Yttrium-90-labeled anti-CD45 antibody followed by a reduced-intensity hematopoietic cell transplantation for patients with relapsed/refractory leukemia or myelodysplasia

被引:17
作者
Phuong Vo [1 ,2 ]
Gooley, Ted [1 ,2 ]
Rajendran, Joseph G. [3 ]
Fisher, Darrell R. [4 ]
Orozco, Johnnie J. [1 ,2 ]
Green, Damian J. [1 ,2 ]
Gopal, Ajay K. [1 ,2 ]
Haaf, Robyn [1 ]
Nartea, Margaret [1 ]
Storb, Rainer [1 ,2 ]
Appelbaum, Frederick R. [1 ,2 ]
Press, Oliver W. [1 ,2 ]
Pagel, John M. [5 ]
Sandmaier, Brenda M. [1 ,2 ]
机构
[1] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA
[2] Univ Washington, Dept Med, Seattle, WA 98195 USA
[3] Univ Washington, Dept Radiol, Seattle, WA 98195 USA
[4] Versant Med Phys & Radiat Safety, Richland, WA USA
[5] Swedish Canc Inst, Seattle, WA USA
基金
美国国家卫生研究院;
关键词
ACUTE MYELOID-LEUKEMIA; MALIGNANCIES; THERAPY; RELAPSE; OLDER; RISK;
D O I
10.3324/haematol.2019.229492
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Outcomes of patients with persistent high-risk leukemia or myelodysplasia prior to allogeneic hematopoietic cell transplantation are dismal. We therefore conducted a phase I trial evaluating the use of CD45-targeted radiotherapy preceding hematopoietic cell transplantation with the goal of improving outcomes for this high-risk scenario. Fifteen patients, median age 62 (range 37-76) years, were treated: ten with advanced acute myeloid leukemia, five with high-risk myelodysplastic syndrome. All patients had evidence of disease prior to treatment including nine with marrow blast counts ranging from 7-84% and six with minimal residual disease. Patients received escalating doses of yttrium-90-labeled anti-CD45 antibody followed by fludarabine and 2 Gy total body irradiation prior to human leukocyte antigen-matched, related or unrelated hematopoietic cell transplantation. Although a maximum dose of 30 Gy was delivered to the liver, no dose-limiting toxicity was observed. Therefore, the maximum-tolerated dose could not be estimated. Treatment led to complete remission in 13 patients (87%). All patients engrafted by day 28. Six patients relapsed, median of 59 (range 6-351) days, after transplantation. The 1-year estimate of relapse was 41%. Eight patients (53%) are surviving with median follow up of 1.8 (range 0.9-5.9) years. Estimated overall survival at one and two years was 66% and 46%, respectively, with progression-free survival estimated to be 46% at each time point. In conclusion, the combination of Y-90-DOTA-BC8 with an allogeneic hematopoietic cell transplantation regimen was feasible and tolerable. This approach appears promising in this high-risk leukemia/myelodysplasia patient population with active disease.
引用
收藏
页码:1731 / 1737
页数:7
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