Henslee-Downey P J, Abhyankar S H, Parrish R S, Pati A R, Godder K T, Neglia W J, Goon-Johnson K S, Geier S S, Lee C G, Gee A P
Division of Transplantation Medicine of the University of South Carolina School of Medicine, Richland Memorial Hospital, Columbia, USA.
Blood. 1997 May 15;89(10):3864-72.
Most patients requiring allogeneic bone marrow transplant (allo-BMT) do not have an HLA-matched sibling donor. A phenotypically matched unrelated donor graft has been made available for approximately 50% of Caucasians and less than 10% of ethnic and racial minorities in need. However, almost all patients have a readily available partially mismatched related donor (PMRD). We summarize our experience with 72 patients who ranged from 1 to 50 years of age (median, 16 years) and who were recipients of a PMRD allo-BMT from haploidentical family members following conditioning therapy using total body irradiation (TBI) and multiagent, high-dose chemotherapy. T-cell depletion and post-BMT immunosuppression were combined for graft-versus-host disease (GVHD) prophylaxis. The probability of engraftment was 0.88 at 32 days. Six of 10 patients who failed to engraft achieved engraftment after secondary transplant. Grade II to IV acute GVHD was seen in 9 of 58 (16%) evaluable patients; extensive chronic GVHD was seen in 4 of 48 (8%) evaluable patients. There was a statistically significant difference in 2-year survival probability between low-risk and high-risk patients (0.55 v 0.27, P = .048). Prognostic factors that affected outcomes in multivariate analysis were (1) a lower TBI dose and 3-antigen rejection mismatch decreased stable engraftment (P = .005 and P = .002, respectively); (2) a higher T-cell dose increased acute GVHD (P = .058); (3) a higher TBI dose increased chronic GVHD (P = .016); and (4) a high-risk disease category increased treatment failure from relapse or death (P = .037). A PMRD transplant can be performed with acceptable rates of graft failure and GVHD. Using sequential immunomodulation, the disease status at the time of transplant is the only prognostic factor significantly associated with long-term successful outcome after PMRD allo-BMT. When allogeneic rather than autologous BMT is indicated, progression in disease status before transplant can be avoided using a PMRD with equal inclusion of all ethnic or racial groups.
大多数需要异基因骨髓移植（allo-BMT）的患者没有人类白细胞抗原（HLA）匹配的同胞供者。对于大约50%的高加索人以及不到10%有需求的少数族裔和种族人群，有表型匹配的无关供者移植物可供使用。然而，几乎所有患者都有随时可用的部分错配相关供者（PMRD）。我们总结了72例患者的经验，这些患者年龄在1至50岁之间（中位数为16岁），在使用全身照射（TBI）和多药、大剂量化疗进行预处理后，接受了来自单倍体家庭成员的PMRD allo-BMT。采用T细胞去除和BMT后免疫抑制相结合的方法预防移植物抗宿主病（GVHD）。32天时植入概率为0.88。10例未植入的患者中有6例在二次移植后实现了植入。58例可评估患者中有9例（16%）出现II至IV级急性GVHD；48例可评估患者中有4例（8%）出现广泛慢性GVHD。低风险和高风险患者的2年生存概率存在统计学显著差异（0.55对0.27，P = 0.048）。多变量分析中影响预后的因素包括：（1）较低的TBI剂量和3抗原错配排斥降低了稳定植入率（分别为P = 0.005和P = 0.002）；（2）较高的T细胞剂量增加了急性GVHD（P = 0.058）；（3）较高的TBI剂量增加了慢性GVHD（P = 0.016）；（4）高风险疾病类别增加了因复发或死亡导致的治疗失败率（P = 0.037）。PMRD移植可以在可接受的移植失败率和GVHD发生率下进行。采用序贯免疫调节，移植时的疾病状态是与PMRD allo-BMT后长期成功结局显著相关的唯一预后因素。当需要进行异基因而非自体BMT时，使用PMRD并平等纳入所有族裔或种族群体可以避免移植前疾病状态的进展。
