[荧光原位杂交技术研究慢性髓性白血病患者异基因骨髓移植后混合嵌合体的时间进程]

[Study of the time course of mixed chimerism by fluorescent in situ hybridization in patients with chronic myeloid leukemia after allogenic transplantation of bone marrow].

作者信息

Vinogradova O A, Savchenko V G, Neverova A L, Diachenko L V, Domracheva E V, Liubimova L S, Mendeleeva L P

出版信息

Ter Arkh. 2001;73(7):26-34.

Abstract

AIM

To determine the type of chimerism in patients with chronic myeloid leukemia (CML) in various periods after allogenic transplantation of bone marrow (TBM) and its association with subsequent relapse.

MATERIALS AND METHODS

Ten patients were examined after allogenic TBM, which was performed during the chronic phase of CML in 9 patients and during acceleration phase in 1. Two patients received therapy with donor lymphocytes during relapse after transplantation. Time course of chimerism and minimum residual illness was studied by standard cytogenetic methods, fluorescent in situ hybridization (FISH) with DNA probes to centromer sites of X and Y chromosomes and BCR and ABL genes. The studies were carried out 30, 60, 90, 180 days, 9 months, 1 year, and then every 6 months after transplantation.

RESULTS

Mixed chimerism was observed in all patients during 9 months after TBM. The count of host cells was 0.1-5.8% in 8 patients; later the count of autologous cells was less than 1% in 5 patients, and in 3 patients complete donor chimerism was observed. Clinical hematological remission was stable in these patients. Relapses of leukemia with 40 and 83.1% host cells occurred in 2 patients 13 and 23 months after transplantation, respectively. Donor lymphocytes were transfused in order to induce the graft versus host effect, and in patient No. 2 restoration of donor hemopoiesis was attained.

CONCLUSION

Highly sensitive FISH method with DNA probe to centromer sites of X and Y chromosomes detects early relapse of the disease and demonstrates the time course of donor hemopoiesis recovery after transfusion of donor lymphocytes. The data indicate that 9 months after transplantation molecular cytogenetic studies should be carried out more often (once a month), particularly in patients with poor prognosis, for earlier detection of the relapse and beginning of immunotherapy.

摘要

目的

确定慢性粒细胞白血病（CML）患者在异基因骨髓移植（TBM）后不同时期的嵌合类型及其与后续复发的关系。

材料与方法

对10例异基因TBM后的患者进行检查，其中9例患者在CML慢性期进行移植，1例在加速期进行移植。2例患者在移植后复发时接受了供体淋巴细胞治疗。通过标准细胞遗传学方法、用针对X和Y染色体着丝粒位点以及BCR和ABL基因的DNA探针进行荧光原位杂交（FISH）研究嵌合状态和微小残留病的时间进程。研究在移植后30、60、90、180天、9个月、1年进行，之后每6个月进行一次。

结果

所有患者在TBM后9个月内均观察到混合嵌合。8例患者的宿主细胞计数为0.1 - 5.8%；之后5例患者的自体细胞计数低于1%，3例患者观察到完全供体嵌合。这些患者的临床血液学缓解稳定。2例患者分别在移植后13个月和23个月出现白血病复发，宿主细胞分别为40%和83.1%。为诱导移植物抗宿主效应输注了供体淋巴细胞，2号患者实现了供体造血恢复。