[Cord blood transplantation supported with ex vivo expanded fraction for a patient with myelodysplastic syndrome and metastatic breast cancer].
Despite the promising outcomes of unrelated cord blood transplantations (UCBT) in pediatric recipients, the major limitation in the widespread use of cord blood (CB) as a source of hematopoietic stem cells (HSC), particularly in adults, is the physiological small number of cells. To overcome this limitation, we developed an ex vivo expansion system for HSC, in which CB CD34+ cells are cultured on feeder cells (HESS-5 cells) in the presence of cytokines (TPO, SCF and Flt3 ligand). A phase I/II clinical trial, approved by our institutional review board, has been started to assess the safety and effectiveness of this system. A 52-year-old woman with metastatic breast cancer and myelodysplastic syndrome (MDS) received a non-myeloablative preparative regimen followed by UCBT. On day 0, 75% of the whole CB and a fraction of CD34 negative cells were transplanted. The remaining 25% of the CB was CD34-selected and expanded on HESS-5 in a non-serum media in the presence of TPO, SCF, and Flt3-L. On day 5, the ex vivo-expanded, CD34+ cells were transplanted. The patient received 1.83 x 10(7)/kg of total nucleated cells and 7.7 X 10(4)/kg of CD34+ cells (expanded and unexpanded). No acute adverse effects were observed after the infusion of the cultured cells. She suffered from pneumonia on day 37, a cerebral hemorrhage on day 48, and died on day 50. Further studies are required to assess the effectiveness of this protocol.
Oki
Masayuki
M
Division of Hematology and Oncology, Department of Medicine, Tokai University School of Medicine.
Ando
Kiyoshi
K
Nakajima
Hikaru
H
Nakano
Yoshiaki
Y
Itagaki
Hiroyuki
H
Nakashioya
Chie
C
Kato
Shunichi
S
Hotta
Tomomitsu
T
D018952:Antigens, CD34 / Q000032:analysis; D019046:Bone Marrow Neoplasms / Q000556:secondary* / Q000628:therapy*; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008565:Membrane Proteins / Q000494:pharmacology; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D019089:Stem Cell Factor / Q000494:pharmacology; D013926:Thrombopoietin / Q000494:pharmacology
D018952:Antigens, CD34; D008565:Membrane Proteins; D019089:Stem Cell Factor; C084881:flt3 ligand protein; D013926:Thrombopoietin