroblastoma. The cells were fractionated by discontinuous Percoll gradient centrifugation, frozen in a programmed freezer and then stored in liquid nitrogen. Following high-dose chemotherapy, the cells were thawed rapidly and re-infused into the patient. Early evidence of marrow recovery was first noted at day 13 and the times required to achieve a granulocyte count of greater than 0.5 x 10(9)/L and a platelet count of greater than 50 x 10(9)/L were 21 days and 30 days, respectively. This new marrow-rescue operation may have potential in cancer therapy as an alternative to bone marrow transplantation and further clinical investigation is warranted.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

[Autologous peripheral stem cell transplantation].

A number of recent reports have now shown that hematopoietic stem cells are present in the circulation, and these cells have the potential to restore complete hematopoiesis following marrow aplasia. Peripheral stem cells have been collected by continuous flow leukapheresis during periods of hematopoietic regeneration after 2 to 3 weeks of intensive chemotherapy. Following marrow ablative chemotherapy or chemoradiotherapy, the autologous peripheral stem cells are thawed and infused intravenously. When a sufficient stem cell dose was given, rapid neutrophil and platelet recovery has been confirmed, as compared with bone marrow transplantation. Acute leukemia, malignant lymphoma and solid tumors may benefit from this approach, and long-lasting remission or cure may result in a significant number of patients.

Acute Disease↗
PubMed1988

[Cryopreservation of circulating stem cells in large quantities].

We have collected peripheral blood mononuclear cells in large quantities by leukapheresis from children with malignant disorders. The cells were fractionated on discontinuous gradients of Percoll for enrichment of hematopoietic stem cells and reduction of sample volume. They were subsequently frozen in a programmed freezer and stored in liquid nitrogen. This procedure allows a reduced DMSO volume to be infused into patients and increases storage space. The recovery rates of progenitors evaluated by freeze-thaw analysis in small aliquots were 89% for granulocyte-macrophage colony-forming units (CFU-GM) and 106% for granulocyte, erythroid, macrophage, megakaryocyte colony-forming units (CFU-GEMM). Hence, we conclude that circulating stem cells can be collected and cryopreserved in large quantities without any loss of capacity. Further studies to evaluate the relevance of performing rescue surgery with these stem cells following marrow-ablative chemotherapy are underway.

Freezing↗
PubMed1987

Pathologic fracture in osteosarcoma. Impact of chemotherapy on primary tumor and survival.

Twenty patients with osteosarcoma and pathologic fractures were treated with a chemotherapeutic regimen consisting of cis-diamminedichloroplatinum-II (CDP), Adriamycin (ADR) (doxorubicin) and high-dose methotrexate with citrovorum factor "rescue" (MTX-CF). Before the introduction of the regimen, the primary tumor in two patients was treated by immediate amputation and in 13 with preoperative intra-arterial CDP. Among these 13 patients, responses (healing) were observed in 11 (one required the addition of radiation therapy). In three patients, the responses were so dramatic that, at their request, surgery was deferred and treatment exclusively with chemotherapy was instituted. Based on this experience, treatment exclusively with chemotherapy was also administered to an additional five patients who were admitted without pathologic fractures. In the course of such treatment, pathologic fractures also developed; notwithstanding, chemotherapy was maintained and healing also occurred. One of the 20 patients had pulmonary metastases at diagnosis; these were resected after treatment and pathologic examination revealed no evidence of viable tumor. The remaining 19 patients were free of pulmonary metastases but these later developed in seven patients. These data were compared to a historical control series in which 16 of 21 patients with pathologic fractures developed pulmonary metastases. Three of the chemotherapy treated patients died of nonosteosarcoma related causes (leukemia, generalized varicella, and a metabolic complication). Overall, survival was improved in the chemotherapy treated patients as compared to the historical control series: 10 of 20 versus 6 of 21, respectively. Pathologic fractures in osteosarcoma may heal under treatment with chemotherapy, which also has a favorable impact on the eradication of pulmonary metastases and survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Therapeutic modalities for central nervous system involvement by granulocytic sarcoma (chloroma) in children with acute nonlymphocytic leukemia.

