2000 Fiscal Year Final Research Report Summary
DETECTION AND DELETION OF MINIMAL RESIDUALTUMOR CELLS IN AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR MULTIPLE MYELOMA
| Project/Area Number |
11672301
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory medicine
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| Research Institution | KYOTO PREFECTURAL UNIVERSITY OF MEDICINE |
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Principal Investigator |
INABA Tohru FACULTY OF MEDICINE, KYOTO PREFECTURAL UNIVERSITY OF MEDICINE, INSTRUCTOR, 医学部, 助手 (60203204)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMAZAKI Chihiro FACULTY OF MEDICINE, KYOTO PREFECTURAL UNIVERSITY OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 講師 (50170931)
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| Project Period (FY) |
1999 – 2000
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| Keywords | MULTIPLE MYELOMA / ABSCT / MINIMAL RESIDUAL DISEASE / FLOW CYTOMETRY / ANTI-IL-6R ANTIBODY / BISPHOSPHONATE / APOPTOSIS |
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| Research Abstract |
We utilized two-color flow cytometry (FCM) to quantify the contaminating myeloma cells in peripheral blood stem cell (PBSC) harvests for autologous peripheral blood stem cell transplantation (ABSCT) in the newly-diagnosed patients with advanced multiple myeloma. There were considerable amount of CD38^<++>/CD138^<++> cells (which represented the characteristic phenotype of plasma cells) in bone marrow at initial diagnosis. Whereas, such characteristic cells were hardly found (≦0.01%) in PBSC harvests after remission-induction chemotherapy in 5 of 11 patients analyzed in this study. As a clinical results, most of the patients who received myeloablative chemotherapy following ABSCT relapsed subsequently even though some of them were treated with tandem ABSCT using myeloma-free grafts. These results suggested that myeloablative chemotherapy following ABSCT could not completely eradicate the residual myeloma cells in patients, and other therapeutic strategies seemed necessary for such chemo-resistant myeloma cells. For this purpose, we performed two-color FCM using Annexin-V and 7-aminoactinomycin D(7AAD) to evaluate the in vitro anti-myelomatous activity of two newly-developed compounds, third-generation bisphosphonate (YM529) and humanized anti-interleukin-6 receptor antibody (hPM1), respectively. It was found that such compounds induced apoptosis of cultured myeloma cell lines such as KPMM2, RPMI8226 or U266 in both time- and dose-dependent manners. Moreover, hPM1 also tended to induce cell-death of freshly isolated myeloma cells from the patient with advanced multiple myeloma in the same manners. Therefore, these compounds seemed useful to purge the contaminating myeloma cells in PBSC grafts or to suppress the cell-growth of residual chemo-resistnant myeloma cells in patients after ABSCT.
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