Delage R, Ritz J, Anderson K C
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Hematol Oncol Clin North Am. 1990 Apr;4(2):369-88.
Bone marrow transplantation is the only treatment that can result in long-term disease-free survival and possible cure in a significant number of patients with CML. Several prognostic features influence relapse and survival following allogeneic BMT for CML. The most important factor is treatment of patients during chronic phase. The timing of BMT in chronic phase CML remains controversial, because the Seattle findings that BMT done within a shorter interval from diagnosis to transplant was associated with improved survival has not been confirmed by the IBMTR. No factor can predict in the individual patient the timing of transformation, even in patients with low-risk chronic phase CML, but we believe that allogeneic BMT should be offered as soon as possible for newly diagnosed patients who have histocompatible siblings. More widespread application of BMT in CML is possible because of effective methods for preventing GVHD, the major cause of morbidity after allogeneic BMT. However, in vitro techniques for the depletion of donor marrow T cells have resulted in higher graft failure and relapse rates. More precise understanding of the immune mechanisms involved may permit more selective depletion techniques which not only abrogate GVHD but also permit sustained engraftment and preserve GVL effect. This may extend application of BMT for patients with mismatched related or histocompatible unrelated donors. It is of interest that cytogenetic relapse after BMT is not invariably followed by hematologic relapse. It is likely that the use of polymerase chain reaction techniques which detect the bcr-abl rearrangement at a very low level will identify the persistence of the malignant clone after allogeneic BMT in even more patients. At present, the significance of such findings is unclear, but further study of the kinetics of disappearance of the CML clone post-BMT may increase our understanding of the immune mechanisms involved in suppression of the malignant clone and determine whether in fact CML can be cured using BMT approaches.
骨髓移植是唯一能使大量慢性粒细胞白血病（CML）患者实现长期无病生存并可能治愈的治疗方法。有几个预后特征会影响CML患者异基因骨髓移植（BMT）后的复发和生存情况。最重要的因素是患者在慢性期的治疗。慢性期CML患者进行BMT的时机仍存在争议，因为西雅图研究发现从诊断到移植的间隔时间较短时进行BMT与生存率提高相关，但国际骨髓移植登记处（IBMTR）并未证实这一结果。没有任何因素能够预测个体患者的病情转变时机，即使是低风险慢性期CML患者也是如此，但我们认为，对于有组织相容性同胞供者的新诊断患者，应尽快进行异基因BMT。由于预防移植物抗宿主病（GVHD）（异基因BMT后发病的主要原因）的有效方法，BMT在CML中的应用可能会更加广泛。然而，体外去除供体骨髓T细胞的技术导致了更高的移植物失败率和复发率。对所涉及免疫机制的更精确理解可能会带来更具选择性的去除技术，这种技术不仅能消除GVHD，还能实现持续植入并保留移植物抗肿瘤（GVL）效应。这可能会扩大BMT在相关配型不符或组织相容性无关供者患者中的应用。有趣的是，BMT后的细胞遗传学复发并不总是紧接着血液学复发。使用能在极低水平检测bcr-abl重排的聚合酶链反应技术，可能会在更多患者中发现异基因BMT后恶性克隆的持续存在。目前，这些发现的意义尚不清楚，但对BMT后CML克隆消失动力学的进一步研究可能会加深我们对抑制恶性克隆所涉及免疫机制的理解，并确定使用BMT方法是否真的能治愈CML。
