BONE-MARROW VERSUS PERIPHERAL-BLOOD PROGENITOR CELLS CD34 SELECTION IN PATIENTS WITH NON-HODGKINS-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 re infused tumor cells contaminating the grafts on the determination of p ostautograft relapses remains unclear, the major interest of CD34(+) c ell selection is to reduce the tumor contamination of the graft. This can be achieved if tumor cells do not express the CD34 antigen. We pre viously showed that this approach was effective with bone marrow (BM) collections in patients with non-Hodgkin's lymphoma (NHL). Because per ipheral blood progenitor cells (PBPC) allow faster hematologic recover y than BM and are expected to contain less tumor contamination, we hav e 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 c hemotherapy followed by granulocyte colony-stimulating factor (G-CSF) administration. The data showed that the final CD34(+) cell purity ach ieved 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 patie nts (22 BM, 16 PBPC). In addition, immunoglobulin heavy chain gene (Ig H) rearrangements were investigated using PCR with consensus IgH prime rs. 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 har vesting. However, because lymphoma tissue specimens from patients at d iagnosis were not available, the malignant character of IgH rearrangem ents could not be confirmed by sequencing and probing with allele-spec ific nucleotides. After CD34(+) cell selection, a reduction to below t he level of detection of BCL2/JH(+) cells of BM and PBPC was effective in seven of 12 informative selections. In contrast, a reduction to be low the level of detection of abnormal IgH(+) cells was effective in o nly three of 15 informative selections. However, the detection of cell s with an abnormal IgH pattern in the context of chemotherapy plus G-C SF progenitor mobilization in patients with NHL and its correlation wi th actual tumor contamination needs further investigation. (C) 1997 by The American Society of Hematology.