Gambella Massimiliano, Bregante Stefania, Raiola Anna Maria, Varaldo Riccardo, Ghiso Anna, Schiavetti Irene, Carmisciano Luca, Bacigalupo Andrea, Angelucci Emanuele
Department of Hematology and Cellular Therapy, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Department of Hematology and Cellular Therapy, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Transplant Cell Ther. 2023 Jan;29(1):49.e1-49.e7. doi: 10.1016/j.jtct.2022.10.015. Epub 2022 Oct 23.
Haploidentical stem cell transplantation is a viable strategy in the absence of an HLA-identical donor, but in myelofibrosis (MF), concerns may rise due to the risk of graft failure. Considering that engraftment is a major issue in MF, we sought to highlight its impact on survival outcomes. In addition, we explored the impact of pretransplantation ruxolitinib administration as an independent variable on outcomes. Here we report the results of a retrospective, monocentric experience with T cell-replete haploidentical bone marrow transplantation with post-transplantation cyclophosphamide as graft-versus-host disease (GVHD) prophylaxis in 51 consecutive MF-affected patients. The median duration of follow-up was 47 months. All 51 patients received a double-alkylating conditioning regimen, and 21 patients (41%) received pretransplantation ruxolitinib. Thirty-seven of 49 evaluable patients (76%) achieved full donor chimerism with neutrophil engraftment, 8 of 49 (16%) experienced graft rejection, and 4 of 49 (8%) had primary poor graft function. Splenectomy was more frequent among patients who engrafted (P = .06). Graft rejection was the sole factor negatively impacting overall survival (hazard ratio [HR], 4.19; 95% confidence interval [CI], 1.37 to 12.80; P = .01) and the major determinant for nonrelapse mortality (HR, 10.31; 95% CI, 2.54 to 41.82; P = .001). The 24-month incidence of relapse was 19% and was negatively impacted by splenectomy (HR, 5.84; 95% CI, 1.28 to 26.72; P = .02). The cumulative incidence of grade II-IV acute GVHD was 27% (95% CI, 20% to 33%), and that of grade III-IV acute GVHD was 8% (95% CI, 4% to 12%). The 24-month cumulative incidence of all-grade chronic GVHD was 28% (95% CI, 21% to 35%). Our data show that T cell-replete haploidentical bone marrow transplantation following double-alkylating conditioning in patients with MF is associated with favorable rates of GVHD and an acceptable relapse risk; nevertheless, rejection is not negligible and is associated with significant mortality. Splenectomy, which favors engraftment, is predictive of a higher risk of relapse.
在缺乏 HLA 配型相合供者的情况下，单倍体相合干细胞移植是一种可行的策略，但在骨髓纤维化（MF）中，由于存在移植物失败的风险，可能会引发担忧。鉴于植入是 MF 中的一个主要问题，我们试图强调其对生存结果的影响。此外，我们探讨了移植前使用芦可替尼作为一个独立变量对结果的影响。在此，我们报告了一项回顾性、单中心研究的结果，该研究纳入了 51 例连续的 MF 患者，采用富含 T 细胞的单倍体相合骨髓移植，并使用移植后环磷酰胺预防移植物抗宿主病（GVHD）。中位随访时间为 47 个月。所有 51 例患者均接受了双烷化预处理方案，21 例患者（41%）在移植前接受了芦可替尼治疗。49 例可评估患者中有 37 例（76%）实现了完全供者嵌合并伴有中性粒细胞植入，49 例中有 8 例（16%）发生移植物排斥，49 例中有 4 例（8%）出现原发性移植物功能不良。在植入的患者中，脾切除术更为常见（P = 0.06）。移植物排斥是唯一对总生存有负面影响的因素（风险比[HR]，4.19；95%置信区间[CI]，1.37 至 12.80；P = 0.01），也是非复发死亡率的主要决定因素（HR，10.31；95%CI，2.54 至 41.82；P = 0.001）。24 个月时的复发率为 19%，脾切除术对其有负面影响（HR，5.84；95%CI，1.28 至 26.72；P = 0.02）。II-IV 级急性 GVHD 的累积发生率为 27%（95%CI，20%至 33%），III-IV 级急性 GVHD 的累积发生率为 8%（95%CI，4%至 12%）。所有级别的慢性 GVHD 的 24 个月累积发生率为 28%（95%CI，21%至 35%）。我们的数据表明，MF 患者在接受双烷化预处理后进行富含 T 细胞的单倍体相合骨髓移植，其 GVHD 发生率良好，复发风险可接受；然而，排斥反应不可忽视，且与显著的死亡率相关。有利于植入的脾切除术预示着更高的复发风险。
