Quantitation of primitive and lineage-committed progenitors in mobilized peripheral blood for prediction of platelet recovery post autologous transplant.
Leukapheresis collections obtained following one of four mobilization regimens from 90 cancer patients were analyzed for their content of various progenitor cell types including erythroid and granulopoietic colony-forming cells in methylcellulose (total CFC), CFC-megakaryocyte (CFC-Mk), CFC detected after 10, 35 and 56 days in long-term culture (LTC), and total CD34+ cells. The number of each of these progenitor cell types collected from individual patients varied over 1000-fold. Nevertheless, within an individual leukapheresis, there was a significant correlation between the number of CD34+ cells and each progenitor type (except day 56 LTC CFC) suggesting that all of them are mobilized by a common mechanism. Patients who had previously received extensive chemotherapy and/or radiotherapy mobilized fewer of all these cell types than those who had not. For the 65 patients who proceeded to autologous transplantation, the median times to an absolute neutrophil count (ANC) of > or =0.5 x 109/l and the last platelet transfusion post transplant were 13 and 11 days, respectively, with 14 (22%) of patients having platelet recovery delayed beyond day 21. There was no significant difference between patients who had or had not received extensive chemo/radiotherapy or among the different mobilization regimens for time to neutrophil or platelet recovery or the number of platelet or red blood cell transfusions received post transplant. Threshold doses of the different cell types transplanted (per kg of patient weight) which predicted rapid platelet recovery were 2 x 106 CD34+ cells, 5 x 105 total CFC and 2.5 x 104CFC-Mk. Corresponding thresholds for progenitor activity measured in LTC could not be established. These results further support the view that standard mobilization regimens yield progenitor numbers that are, in most cases, nonlimiting for generating neutrophil and platelet recoveries within 2 to 3 weeks after myeloablative therapy. Assessment of the CD34+ cell and/or CFC content of leukapheresis collections may identify patients in whom platelet recovery is likely to be significantly delayed although CFC-Mk enumeration does not appear to offer any unique predictive advantage.
Hogge
D E
DE
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, Canada.
Lambie
K
K
Sutherland
H J
HJ
Benny
W B
WB
Dalal
B
B
Currie
C
C
Barnett
M J
MJ
Eaves
A C
AC
Eaves
C J
CJ
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000097:blood / Q000187:drug effects; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007377:Interleukin-3 / Q000008:administration & dosage; D007937:Leukapheresis; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D017713:Platelet Transfusion; D011379:Prognosis; D012737:Sex Factors; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects*; D013997:Time Factors; D014182:Transplantation, Autologous
D018952:Antigens, CD34; D007166:Immunosuppressive Agents; D007377:Interleukin-3; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide