Clinical and molecular follow-up by amplification of the CDR-III IgH region in multiple myeloma patients after autologous transplantation of hematopoietic CD34(+) stem cells

Background and Objective. Autologous blood stem cell transplantation (ABSCT ) using chemotherapy-induced mobilization of peripheral blood stem cells (P BSC) is being increasingly used in the treatment of multiple myeloma (MM). We report the clinical and molecular follow-up of 10 MM patients who underw ent autologous stem cell transplantation with peripheral blood selected CD3 4(+) cells, as support therapy following a myeloablative conditioning regim en. Design and Methods. The CDR-III coding region of the IgH gene was studied b y a) consensus PCR applied to 8 MM patients, or b) by direct sequencing of PCR product generated by family-specific primers in the remaining two patie nts (who became immunofixation analysis (IF) negative). in this case, two p atient-specific primers were generated, thus obtaining a high PCR assay sen sitivity and specificity (ASO PCR). Results. Seven patients are alive: 4 of them have serum M protein assessabl e by IF, while 1 was not a secretor and 2 converted from serum IF positivit y to negativity 6 and 12 months after ABSCT. Three patients died: 1 from di sease progression and 2 from infective complications during clinical remiss ion. The molecular analysis during the follow-up showed that the bone marro w samples from the two patients who obtained IF negativity were persistentl y PCR positive for the presence of rearranged con-III region. More over, de spite the remarkable reduction of myeloma burden, a minimal level of residu al myeloma cells was still detectable by molecular analysis. Interpretation and Conclusions. These results confirm that although positiv e selection of CD34(+) cells markedly reduces the contamination of myeloma cells from apheresis products by up to 3 log, and provides a cell suspensio n capable of restoring normal hematopoiesis after ablative conditioning reg imen, it does not abrogate myeloma cell contamination in most of the aphere sis products. (C)1999, Ferrata Storti Foundation.