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  • Wiley  (3)
  • Nakahata, Tatsutoshi  (3)
  • Yoshida, Makoto  (3)
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  • Wiley  (3)
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  • 1
    Online Resource
    Online Resource
    Outcome of childhood acute lymphoblastic leukemia with induction failure treated by the Japan Association of Childhood Leukemia Study (JACLS) ALL F‐protocol
    Wiley ; 2010
    In:  Pediatric Blood & Cancer Vol. 54, No. 1 ( 2010-01), p. 71-78
    Details
    In: Pediatric Blood & Cancer, Wiley, Vol. 54, No. 1 ( 2010-01), p. 71-78
    Abstract: Children with acute lymphoblastic leukemia (ALL) who fail to achieve complete remission (CR) after induction therapy (induction failure: IF) have a poor prognosis; however, there have been few prospective studies in patients with IF. Patients and Methods Between April 1997 and March 2005, 27 of 1,237 leukemic patients (2.2%) failed to achieve CR after four‐ or five‐drug induction therapy. Twenty‐three of these patients entered the F‐protocol study, which mainly consisted of acute‐myeloid‐leukemia‐oriented chemotherapy followed by scheduled hematopoietic cell transplantation (HCT). Results Seventeen (73.9%) of the 23 patients responded to re‐induction chemotherapy with CR. Of note, 15 (93.8%) of 16 patients with Philadelphia‐chromosome‐negative (non‐Ph + ) ALL achieved CR; in contrast, only 2 (28.6%) of 7 Ph + patients achieved CR. Fourteen (82.4%) of 17 patients remained in CR (CCR) until their scheduled HCT, 12 of the 14 with CCR underwent HCT as scheduled, and 6 patients remain in first CR after a median of 78 months (range, 49–107 months). The 5‐year overall survival (OS) rates of 16 patients with non‐Ph + and 7 patients with Ph + were 43.8 ± 12.4% and 14.3 ± 13.2%, respectively ( P  = 0.012). The 5‐year OS rate of the 17 patients who obtained CR by re‐induction therapy and the 6 who did not were 47.1 ± 12.1% and 0%, respectively ( P   〈  0.001). Conclusion Acute‐myeloid‐leukemia‐oriented chemotherapy followed by scheduled HCT is a promising treatment strategy for non‐Ph + ALL patients with IF. Pediatr Blood Cancer 2010; 54:71–78. © 2009 Wiley‐Liss, Inc.
    Type of Medium: Online Resource
    ISSN: 1545-5009 , 1545-5017
    URL: Issue
    URL: Article
    DOI: 10.1002/pbc.v54:1
    DOI: 10.1002/pbc.22217
    Language: English
    Publisher: Wiley
    Publication Date: 2010
    detail.hit.zdb_id: 2130978-4
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  • 2
    Online Resource
    Online Resource
    Thrombopoietin alone stimulates the early proliferation and survival of human erythroid, myeloid and multipotential progenitors in serum‐free culture
    Wiley ; 1997
    In:  British Journal of Haematology Vol. 98, No. 2 ( 1997-08), p. 254-264
    Details
    In: British Journal of Haematology, Wiley, Vol. 98, No. 2 ( 1997-08), p. 254-264
    Abstract: We examined the effects of recombinant human thrombopoietin (TPO, c‐Mpl ligand) on the proliferation and differentiation of human haemopoietic progenitors other than megakaryocytic progenitors using serum‐free cultures. TPO alone supported the generation of not only megakaryocytic (MK) but also blast cell (blast) colonies from cord blood CD34 + cells. Delayed addition of a cytokine cocktail (cytokines; interleukin (IL)‐3, IL‐6, stem cell factor, erythropoietin, granulocyte‐macrophage colony‐stimulating factor, and TPO) to cultures with TPO alone on day 7 induced various colonies including granulocyte‐macrophage (GM) colonies, erythroid bursts (E), granulocyte‐erythrocyte‐macrophage‐megakaryocyte (GEMM) colonies. Replating experiments of blast colonies supported by TPO alone for culture with cytokines revealed that approximately 60% of the blast colonies contained various haemopoietic progenitors. Single cell cultures of clone‐sorted CD34 + cells indicated that TPO supported the early proliferation and/or survival of both primitive and committed haemopoietic progenitors. In serum‐free suspension cultures, TPO alone significantly stimulated the production of progenitors for MK, GM, E and GEMM colonies as well as long‐term culture‐initiating cells. These effects were completely abrogated by anti‐TPO antibody. These results suggest that TPO is an important cytokine in the early proliferation of human primitive as well as committed haemopoietic progenitors, and in the ex vivo manipulation of human haemopoietic progenitors.
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Article
    DOI: 10.1046/j.1365-2141.1997.2283045.x
    RVK:
    XA 34100
    Language: English
    Publisher: Wiley
    Publication Date: 1997
    detail.hit.zdb_id: 1475751-5
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  • 3
    Online Resource
    Online Resource
    Thrombopoietin‐independent effect of interferon‐γ on the proliferation of human megakaryocyte progenitors
    Wiley ; 1997
    In:  British Journal of Haematology Vol. 98, No. 2 ( 1997-08), p. 265-273
    Details
    In: British Journal of Haematology, Wiley, Vol. 98, No. 2 ( 1997-08), p. 265-273
    Abstract: Flow cytometric study revealed that almost all CD34 + cells in human umbilical cord blood expressed interferon‐γ receptor (IFN‐γR). To clarify the precise functional roles of IFN‐γR in human CD34 + cells, we examined the effect of IFN‐γ alone and in combination with various cytokines on the growth of haemopoietic progenitor cells in CD34 + cells using a serum‐free clonal culture. Surprisingly, IFN‐γ alone supported only megakaryocyte (MK) colonies in a dose‐dependent manner with a plateau level at 1000 U/ml of IFN‐γ. IFN‐γ at 1000 U/ml induced 10 ± 1.2 MK colonies from 1 × 10 3 CD34 + cells, whereas thrombopoietin (TPO), interleukin (IL)‐3, stem cell factor (SCF) or IL‐6 alone induced 22 ± 4.0, 22 ± 4.2, 4 ± 0.6 and 0 MK colonies, respectively. The addition of anti‐IFN‐γ monoclonal antibody (mAb) to the IFN‐γ culture completely abrogated MK colony formation, whereas the mAb had no effect on TPO‐dependent production of MK colonies. In contrast, although anti‐TPO polyclonal Ab almost completely blocked TPO‐dependent MK colony formation, it failed to inhibit the generation of MK colonies induced by IFN‐γ, suggesting that the observed effect of IFN‐γ on the proliferation of human MK progenitor cells is independent of TPO. The addition of IFN‐γ to culture with TPO or SCF significantly augmented the development of MK colonies, whereas it did not affect IL‐3‐dependent MK colony formation. Additionally, IFN‐γ induced the increase of DNA content of cultured glycoprotein IIb/IIIa‐positive megakaryocytes. These results suggest that IFN‐γ may have regulatory roles in human megakaryocytopoiesis.
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Article
    DOI: 10.1046/j.1365-2141.1997.2303047.x
    RVK:
    XA 34100
    Language: English
    Publisher: Wiley
    Publication Date: 1997
    detail.hit.zdb_id: 1475751-5
    Location Call Number Limitation Availability
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    Online Resource
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