TY - JOUR
T1 - Transplantation of ex vivo expanded cord blood
AU - Shpall, Elizabeth J.
AU - Quinones, Ralph
AU - Giller, Roger
AU - Zeng, Chan
AU - Baron, Anna E.
AU - Jones, Roy B.
AU - Bearman, Scott I.
AU - Nieto, Yago
AU - Freed, Brian
AU - Madinger, Nancy
AU - Hogan, Christopher J.
AU - Slat-Vasquez, Vicki
AU - Russell, Peggy
AU - Blunk, Betsy
AU - Schissel, Deborah
AU - Hild, Elaine
AU - Malcolm, Janet
AU - Ward, William
AU - McNiece, Ian K.
N1 - Funding Information:
This work was supported by research grants from the National Cancer Institute RO1-CA7-5163 (E.J.S.), National Cancer Institute RO1-CA88878-02 (I.K.M.), National Heart, Lung, and Blood Institute RO1 HL61382 (C.J.H.), and Amgen (E.J.S., I.K.M.).
PY - 2002
Y1 - 2002
N2 - 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 × 107 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.
AB - 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 × 107 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.
KW - Cord blood transplantation
KW - Ex vivo expansion
KW - Unrelated allotransplantation
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U2 - 10.1053/bbmt.2002.v8.pm12171483
DO - 10.1053/bbmt.2002.v8.pm12171483
M3 - Article
C2 - 12171483
AN - SCOPUS:0036049672
SN - 1083-8791
VL - 8
SP - 368
EP - 376
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 7
ER -