Elmaagacli A H, Becks H W, Beelen D W, Stockova J, Bützler R, Opalka B, Schaefer U W
Department of Bone Marrow Transplantation, University Hospital of Essen, Germany.
Bone Marrow Transplant. 1995 Dec;16(6):823-9.
We investigated the persistence of host-type hematopoiesis as defined by mixed chimerism (MC) in 28 male patients with chronic myelogenous leukemia (CML) who underwent opposite sex, non-T cell-depleted bone marrow transplantation (BMT) by amplification of Y-chromosome specific sequences, and correlated these results with the detection of minimal residual disease (MRD) by BCR/ABL mRNA amplification. Patients were studied at two time periods (> 3 months and > 24 months post-BMT). All but two patients were conditioned with total body irradiation (TBI) and cyclophosphamide (CY). One patient received busulfan (Bu), thiothepa (Thio) and CY, another patient CY and Bu. Detection of MRD occurred exclusively among patients with a MC (significance P < 0.04). Six of 18 patients with MC had detectable MRD, four of these consecutively developed cytogenetic and hematological relapse. Of 28 patients studied more than 3 months post-transplant, 18 (64%) had mixed chimerism and 10 (36%) had exclusively donor-derived blood cells. Nineteen patients were followed for their chimeric status between 24 months and 136 months post-BMT. Four patients converted from MC to complete chimerism and 10 patients (53%) remained mixed chimeric. The high incidence of MC in patients who underwent BMT without T cell depletion was measured by using a PCR assay with a sensitivity of 0.001%. As previously described by other investigators patients with complete chimerism developed more acute GVHD grade I-II (seven of 10 patients (70%) than patients with MC (nine of 18 patients (50%), not significant). This study also suggests that chimeric status might depend upon the regimen to prevent GVHD. One of four patients who received weekly methotrexate as GVHD prophylaxis developed MC, whereas in 11 of 18 patients receiving short course methotrexate and cyclosporine MC was detectable. All of six patients, prophylactically treated with a murine monoclonal antibody directed to the human alpha/beta T cell receptor in combination with cyclosporine, were mixed chimeras.
我们通过Y染色体特异性序列扩增，对28例接受异性、非T细胞去除性骨髓移植（BMT）的慢性粒细胞白血病（CML）男性患者中由混合嵌合体（MC）定义的宿主型造血持续性进行了研究，并将这些结果与通过BCR/ABL mRNA扩增检测微小残留病（MRD）相关联。在两个时间段（BMT后>3个月和>24个月）对患者进行了研究。除两名患者外，所有患者均接受全身照射（TBI）和环磷酰胺（CY）预处理。一名患者接受白消安（Bu）、噻替派（Thio）和CY，另一名患者接受CY和Bu。MRD检测仅在有MC的患者中出现（P<0.04，有统计学意义）。18例有MC的患者中有6例可检测到MRD，其中4例随后相继发生细胞遗传学和血液学复发。在移植后3个月以上接受研究的28例患者中，18例（64%）有混合嵌合体，10例（36%）仅有供体来源的血细胞。19例患者在BMT后24个月至136个月期间随访其嵌合状态。4例患者从MC转变为完全嵌合体，10例患者（53%）仍为混合嵌合体。通过灵敏度为0.001%的PCR检测法测定了未进行T细胞去除的BMT患者中MC的高发生率。如其他研究者先前所述，完全嵌合体患者发生I-II级急性移植物抗宿主病（GVHD）的比例（10例患者中有7例（70%））高于有MC的患者（18例患者中有9例（50%）），但无统计学意义。本研究还提示嵌合状态可能取决于预防GVHD的方案。接受每周一次甲氨蝶呤预防GVHD的4例患者中有1例出现MC，而在接受短疗程甲氨蝶呤和环孢素的18例患者中有11例可检测到MC。所有6例接受针对人α/βT细胞受体的鼠单克隆抗体联合环孢素预防性治疗的患者均为混合嵌合体。
