Ex vivo expansion of megakaryocyte precursor cells in autologous stem cell transplantation for relapsed malignant lymphoma.
To evaluate the impact of ex vivo expanded megakaryocyte (MK) progenitors on high-dose chemotherapy-induced thrombocytopenia, we conducted a phase II study in 10 patients with relapsed lymphoma. Two fractions of peripheral blood progenitor cells (PBPC) were cryopreserved, one with enough cells for at least 2 x 10(6) CD34+ cells/kg and a second obtained after CD34+ selection. Ten days before autologous stem cell transplantation, the CD34+ fraction was cultured with MGDF+SCF for 10 days. After BEAM (BCNU, cyclophosphamide, cytarabine, and melphalan) chemotherapy, patients were reinfused with standard PBPC and ex vivo expanded cells. No toxicity was observed after reinfusion. The mean fold expansion was 9.27 for nucleated cells, 2 for CD34+ cells, 676 for CD41+ cells, and 627 for CD61+ cells. The median date of platelet transfusion independence was day 8 (range: 7-12). All patients received at least one platelet transfusion. In conclusion, ex vivo expansion of MK progenitors was feasible and safe, but this procedure did not prevent BEAM-induced thrombocytopenia. Future studies will determine if expansion of higher numbers of CD34+ cells towards the MK-differentiation pathway will translate into a functional effect in terms of shortening of BEAM-induced thrombocytopenia.
Department of Clinical Hematology, Institut Curie, Paris, France.
D
D
Decaudin
J-M
JM
Vantelon
J-H
JH
Bourhis
F
F
Farace
M-L
ML
Bonnet
M
M
Guillier
N
N
Greissenger
M-C
MC
Marracho
S
S
Assari
A-L
AL
Bennaceur
F
F
Némati
J
J
Michon
A G
AG
Turhan
C
C
Boccaccio
D018952:Antigens, CD34 / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use / Q000633:toxicity; D002330:Carmustine / Q000008:administration & dosage; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000187:drug effects / Q000637:transplantation; D006801:Humans; D039661:Integrin beta3 / Q000032:analysis; D008223:Lymphoma / Q000150:complications / Q000628:therapy; D008533:Megakaryocytes / Q000166:cytology* / Q000637:transplantation; D008558:Melphalan / Q000008:administration & dosage; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D040201:Platelet Membrane Glycoprotein IIb / Q000032:analysis; D017713:Platelet Transfusion; D016879:Salvage Therapy; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control; D013926:Thrombopoietin / Q000494:pharmacology; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D018952:Antigens, CD34; D039661:Integrin beta3; D040201:Platelet Membrane Glycoprotein IIb; D003561:Cytarabine; D003520:Cyclophosphamide; D013926:Thrombopoietin; D008558:Melphalan; D002330:Carmustine