A phase I/II study of the safety and efficacy of the addition of sirolimus to tacrolimus/methotrexate graft versus host disease prophylaxis after allogeneic haematopoietic cell transplantation in paediatric acute lymphoblastic leukaemia (ALL).
A phase I/II study of the safety and efficacy of the addition of sirolimus to tacrolimus/methotrexate graft versus host disease prophylaxis after allogeneic haematopoietic cell transplantation in paediatric acute lymphoblastic leukaemia (ALL).
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DOI：
10.1111/j.1365-2141.2009.07889.x
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发表时间：
2009-12
影响因子：
6.5
通讯作者：
Bunin N
中科院分区：
文献类型：
--
作者：
Pulsipher MA;Wall DA;Grimley M;Goyal RK;Boucher KM;Hankins P;Grupp SA;Bunin N
西罗莫司已被证明在用于免疫抑制的血清水平上对人类急性淋巴细胞白血病有活性。我们假设在他克莫司/甲氨蝶呤移植物抗宿主病（GVHD）预防方案中加入西罗莫司可以减少造血干细胞移植后的复发，并启动了一项I/II期研究来证明安全性、可行性和有效性。研究队列包括18例高危（HR）首次完全缓解（CR1）患者，16例高危（HR） CR2患者，17例中危（IR） CR2患者和12例CR3+患者。该队列的2年无事件生存率（EFS）为66%（标准误差6.4）。CR1、IR CR2、HR CR2和CR3+患者的风险组EFS分别为74%、81%、44%和46%，且因干细胞来源而无差异。急性GVHD II-IV级和III-IV级累积发病率分别为38%和21%，慢性GVHD累积发病率为32%。移植相关死亡率和复发率的累积发生率分别为10%和25%。显著的毒性包括静脉闭塞性疾病[7例（11%）]、移植相关微血管病变（3例）和特发性肺炎（1例）。总之，基于西罗莫司的GVHD预防在这一人群中是安全的，早期生存结果是有希望的。一项用于测试西罗莫司是否减少ALL移植后复发和改善预后的III期试验正在进行中。
Sirolimus has been shown to have activity against human acute lymphoblastic leukaemia at serum levels used for immunosuppression. We hypothesized that the addition of sirolimus to a tacrolimus/methotrexate graft-versus-host disease (GVHD) prophylaxis regimen would decrease relapse after haematopoietic stem cell transplantation and initiated a phase I/II study to demonstrate safety, feasibility, and efficacy. The study cohort included 18 patients in high-risk (HR) first complete remission (CR1), 16 in HR CR2, 17 in intermediate risk (IR) CR2, and 12 in CR3+. The 2-year event-free survival (EFS) of the cohort was 66% (standard error 6·4). EFS of risk groups was 74%, 81%, 44% and 46% for CR1, IR CR2, HR CR2 and CR3+ patients respectively, and did not differ by stem cell source. Cumulative incidence of acute GVHD grade II–IV and III–IV was 38% and 21% respectively, while the cumulative incidence of chronic GVHD was 32%. Cumulative incidence of transplant-related mortality and relapse was 10% and 25% respectively. Significant toxicities included veno-occlusive disease [seven patients (11%)], transplant-associated microangiopathy (three patients), and idiopathic pneumonitis (one patient). In summary, sirolimus-based GVHD prophylaxis can be given safely in this population and early survival results are promising. A phase III trial to test whether sirolimus decreases relapse and improves outcome after transplantation for ALL is ongoing.
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影响因子：
20.3
作者：
Antin, JH;Kim, HT;Soiffer, RJ
通讯作者：
Soiffer, RJ
影响因子：
20.3
作者：
Eapen, M;Raetz, E;Davies, SM
通讯作者：
Davies, SM
影响因子：
6.2
作者：
Campistol, JM;Gutierrez-Dalmau, A;Torregrosa, JV
通讯作者：
Torregrosa, JV
影响因子：
158.5
作者：
Aricò, M;Valsecchi, MG;Masera, G
通讯作者：
Masera, G
影响因子：
20.3
作者：
Borowitz, Michael J.;Devidas, Meenakshi;Camitta, Bruce M.
通讯作者：
Camitta, Bruce M.