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[光动力疗法用于清除造血祖细胞自体移植中残留白血病细胞的应用]

[Use of photodynamic therapy for elimination of residual leukemic cells in autologous transplants of hematopoietic progenitor cells].

作者信息

Hrkal Z, Grebenová D, Cajthamlová H, Soucek J, Bartosová J, Fuchs O, Marinov I, Kobylka P, Klamová H, Sponerová D

机构信息

Ustav hematologie a krevní transfuze, Praha.

出版信息

Cas Lek Cesk. 2002 Sep 22;141 Suppl:41-6.

Abstract

BACKGROUND

The increasing use of autologous hematopoietic cell support in various malignancies including leukemia and lymphoma currently bears the problem of tumor contamination of the graft with tumor cells which after re-infusion contribute to the disease relapses. It is therefore desirable to eradicate the cancer cell fraction of the graft without causing damage to the normal stem cell fraction. The purging processes based on photodynamic treatments appear to be perspective means for this purpose.

METHODS AND RESULTS

We investigated the effects of 5-aminolevulinic acid (ALA)--based photodynamic treatment (ALA-PDT) on the proliferation of human leukemia cell lines HL60 (promyelocytic leukemia), ML2 (myelomonocytic leukemia) and HEL (erythroleukemia) by 3H-thymidine incorporation into the cell DNA, on the viability of cell lines HL60, HEL, DAUDI (B-cell leukemia) and JURKAT (T-cell lymphoma) as well as of blast cells of acute myeloid leukemia (AML) patients by flow cytometry-propidium iodide assay, and on the clonogenic activities of normal human bone marrow cells by in vitro cloning assays. Under the conditions used (treatment with 1 mM ALA for 4 h at 37 degrees C followed by exposure to blue light dose of 18 J/cm2) the number of proliferating HL60 cells was reduced by 2.4 logs, of ML2 cells by 3.2 logs and of HEL cells by 1 log. From the mononuclear cell preparations of AML patients the blast cells were substantially reduced in eight out of ten patients. The clonogenic activities of normal bone marrow progenitor cells were largely spared: 52.5 +/- 8.9% of colony-forming units--granulocytes macrophages (CFU-GM), and 48.6 +/- 9.7% burst forming units--erythrocytes (BFU-E).

CONCLUSIONS

ALA-PDT appears to be usable principle for the depletion of residual leukemic cells from autologous transplants.

摘要

背景

目前,自体造血细胞支持在包括白血病和淋巴瘤在内的各种恶性肿瘤中的应用日益增加,这带来了移植的移植物被肿瘤细胞污染的问题,重新输注后这些肿瘤细胞会导致疾病复发。因此,期望在不损害正常干细胞部分的情况下清除移植物中的癌细胞部分。基于光动力治疗的清除过程似乎是实现这一目的的有前景的手段。

方法与结果

我们通过将³H-胸腺嘧啶核苷掺入细胞DNA,研究了基于5-氨基乙酰丙酸(ALA)的光动力治疗(ALA-PDT)对人白血病细胞系HL60(早幼粒细胞白血病)、ML2(粒单核细胞白血病)和HEL(红白血病)增殖的影响;通过流式细胞术-碘化丙啶测定法,研究了其对细胞系HL60、HEL、DAUDI(B细胞白血病)和JURKAT(T细胞淋巴瘤)以及急性髓性白血病(AML)患者原始细胞活力的影响;通过体外克隆试验,研究了其对正常人骨髓细胞克隆形成活性的影响。在所使用的条件下(在37℃用1 mM ALA处理4小时,随后暴露于18 J/cm²的蓝光剂量),增殖的HL60细胞数量减少了2.4个对数级,ML2细胞减少了3.2个对数级,HEL细胞减少了1个对数级。在十名AML患者的单核细胞制备物中,十名患者中有八名的原始细胞显著减少。正常骨髓祖细胞的克隆形成活性在很大程度上得以保留:粒细胞巨噬细胞集落形成单位(CFU-GM)为52.5±8.9%,红细胞爆式集落形成单位(BFU-E)为48.6±9.7%。

结论

ALA-PDT似乎是用于从自体移植中清除残留白血病细胞的可行方法。

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