Jiang Jie-Ling, Gao Wen-Hui, Wang Li-Ning, Wan Ming, Wang Ling, Hu Jiong
Shanghai Institute of Hematology, Department of Hematology, Blood & Marrow Transplantation Center, Collaborative Innovation Center of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Clinical Research Center (SCRC), Feng Lin International Centre, Shanghai, China.
Front Med (Lausanne). 2021 Mar 18;8:630160. doi: 10.3389/fmed.2021.630160. eCollection 2021.
The PT-Cy was considered as one of the mainstay protocol for graft verus host disease (GVHD) prophylaxis. Recent study demonstrated that PT-Cy combined with other immunosuppressants could further reduce the incidence of GVHD and improve the GVHD and relapse free survival (GRFS). In this prospective phase II study, we evaluated the effect of a new GVHD prophylaxis consist of PT-Cy combined with tacrolimus and low dose anti-thymoglobulin (ATG). A total of 23 patients were enrolled including 20 patients with acute lymphoblastic leukemia (ALL) and three patients with T cell lymphoma. The median age was 29 years (range, 1658 years). Patients with HLA-matched related donor (MSD, =7) received PT-Cy combined with tacrolimus, while patients with HLA matched unrelated (MUD, = 2) or haplo-identical (Haplo, = 14) donor received additional ATG at 2.5 mg/kg on day 15 or day 22 after engraftment of neutrophils. As to the acute GVHD (aGVHD), only three patients developed grade I ( = 1) or grade II ( = 2) aGVHD with 100-day incidence of all aGVHD and II-IV aGVHD at 13.0 ± 5.1% and 9.1 ± 6.1% respectively. Only two patients had mild and one had moderate chronic GVHD (cGVHD), with 1-year incidence of cGVHD and moderate/severe cGVHD at 15.2 ± 8.7% and 4.6 ± 4.4% respectively. A high incidence of CMV reactivation was documented (14/16 with MUD/Haplo donor and 2/7 with MSD) with only 1 CMV disease documented. There were two EBV reactivation without post-transplantation lymphoproliferative disease (PTLD) documented. With a median follow-up of 303 days (range, 75700 days), three patients relapsed leading to 1-year cumulative incidence of relapse (CIR) at 12.8 ± 9.2%. Only one patient died of CMV pneumonia on day 91 with both 100-day and 1-year non-relapse mortality (NRM) at 4.6 ± 4.4%. The 1-year overall survival (OS), event-free survival (EFS) and GRFS were 95.5 ± 4.4%, 82.6 ± 9.5%, and 68.0 ± 11.3% respectively. Based on Simon's stage II design, our primary data showed that the PT-Cy+tacrolimus ± ATG protocol was promising in preventing aGVHD and cGVHD, which may translate into low NRM without increased CIR. Further clinical trial with large number of patients should be warranted. This trial was registered at www.clinicaltrials.gov as #NCT04118075.
PT-Cy被认为是移植物抗宿主病（GVHD）预防的主要方案之一。最近的研究表明，PT-Cy与其他免疫抑制剂联合使用可进一步降低GVHD的发生率，并改善无GVHD和无复发生存期（GRFS）。在这项前瞻性II期研究中，我们评估了一种新的GVHD预防方案的效果，该方案由PT-Cy联合他克莫司和低剂量抗胸腺细胞球蛋白（ATG）组成。共纳入23例患者，其中20例急性淋巴细胞白血病（ALL）患者和3例T细胞淋巴瘤患者。中位年龄为29岁（范围16至58岁）。人类白细胞抗原（HLA）匹配的相关供者（MSD，=7）的患者接受PT-Cy联合他克莫司治疗，而HLA匹配的无关供者（MUD，=2）或单倍体相合供者（单倍体，=14）的患者在中性粒细胞植入后第15天或第22天接受额外的2.5mg/kg ATG治疗。至于急性GVHD（aGVHD），只有3例患者发生I级（=1）或II级（=2）aGVHD，所有aGVHD和II-IV级aGVHD的100天发生率分别为13.0±5.1%和9.1±6.1%。只有2例患者有轻度慢性GVHD（cGVHD），1例有中度cGVHD，cGVHD和中度/重度cGVHD的1年发生率分别为15.2±8.7%和4.6±4.4%。记录到巨细胞病毒（CMV）再激活的发生率较高（MUD/单倍体供者组14/16，MSD组2/7），仅记录到1例CMV病。记录到2例EB病毒再激活，无移植后淋巴细胞增殖性疾病（PTLD）。中位随访303天（范围75至700天），3例患者复发，1年累积复发率（CIR）为12.8±9.2%。仅1例患者在第91天死于CMV肺炎，100天和1年无复发死亡率（NRM）均为4.6±4.4%。1年总生存率（OS）、无事件生存率（EFS）和GRFS分别为95.5±4.4%、82.6±9.5%和68.0±11.3%。根据西蒙II期设计，我们的主要数据表明，PT-Cy+他克莫司±ATG方案在预防aGVHD和cGVHD方面很有前景，这可能转化为低NRM且不增加CIR。应进行更多患者的进一步临床试验。该试验已在www.clinicaltrials.gov注册，注册号为#NCT04118075。
