Transplantation of umbilical cord blood after myeloablative therapy: analysis of engraftment.
The possibility that umbilical cord and placental blood from an HLA-identical sibling might produce stable donor-derived lymphohematopoietic engraftment was tested in a patient with juvenile chronic myelogenous leukemia (JCML). After conditioning with high-dose busulfan and cyclophosphamide, cryopreserved umbilical cord blood, containing 0.5 x 10(8) nucleated cells/kg and 2.7 x 10(4) colony forming units-granulocyte, macrophage (CFU-GM)/kg, was infused. A leukocyte count greater than 1,000/microL, absolute neutrophil count (ANC) greater than 500/microL, and platelet count greater than 20,000/microL (untransfused) were observed on days 39, 39, and 47 after transplantation, respectively. Donor cell engraftment was documented in the peripheral blood and bone marrow by cytogenetic analysis, restriction fragment length polymorphism (RFLP), and polymerase chain reaction (PCR) as early as day 21. Furthermore, the donor origin of each lymphohematopoietic lineage (ie, CD5+ T cells, CD19/20+ B cells, CFU-GM, and burst-forming unit-erythrocyte [BFU-E]) was confirmed. On day 200, assays of the peripheral blood and bone marrow showed an abnormal proliferation of CFU-GM at low seeding densities in the absence of exogenous growth factors, as well as a hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF), both pathophysiologic characteristics of JCML. Recurrent disease was confirmed histologically on day 225. Together, these results demonstrate that umbilical cord blood contains sufficient numbers of hematopoietic stem cells necessary for the engraftment of leukemia patients treated with myeloablative therapy and that the detection of "spontaneous" CFU-GM and hypersensitivity to GM-CSF after treatment is a marker of residual or recurrent disease in patients with JCML.
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD.
J E
JE
Wagner
H E
HE
Broxmeyer
R L
RL
Byrd
B
B
Zehnbauer
B
B
Schmeckpeper
N
N
Shah
C
C
Griffin
P D
PD
Emanuel
K S
KS
Zuckerman
S
S
Cooper
D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology; D002066:Busulfan / Q000627:therapeutic use; D002455:Cell Division; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000627:therapeutic use; D005312:Fetal Blood / Q000166:cytology*; D006098:Granulocytes / Q000473:pathology; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000628:therapy*; D007958:Leukocyte Count; D008264:Macrophages / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009504:Neutrophils; D010976:Platelet Count
D003520:Cyclophosphamide; D002066:Busulfan