title: Radiolabeled anti-CD45 antibody with reduced-intensity conditioning and allogeneic transplantation for younger patients with advanced acute myeloid leukemia or myelodysplastic syndrome.
abstract: We treated patients under age 50 years with iodine-131 ((131)I)-anti-CD45 antibody combined with fludarabine and 2 Gy total body irradiation to create an improved hematopoietic cell transplantation (HCT) strategy for advanced acute myeloid leukemia or high-risk myelodysplastic syndrome patients. Fifteen patients received 332 to 1561 mCi of (131)I, delivering an average of 27 Gy to bone marrow, 84 Gy to spleen, and 21 Gy to liver. Although a maximum dose of 28 Gy was delivered to the liver, no dose-limiting toxicity was observed. Marrow doses were arbitrarily capped at 43 Gy to avoid radiation-induced stromal damage; however, no graft failure or evidence of stromal damage was observed. Twelve patients (80%) developed grade II graft-versus-host disease (GVHD), 1 patient developed grade III GVHD, and no patients developed grade IV GVHD during the first 100 days after HCT. Of the 12 patients with chronic GVHD data, 10 developed chronic GVHD, generally involving the skin and mouth. Six patients (40%) are surviving after a median of 5.0 years (range, 4.2 to 8.3 years). The estimated survival at 1 year was 73% among the 15 treated patients. Eight patients relapsed, 7 of whom subsequently died. The median time to relapse among these 8 patients was 54 days (range, 26 to 1364 days). No cases of nonrelapse mortality were observed in the first year after transplantation. However, 2 patients died in remission from complications of chronic GVHD and cardiomyopathy, at 18 months and 14 months after transplantation, respectively. This study suggests that patients may tolerate myeloablative doses >28 Gy delivered to the liver using (131)I-anti-CD45 antibody in addition to standard reduced-intensity conditioning. Moreover, the arbitrary limit of 43 Gy to the marrow may be unnecessarily conservative, and continued escalation of targeted radioimmunotherapy doses may be feasible to further reduce relapse.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Raya
authors.initials: R
authors.lastname: Mawad
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Ted A
authors.initials: TA
authors.lastname: Gooley
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Rajendran
authors.affiliation: Dade Moeller Health Group, Richland, Washington.
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Fisher
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Gopal
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Shields
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Mohamed L
authors.initials: ML
authors.lastname: Sorror
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Hans Joachim
authors.initials: HJ
authors.lastname: Deeg
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Damian J
authors.initials: DJ
authors.lastname: Green
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Press
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington. Electronic address: jpagel@fhcrc.org.
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
mesh_terms: D000328:Adult; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D009364:Neoplasm Recurrence, Local; D016499:Radioimmunotherapy / Q000379:methods*; D019172:Transplantation Conditioning / Q000009:adverse effects*; D014184:Transplantation, Homologous / Q000009:adverse effects*; D055815:Young Adult
keywords: Acute myeloid leukemia; Anti-CD45 antibody; Hematopoietic cell transplantation; Iodine-131; Myelodysplastic syndrome; Radioimmunotherapy