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/l 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, 4x10(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.
Department of Cellular Biotechnology and Haematology, University La Sapienza, Rome, Italy.
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Sala
F R
FR
Mauro
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Bellucci
M S
MS
De Propris
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I
Cordone
A
A
Lisci
R
R
Foà
P
P
de Fabritiis
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells / Q000166:cytology; D003114:Colony-Forming Units Assay; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000188:drug therapy*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
D018952:Antigens, CD34; D000970:Antineoplastic Agents; D014740:Vidarabine; C024352:fludarabine