Allogeneic hematopoietic cell transplantation after conditioning with 131I-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome.
We conducted a study to estimate the maximum tolerated dose (MTD) of (131)I-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the blood by day 28 after the transplantation. The MTD of (131)I-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at www.clinicaltrials.gov as #NCT00008177.
Pagel
John M
JM
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. jpagel@fhcrc.org
Gooley
Theodore A
TA
Rajendran
Joseph
J
Fisher
Darrell R
DR
Wilson
Wendy A
WA
Sandmaier
Brenda M
BM
Matthews
Dana C
DC
Deeg
H Joachim
HJ
Gopal
Ajay K
AK
Martin
Paul J
PJ
Storb
Rainer F
RF
Press
Oliver W
OW
Appelbaum
Frederick R
FR
D000208:Acute Disease; D000368:Aged; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007951:Leukemia, Myeloid / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012307:Risk Factors; D016019:Survival Analysis; D015996:Survival Rate; D014018:Tissue Distribution; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation
D000906:Antibodies; D007457:Iodine Radioisotopes; D017493:Leukocyte Common Antigens; D014740:Vidarabine; C024352:fludarabine