Morphologic, immunophenotypic and in vitro growth characteristics of blood and bone marrow associated with stem cell mobilisation in patients with lymphoma.
The proportion of CD34+ cells in the bone marrow (BM) is predictive of the size of progenitor cell mobilisation into the blood (PB). To investigate which other PB and BM parameters may be related to mobilisation, we analysed at steady state PB and BM of 23 patients with relapsed or resistant lymphoma before administering high-dose cyclophosphamide and G-CSF Cell morphology, number of CD34+ cells, and growth in clonogenic assay and in long-term cultures (LTC) were determined and then correlated with mobilisation extent (CD34+ and GM-CFC) and quality (growth of harvested cells in LTC). We found that the good mobilising patients (CD34 > 50 x 10(3)/ml, n=10) had several baseline BM characteristics (number of CD34+ MNC, GM-CFC, BFU-E, production of CFCs in LTC) similar to a group of 12 healthy controls, while patients with reduced mobilisation (CD34 < 50 x 10(3)/ml, n=13) had clearly reduced BM progenitors and LTC growth (p< 0.05). In a multivariate analysis including baseline clinical, blood and bone marrow characteristics, the most significant PB and BM factors independently associated with a higher number and/or quality of mobilised cells were a higher number of CD34+ and GM-CFC in the BM and a higher baseline haemoglobin, platelet, and CD34+ blood count. The capacity to release progenitor cells into the circulation is therefore not predicted by the distribution of morphologically distinguishable cells, marginally predicted by the BM content of highly undifferentiated cells (growth in long term culture), while it is proportional to the number of BM progenitors (CD34+, GM-CFC and BFU-E).
Ghielmini
M
M
Istituto Oncologico della Svizzera Italiana, Ospedale S. Giovanni, Bellinzona, Switzerland.
Marangoni
G
G
Pampallona
S
S
Tamasy
P
P
Cavalli
F
F
D000328:Adult; D000818:Animals; D001772:Blood Cell Count; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008223:Lymphoma / Q000097:blood / Q000473:pathology* / Q000628:therapy; D008297:Male; D051379:Mice; D008875:Middle Aged; D010976:Platelet Count; D011446:Prospective Studies; D016879:Salvage Therapy; D017154:Stromal Cells / Q000166:cytology; D014019:Tissue Donors
D006454:Hemoglobins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide