Up to 50% of patients with high-risk myeloid malignancies die of relapse after allogeneic stem cell transplantation. Current sequential conditioning regimens like the FLAMSA protocol combine intensive induction therapy with TBI or alkylators. Venetoclax has synergistic effects to chemotherapy. In a retrospective survey among German transplant centers, we identified 61 patients with myeloid malignancies that had received FLAMSA-based sequential conditioning with venetoclax between 2018 and 2022 as an individualized treatment approach. Sixty patients (98%) had active disease at transplant and 74% had genetic high-risk features. Patients received allografts from matched unrelated, matched related, or mismatched donors. Tumor lysis syndrome occurred in two patients but no significant non-hematologic toxicity related to venetoclax was observed. On day +30, 55 patients (90%) were in complete remission. Acute GvHD II°–IV° occurred in 17 (28%) and moderate/severe chronic GvHD in 7 patients (12%). Event-free survival and overall survival were 64% and 80% at 1 year as well as 57% and 75% at 2 years, respectively. The off-label combination of sequential FLAMSA-RIC with venetoclax appears to be safe and highly effective. To further validate these insights and enhance the idea of smart conditioning, a controlled prospective clinical trial was initiated in July 2023.
高达50%的高危髓系恶性肿瘤患者在异基因造血干细胞移植后死于复发。目前如FLAMSA方案等序贯预处理方案将强化诱导治疗与全身照射或烷化剂相结合。维奈克拉与化疗具有协同作用。通过对德国移植中心开展回顾性调查，我们确定了2018年至2022年间61例接受基于FLAMSA序贯预处理联合维奈克拉个体化治疗的髓系恶性肿瘤患者。其中60例（98%）患者在移植时存在活动性疾病，74%具有遗传学高危特征。患者接受来自匹配无关供者、匹配相关供者或不完全匹配供者的异体移植物。2例患者发生肿瘤溶解综合征，但未观察到与维奈克拉相关的显著非血液学毒性。移植后第30天，55例患者（90%）达到完全缓解。17例（28%）发生II°–IV°急性移植物抗宿主病，7例（12%）发生中度/重度慢性移植物抗宿主病。无事件生存率和总生存率在1年时分别为64%和80%，在2年时分别为57%和75%。FLAMSA-RIC序贯方案与维奈克拉的标签外联合应用显示出良好的安全性和显著疗效。为深入验证这些发现并完善智能预处理理念，一项前瞻性对照临床试验已于2023年7月启动。
肿瘤(癌症)患者之家