Immunologic purging of autologous peripheral blood stem cell products based on CD34 and CD133 expression can be effectively and safely applied in half of the acute myeloid leukemia patients.
OBJECTIVE
Several studies have shown survival benefit by autologous stem cell transplantation in acute myeloid leukemia (AML) after purging of grafts. This has, however, not been confirmed in randomized studies due to high toxicity of purging modalities for normal progenitor/stem cells. In this study, we investigated whether positive selection for CD34+ and/or CD133+ cells, which results in high recovery of normal progenitor/stem cells, is applicable for purging AML grafts.


METHODS
Positive selections of normal stem cells using CD34 and/or CD133 can be done if one or both markers are absent or have dim expression and remain so during the course of the disease. Marker expressions in newly diagnosed AML were measured with flow cytometry using a cutoff value for positivity of 1%. Stability of marker expression was studied by pairwise comparison of material at diagnosis and relapse. Leukemia associated phenotype expression was used to measure the efficacy of tumor cell reduction.


RESULTS
In newly diagnosed AML (n = 165), we found no CD34 and/or CD133 expression in 32% of the cases and dim expression in 20% of the cases. No increase in the percentage of CD34+ cells (n = 44) and CD133+ cells (n = 29) was found in corresponding relapses. Positive selection using grafts contaminated with AML blasts, showing either no or dim expression of CD34 or CD133, resulted in a 3 to 4 log tumor cell reduction (n = 11) with median 50% recovery of normal stem cells.


CONCLUSIONS
Purging by positive selection of CD34+ and/or CD133+ cells can safely, effectively, and reproducibly be applied in about 50% of AML cases.
Department of Hematology, VU University Medical Center, Amsterdam, the Netherlands.
Nicole
N
Feller
Marjolein A
MA
van der Pol
Taco
T
Waaijman
Geert W D
GW
Weijers
Guus
G
Westra
Gert J
GJ
Ossenkoppele
Gerrit J
GJ
Schuurhuis
D000071916:AC133 Antigen; D000208:Acute Disease; D015703:Antigens, CD / Q000276:immunology*; D018952:Antigens, CD34 / Q000276:immunology*; D016465:Bone Marrow Purging / Q000379:methods*; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology / Q000628:therapy*; D017493:Leukocyte Common Antigens / Q000276:immunology; D016256:Lewis X Antigen / Q000276:immunology; D008297:Male; D010455:Peptides / Q000276:immunology*; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D016896:Treatment Outcome
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; D016256:Lewis X Antigen; C000606023:PROM1 protein, human; D010455:Peptides; D017493:Leukocyte Common Antigens