Expression of adhesion molecules on CD34+ cells: CD34+ L-selectin+ cells predict a rapid platelet recovery after peripheral blood stem cell transplantation.
Adhesion molecules play a role in the migration of hematopoietic progenitor cells and regulation of hematopoiesis. To study whether the mobilization process is associated with changes in expression of adhesion molecules, the expression of CD31, CD44, L-selectin, sialyl Lewisx, beta 1 integrins very late antigen 4 (VLA-4) and VLA-5, and beta 2 integrins lymphocyte function-associated 1 and Mac-1 was measured on either bone marrow (BM) CD34+ cells or on peripheral blood CD34+ cells mobilized with a combination of granulocyte colony-stimulating factor (G-CSF) and chemotherapy. beta 1 integrin VLA-4 was expressed at a significantly lower concentration on peripheral blood progenitor cells than on BM CD34+ cells, procured either during steady-state hematopoiesis or at the time of leukocytapheresis. No differences in the level of expression were found for the other adhesion molecules. To obtain insight in which adhesion molecules may participate in the homing of peripheral blood stem cells (PBSCs), the number of CD34+ cells expressing these adhesion molecules present in leukocytapheresis material was quantified and correlated with hematopoietic recovery after intensive chemotherapy in 27 patients. The number of CD34+ cells in the subset defined by L-selectin expression correlated significantly better with time to platelet recovery after PBSC transplantation (r = -.86) than did the total number of CD34+ cells (r = -.55). Statistical analysis of the relationship between the number of CD34+L-selectin+ cells and platelet recovery resulted in a threshold value for rapid platelet recovery of 2.1 x 10(6) CD34+ L-selectin+ cells/kg. A rapid platelet recovery (< or = 14 days) was observed in 13 of 15 patients who received > or = 2.1 x 10(6) CD34+ L-selectin+ cells/kg (median, 11 days; range, 7 to 16 days), whereas 10 of 12 patients who received less double positive cells had a relative slow platelet recovery (median, 20 days; range, 13 to 37 days). The L-selectin+ subpopulation of CD34+ cells also correlated better with time to neutrophil recovery (r = -.70) than did the total number of reinfused CD34+ cells (r = -.51). However, this latter difference failed to reach statistical significance. This study suggests that L-selectin is involved in the homing of CD34+ cells after PBSC transplantation.
Dercksen
M W
MW
European Cancer Centre, Amsterdam, The Netherlands.
Gerritsen
W R
WR
Rodenhuis
S
S
Dirkson
M K
MK
Slaper-Cortenbach
I C
IC
Schaasberg
W P
WP
Pinedo
H M
HM
von dem Borne
A E
AE
van der Schoot
C E
CE
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D016190:Carboplatin / Q000008:administration & dosage; D002330:Carmustine / Q000008:administration & dosage; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015870:Gene Expression; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D019041:L-Selectin; D007958:Leukocyte Count; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000628:therapy; D009504:Neutrophils; D010976:Platelet Count; D011034:Podophyllotoxin / Q000008:administration & dosage; D016029:Receptors, Very Late Antigen / Q000096:biosynthesis / Q000502:physiology*; D013852:Thiotepa / Q000008:administration & dosage
D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D016029:Receptors, Very Late Antigen; D003561:Cytarabine; D019041:L-Selectin; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D005047:Etoposide; D003520:Cyclophosphamide; D013852:Thiotepa; D016190:Carboplatin; D011034:Podophyllotoxin; D008558:Melphalan; D005472:Fluorouracil; D002330:Carmustine; D007069:Ifosfamide