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诱导移植物抗宿主病作为复发慢性髓性白血病的免疫疗法。

Induction of graft-versus-host disease as immunotherapy for relapsed chronic myeloid leukemia.

作者信息

Porter D L, Roth M S, McGarigle C, Ferrara J L, Antin J H

机构信息

Division of Hematology-Oncology, Brigham and Women's Hospital, Boston, MA 02115.

出版信息

N Engl J Med. 1994 Jan 13;330(2):100-6. doi: 10.1056/NEJM199401133300204.

DOI:10.1056/NEJM199401133300204
PMID:8259165
Abstract

BACKGROUND

The ability of allogeneic bone marrow transplantation to cure chronic myeloid leukemia (CML) is due to both the conditioning regimen and the antileukemic effects of the lymphocytes in the grafted marrow. We studied the ability of interferon alfa-2b and infusions of mononuclear cells from the marrow donor to induce a graft-versus-leukemia reaction in patients with CML in relapse after bone marrow transplantation.

METHODS

Eleven patients with relapsed CML after allogeneic bone marrow transplantation were treated with interferon alfa-2b and infusions of mononuclear cells. The patients were monitored for toxic effects, for hematologic and cytogenetic responses, and, with use of the polymerase chain reaction, for elimination of cells containing the bcr/abl messenger RNA transcript characteristic of the leukemic cells.

RESULTS

Six of the eight patients with stable CML after relapse had complete remissions according to molecular genetic criteria, since no cells with bcr/abl messenger RNA transcripts were detected (the method can identify 1 leukemic cell among 1 million normal cells). The three patients with accelerated CML after relapse did not enter remission. Myelosuppression was prominent in eight patients. Grade I acute graft-versus-host disease (GVHD) occurred in six patients, and grade III acute GVHD occurred in three. Limited chronic GVHD developed in five patients.

CONCLUSIONS

The induction of a graft-versus-leukemia reaction with interferon alfa-2b and infusions of donor mononuclear cells in patients with CML in relapse after bone marrow transplantation is an effective antileukemic therapy that may offer an alternative to a second marrow transplantation.

摘要

背景

异基因骨髓移植治愈慢性粒细胞白血病(CML)的能力归因于预处理方案以及移植骨髓中淋巴细胞的抗白血病作用。我们研究了α-2b干扰素和输注来自骨髓供体的单个核细胞在骨髓移植后复发的CML患者中诱导移植物抗白血病反应的能力。

方法

11例异基因骨髓移植后复发的CML患者接受了α-2b干扰素和单个核细胞输注治疗。对患者进行毒性作用、血液学和细胞遗传学反应监测,并使用聚合酶链反应检测是否消除了含有白血病细胞特征性bcr/abl信使RNA转录本的细胞。

结果

8例复发后病情稳定的CML患者中有6例根据分子遗传学标准达到完全缓解,因为未检测到带有bcr/abl信使RNA转录本的细胞(该方法可在100万个正常细胞中识别出1个白血病细胞)。3例复发后病情加速的CML患者未进入缓解期。8例患者出现明显的骨髓抑制。6例患者发生I级急性移植物抗宿主病(GVHD),3例发生III级急性GVHD。5例患者出现局限性慢性GVHD。

结论

对于骨髓移植后复发的CML患者,用α-2b干扰素和输注供体单个核细胞诱导移植物抗白血病反应是一种有效的抗白血病治疗方法,可能为二次骨髓移植提供替代方案。

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