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T Sumikuma

Publications and source records attributed to T Sumikuma.

At least 19 recordsLinked to original sources
PubMed2002

Successful non-T cell-depleted HLA haplo-identical three-loci mismatched hematopoietic stem cell transplantation from mother to son based on the feto-maternal microchimerism in chronic myelogenous leukemia.

A 17-year-old male with chronic myelogenous leukemia in blast crisis received a non-T cell-depleted (TCD) HLA haplo-identical three-loci mismatched hematopoietic stem cell transplant (HSCT) from his mother. Long-term feto-maternal microchimerism was detected by nested polymerase chain reaction with sequence-specific primer typing. The post-transplantation prophylaxis against graft-versus-host disease (GVHD) was tacrolimus with minidose methotrexate. Sustained engraftment was obtained. Acute GVHD (grade 2) developed, but improved rapidly. Bone marrow aspiration on day 120 showed complete remission. Non-TCD HLA haplo-identical HSCT based on feto-maternal microchimerism might be feasible and has important implications in the selection of alternative family donors in HSCT.

Adolescent↗
PubMed2001

Clinicopathological features of myeloid/natural killer (NK) cell precursor acute leukemia.

Four patients (three males and one female) were diagnosed as myeloid/natural killer (NK) cell precursor acute leukemia in our department. Two patients showed the extramedullary involvement at initial presentation. Leukemic cells expressed CD7, CD33, CD45 and CD56 in all patients. Additionally, CD13, CD34, HLA-DR, cytoplasmic CD3 and myeloperoxidase were expressed in some patients. Trisomy 10 was found in two patients, which has not been reported in this disease. Therefore, myeloid/NK cell precursor acute leukemia might be rather heterogeneous especially in chromosomal abnormality though it seemed to constitute the distinct clinical entity among acute myeloid leukemia of M0 subtype.

Acute Disease↗
PubMed2001

[Therapy-related myeloid leukemia following platinum-based chemotherapy for ovarian cancer].

A 40-year-old woman, who had suffered from AML (M1) in 1983, developed ovarian cancer (stage IIIc) in December 1996 after long-term remission. She underwent surgical resection of the cancer, 10 courses of standard chemotherapy and tandem PBSCT (total dose: CBDCA 6,750 mg, CDDP 200 mg, CPA 16,000 mg, THP-ADR 450 mg). After receiving the last course of chemotherapy in June 1998, she was referred to our hospital in September 1998 because of pancytopenia. Laboratory findings showed pancytopenia with 34% leukemic cells, which were positive for alpha NBE and negative for POX and CAE. Surface-marker analysis of the leukemic cells showed positivity for CD11c, CD33, CD56, and DR, and chromosome analysis revealed 47, XX, +8. The patient was diagnosed as having AML (M5a), and received induction therapy consisting of IDR and Ara-C, which led to complete remission. As she had not received etoposide, this case was thought to have been therapy-related leukemia due to the platinum agents used for treating the ovarian cancer.

Adult↗
PubMed2000

Mobilization of hematopoietic primitive and committed progenitor cells into blood in mice by anti-vascular adhesion molecule-1 antibody alone or in combination with granulocyte colony-stimulating factor.

