Contamination of autologous peripheral blood progenitor cell grafts predicts overall survival after high-dose chemotherapy in multiple myeloma

BACKGROUND: Despite of the introduction of novel treatment modalities for multiple myeloma, high-dose chemotherapy with hematopoietic stem-cell rescue is still considered the standard of care for eligible patients <65 years of age. As we have previously reported, stem-cell grafts regularly contain quantities of plasma cells measurable by flow cytometry. However, the pathogenetic significance of this finding remains unknown.

METHODS: Multiple myeloma patients (n = 60) were mobilized with chemotherapy and filgrastim. Peripheral blood stem cell grafts were obtained by standard leukapheresis, and the number of CD38++/CD138+ cells/kg was determined by flow cytometry. Plasma cell contamination above a threshold of 4.5 x 10(5) plasma cells/kg was considered "high", whereas lower quantities of plasma cells or absent plasma cells in the graft were considered "low".

RESULTS: Progression-free survival: the median statistical progression-free survival was 33.5 months (range 11-99 months) in the high-contamination group (n = 16) versus 47 months (range 8-148 months) in the low-contamination group (n = 44). This difference turned out not to be statistically significant (P = 0.15). However, the difference was highly significant regarding overall survival with 53 months (range 11-119 months) in the high-contamination group and with 114 months (range 8-158 months) in the low-contamination group (P = 0.012).

CONCLUSIONS: Patients with >4.5 x 10(5) plasma cells/kg contaminating the peripheral blood stem cell graft received after high-dose chemotherapy have a significantly reduced overall survival. Whether high contamination of grafts with plasma cells might reflect residual in vivo tumor mass prior to stem cell transplantation and a generally more aggressive behavior of malignant myeloma cells in these patients, or whether reinfused plasma cells contribute to an unfavorable course of disease remains to be determined.