Evaluation of marrow and blood haemopoietic progenitors in chronic lymphocytic leukaemia before and after chemotherapy

We have evaluated the number and differentiation pattern of CD34 + cells as well as the CFU-GM, BFU-E and CFU-GEMM progenitors from the blood (PB) and marrow (BM) of 53 chronic lymphocytic leukaemia (CLL) patients Twenty-four patients were untreated and 29 were studied at 2 months from the last course of fludarabine or chlorambucil; 6 patients, studied after fludarabine therapy, were further evaluated after mobilization with cyclophosphamide and G-CSF. PB of untreated patients showed a median number of CD34 + cells, CFU-GM, BFU-E and CFU-GEMM/10 5 seeded cells and per litre of PB similar to those of normal controls No differences were also found in the number of clonogenic progenitors/10 5 cells in patients studied before and after therapy, while significantly fewer BFU-E/I of PB were found after fludarabine. The number of circulating CD34 + cells/l of PB was significantly lower in patients treated with fludarabine or chlorambucil compared to untreated patients BM growth was significantly reduced in untreated CLL patients compared to healthy donors Treatment with fludarabine or chlorambucil restored BM progenitors at levels similar to those of normal controls; this effect did not occur for CFU-GM in patients treated with fludarabine. Three-colour fluorescence analysis demonstrated a differentiation pattern of CD34 + cells with a greater expression of CD13 and CD33 after treatment with fludarabine compared to untreated patients and normal controls In 4 patients previously treated with fludarabine who underwent a successful cyclophosphamide and G-CSF mobilization therapy, 4×10 6 CD34 + cells/kg were collected. These 4 patients showed a notable increase of CD34 + cells and of clonogenic cells in the PB, but a marked decrease of BM progenitor cells. The 2 patients who failed CD34 + cell mobilization had a reduced CFU-GM growth both in the PB and in the BM. Taken together, these studies indicate that residual haemopoietic progenitors are present in untreated CLL patients and that stem cell mobilization and collection can be carried out following fludarabine treatment.