Transplantation of ex vivo expanded cord blood.
Umbilical cord blood (CB) from unrelated donors is increasingly used to restore hematopoiesis after myeloablative therapy. CB transplants are associated with higher rates of delayed and failed engraftment than are bone marrow transplants, particularly for adult patients. We studied the ex vivo expansion of CB in an attempt to improve time to engraftment and reduce the graft failure rate in the recipients. In this feasibility study, 37 patients (25 adults, 12 children) with hematologic malignancies (n = 34) or breast cancer (n = 3) received high-dose therapy followed by unrelated allogeneic CB transplantation. A fraction of each patient's CB allograft was CD34-selected and cultured ex vivo for 10 days prior to transplantation in defined media with stem cell factor, granulocyte colony-stimulating factor, and megakaryocyte growth and differentiation factor. The remainder of the CB graft was infused without further manipulation. Two sequential cohorts of patients were accrued to the study. The first cohort had 40% and the second cohort had 60% of their CB graft expanded. Patients received a median of 0.99 x 10(7) total nucleated cells (expanded plus unexpanded) per kilogram. The median time to engraftment of neutrophils was 28 days (range, 15-49 days) and of platelets was 106 days (range, 38-345 days). All evaluable patients who were followed for 28 days or longer achieved engraftment of neutrophils. Grade III/IV acute GVHD was documented in 40% and extensive chronic GVHD in 63% of patients. At a median follow-up of 30 months, 13 (35%) of 37 of patients survived. This study demonstrates that the CD34 selection and ex vivo expansion of CB prior to transplantation of CB is feasible. Additional accrual will be required to assess the clinical efficacy of expanded CB progenitors.
Shpall
Elizabeth J
EJ
University of Colorado Adult Bone Marrow Transplant Program, Denver, USA. eshpall@mail.mdanderson.org
Quinones
Ralph
R
Giller
Roger
R
Zeng
Chan
C
Baron
Anna E
AE
Jones
Roy B
RB
Bearman
Scott I
SI
Nieto
Yago
Y
Freed
Brian
B
Madinger
Nancy
N
Hogan
Christopher J
CJ
Slat-Vasquez
Vicki
V
Russell
Peggy
P
Blunk
Betsy
B
Schissel
Deborah
D
Hild
Elaine
E
Malcolm
Janet
J
Ward
William
W
McNiece
Ian K
IK
D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34; D001943:Breast Neoplasms / Q000401:mortality / Q000628:therapy; D018929:Cell Culture Techniques / Q000379:methods; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D005240:Feasibility Studies; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006085:Graft Survival; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D006801:Humans; D007223:Infant; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology
D018952:Antigens, CD34