Incidence Of II-IV Acute GVHD Research Articles

A Multi-Center Retrospective Analysis of Outcomes Post Allogeneic Stem Cell Transplantation in AML Patients with TET2 Mutations: A Study on Behalf of the Global Committee and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Background Mutations in TET2 present in about 15% of adult AML are reported in some limited series as an adverse prognostic factor for overall survival. However the impact of allogeneic hematopoietic cell transplantation (allo-HCT) for the treatment of these patients remains unclear. We addressed this issue in a EBMT global multi-center registry-based study. Patients and Methods 644 adult AML patients with TET2 mutations receiving first non ex-vivo depleted allo-HCT from 2013-2022 in 127 centers were analyzed. All patients achieved first complete remission (CR1) before allo-HCT. Results The median age of the 644 AML patients was 59.4 (range, 18.1-86.3) years. 556 patients (86.3%) had de novo, and 88 (13.7%) had secondary AML, respectively. 367 (57.2%) patients were male. The median interval from diagnosis to allo-HCT was 4.9 (IQR, 3.8-6.2) months. Patients were categorized into favorable -(N=23, 3.9%), intermediate-(N=475, 79.8%) and adverse (N=97, 16.3%) risk categories according to cytogenetic characteristics. Conditioning regimen was myeloablative (MAC) in 46.7% of patients. 149 patients (23.1%) received a matched-sibling donor, 176 (27.3%) a haploidentical donor (Haplo), 268 (41.6%) a 10/10 unrelated donor (UD) and 51 (7.9%) a 9/10 UD allo-HCT, respectively. For the entire cohort, with a median follow-up of 1.9 years, the 30-day cumulative incidence of engraftment was 97.6%. The 100-day cumulative incidence of grade II-IV aGVHD was 22.9% and the 2-year cumulative incidence of extensive cGVHD was 13.7%. In addition, the 2-year relapse incidence and NRM were 23.2% and 12.8%, respectively. Finally, the 2-year OS, LFS and GRFS were 69.8%, 63.9% and 49.8%, respectively. In multivariable analyses, a donor type 9/10 UD was associated with a higher RI (HR=2.33, 95% CI 1.21-4.48; p=0.01), a lower LFS (HR=2.20, 95% CI 1.31-3.70; p<0.01) and OS (HR=2.29, 95% CI 1.33-3.96; p<0.01) as compared to MSD as reference. Compared to MSD, 10/10 UD and Haplo had similar outcomes. The adverse-cytogenetic group was associated with higher RI (HR=1.85, 95% CI 1.19-2.86; p<0.01), and higher incidence of grade II-IV acute GVHD (HR=1.74, 95% CI 1.14-2.64; p=0.01) as compared to other groups combined as reference. Compared to de novo AML (reference), secondary AML was associated with lower LFS (HR=1.49, 95% CI 1.03-2.15; p<0.05) and OS (HR=1.68, 95% CI 1.15-2.45; p<0.01). When age increased, patients faced higher RI (HR for 10y increment=1.24, 95% CI 1.01-1.53; p<0.05) and extensive chronic GVHD (HR=1.34, 95% CI 1.02-1.77; p<0.05), which translated into higher NRM (HR=1.66, 95% CI 1.23-2.24; p<0.01), lower LFS (HR=1.36, 95% CI 1.14-1.62; p<0.01) and OS (HR=1.60, 95% CI 1.31-1.96; p<0.01). Later year of transplantation was associated with lower incidence of II-IV acute GVHD (HR for 2y increment=0.76, 95% CI 0.63-0.92; p<0.01), chronic GVHD (HR=0.67, 95% CI 0.54-0.83; p<0.01) and extensive chronic GVHD (HR=0.72, 95% CI 0.52-0.99; p<0.05). Female to male, patient CMV status and interval between diagnosis and HCT did not affect significantly the transplant outcomes in multivariable analysis. Conclusion No significant difference was observed in outcomes of AML patients with TET2 mutations following MSD, HAPLO and 10/10 UD allo-HCTs, while 9/10 UD was associated with higher relapse incidence and lower survival outcomes. Higher patient age, secondary AML and adverse cytogenetics predicted worse transplant outcomes. GVHD prevention improved with time for these patients.

