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非定型性白血病の治療法の確立に関する基礎的臨床的研究

建立非典型白血病治疗方法的基础临床研究

基本信息

批准号：
61015037
负责人：
内野治人
金额：
$ 2.05万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Cancer Research
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1988
项目状态：
已结题

项目摘要

1まず非定型性白血病を主とする急性非リンパ性白血病(ANLLと略)未治療26例、多剤併用施行例17例、及びMDS12例に対するAra-C少量療法の臨床効果を検討し下の結果を得た。(1)未治療のANLLに有効で、FAB分類の【M_1】,【M_2】に高い寛解率(70%,85.7%)を得た。寛解,非寛解症例間に骨髄のNCC,芽球百分率、芽球実数に有意の差を認めない。一方、既治療例では寛解率は低い(29.4%)。寛解期間は、未治療例では3〜17カ月(中央値8カ月)、既治療例では8〜23カ月(中央値12カ月)であった。生存期間は全例、寛解症例、非寛解症例順に未治療例16カ月,22カ月,4カ月(寛解、非寛解の差は有意P=0.0005)、既治療例4カ月,23カ月,3カ月(寛解,非寛解の差は有意P=0.0072)であった。(2)MDS症例に対しては、完全寛解、12%,不完全寛解、50%であった。寛解期間は2〜12カ月(中央値6カ月)、生存期間は全例,寛解,非寛解期間別に31カ月,31カ月,6カ月(寛解,非寛解の差は有意でないP=0.1439)であった。上記の結果からAra-C少量療法は、未治療の非定型性白血病に有効性が示されたがMDSに対する有効性は更に多数例の検討が必要である。2MDSに対する有効な治療を開発する為1α(OH)【D_3】(9μg/day)Ara-C少量(10mg/【m^2】SC twice a day)併用療法の臨床的有用性を少数例につき検討した。上記の3日投与,4日休薬を繰り返すことにより5例中3例に寛解を得た。上記投与法により1α25【(OH)_2】【D_3】の血中濃度は3〜4日目に100〜120Pg/mlとなった。3各種分化誘導剤の分化能を増強する因子についてHL-60細胞を用いて検討し、細胞内Ca mabilizationを抑制する高濃度verapamilやTMB-8、又、protein kinase C活性阻害剤であるstauro sporineが分化増強効果を示すことを見い出した。4HL-60細胞の分化誘導機構をcommitmentとphenotype expressionの時期に分け観察し、commitmentを生ずる細胞内因子の存在について報告した。

The clinical results of Ara-C low-dose therapy were evaluated in 26 untreated cases, 17 multiple-drug cases, and 12 MDS cases. (1)High medium-to-high remission rates (70% and 85.7%) were obtained for untreated ANLL, FAB classification and [M_1] and [M_2]. NCC, percentage of buds, number of buds, intentional difference between cases of relaxation and non-relaxation. The rate of remission was low (29.4%). The treatment period is 3 ~ 17 months (8 months in the center) for untreated cases and 8 ~ 23 months (12 months in the center) for treated cases. The survival time was 16 months, 22 months and 4 months for all cases, 23 months and 3 months for all cases, respectively. (2)MDS cases were divided into two groups: complete remission, 12%, incomplete remission, 50%. Relaxation period is 2 ~ 12 months (central value 6 months), survival period is complete, relaxation period is 31 months, non-relaxation period is 31 months, 6 months (relaxation period, non-relaxation period is intentional P=0.1439). The results noted above indicate that Ara-C low-dose therapy is effective for untreated non-classified leukemia and effective for MDS. 2. The clinical usefulness of MDS in combination with small amounts of Ara-C (10mg/m2 SC twice a day) was discussed in a few cases. The above mentioned 3-day cast and 4-day break were obtained in 3 cases The blood concentration of 1α25 [(OH)_2][D_3] was 100 ~ 120Pg/ml on 3 ~ 4 days. 3 Various differentiation inducers and differentiation enhancement factors were used in HL-60 cells, and intracellular Ca activation was inhibited by high concentrations of verapamil and TMB-8, and protein kinase C activity inhibitors. 4. The mechanism of differentiation induction of HL-60 cells was investigated during the period of commitment and phenotype expression, and the existence of intracellular factors during the period of commitment and phenotype expression was reported.