Pediatric Blood and Marrow Transplantation, Levine Children's Hospital at Carolinas Medical Center, Charlotte, North Carolina.
Pediatric Blood and Marrow Transplantation, St. Jude Children's Research Hospital, Memphis, Tennessee.
Am J Hematol. 2018 Feb;93(2):169-178. doi: 10.1002/ajh.24949. Epub 2017 Nov 17.
CD34+ cell selection minimizes graft-versus-host disease (GVHD) after haploidentical donor stem cell transplant but is associated with slow immune recovery and infections. We report a Phase I/II study of prophylactic donor lymphocyte infusion (DLI) followed by methotrexate (MTX) GVHD prophylaxis after CD34-selected haploidentical donor transplant. A prophylactic DLI was given between day +30 and +42. Rituximab was given with DLI for the last 10 patients. The goal of the study was to determine a DLI dose that would result in a CD4+ cell count > 100/µL at Day +120 in ≥ 66% of patients with ≤ 33% grade II-III, ≤ 17% grade III, and no grade IV acute GVHD by Day +180. Thirty-five patients with malignant (n = 25) or nonmalignant disease (n = 10) were treated after CD34-selected haploidentical donor peripheral blood stem cell transplant. The DLI dose of 5 × 10 /kg met the CD4/GVHD goal with 67% of patients having CD4+ cells > 100/µL and 11% grade II-IV acute GVHD. The cumulative incidence of chronic GVHD was 16%. Fatal viral and fungal infections occurred in 11%. The 2 year estimated overall survival was 69% and the relapse rate was 14% for patients in remission at transplant. There was no effect of NK alloreactivity on relapse. Nine of ten patients at the target DLI dose cohort of 5 × 10 /kg are alive with median follow-up of 18 mos (range 6-29). Delayed prophylactic DLI and MTX was associated with promising outcomes at the target DLI dose. This trial was registered at clinicaltrials.gov, # NCT01027702.
CD34+ 细胞选择可最大程度减少单倍体供者干细胞移植后的移植物抗宿主病（GVHD），但与免疫恢复缓慢和感染有关。我们报告了一项 1/2 期研究，即在 CD34 选择的单倍体供者移植后，进行预防性供者淋巴细胞输注（DLI），然后用甲氨蝶呤（MTX）进行 GVHD 预防。预防性 DLI 在第+30 天至第+42 天之间给予。最后 10 例患者用利妥昔单抗联合 DLI。该研究的目的是确定 DLI 剂量，使至少 66%的患者在第+120 天 CD4+细胞计数>100/µL，≤33%的患者发生 II-III 级、≤17%的患者发生 III 级、无 IV 级急性 GVHD，在第+180 天。35 例恶性（n=25）或非恶性疾病（n=10）患者在 CD34 选择的单倍体供者外周血干细胞移植后接受治疗。DLI 剂量为 5×10 /kg，符合 CD4/GVHD 目标，67%的患者 CD4+细胞计数>100/µL，11%的患者发生 II-IV 级急性 GVHD。慢性 GVHD 的累积发生率为 16%。11%的患者发生致命性病毒和真菌感染。移植时缓解的患者 2 年估计总生存率为 69%，复发率为 14%。NK 同种异体反应对复发没有影响。在目标 DLI 剂量组（5×10 /kg）的 10 例患者中，有 9 例存活，中位随访时间为 18 个月（范围 6-29）。延迟预防性 DLI 和 MTX 与目标 DLI 剂量相关的有希望的结果。该试验在 clinicaltrials.gov 上注册，编号为 NCT01027702。
