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Biomedical subjects

E Ashihara

Publications and source records attributed to E Ashihara.

70 records · Page 4Linked to original sources

Reconstitution of lymphocyte subsets after peripheral blood stem cell transplantation: two-color flow cytometric analysis.

The reconstitution of lymphocyte subsets after high-dose chemotherapy followed by peripheral blood stem cell transplantation (PBSCT) was studied using two-color flow cytometry in 14 patients with acute leukemia (four AML and two ALL) and malignant lymphoma (six NHL and two HD). The CD3+HLA-DR+ lymphocytes (activated T cells) and CD8+ lymphocytes increased markedly by 4 weeks after PBSCT. Most of the increased CD8+ lymphocytes were CD11b-, S6F1+ cells and CD8+CD11b+ cells remained low throughout the follow-up period. The CD4+ lymphocytes remained below the normal range up to 34 weeks after PBSCT. The ratio of CD4+ to CD8+ lymphocytes (CD4/CD8 ratio) transiently increased and then decreased below 1.0 at 2 weeks after PBSCT. The CD19+ lymphocytes and the CD3-CD16+CD56+ lymphocytes returned to normal levels in the early period. The CD4+CD45RA+ lymphocytes (suppressor-inducer) decreased to below the normal range, while the CD4+CD45RO+ lymphocytes (helper-inducer) increased more rapidly than the CD4+CD45RA+ lymphocytes. This study shows that an immunosuppressed state exists after PBSCT as is seen after bone marrow transplantation (BMT) and that B cell reconstitution is more rapid in PBSCT than in BMT.

Acute Disease↗

[Neoplastic angioendotheliosis presenting Tolosa-Hunt syndrome, intraspinal invasion and intraorbital tumor].

A 76-year-old woman with painful erythema on legs and right oculomotor disturbance was diagnosed as neoplastic angioendotheliosis (NAE, B cell type) by skin biopsy. Remission was obtained by 2 courses of VEPA regimen. But 3 months later, she relapsed with right oculomotor, optic, trochlear and trigeminal nerve disturbance which suggested that she had Tolosa-Hunt syndrome. Cerebrospinal fluid (CSF) revealed infiltration of lymphoma cells. She developed intraorbital tumor and died of respiratory failure due to tumor emboli. Autopsy revealed infiltration of tumor cells in the small vessels of systemic organs. This rare case presented intracerebrospinal and intraorbital tumor growth in addition to intravascular infiltration of tumor cells.

Aged↗

[Aggressive myeloma with subcutaneous tumor and pericardial involvement].

A 67-year-old male was admitted to our hospital because of anemia, thrombocytopenia, and renal failure. On admission he showed splenomegaly and elevated serum LDH level. Bone marrow showed hypercellularity with massive infiltration of lymphoblastoid cells. He was diagnosed as having multiple myeloma (BJ-kappa, stage IIIB). He transiently responded to intensive chemotherapy (VAD, MP, IFN alpha) but relapsed with multiple subcutaneous tumors and pericardial effusion. This is a rare case that the myeloma cell invasion to pericardial space was diagnosed before his death. The level of interleukin 6 (IL-6) in pericardial effusion was 16382 pg/ml, and the myeloma cells obtained from the pericardial effusion responded to IL-6, which suggested that high level of IL-6 closely related to the proliferation of myeloma cells in this case.

Aged↗

Inversion of chromosome 16 and eosinophilia in refractory anemia with ring sideroblasts: report of a case.

A 72-year-old male who was admitted to our hospital with severe anemia was diagnosed as refractory anemia with ring sideroblasts (RARS), according to the French-American-British (FAB) classification of myelodysplastic syndromes (MDS). The patient showed persistent eosinophilia with no definite signs of either allergy or a parasitic infection. Chromosomal analysis of bone marrow cells revealed inv(16)(p13q22), a known characteristic of M4Eo acute myeloid leukemia (AML) in the FAB classification. This patient didn't exhibit leukemic transformation during his 20-month clinical course, nor was any found at autopsy. Therefore, this is the first case of RARS to speculate that the chromosomal characteristic inv(16)(p13q22) might be specific for eosinophilia rather than AML.

Aged↗

Trilineage response in severe aplastic anemia following long-term therapy with recombinant human granulocyte colony-stimulating factor.

We investigated the effects of long-term therapy with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in a 69-year-old man with severe aplastic anemia (SAA). The patient was too old to receive a bone marrow transplantation, and high-dose methylprednisolone and antilymphocyte globulin were ineffective. We administered rhG-CSF in combination with metenolone acetate. Trilineage blood cell components were recovered 6 months later. These findings suggest that long-term G-CSF therapy may be beneficial in patients with SAA who are not candidates for bone marrow transplantation.

Aged↗

Recombinant human granulocyte colony-stimulating factor in combination with continuous infusion of cytosine arabinoside for the treatment of refractory acute myelogenous leukemia.

