Gorin N C
J Natl Cancer Inst. 1986 Jun;76(6):1281-7.
Autologous bone marrow transplantation (ABMT), which was developed in the past decade, is currently under investigation for the treatment of leukemias, lymphomas, and a few solid tumors. It consists of engrafting a patient, after ablative chemotherapy and/or total-body irradiation (TBI), with marrow taken from the patient at a propitious time in the history of the disease and usually cryopreserved. This technique has two major consequences: ABMT by reducing the length and variability of posttreatment aplasia can be considered a super hematologic support. It allows the use of chemotherapeutic agents and/or TBI at doses that surpass the dose for effecting the threshold of myelotoxicity. Therefore, a greater tumor cell kill can be expected at a reasonably low cost in terms of toxicity. In patients with acute leukemia (AL), however, the contribution of ABMT may go far beyond. In the initial trials (1974-79), the marrow of patients with AL was collected during complete remission and cryopreserved, with the idea of preserving "the remission status." At relapse this marrow was re-infused after high-dose chemotherapy and/or TBI, for achieving another complete remission. The result could be considered a chronologic chimera; the autograft, which had stem cells younger than those of the organism, reproduced, over the course of a few months or years, the evolution of the remission during which it was collected. As predicted, however, all patients who received this treatment eventually relapsed. For a more aggressive technique, some teams gave autografts to patients earlier, during remission, to allow ablative therapy in the consolidation mode; the whole procedure, including the pretransplant cytoreductive regimen, was modeled on that of allografting. Because allogeneic bone marrow transplantation currently offers the best chance of long-term survival but remains severely restricted, by age and availability of an HLA-identical donor, to less than 10% of the patients, ABMT may be considered an alternative source of stem cells to the other patients. In addition, ABMT avoids the risks of graft-versus-host disease with its associated immunosuppression. However, one major impediment to effective ABMT may be the persistence of leukemia cells in the marrow autograft, although the marrow was collected during earlier remission. The recent development of numerous techniques to cleanse the marrow prior to ABMT has considerably increased the possibility of ABMT becoming a major tool in the cure of leukemia. This report reviews the early data and essentially focuses on recent results of ABMT effected in or done in remission with use of cleansed and uncleansed marrow.
自体骨髓移植(ABMT)是在过去十年中发展起来的,目前正在研究用于治疗白血病、淋巴瘤和一些实体瘤。它包括在进行清髓性化疗和/或全身照射(TBI)后,给患者输入在疾病过程中合适时间采集并通常冷冻保存的患者自身骨髓。这项技术有两个主要结果:通过减少治疗后再生障碍期的长度和变异性,ABMT可被视为一种超级血液学支持。它允许使用超过骨髓毒性阈值剂量的化疗药物和/或TBI。因此,在毒性方面以合理的低成本有望实现更大程度的肿瘤细胞杀伤。然而,在急性白血病(AL)患者中,ABMT的作用可能远不止于此。在最初的试验(1974 - 1979年)中,AL患者的骨髓在完全缓解期采集并冷冻保存,目的是保持“缓解状态”。复发时,在大剂量化疗和/或TBI后重新输入这种骨髓,以实现再次完全缓解。结果可被视为一种时间上的嵌合体;自体移植物中的干细胞比机体的干细胞年轻,在几个月或几年的时间里,重现了采集时缓解期的演变过程。然而,正如所预测的,所有接受这种治疗的患者最终都复发了。对于一种更激进的技术,一些团队在缓解期更早地给患者进行自体移植,以便在巩固模式下进行清髓治疗;整个过程,包括移植前的细胞减灭方案,都仿照同种异体移植。由于目前同种异体骨髓移植提供了最佳的长期生存机会,但由于年龄和HLA匹配供体的可获得性,仍严重受限,只有不到10%的患者能够进行,ABMT可被视为其他患者的替代干细胞来源。此外,ABMT避免了移植物抗宿主病及其相关免疫抑制的风险。然而,有效的ABMT的一个主要障碍可能是骨髓自体移植物中白血病细胞的持续存在,尽管骨髓是在早期缓解期采集的。最近在ABMT之前进行骨髓净化的众多技术的发展,大大增加了ABMT成为治疗白血病主要手段的可能性。本报告回顾了早期数据,并主要关注使用净化和未净化骨髓在缓解期进行或完成的ABMT的近期结果。