OBJECTIVE: One of the mechanisms for mobilization of hematopoietic stem cells and progenitor cells is alternation of adhesion molecules. We investigated the mobilization of hematopoietic progenitor cells in blood by administration of anti-vascular cell adhesion molecule (VCAM)-1 antibody (Ab) in mice. MATERIALS AND METHODS: Twelve- to 14-week old C57BL/6J mice were injected intravenously with anti-VCAM-1 Ab and anti-very late antigen (VLA)-4 Ab at a dose of 5 mg/kg for 2 days. RESULTS: The number of colony-forming cells (CFCs) in blood was increased 11.4-fold after anti-VCAM-1 Ab treatment, but the number of CFCs was not increased after treatment with anti-VLA-4 Ab. The number of colony-forming unit spleen (CFU-S) also was increased 21.6-fold in the peripheral blood by administration of anti-VCAM-1 Ab. The number of CFCs and CFU-S in the bone marrow of mice treated with anti-VCAM-1 Ab was decreased and that in the spleen also was decreased. On administration of recombinant human granulocyte colony-stimulating factor (125 microg/kg twice daily) with anti-VCAM-1 Ab, the numbers of CFCs and CFU-S were increased 141.8-fold and 439-fold, respectively. CONCLUSIONS: These observations demonstrated that administration of anti-VCAM-1 Ab induced mobilization of hematopoietic progenitor cells into blood from bone marrow and spleen and that granulocyte colony-stimulating factor has synergistic effects on anti-VCAM-1 Ab-induced mobilization.

Animals↗
PubMed2000

Expression of T-cell-associated antigens in B-cell non-Hodgkin's lymphoma.

We performed the immunophenotyping of 101 patients with B-cell non-Hodgkin's lymphoma (B-NHL) using two-colour flow cytometry (FCM) and found that lymphoma cells coexpressed at least one kind of T-cell-associated antigen (T-Ag; CD2, CD5, CD7) in 25 patients (24. 8%). Among these three T-Ags, CD5 was the most frequently expressed, in 21 patients (20.8%), followed by CD7, expressed in five patients (5.0%), and CD2, which was expressed in two patients (2.0%). Two kinds of T-Ag were simultaneusly expressed in three patients (CD2/CD5, CD2/CD7, and CD5/CD7, each expressed in one patient). Concerning the expression pattern of T-Ag, there were no significant differences between lymph nodes and extranodal organs in the three patients with T-Ag-positive B-NHL (T-Ag(+) B-NHL) who were analysed. When comparing the clinical features between T-Ag(+) B-NHL and T-Ag-negative B-NHL (T-Ag(-) B-NHL), extranodal involvement and higher International Prognostic Index (H and H.I.) were significantly frequent in the former subgroup (P = 0.0119 and P = 0. 0302 respectively).

Adolescent↗
PubMed2000

[Werner's syndrome associated with acute myelofibrosis].

A 47-year-old man was admitted to our hospital in June 1997 because of nasal bleeding. He presented with anemia in addition to physical characteristics of Werner's syndrome (WS). Peripheral blood examination disclosed pancytopenia with 4% blasts. Bone marrow aspiration was a dry tap; biopsy specimens revealed myelofibrosis. Chromosomal analysis of peripheral blood revealed hypodiploidy with complex abnormalities including -5 and del(7)(q21). Serum levels of PDGF, FGF, and TGF beta 1 were normal. A diagnosis of acute myelofibrosis was made. The patient's condition became quickly deteriorated and he died of pneumonia in October 1997. In the literature, we found 6 reported cases of myelofibrosis associated with WS. Considering that only approximately 1,100 cases of WS have been reported so far, the incidence of myelofibrosis in WS seems relatively high. This case suggested a link between WS and myelofibrosis, and the mechanism of myelofibrosis in WS was discussed.

Acute Disease↗
PubMed1999

Successful peripheral blood stem cell transplantation for myelodysplastic syndrome.

Wilms' tumor (WT1) gene expression is increased in patients with leukemia as well as myelodysplastic syndrome (MDS) and is useful for detection of minimal residual disease (MRD). A 47-year-old man given a diagnosis of refractory anemia with excess of blasts in transformation (RAEB-T) received myeloablative therapy followed by autologous peripheral blood stem cell transplantation (PBSCT). MRD by WT1 expression was not detected in the graft. The patient has been in CR for 25 months after PBSCT. These observations suggest that PBSCT is feasible for patients with RAEB-T and analysis of WT1 expression can be applied for patients with high risk MDS.