Because recombinant human granulocyte colony-stimulating factor (G-CSF) has been reported to increase the sensitivity of acute myelogenous leukemia (AML) blast cells to cytosine arabinoside (Ara-C) in vitro, we treated a patient with refractory AML with an Ara-C-based regimen in combination with G-CSF (G-CSF/Ara-C therapy). G-CSF (50 micrograms/m2/day, subcutaneous injection) was administered simultaneously with a continuous intravenous infusion of Ara-C (70 mg/m2/day). Complete remission was achieved, however, severe neutropenia, documented infection, stomatitis, and diarrhea were observed. In vitro studies using 3H-thymidine uptake and dual parameter flow-cytometric analysis of DNA and proliferating cell nuclear antigen showed that leukemic blast cells in S phase were increased after incubation with G-CSF. G-CSF also enhanced expression of the transferrin receptor (CD71) on blast cells in vitro. These observations suggest that G-CSF/Ara-C therapy may be useful in the treatment of high-risk AML.

Bone Marrow↗

[Acute basophilic leukemia: a case report].

A 56-year-old woman was admitted to our hospital in January, 1990 because of fever and petechiae. Leukocyte count of peripheral blood showed 41,000/microliters with 89% immature cells, and bone marrow was normocellular with 96.2% immature cells. They were medium to large in size, positive for peroxidase staining, CD-13 and CD-33. Half of them contained azurophilic granules. They showed metachromasia by toluidine blue, contained basophilic granules in electron microscopic examination and reacted to G-CSF, G-CSF and IL-3. She was diagnosed as acute basophilic leukemia and treated with BHAC-DMP and B triple-V regimen, but remission was not attained. She died of peritonitis due to gastrointestinal tract perforation and pneumonia in March, 1990. This is the fifteenth case of acute basophilic leukemia reported in Japan, and the hematological examinations performed in this patient were demonstrated.

Bone Marrow↗

Autoimmune thrombocytopenia following peripheral blood stem cell autografting.

A 22-year-old woman diagnosed as AML (M3) received myeloablative chemotherapy followed by autologous peripheral stem cell transplantation (PBSCT). Rapid hematopoietic reconstitution occurred. By day 10, the neutrophil count was > 0.5 x 10(9)/l and the platelet count > 50 x 10(9)/l. The platelet count was 145 x 10(9)/l on day 20. Purpura developed on the anterior chest and legs on day 50, at which time the platelet count fell to 17 x 10(9)/l. The BM was hypocellular with an increase in megakaryocytes. Platelet-associated IgG (PAIgG) was 88.1 ng/10(7) platelets (normal range 9-25 ng/10(7)); a diagnosis of idiopathic thrombocytopenic purpura (ITP) was made. Prednisolone administration led to an increase in the platelet count and a decrease in PAIgG. Analysis of lymphocyte subsets revealed an increased number of CD3+ gamma/delta T cells. It is postulated that the thrombocytopenia in this case was due to an autoimmune mechanism such as ITP.

Adult↗

Immunophenotype and DNA content of myeloma cells in primary plasma cell leukemia.

To clarify the biological characteristics of the myeloma cells in primary plasma cell leukemia (PCL), we studied the immunological phenotype and DNA content of cells from five patients with primary PCL as compared to those from the patients with typical multiple myeloma (MM). In two of five patients with PCL myeloma cells had B-cell-associated antigens (B1, J5) and surface immunoglobulin in addition to plasma cell associated antigens, suggesting that these cells are immunologically immature as compared to mature plasma cells. Concerning the DNA content of myeloma cells, two of four patients had hypodiploid while two had diploid myeloma cells. In contrast, 24 of the 37 (65%) patients with typical MM had hyperdiploid and 1 had hypodiploid myeloma cells. These observations suggest that the myeloma cells in PCL are immunologically heterogeneous. The increased incidence of hypodiploidy in PCL may explain its relatively poor prognosis as previously shown in those with typical MM and hypodiploid DNA content.

Adult↗

Novel type of clonally involved cytoplasmic immunoglobulin-negative cells in multiple myeloma: flow cytometric study.

In order to identify myeloma cells and their precursor cells, we studied bone marrow samples from 39 patients with multiple myeloma, including 2 with plasma cell leukemia, using dual parameter cytometry of both DNA and cytoplasmic immunoglobulin (Cyt-Ig). Myeloma cells from 25 patients (64.1%) were aneuploid and those from the remaining 14 patients were diploid. In 25 patients with aneuploid myeloma, we found a small component of cells which had aneuploid DNA content without Cyt-Ig in addition to myeloma cells showing aneuploidy with Cyt-Ig. These aneuploid Cyt-Ig-negative cells were considered to be clonally involved because they were aneuploid, and detected predominantly in patients with stage III myeloma. This suggests that these cells may contribute to disease progression. The characteristics of these cells are described and the relationship between these cells and myeloma precursor cells is discussed.

Aneuploidy↗

Effects of interleukin-3 and interleukin-6 on peripheral blood cells from multiple myeloma patients and their clinical significance.

