THE HEMATOPOIETIC STEM-CELL ANTIGEN, CD34, IS NOT EXPRESSED ON THE MALIGNANT-CELLS IN MULTIPLE-MYELOMA

Autologous stem cell transplantation has become an important therapy i n multiple myeloma (MM). To develop adequate autograft purging methods , it is necessary to determine whether antigens expressed on early hem atopoietic progenitors exist on malignant cells. The Ig heavy chain pr oduced by the MM cells shows evidence of prior somatic mutation withou t intraclonal diversity. As a result, this sequence can be used as a s pecific marker to detect all members of the malignant clone. The Ig he avy chain sequence expressed by the MM cells was obtained in five pati ents with advanced disease. Patient specific oligonucleotide primers w ere designed based on the complementarity determining regions (CDR) of each MM Ig sequence and used to amplify DNA by polymerase chain react ion for the detection of malignant cells. A highly purified collection of CD34(+) cells was obtained after passage of the initial bone marro w cells through an immunoadsorption column and fluorescence-activated cell sorting. Despite an assay sensitivity of 1 tumor cell in 2,500 to 44,000 normal cells, none of the CD34(+) samples showed product with the myeloma-specific CDR primers. Therefore, positive selection for ce lls bearing this antigen should yield a tumor-free autograft capable o f providing hematopoietic recovery after myeloablative chemotherapy. ( C) 1994 by The American Society of Hematology.