Anemia, Refractory, with Excess of Blasts↗
PubMed1999

[Discrimination of leukoencephalopathy from leukemic cell invasion by MR spectroscopy in a patient with acute lymphoblastic leukemia].

A 58-year-old man was admitted to our hospital in November 1992 because of fever and arthralgia. He was given a diagnosis of acute lymphoblastic leukemia and treated with an Ad-VP regimen, which resulted in complete remission. After two courses of consolidation therapy and intrathecal (IT) injections of methotrexate, Ara-C, and prednisolone the patient received high-dose Ara-C plus VP-16 followed by recombinant human G-CSF for the collection of peripheral blood stem cells. However, he relapsed with the appearance of leukemic cells in cerebrospinal fluid (CSF), and was accordingly given IT injections 8 more times. After the disappearance of leukemic cells from CSF, the patient received a peripheral blood stem cell transplant (PBSCT) and achieved rapid hematopoietic recovery. However, he suffered mental aberrations and loss of consciousness 9 days after PBSCT. Proton magnetic resonance spectroscopy (1H-MRS) disclosed severe necrosis due to leukoencephalopathy in the frontal lobe and invasion of leukemic cells around the lateral ventricles. The patient did not receive any therapy for neurological symptoms because of severe necrosis in the frontal lobe, and died of bone marrow relapse in April 1995. MRS is useful for the discrimination of leukoencephalopathy from leukemic cell invasion.

Antineoplastic Agents↗
PubMed1998

Flow cytometric analysis of Thy-1 expression in myelodysplastic syndrome.

We analyzed the expression of Thy-1 (CD90) antigen on CD34+ bone marrow mononuclear cells (BMMNC) obtained from 25 patients with myelodysplastic syndrome (MDS) by two-color flow cytometry. Five of nine patients (55.6%) with refractory anemia with excess of blasts (RAEB) and two of 16 (12.5%) with RAEB in transformation (RAEB-t) showed more than 20% of Thy-1 expression of their CD34+ BMMNC. Regarding chromosomal abnormalities, -5/5q- or -18 might be correlated with the expression of Thy-1 on CD34+ BMMNC in MDS. Nine patients were analyzed twice, once before and once after leukemic transformation and showed no significant change in Thy-1 expression. These results show that Thy-1 was expressed on CD34+ BMMNC in certain patients with MDS before leukemic transformation and that it was maintained during the disease progression. In contrast, expression of Thy-1 did not seem essential to the leukemic transformation in MDS though the patients with high Thy-1 expression might have poorer prognosis compared with those with low Thy-1 expression.

Adolescent↗
PubMed1998

CD34+/CD41a+ cells best predict platelet recovery after autologous peripheral blood stem cell transplantation.

Reliable markers for megakaryocytic reconstitution after peripheral blood stem cell transplantation (PBSCT) have not been established. To determine a convenient and reliable predictor, we measured the number of megakaryocyte progenitor cells in PBSC grafts by clonogenic and flow cytometric assays. Seventeen patients with hematological and solid malignancies were included in this study. For the clonogenic assay, we used thrombopoietin (TPO) as a growth factor to evaluate the maximum number of megakaryocyte progenitor cells. Using a flow cytometric assay, we examined the expression of platelet glycoproteins on CD34+ cells to count the number of megakaryocyte progenitor cells. We used buffer containing EDTA to prevent platelet adhesion to CD34+ cells and selected CD34+ cells by immunomagnetic beads. The best correlation was observed between the number of CD34+/CD41a+ cells and the time to platelet recovery (P = 0.0205), rather than the total number of CD34+ cells. In addition, a close correlation was observed between the number of CD34+/CD41a+ cells and colony-forming unit megakaryocyte (CFU-MK) (P = 0.0018). These observations suggest that the number of CD34+/CD41a+ cells is the best predictor for platelet reconstitution after PBSCT.

Adolescent↗
PubMed1998

FLT-3 ligand mobilizes hematopoietic primitive and committed progenitor cells into blood in mice.