The effects of interleukin-3 (IL-3) and interleukin-6 (IL-6) on nonadherent mononuclear cells (NMC) from the peripheral blood of 28 patients with multiple myeloma (MM), 3 patients with monoclonal gammopathy of undetermined significance (MGUS), and 3 normal controls were investigated. In 15 of 27 evaluable patients with MM, monoclonal-cytoplasmic-immunoglobulin (cIg)-positive plasma cells appeared from the T-cell-depleted NMC after 10 days of culture in the presence of IL-3 and IL-6. These changes were not observed in the T cell fraction of myeloma blood or in the T-cell-depleted NMC obtained from cases of MGUS or from normal controls. The percentage of cIg-positive plasmacytoid cells after 10 days of culture was significantly higher in the presence of both IL-3 and IL-6 than with each interleukin alone or the control medium. Furthermore, these changes were often observed in untreated patients. These findings suggest that myeloma precursor cells exist in the peripheral blood of MM patients, especially at diagnosis, and differentiate into cIg-positive cells in the presence of IL-3 and IL-6. This assay may be useful in discriminating the early stage of myeloma from MGUS.

Antigens, CD↗

[Auer rods-positive neutrophils observed at diagnosis increased after remission induction in patient with acute promyelocytic leukemia].

50-year-old male was admitted to our hospital because of gingival bleeding and fever in August 1987. The leukocyte count was 13,300/microliters with 80.5% leukemic promyelocytes and bone marrow was hypercellular with 86.4% leukemic promyelocytes. A small number of mature neutrophils containing Auer rods were seen in bone marrow. On a diagnosis of acute promyelocytic leukemia and treated with induction chemotherapy consisting of behenoyl-arabinofuranosyl cytosine (BHAC), daunorubicin, 6-mercaptopurine (6-MP) and prednisolone (PSL) was reformed. After cytoreduction, leukemic cells reappeared in the peripheral blood, concomitant with mature neutrophils having Auer rods. Vitamin D3 was not effective as a differentiation inducing agent. Complete remission was obtained in November 1987 by the reinduction chemotherapy consisting of BHAC, aclarubicin, 6-MP and PSL. In this case, neutrophils with Auer rods might have been derived from the leukemic clone and differentiation of leukemic promyelocytes by intensive chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Collection of peripheral blood stem cells mobilized by high-dose Ara-C plus VP-16 or aclarubicin followed by recombinant human granulocyte-colony stimulating factor.

We developed an effective method for harvesting large numbers of peripheral blood stem cells (PBSC) for use in autotransplantation. Twenty patients with hematological malignancies were treated with high doses of Ara-C (12 g/m2) and VP-16/aclarubicin followed by administration of rhG-CSF (50 micrograms/m2). The optimal time for starting PBSC collection was determined by monitoring the CD34-positive stem cells in blood using immunomagnetic beads. PBSC were collected with a CS-3000 blood cell separator. A total blood volume between 7000 and 9000 ml was processed in each apheresis. Under these conditions, a total of 64 apheresis procedures was performed in the 20 patients. The mean numbers of mononuclear cells and of CFU-GM harvested per apheresis were 4.1 x 10(8)/kg and 110 x 10(4)/kg, respectively. A number of CFU-GM sufficient for engraftment (> 30 x 10(4)/kg) could be harvested by a single apheresis in 15 of the 20 patients. So far, 11 patients have been transplanted with PBSC and obtained rapid hematopoietic recovery. The median time to recover neutrophils more than 0.5 x 10(9)/l was 10 days, and that for platelets 50 x 10(9)/l was 11 days. This method for harvesting large numbers of PBSC allows safer autotransplantation in patients with chemoradiosensitive tumors, and is applicable to older patients.

Aclarubicin↗

[Rapid disappearance of M-protein in multiple myeloma complicated by pneumonia during treatment with HLBI].

A 64-year-old female was admitted for treatment of refractory myeloma (IgG-lambda). Because of severe liver cirrhosis, the patient was treated with interferon (IFN) alone (natural IFN 6 x 10(6) IR/day i.m. for 28 days). Pneumonia developed during IFN therapy. The IFN therapy was completed, restoring suppressed IgM and IgA to their normal ranges, while pneumonia was cured by antibiotics. Because the M-component remained, an additional IFN therapy was resumed and M-protein disappeared. As the period within which the M-component disappeared in this case was shorter than that reported previously, we supposed that the pneumonia might have enhance the effects of IFN. To verify this, we administered OK-432 for 4 weeks as a model of immunoactivation by pneumonia between two successive courses of IFN therapy when M-protein reappeared. To monitor the immune state, natural killer (NK) and lymphokine activated killer (LAK) activities were measured: NK activity suppressed by IFN was restored by OK-432 and was suppressed less by subsequent IFN administration. LAK activity was increased by IFN and OK-432. These observations suggested synergic effects of OK-432 on IFN-activated immunity. This case suggests that IFN combined with immunotherapy may be effective in some cases of myeloma.

Drug Administration Schedule↗