Sun J, Wu B, Liu Q, Feng R, Liu X, Meng F, Zhou S
Department of Hematology, Nanfang Hospital, the First Military Medical University, Guangzhou 510515, China.
Zhonghua Xue Ye Xue Za Zhi. 2000 Aug;21(8):400-2.
To investigate the efficacy of autologous bone marrow transplantation (ABMT) for patients with chronic myelogenous leukemia (CML) after in vitro purging of the graft with bcr/abl antisense oligodeoxynucleotides (AS-ODN).
Five CML patients, 2 in chronic phase (CP), 1 in accelerated phase (AP) and 2 in blast crisis (BC), all confirmed the presence of b3a2 bcr/abl mRNA by RT-PCR (reverse transcriptase-polymerase chain reaction). Patients had received 2 courses of intensive chemotherapy for "in vivo purging" before bone marrow harvesting. The autologous bone marrow cells were concentrated by CS3000plus and then incubated with 18-mer phosphorothioate bcr/abl AS-ODN (40 - 60 microg/ml, for 48 - 60 h). Conditioning regimens were TBI + Cy (total body irradiation + cyclophosphamide) or MAC + CCNU.
After intensive chemotherapy, ph(+) cells in bone marrow reduced to 34% (24% - 46%) and the numbers of bcr/abl mRNA (+) CFU-GM to 45.6% (33% - 58%). After bcr/abl AS-ODN in vitro purging, two patients were bcr/abl mRNA negative and three positive with the number of bcr/abl mRNA (+) CFU-GM markedly reduced. Delayed hematopoietic reconstitutions were observed in all patients after ABMT. During a more than 2 years follow-up period, three patients obtained major cytogenetic remission (MCR) and lasted for 9 - 12 months and the durations of CP after ABMT were longer than that before ABMT. One of this three in BC before ABMT being survived disease-freely for 37 months with bcr/abl mRNA (-) after ABMT. Another patient in BC had a short duration of MCR and relapsed at +7 months. One patient died from severe infection and bleeding at day +74 because of delayed reconstitution.
ABMT with bcr/abl AS-ODN purged graft can result in quite long duration of MCR and prolonged CP in some patients with CML.
探讨用bcr/abl反义寡脱氧核苷酸（AS-ODN）体外净化移植物后自体骨髓移植（ABMT）治疗慢性粒细胞白血病（CML）患者的疗效。
5例CML患者，2例处于慢性期（CP），1例处于加速期（AP），2例处于急变期（BC），均通过逆转录聚合酶链反应（RT-PCR）证实存在b3a2 bcr/abl mRNA。患者在采集骨髓前接受了2个疗程的强化化疗进行“体内净化”。自体骨髓细胞经CS3000plus浓缩，然后与18聚体硫代磷酸酯bcr/abl AS-ODN（40 - 60μg/ml，共48 - 60小时）孵育。预处理方案为全身照射（TBI）+环磷酰胺（Cy）或马法兰（MAC）+洛莫司汀（CCNU）。
强化化疗后，骨髓中ph(+)细胞降至34%（24% - 46%），bcr/abl mRNA(+)粒-巨噬细胞集落形成单位（CFU-GM）数量降至45.6%（33% - 58%）。经bcr/abl AS-ODN体外净化后，2例患者bcr/abl mRNA呈阴性，3例呈阳性，bcr/abl mRNA(+)CFU-GM数量明显减少。ABMT后所有患者均观察到造血重建延迟。在超过2年的随访期内，3例患者获得主要细胞遗传学缓解（MCR），持续9 - 12个月，ABMT后慢性期持续时间长于ABMT前。其中1例ABMT前处于急变期的患者在ABMT后无病生存37个月，bcr/abl mRNA(-)。另1例急变期患者MCR持续时间短，在+7个月时复发。1例患者因造血重建延迟于+74天死于严重感染和出血。
用bcr/abl AS-ODN净化移植物的ABMT可使部分CML患者获得较长时间的MCR并延长慢性期。