We investigated the effects of the administration of FLT-3 ligand (FL) on mobilization of primitive and committed progenitor cells in mice. C57bl/6J mice were injected subcutaneously with FL once a day for 5 d at doses of 20, 100 and 200 microg/kg. After the collection of peripheral blood, we determined the number of white blood cells (WBCs) with the differential counts. The formation of colony-forming cells (CFCs) in peripheral blood, bone marrow and spleen was evaluated. Although the administration of FL, 20 microg/kg, did not stimulate leukocytosis, its administration at doses of 100 and 200 microg/kg increased the number of WBC up to 1.7- and 2.4-fold, respectively. Committed progenitor cells were mobilized into the peripheral blood dose-dependently and the number of CFCs was increased up to 5.5-fold by the administration of FL at 200 microg/kg on d 5. The number of CFCs in the bone marrow increased, but not dose-dependently. The number of CFCs in the spleen also increased up to 32-fold at a dose of 200 microg/kg FL. Mobilized peripheral blood mononuclear cells were transplanted into lethally irradiated mice and the number of CFU-S (d 12) was scored. A dose-dependent mobilization of CFU-S (d 12) into peripheral blood was also observed. These observations suggest that FL can mobilize hematopoietic primitive and committed progenitor cells into the peripheral blood of mice and those cells mobilized by FL may be applicable to peripheral blood stem cell transplantation.

Animals↗
PubMed1997

Synergistic effect of FLT-3 ligand on the granulocyte colony-stimulating factor-induced mobilization of hematopoietic stem cells and progenitor cells into blood in mice.

We have previously shown that FLT-3 ligand (FL) mobilizes murine hematopoietic primitive and committed progenitor cells into blood dose-dependently. Whether FL also acts synergistically with granulocyte colony-stimulating factor (G-CSF) to induce such mobilization has now been investigated. Five- to 6-week-old C57BL/6J mice were injected subcutaneously with recombinant human G-CSF (250 microg/kg), Chinese hamster ovarian cell-derived FL (20 microg/kg), or both cytokines daily for 5 days. The number of colony-forming cells (CFCs) in peripheral blood increased approximately 2-, 21-, or 480-fold after administration of FL, G-CSF, or the two cytokines together, respectively, for 5 days. The number of CFCs in bone marrow decreased after 3 days but was increased approximately twofold after 5 days of treatment with G-CSF. The number of CFCs in the bone marrow of mice treated with both FL and G-CSF showed a 3.4-fold increase after 3 days and subsequently decreased to below control values. The number of CFCs in spleen was increased 24.2- and 93.7-fold after 5 days of treatment with G-CSF alone or in combination with FL, respectively. The number of colony-forming unit-spleen (CFU-S) (day 12) in peripheral blood was increased 13.2-fold by G-CSF alone and 182-fold by G-CSF and FL used together after 5 days of treatment. Finally, the number of preCFU-S mobilized into peripheral blood was also increased by the administration of FL and G-CSF. These observations show that FL synergistically enhances the G-CSF-induced mobilization of hematopoietic stem cells and progenitor cells into blood in mice, and that this combination of growth factors may prove useful for obtaining such cells in humans for transplantation.

Animals↗
PubMed1997

A translocation between 3q21 and 12q24 in a patient with minimally differentiated acute myeloid leukemia (AML-M0).

Only a small number of reports have described the cytogenetic analysis of minimally differentiated acute myeloid leukemia (AML, M0). We performed a cytogenetic analysis on a patient with AML (M0) with a normal platelet count. It revealed a chromosomal translocation between chromosome bands 3q21 and 12q24. 3q. Abnormalities in AML are known to be associated with normal or elevated platelet counts. 3q21 and 12q24 are common translocation sites in AML patients, but this is the first report of translocation t(3;12)(q21;q24) in an AML patient.

