Levine John E, Braun Thomas, Penza Samuel L, Beatty Patrick, Cornetta Kenneth, Martino Rodrigo, Drobyski William R, Barrett A John, Porter David L, Giralt Sergio, Leis Jose, Holmes Houston E, Johnson Matthew, Horowitz Mary, Collins Robert H
University of Michigan, Ann Arbor, MI, USA.
J Clin Oncol. 2002 Jan 15;20(2):405-12. doi: 10.1200/JCO.2002.20.2.405.
Patients with advanced myeloid malignancies who experience relapse after allogeneic bone marrow transplantation (BMT) have a poor prognosis. Long-term survival after chemotherapy alone, second myeloablative transplant, or donor leukocyte infusions (DLIs) alone is unusual. DLIs may have minimal effectiveness in advanced disease because adequate cellular responses are not able to develop in the presence of bulky, fast-growing disease. A chemotherapy strategy was used to debulk disease before administration of granulocyte colony-stimulating factor (G-CSF)-primed DLIs.
Sixty-five patients experiencing hematologic relapse of myeloid malignancy after HLA-matched sibling BMT were prospectively treated with cytarabine-based chemotherapy, then G-CSF-primed DLIs. No prophylactic immunosuppression was provided.
Twenty-seven of 57 assessable patients experienced a complete response. Graft-versus-host disease (GVHD) was observed in 56% of the patients. Treatment-related mortality was 23%. Overall survival at 2 years for the entire cohort was 19%. Patients with a complete response were more likely to survive, with 1- and 2-year survival rates of 51% and 41%, respectively, with a median follow-up of more than 2 years. The 1-year survival for nonresponders was 5%. A posttransplant remission lasting more than 6 months before relapse was associated with a higher likelihood of response. GVHD was not required for durable remission.
Salvage treatment with chemotherapy before DLI can help some patients with advanced myeloid relapse and is not dependent on GVHD. Patients with short remissions after BMT are unlikely to benefit from this approach, and the approach is associated with significant treatment-related mortality. Modifications of this approach or entirely different approaches will be required for most patients with this difficult clinical problem.
异基因骨髓移植（BMT）后复发的晚期髓系恶性肿瘤患者预后较差。单纯化疗、二次清髓性移植或单纯供体白细胞输注（DLI）后的长期生存并不常见。在晚期疾病中，DLI可能效果甚微，因为在存在大量快速生长的疾病时，无法产生足够的细胞反应。在给予粒细胞集落刺激因子（G-CSF）预处理的DLI之前，采用化疗策略来减少肿瘤负荷。
65例HLA匹配的同胞BMT后发生髓系恶性肿瘤血液学复发的患者前瞻性地接受了以阿糖胞苷为基础的化疗，然后接受G-CSF预处理的DLI。未给予预防性免疫抑制。
57例可评估患者中有27例获得完全缓解。56%的患者观察到移植物抗宿主病（GVHD）。治疗相关死亡率为23%。整个队列2年的总生存率为19%。获得完全缓解的患者更有可能存活，1年和2年生存率分别为51%和41%，中位随访时间超过2年。未缓解患者的1年生存率为5%。复发前持续超过6个月的移植后缓解与更高的缓解可能性相关。持久缓解不需要GVHD。
在DLI之前用化疗进行挽救治疗可帮助一些晚期髓系复发患者，且不依赖于GVHD。BMT后缓解期短的患者不太可能从这种方法中获益，且该方法与显著的治疗相关死亡率相关。对于大多数有这个棘手临床问题的患者，需要对这种方法进行改进或采用完全不同的方法。
