Yttrium-90-labeled anti-CD45 antibody followed by a reduced-intensity hematopoietic cell transplantation for patients with relapsed/refractory leukemia or myelodysplasia
Phuong Vo,
Ted A. Gooley,
Joseph G. Rajendran,
Darrell R. Fisher,
Johnnie J. Orozco,
Damian J. Green,
Ajay K. Gopal,
Robyn Haaf,
Margaret Nartea,
Rainer Storb,
Frederick R. Appelbaum,
Oliver W. Press,
John M. Pagel,
Brenda M. Sandmaier
Affiliations
Phuong Vo
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle;Department of Medicine, University of Washington, Seattle
Ted A. Gooley
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle;Department of Medicine, University of Washington, Seattle
Joseph G. Rajendran
Department of Radiology, University of Washington, Seattle
Darrell R. Fisher
Versant Medical Physics and Radiation Safety, Richland
Johnnie J. Orozco
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle;Department of Medicine, University of Washington, Seattle
Damian J. Green
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle;Department of Medicine, University of Washington, Seattle
Ajay K. Gopal
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle;Department of Medicine, University of Washington, Seattle
Robyn Haaf
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle
Margaret Nartea
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle
Rainer Storb
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle;Department of Medicine, University of Washington, Seattle
Frederick R. Appelbaum
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle;Department of Medicine, University of Washington, Seattle
Oliver W. Press
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle;Department of Medicine, University of Washington, Seattle
John M. Pagel
Swedish Cancer Institute, Seattle, WA, USA
Brenda M. Sandmaier
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle;Department of Medicine, University of Washington, Seattle
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 90Y-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. (Trial registered at clinicaltrials.gov identifier: NCT01300572.)