Reduced-intensity conditioning followed by unrelated umbilical cord blood transplantation for advanced hematologic malignancies: rapid engraftment in bone marrow.
Reduced-intensity (RI) conditioning followed by cord blood transplantation (CBT) is a new treatment modality, but failure to engraft is a major concern. We describe 12 patients with advanced hematologic malignancies who underwent RI conditioning and CBT with a conditioning regimen consisting of 200 mg/m(2) fludarabine (Flu), 50 mg/kg cyclophosphamide (CY), and 3 Gy total body irradiation (TBI). Cyclosporin A and/or methotrexate were used for graft-versus-host disease prophylaxis. Cord blood grafts were not mismatched for more than 2 serologically defined HLA alleles but were later found by high-resolution DNA typing to be mismatched for 2 to 4 alleles in most cases. Short tandem repeat analysis of bone marrow cells at day 14 showed complete donor chimerism in 6 of the patients and mixed chimerism in 5, indicating rapid engraftment in the bone marrow, whereas the remaining patient experienced graft rejection. Neutrophil recovery was achieved at a median of day 17 (range, days 11-24) in 10 of the 11 patients with marrow chimerism at day 14. Of these 10 patients, however, transplantation-related mortality within 100 days occurred in 4 patients who showed failed platelet recovery and a lack of durable engraftment. Overall survival and disease-free survival rates were 41.7% and 33.3%, respectively. These results show that CB mismatched at 2 to 4 HLA alleles and transplanted with the Flu/CY/3 Gy TBI regimen is able to engraft in the bone marrow as early as day 14.
Misawa
Mahito
M
Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Kai
Shunro
S
Okada
Masaya
M
Nakajima
Toshiyuki
T
Nomura
Kaori
K
Wakae
Takeshi
T
Toda
Akinari
A
Itoi
Hisayuki
H
Takatsuka
Hiroyuki
H
Itsukuma
Takeyoshi
T
Nishioka
Keisuke
K
Fujimori
Yoshihiro
Y
Ogawa
Hiroyasu
H
Hara
Hiroshi
H
D000328:Adult; D001853:Bone Marrow; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods / Q000401:mortality; D003520:Cyclophosphamide / Q000008:administration & dosage; D016572:Cyclosporine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000528:radiation effects; D006086:Graft vs Host Disease / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods / Q000401:mortality; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation / Q000379:methods / Q000401:mortality
D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D016572:Cyclosporine; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine; D008727:Methotrexate