Division of Haematology and Bone Marrow Transplantation, Policlinico San Martino, IRCCS Ospedale Policlinico San Martino, Genoa, Italy per l'Oncologia, Genoa, Italy; Haematology Clinic, Department of Internal Medicine, University of Genoa, Policlinico San Martino, IRCCS Ospedale Policlinico San Martino, Genoa, Italy per l'Oncologia, Genoa, Italy.
Division of Haematology and Bone Marrow Transplantation, Policlinico San Martino, IRCCS Ospedale Policlinico San Martino, Genoa, Italy per l'Oncologia, Genoa, Italy.
Biol Blood Marrow Transplant. 2018 Dec;24(12):2501-2508. doi: 10.1016/j.bbmt.2018.07.025. Epub 2018 Jul 21.
Disease relapse remains an unmet medical need for patients with Hodgkin lymphoma (HL) receiving an allogeneic hematopoietic cell transplantation (HCT). With the aim of identifying patients at high risk for post-transplant relapse, we retrospectively reviewed 41 HL patients who had received haploidentical (haplo) nonmyeloablative (NMA) HCT with high dose post-transplant cyclophosphamide (PT-Cy) for graft-versus-host (GVHD) prophylaxis. Primary refractory disease, relapse within 6 months from autologous stem cell transplantation, age, pretransplant chemotherapy, HCT comorbidity index (HCT-CI), sex mismatch, tumor burden and pretransplant fluorodeoxyglucose positron emission tomography (FDG-PET) status, assessed by Deauville score, were analyzed as variables influencing outcomes. All but 1 patient engrafted: median time to neutrophil and platelet recovery was 15 (interquartile range, 13 to 23) days and 19 (interquartile range, 12 to 28) days, respectively. Cumulative incidence of severe (grade III to IV) acute graft-versus-host disease (GVHD) and 3-year moderate-severe chronic GVHD was 2.4% and 11.8%, respectively. The 3-year overall (OS), progression free (PFS), and graft relapse-free survival (GRFS) were 75.6%, 43.9%, and 39%, respectively. On multivariate analysis, 3-year OS was significantly worse in patients with HCT-CI ≥3 (hazard ratio [HR], 5.0; 95% confidence interval [CI], 1.1 to 21.8; P = .03). Three-year relapse rate, 3-year PFS, and 3-year GRFS were significantly worse in patients with HCT-CI ≥3 (HR, 3.5; 95% CI, 1.3 to 9.3; P = .01; HR, 3.3; 95% CI, 1.2 to 9.0; P = .02; and HR, 4.2; 95% CI, 1.7 to 9.9; P = .001, respectively) and in patients with a Deauville score ≥4 on pretransplant FDG-PET (HR, 4.4; 95% CI, 1.6-12.4; P = .005, HR, 3.8; 95% CI, 1.5 to 9.7; P = .005; and 3.2; 95% CI, 1.3 to 7.9; P = .01, respectively). On univariate analysis, 3-year NRM was significantly worse only in patients with a HCT-CI ≥3 (HR, 17.6; 95% CI, 1.4 to 221.0). Among relapsed or refractory HL patients undergoing haplo NMA HCT with PT-Cy, pretransplant FDG-PET with a Deauville score ≥4 and HCT-CI ≥3 identified patients at high risk of relapse. Moreover, an HCT-CI ≥3 was associated with higher NRM and lower OS.
对于接受异基因造血细胞移植（HCT）的霍奇金淋巴瘤（HL）患者，疾病复发仍然是一个未满足的医疗需求。为了确定移植后复发风险较高的患者，我们回顾性分析了 41 例接受单倍体（haplo）非清髓性（NMA）HCT 联合高剂量移植后环磷酰胺（PT-Cy）预防移植物抗宿主病（GVHD）的 HL 患者。主要难治性疾病、自体干细胞移植后 6 个月内复发、年龄、移植前化疗、HCT 合并症指数（HCT-CI）、性别不匹配、肿瘤负担和移植前氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）状态（用 Deauville 评分评估）被分析为影响结果的变量。除 1 例患者外，所有患者均植入：中性粒细胞和血小板恢复的中位时间分别为 15（四分位距，13 至 23）天和 19（四分位距，12 至 28）天。严重（III 级至 IV 级）急性移植物抗宿主病（GVHD）和 3 年中度至重度慢性 GVHD 的累积发生率分别为 2.4%和 11.8%。3 年总生存（OS）、无进展生存（PFS）和移植物无复发生存（GRFS）分别为 75.6%、43.9%和 39%。多变量分析显示，HCT-CI≥3 的患者 3 年 OS 显著较差（风险比[HR]，5.0；95%置信区间[CI]，1.1 至 21.8；P=0.03）。HCT-CI≥3 的患者 3 年复发率、3 年 PFS 和 3 年 GRFS 明显较差（HR，3.5；95%CI，1.3 至 9.3；P=0.01；HR，3.3；95%CI，1.2 至 9.0；P=0.02；HR，4.2；95%CI，1.7 至 9.9；P=0.001），移植前 FDG-PET Deauville 评分≥4 的患者 3 年复发率、3 年 PFS 和 3 年 GRFS 也明显较差（HR，4.4；95%CI，1.6-12.4；P=0.005；HR，3.8；95%CI，1.5 至 9.7；P=0.005；HR，3.2；95%CI，1.3 至 7.9；P=0.01）。单变量分析显示，仅 HCT-CI≥3 的患者 3 年 NRM 显著较差（HR，17.6；95%CI，1.4 至 221.0）。在接受 haplo NMA HCT 联合 PT-Cy 治疗的复发或难治性 HL 患者中，移植前 FDG-PET 的 Deauville 评分≥4 和 HCT-CI≥3 可识别出复发风险较高的患者。此外，HCT-CI≥3 与较高的 NRM 和较低的 OS 相关。
