Transplantation of umbilical cord blood after myeloablative therapy: Analysis of engraftment

J. E. Wagner, H. E. Broxmeyer, R. L. Byrd, B. Zehnbauer, B. Schmeckpeper, N. Shah, C. Griffin, P. D. Emanuel, K. S. Zuckerman, S. Cooper, C. Carow, W. Bias, G. W. Santos

Research output: Contribution to journalArticle

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Abstract

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 108 nucleated cells/kg and 2.7 x 104 colony forming units-granulocyte, macrophage (CFU-GM)/kg, was infused. A leukocyte count greater than 1,000/μL, absolute neutrophil count (ANC) greater than 500/μL, and platelet count greater than 20,000/μL (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.

Original languageEnglish (US)
Pages (from-to)1874-1881
Number of pages8
JournalBlood
Volume79
Issue number7
StatePublished - Jan 1 1992

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Granulocyte-Macrophage Progenitor Cells
Juvenile Myelomonocytic Leukemia
Fetal Blood
Macrophages
Blood
Transplantation
Tissue Donors
Granulocyte-Macrophage Colony-Stimulating Factor
Hypersensitivity
Bone Marrow
Bone
Busulfan
Cytogenetic Analysis
Therapeutics
Hematopoietic Stem Cells
Platelet Count
Leukocyte Count
Restriction Fragment Length Polymorphisms
T-cells
Cyclophosphamide

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Wagner, J. E., Broxmeyer, H. E., Byrd, R. L., Zehnbauer, B., Schmeckpeper, B., Shah, N., ... Santos, G. W. (1992). Transplantation of umbilical cord blood after myeloablative therapy: Analysis of engraftment. Blood, 79(7), 1874-1881.

Transplantation of umbilical cord blood after myeloablative therapy : Analysis of engraftment. / Wagner, J. E.; Broxmeyer, H. E.; Byrd, R. L.; Zehnbauer, B.; Schmeckpeper, B.; Shah, N.; Griffin, C.; Emanuel, P. D.; Zuckerman, K. S.; Cooper, S.; Carow, C.; Bias, W.; Santos, G. W.

In: Blood, Vol. 79, No. 7, 01.01.1992, p. 1874-1881.

Research output: Contribution to journalArticle

Wagner, JE, Broxmeyer, HE, Byrd, RL, Zehnbauer, B, Schmeckpeper, B, Shah, N, Griffin, C, Emanuel, PD, Zuckerman, KS, Cooper, S, Carow, C, Bias, W & Santos, GW 1992, 'Transplantation of umbilical cord blood after myeloablative therapy: Analysis of engraftment', Blood, vol. 79, no. 7, pp. 1874-1881.
Wagner JE, Broxmeyer HE, Byrd RL, Zehnbauer B, Schmeckpeper B, Shah N et al. Transplantation of umbilical cord blood after myeloablative therapy: Analysis of engraftment. Blood. 1992 Jan 1;79(7):1874-1881.
Wagner, J. E. ; Broxmeyer, H. E. ; Byrd, R. L. ; Zehnbauer, B. ; Schmeckpeper, B. ; Shah, N. ; Griffin, C. ; Emanuel, P. D. ; Zuckerman, K. S. ; Cooper, S. ; Carow, C. ; Bias, W. ; Santos, G. W. / Transplantation of umbilical cord blood after myeloablative therapy : Analysis of engraftment. In: Blood. 1992 ; Vol. 79, No. 7. pp. 1874-1881.
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abstract = "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 108 nucleated cells/kg and 2.7 x 104 colony forming units-granulocyte, macrophage (CFU-GM)/kg, was infused. A leukocyte count greater than 1,000/μL, absolute neutrophil count (ANC) greater than 500/μL, and platelet count greater than 20,000/μL (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.",
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