Four cases of central nervous system involvement by granulocytic sarcoma (three intracranial and one paraspinal) in children with acute nonlymphocytic leukemia (FAB M1 or M2 subtype) are presented, and therapeutic modalities are discussed. All tumors were noted at initial presentation with diagnosis being made on clinical and radiological findings without biopsy. All patients had karyotypic abnormalities: three had translocation of chromosomes 8 and 21, and one had an unspecified hypodiploid clone. The three patients who developed intracranial tumors responded well to triple agent (cytosine arabinoside, hydrocortisone, and methotrexate) intrathecal chemotherapy and systemic chemotherapy, with or without local irradiation, as evidenced by rapid disappearance of the tumors. Two children are disease-free after 17 and 57 months. One patient with paraspinal tumor failed to achieve a systemic remission but had no evidence of granulocytic sarcoma at autopsy. Thus, the prognosis of CNS granulocytic sarcoma is not uniformly gloomy if treated aggressively by combined modalities. The value of surgical intervention in terms of primary management, however, is limited.

Acute Disease↗
PubMed1987

[Recent advances in the treatment of childhood osteosarcoma: therapeutic modalities at the M.D. Anderson Hospital and Tumor Institute].

Osteosarcoma (OS) is the most common malignant tumor of bone affecting the preteenage and teenage individual. During the past decade, major progress has been made in the treatment of OS. Multi-drug combination chemotherapy has been utilized as adjuvant therapy for destruction of micrometastases which are considered to be present in most patients at diagnosis. This approach has produced three-year survival rates of between 55 and 80%, as opposed to the figure of less than 20% among historical control patients. Recent advances with intraarterial chemotherapy have secured the local control of the tumor and offer hope that increased numbers of patients may become eligible for limb-salvage procedure.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Limiting-dilution analysis of the effects of colony-stimulating factors, phytohemagglutinin, and hydrocortisone on hematopoietic progenitor cell growth.

The effects of colony-stimulating factors (CSFs), phytohemagglutinin (PHA), and hydrocortisone on the growth of human bone marrow hematopoietic progenitor cells (granulocyte-macrophage; GM) were analyzed in a limiting-dilution assay (LDA). Both low-density bone marrow cells separated by discontinuous Percoll gradients and a T cell-depleted and progenitor-enriched cell fraction obtained by the combination of counterflow elutriation centrifugation and Percoll gradients were examined in LDA. GCT (monocytoid cell line-conditioned medium containing GM-CSF), human placenta-conditioned medium, bladder carcinoma cell line 5637-conditioned medium (containing GM- and G-CSF), and recombinant CSF (G-CSF) directly induced proliferation of progenitors with single-hit kinetics. In some instances, however, PHA-stimulated lymphocyte-conditioned medium (containing G- and GM-CSF) showed deviation from single-hit kinetics, which demonstrated the presence of factor(s) suppressive to progenitor growth. In a T cell-depleted, progenitor-enriched fraction, PHA alone was found to suppress progenitor growth at a level as low as 100 ng/mL. The addition of hydrocortisone (10(-6) mol/L) increased the progenitor frequency but suppressed progenitor growth at 10(-4) mol/L. LDA appears to be a valuable method for exploring mechanisms of factors regulating hematopoietic cell growth.

Bone Marrow Cells↗
PubMed1987

Limiting dilution clonal assay of human bone marrow hematopoietic progenitors (granulocytes-macrophages).

We have developed a limiting dilution assay for human bone marrow hematopoietic precursor (granulocytes-macrophages) in microwells. Bone marrow cells were fractionated by discontinuous Percoll gradients and diluted in culture medium containing colony-stimulating factors. They were diluted and cultured in medium containing colony-stimulating factor and 10(-5) M hydrocortisone in microwells over a range of cell densities that allowed calculation of the frequency of growth-inducible precursors. After 10 days, the wells were examined for clonal growth. Clonal proliferation followed the single-hit model of the Poisson distribution. More progenitors were detected in this assay than in simultaneous methylcellulose colony assays or agar cultures. Thymidine suicide experiments led to an increase in the frequency of progenitors detected in this assay, but a decrease in the frequency of methylcellulose colonies. This system may detect additional, less mature progenitors than are detected in semisolid culture systems.

Bone Marrow Cells↗