Punatar Sachin, Kumbhalwar Komal, Kalantri Siddhesh A, Gokarn Anant, Nayak Lingaraj, Chichra Akanksha, Mirgh Sumeet, Jindal Nishant, Mathew Libin, Kannan Sadhana, Khattry Navin
HSCT unit, Department of Medical Oncology/Advanced Centre For Treatment Research & Education in Cancer, Tata Memorial Centre, Navi Mumbai, India.
Homi Bhabha National Institute, Mumbai, India.
Blood Cell Ther. 2025 May 25;8(2):210-216. doi: 10.31547/bct-2024-029.
We have previously reported that pre-transplant use of tyrosine kinase inhibitors (TKIs) is independently associated with the occurrence of transplant-associated thrombotic microangiopathy (TA-TMA). However, the precise TKI-related factors which predispose to TA-TMA are unknown. In this retrospective analysis, we identify the TKI-related factors that are associated with TA-TMA.
This was a single center retrospective analysis of all patients with Philadelphia chromosome-positive (Ph+) malignancies who received BCR-ABL TKIs prior to transplant and underwent allogeneic hematopoietic stem cell transplantation (HSCT) between January 2008 and March 2019. Definite TA-TMA was defined as per Blood & Marrow Transplant Clinical Trials Network (BMT CTN) criteria and probable TMA as per Cho criteria. Details about the timing of the start and stop of TKI pre-transplant, the dose of TKIs used, and the number of TKIs exposed to pre-transplant were obtained. Imatinib > 400 mg/day, dasatinib > 100 mg/day, or nilotinib > 800 mg/day were considered as high dose TKI.
Seventy-two patients with chronic myeloid leukemia (CML)/Ph+ acute leukemias underwent transplant in the above period. Patient, donor, and transplant characteristics are shown in Table 1 and were well-matched between those with and without TMA. Overall, 13 (18%) had TA-TMA (median day +128), with 9 definite and 4 probable. The only TKI-related factor significantly associated with TA-TMA was the use of high-dose TKI (=0.04). Among non-TKI-related factors, acute graft versus host disease (GVHD) was associated with TA-TMA (=0.01). On multivariate analysis, high dose TKI did not remain statistically significant (Odds Ratio (OR) 4.6, =0.16). TA-TMA was associated with significantly worse long-term survival (6-year survival was 30% with TMA versus 62% without TMA, =0.026).
Pre-transplant use of TKI was associated with risk of TMA in about one-fifth of patients. High-dose TKI and acute GVHD increased the risk of TA-TMA. Prospective studies are warranted to confirm these findings. TA-TMA was associated with significantly worse long-term survival.
我们之前报道过，移植前使用酪氨酸激酶抑制剂（TKIs）与移植相关血栓性微血管病（TA-TMA）的发生独立相关。然而，导致TA-TMA的精确的TKI相关因素尚不清楚。在这项回顾性分析中，我们确定了与TA-TMA相关的TKI相关因素。
这是一项单中心回顾性分析，纳入了2008年1月至2019年3月期间所有在移植前接受BCR-ABL TKIs治疗并进行异基因造血干细胞移植（HSCT）的费城染色体阳性（Ph+）恶性肿瘤患者。明确的TA-TMA根据血液与骨髓移植临床试验网络（BMT CTN）标准定义，可能的TMA根据Cho标准定义。获取了移植前TKI开始和停止的时间、使用的TKI剂量以及移植前接触的TKI数量的详细信息。伊马替尼>400mg/天、达沙替尼>100mg/天或尼洛替尼>800mg/天被视为高剂量TKI。
在此期间，72例慢性髓性白血病（CML）/Ph+急性白血病患者接受了移植。患者、供体和移植特征见表1，有TMA和无TMA的患者之间匹配良好。总体而言，13例（18%）发生了TA-TMA（中位时间为+128天），其中9例明确诊断，4例可能诊断。与TA-TMA显著相关的唯一TKI相关因素是使用高剂量TKI（P=0.04）。在非TKI相关因素中，急性移植物抗宿主病（GVHD）与TA-TMA相关（P=0.01）。多因素分析中，高剂量TKI不再具有统计学意义（比值比（OR）为4.6，P=0.16）。TA-TMA与显著更差的长期生存率相关（有TMA的患者6年生存率为30%，无TMA的患者为62%，P=0.026）。
移植前使用TKI与约五分之一患者发生TMA的风险相关。高剂量TKI和急性GVHD增加了TA-TMA的风险。需要进行前瞻性研究以证实这些发现。TA-TMA与显著更差的长期生存率相关。
