Reduced bone marrow stem cell pool and progenitor mobilisation in multiplemyeloma after melphalan treatment

The content of stem cells was analysed in bone marrow samples from 75 multi ple myeloma patients. In unstimulated bone marrow the percentage of CD34+ c ells was significantly reduced in 11 patients previously treated with melph alan-prednisolone (MP)(median = 0.15%) compared to median 0.87% in 31 untre ated patients (P = 0.0001). The bone marrow cellularity in the two groups d id not differ. There was no correlation between the number of courses or to tal dose of melphalan and content of CD34+ cells in the bone marrow. The cl onogenicity as well as the ability to expand the marrow stem cell pool duri ng growth factor treatment were also reduced in MP treated patients compare d to untreated patients. Analysis of different subsets of CD34+ cells revea led no influence on the pre B cell compartment in the bone marrow by MP tre atment, but the committed stem cells (CD34+CD38+) were reduced more than th e uncommitted stem cells (CD34+CD38-) in the MP treated group compared to t he untreated patients, Mobilisation to and harvest of total number of CD34 cells from peripheral blood was also reduced in the MP treated group. Ther e was, however, no difference in the distribution between CD34+CD38+ and CD 34+CD38- populations in the leukapheresis products in the untreated and the melphalan-treated group, suggesting selective mobilisation of CD34+CD38+ c ells and/or differentiation of CD34+CD38- cells during growth factor stimul ation. We conclude that melphalan decreased the number of stem cells in the bone m arrow, the ability to expand the stem cell pool and mobilise stem cells to the pheripheral blood.