Bone marrow versus peripheral blood progenitor cells CD34 selection in patients with non-Hodgkin's lymphomas: different levels of tumor cell reduction. Implications for autografting.
Human CD34+ selected cells are able to reconstitute hematopoiesis in patients receiving a myeloablative treatment. Although the role of reinfused tumor cells contaminating the grafts on the determination of postautograft relapses remains unclear, the major interest of CD34+ cell selection is to reduce the tumor contamination of the graft. This can be achieved if tumor cells do not express the CD34 antigen. We previously showed that this approach was effective with bone marrow (BM) collections in patients with non-Hodgkin's lymphoma (NHL). Because peripheral blood progenitor cells (PBPC) allow faster hematologic recovery than BM and are expected to contain less tumor contamination, we have compared the results of CD34+ cell selection in 35 BM and 16 PBPC from 48 patients with NHL. The PBPC were collected after a course of chemotherapy followed by granulocyte colony-stimulating factor (G-CSF) administration. The data showed that the final CD34+ cell purity achieved with PBPC was higher than with BM (medians, 70% v 50%; P = .02). The CD34+ cell recovery was also better for PBPC (medians, 42% v 24%; P = .001). Tumor contamination was assessed by detection of BCL2/JH rearrangement using polymerase chain reaction (PCR) in 38 of 48 patients (22 BM, 16 PBPC). In addition, immunoglobulin heavy chain gene (IgH) rearrangements were investigated using PCR with consensus IgH primers. At harvesting, 10 of 22 BM and two of 16 PBPC contained BCL2/JH+ cells, one of 22 BM and 14 of 16 PBPC contained abnormal IgH+ cells (one PBPC contained both BCL2/JH+ and abnormal IgH+ cells) at harvesting. However, because lymphoma tissue specimens from patients at diagnosis were not available, the malignant character of IgH rearrangements could not be confirmed by sequencing and probing with allele-specific nucleotides. After CD34+ cell selection, a reduction to below the level of detection of BCL2/JH+ cells of BM and PBPC was effective in seven of 12 informative selections. In contrast, a reduction to below the level of detection of abnormal IgH+ cells was effective in only three of 15 informative selections. However, the detection of cells with an abnormal IgH pattern in the context of chemotherapy plus G-CSF progenitor mobilization in patients with NHL and its correlation with actual tumor contamination needs further investigation.
Lopez
M
M
Inserm U76, CHU St-Antoine, Paris, France.
Lemoine
F M
FM
Firat
H
H
Fouillard
L
L
Laporte
J P
JP
Lesage
S
S
Isnard
F
F
Stachowiak
J
J
Ferrer-Le Coeur
F
F
Morel
P
P
Najman
A
A
Douay
L
L
Gorin
N C
NC
D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology*; D002469:Cell Separation / Q000379:methods*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry; D007144:Immunoglobulin J-Chains / Q000235:genetics; D016130:Immunophenotyping; D007937:Leukapheresis / Q000379:methods*; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D009360:Neoplastic Cells, Circulating; D014411:Neoplastic Stem Cells / Q000473:pathology*; D015514:Oncogene Proteins, Fusion; D016133:Polymerase Chain Reaction; D014182:Transplantation, Autologous
D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D007143:Immunoglobulin Heavy Chains; D007144:Immunoglobulin J-Chains; D015514:Oncogene Proteins, Fusion; D016179:Granulocyte Colony-Stimulating Factor