Cell Differentiation↗
PubMed1997

Flow cytometric analysis of Thy-1 expression in CD34-positive acute leukemia.

We analyzed the expression of the Thy-1 antigen (CD90) in CD34+ acute leukemia using two-color flow cytometry. Leukemic cells were obtained from the bone marrow (BM) and/or the peripheral blood (PB) of 57 patients: 37 with acute myelogenous leukemia (AML) including nine with secondary AML following myelodysplastic syndrome (MDS/AML), and 20 with acute lymphoblastic leukemia (ALL) including three with chronic myelogenous leukemia in blast crisis (CML-BC) of the lymphoid type. Among these patients, one (3.6%) with de novo AML, two (22.2%) with MDS/AML, three (17.6%) with de novo ALL, and two (66.7%) with CML-BC coexpressed CD34 and Thy-1 (CD34+ Thy-1+) on more than 20% of the mononuclear cells within 'lymph' plus 'blast' window. Thy-1 was rarely expressed in de novo acute leukemia especially in AML. Interestingly, in 1 patient with CML-BC, the leukemic cells in BM were divided into two subpopulations (CD34+ Thy-1low and CD34+ Thy-1high), whereas most of the CD34+ leukemic cells in PB were Thy-1high. However, the mechanism for the mobilization of CD34+ Thy-1high leukemic cells into the PB is unknown.

Acute Disease↗
PubMed1997

Serum thrombopoietin levels in patients undergoing autologous peripheral blood stem cell transplantation.

Recently, the ligand for c-mpl has been cloned and initial studies have shown it to be the platelet regulatory factor, thrombopoietin (TPO). To elucidate the role of TPO in the reconstitution of megakaryopoiesis and platelet production after stem cell transplantation, we measured serum TPO levels in nine patients undergoing autologous peripheral blood stem cell transplantation (PBSCT) and in healthy volunteers. Serum TPO levels significantly correlated with the degree of peripheral thrombocytopenia and a strong inverse correlation between serum TPO level and platelet count was observed (r = -0.700, P < 0.001). Serum TPO levels began to rise as the platelet count decreased after chemotherapy, TPO levels peaked at over 25.00 fmoles/ml between days 0 and 10; TPO levels then decreased gradually as the platelet count began to rise. One patient with multiple myeloma received purified CD34+ peripheral blood stem cells. No difference was observed in the kinetics of serum TPO levels between unfractionated and purified PBSCT. These observations suggest that TPO plays a critical role in the reconstitution of megakaryopoiesis and platelet production after PBSCT.

Adolescent↗
PubMed1997

Effects of thrombopoietin (c-mpl ligand) on growth of blast cells from patients with transient abnormal myelopoiesis and acute myeloblastic leukemia.

Thrombopoietin (TPO) is a ligand for c-mpl that promotes both proliferation and differentiation of megakaryocytes in vivo and in vitro. We investigated the expression of c-mpl transcripts and the effects of recombinant human TPO (rhTPO) on the proliferation and differentiation of human leukemic cell lines or fresh samples obtained from 32 patients with transient abnormal myelopoiesis (TAM) or acute myeloblastic leukemia (AML). Cells were cultured with TPO alone or combined with rh interleukin-3 (IL-3) or stem cell factor (SCF). Expression of c-mpl was verified in 6 of 13 cases tested. All but one of the cases that showed c-mpl expression responded to TPO. Blasts from all cases of TAM or French-American-British (FAB) subtype M7 showed growth responses to TPO with higher sensitivity than cells of other FAB subtypes and these responses were increased by addition of rhIL-3 or rhSCF in some cases. Responses of cells of other FAB subtypes varied. In addition, increased expression of platelet-specific surface antigens on MO7E cells after incubation with rhTPO was observed. These data suggest that TPO may be involved in the abnormal proliferation and differentiation of human leukemic cells, especially of M7 and TAM cells, considered to be of megakaryocytic lineage.

Adult↗