Bone Marrow Transplantation Program, University of Minnesota Medical Center, Minneapolis, Minnesota 55455, USA.
Biol Blood Marrow Transplant. 2012 Mar;18(3):480-6. doi: 10.1016/j.bbmt.2011.11.030. Epub 2011 Dec 10.
Few therapeutic strategies exist for hematologic malignancies relapsing post allogeneic hematopoietic cell transplantation. We present outcomes on 35 patients with nonchronic myelogenous leukemia (CML) hematologic malignancies, the majority having acute myelogenous leukemia (AML) or myelodysplastic syndromes/myeloproliferative disorders (MDS/MPD) (n = 22) receiving lymphodepleting chemotherapy followed by donor lymphocyte infusion (DLI) at 2 T cell dose levels (0.5 and 1.0 × 10(8) CD3/kg). Forty-nine percent of patients achieved complete remission (CR), with a median duration of remission of 6 months (range: 2-71+). CR rates were similar between the 2 groups. The incidence of acute graft-versus-host disease (aGVHD) of any grade was 49%. We saw a higher incidence of grade II-IV aGVHD, with a rate of 66% using the higher-dose DLI (grade III, 33% and grade 4, 20%) versus only 25% (10% grade III-IV) with the lower-dose DLI (P = .06). Overall survival at 1 and 2 years was 30% (95% confidence interval [CI], 16%-45%) and 19% (95% CI, 8%-34%); however, for those achieving CR, 1- and 2-year survival was improved at 44% (95% CI, 20%-66%) and 28% (95% CI, 8%-52%) (P = .03), respectively. These results demonstrate that DLI after lymphodepleting chemotherapy for relapsed hematologic malignancies results in frequent CRs. The lower DLI dose regimen improved the tolerability of this therapeutic approach, with modest rates of severe aGVHD.
对于异基因造血细胞移植后复发的血液系统恶性肿瘤,目前几乎没有治疗策略。我们报告了 35 例非慢性髓性白血病(CML)血液系统恶性肿瘤患者的结果,其中大多数为急性髓性白血病(AML)或骨髓增生异常综合征/骨髓增生性疾病(MDS/MPD)(n = 22),接受淋巴细胞耗竭化疗后,采用两种 T 细胞剂量水平(0.5 和 1.0×10(8) CD3/kg)输注供者淋巴细胞(DLI)。49%的患者达到完全缓解(CR),缓解期中位数为 6 个月(范围:2-71+)。两组间 CR 率相似。任何级别急性移植物抗宿主病(aGVHD)的发生率为 49%。我们观察到较高的 II-IV 级 aGVHD 发生率,高剂量 DLI 组发生率为 66%(III 级,33%;IV 级,20%),而低剂量 DLI 组仅为 25%(10%为 III-IV 级)(P =.06)。1 年和 2 年总生存率分别为 30%(95%置信区间 [CI],16%-45%)和 19%(95% CI,8%-34%);然而,对于那些达到 CR 的患者,1 年和 2 年的生存率分别提高到 44%(95% CI,20%-66%)和 28%(95% CI,8%-52%)(P =.03)。这些结果表明,淋巴细胞耗竭化疗后输注 DLI 可导致复发血液系统恶性肿瘤频繁获得 CR。低剂量 DLI 方案改善了这种治疗方法的耐受性,严重 aGVHD 的发生率较低。