Effect of KIR/HLA receptor-ligand mode on prognosis of single unrelated cord blood transplantation in patients with hematological malignancies

目的探讨自然杀伤细胞免疫球蛋白样受体（KIR）与人类白细胞抗原（HLA）受配体模式对血液病患者单份非血缘脐血移植（sUCBT）预后的影响。方法回顾性分析2012年7月至2018年6月270例接受sUCBT的血液病患者。移植前脐血及患者均进行HLA12个位点高分辨配型，选择移植物（脐血）的KIR均同时表达2DL1和2DL2/2DL3抑制性基因，根据患者KIR配体情况分为缺失组（C1/C1或C2/C2）和无缺失组（C1/C2）。结果270例血液病患者中男146例（54.1％），女124例（45.9％），中位年龄13（1～62）岁；缺失组174例（64.4％），无缺失组96例（35.6％）。全部患者均采用不含抗胸腺细胞球蛋白（ATG）清髓性预处理方案。缺失组、无缺失组粒细胞植入率均为98.9％（172/174、95/96），中位植入时间分别为16（10～41）d、17（11～33）d（P＝0.705）；血小板植入率分别为88.5％（154/174）、87.5％（84/96），中位植入时间分别为35（11～113）d、38.5（13～96）d（P＝0.317）；缺失组、无缺失组Ⅱ～Ⅳ级急性GVHD发生率分别为38.7％（95％CI 31.4％～45.9％）、50.0％（95％CI 39.6％～59.6％）（P＝0.075），多因素分析显示KIR配体缺失是影响Ⅱ～Ⅳ度急性GVHD发生的独立保护性因素（P＝0.036）。移植后3年累积复发率分别为17.7％（95％CI 11.7％～24.9％）、22.7％（95％CI14.4％～32.2％）（P＝0.288）。中位随访时间742（335～2 512）d，缺失组、无缺失组3年总生存率分别为72.1％（95％CI 64.1％～78.6％）、60.5％（95％CI 47.9％～69.2％）（χ2＝3.629，P＝0.079），3年无病生存率分别为64.9％（95％CI 56.2％～72.3％）、55.4％（95％CI 44.4％～65.0％）（χ2＝3.027，P＝0.082），移植后180 d 非复发死亡率分别为12.1％（95％CI 7.7％～17.4％）、16.7％（95％CI 10.0％～24.8％）（P＝0.328）。结论在不含ATG清髓性预处理sUCBT血液病治疗体系中，缺失抑制性KIR配体患者移植后急性GVHD发生率更低。

HLA-haploidentical hematopoietic SCT from collateral related donors without in vitro T-cell depletion for hematological malignancies

HLA-haploidentical hematopoietic SCT (HSCT) provides an opportunity for almost all patients who lack HLA-matched sibling donors. The donor availability can be increased by including the collateral related donors (CRDs). We compared clinical outcomes of patients with hematological malignancies, who underwent haploidentical HSCT from CRD (n=30) and immediate related donors (IRDs; n=120). In CRDs, 29 (96.7%) patients achieved sustained engraftment. In CRDs and IRDs, the median times of myeloid recovery were 13 (range 10-20 days) and 14 days (range 12-23 days), and the median times of platelet recovery were 18 (range 7-270) and 15 days (range 7-132 days; P=0.027). The incidences of II-IV acute GVHD were 27.6% versus 39.4% (P=0.058). The 2-year cumulative incidences of chronic GVHD (cGVHD) were 63.3% versus 57.8% (P=0.365). The 2-year incidence of extensive cGVHD of CRDs was significantly higher than that of IRDs (36.7% versus 20.2%, P=0.03). The 2-year incidences of relapse, 3-year probability of OS and leukemia-free survival for the two groups were 26.7% versus 14.8% (P=0.17), 56.7% versus 70.4% (P=0.224) and 50.0% versus 65.4% (P=0.103), respectively. This study shows that haploidentical HSCT from CRDs can provide a safe and effective treatment for patients with hematological malignancies. CRDs could be an alternative when there was no suitable IRDs.