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使用免疫磁珠清除BCR-ABL阳性急性淋巴细胞白血病:通过半定量聚合酶链反应比较骨髓与外周血干细胞中残留白血病及清除效率

Purging in BCR-ABL-positive acute lymphoblastic leukemia using immunomagnetic beads: comparison of residual leukemia and purging efficiency in bone marrow vs peripheral blood stem cells by semiquantitative polymerase chain reaction.

作者信息

Atta J, Fauth F, Keyser M, Petershofen E, Weber C, Lippok G, Hoelzer D, Martin H

机构信息

Department of Hematology and Oncology, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.

出版信息

Bone Marrow Transplant. 2000 Jan;25(1):97-104. doi: 10.1038/sj.bmt.1702096.

DOI:10.1038/sj.bmt.1702096
PMID:10654022
Abstract

Twenty autologous bone marrow (BM) and 25 peripheral blood stem cell (PBSC) grafts were collected from a total of 40 consecutive patients with BCR-ABL+ acute lymphoblastic leukemia (ALL) in first (n = 37) or second (n = 3) complete morphological remission and subsequently purged with a cocktail of anti-CD19, -CD10, AB4 MoAbs and immunomagnetic beads (IMB). Residual BCR-ABL-positive cells before purging were detected in 19 of 20 BM grafts at a median of 4 (range 0-6) logs and in 17 of 25 evaluable PBSC grafts at a median of 1 (range 0-3) log above the limit of detection assessed by a semiquantitative limiting log10-dilution RT-PCR (P < 0.0001). IMB purging depleted a median of 2.5 (range 1-4) log of residual BCR-ABL+ cells from BM and a median of 1 (range 0-2) log from PBSC grafts, achieving RT-PCR negativity in 1/20 BM and 12/25 PBSC grafts after purging. Cell recoveries were 62% and 86% (P < 0.0001) of MNC and 74% and 97% (P = 0.065) of CD34+ cells after BM and PBSC purging, respectively. BM purging was superior using the triple MoAb cocktail which depleted 2.64 +/- 0.4 log (n = 14) compared to 1.6 +/- 0.4 log (n = 5) using the MoAb cocktail not including AB4 (P = 0. 02). We conclude that unpurged BM grafts contain 2-3 log more residual BCR-ABL+ cells than unpurged PBSC grafts and that purging efficacy is superior in BM compared to PBSC grafts, but median titers in purged BM grafts still exceed those in purged PBSC grafts. Bone Marrow Transplantation (2000) 25, 97-104.

摘要

从40例连续的BCR-ABL+急性淋巴细胞白血病(ALL)患者中收集了20份自体骨髓(BM)移植物和25份外周血干细胞(PBSC)移植物,这些患者处于首次(n = 37)或第二次(n = 3)完全形态学缓解期,随后用抗CD19、-CD10、AB4单克隆抗体(MoAbs)和免疫磁珠(IMB)的混合物进行净化。在20份BM移植物中,有19份在净化前检测到残留的BCR-ABL阳性细胞,中位数为4(范围0 - 6)对数;在25份可评估的PBSC移植物中,有17份检测到残留细胞,中位数为1(范围0 - 3)对数,高于通过半定量极限log10稀释逆转录聚合酶链反应(RT-PCR)评估的检测限(P < 0.0001)。IMB净化使BM中残留的BCR-ABL+细胞中位数减少2.5(范围1 - 4)对数,PBSC移植物中减少中位数为1(范围0 - 2)对数,净化后20份BM移植物中有1份、25份PBSC移植物中有12份实现RT-PCR阴性。BM和PBSC净化后,单个核细胞(MNC)的细胞回收率分别为62%和86%(P < 0.0001),CD34+细胞的回收率分别为74%和97%(P = 0.065)。使用三联单克隆抗体混合物进行BM净化效果更佳,其减少了2.64±0.4对数(n = 14),而不包括AB4的单克隆抗体混合物减少了1.6±0.4对数(n = 5)(P = 0.02)。我们得出结论,未净化的BM移植物中残留的BCR-ABL+细胞比未净化的PBSC移植物多2 - 3对数,并且BM的净化效果优于PBSC移植物,但净化后的BM移植物中的中位数滴度仍超过净化后的PBSC移植物。《骨髓移植》(2000年)25卷,97 - 104页 。

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