Transplantation of ex vivo expanded cord blood cells using the copper chelator tetraethylenepentamine: a phase I/II clinical trial.
The copper chelator tetraethylenepentamine (TEPA; StemEx) was shown to attenuate the differentiation of ex vivo cultured hematopoietic cells resulting in preferential expansion of early progenitors. A phase I/II trial was performed to test the feasibility and safety of transplantation of CD133+ cord blood (CB) hematopoietic progenitors cultured in media containing stem cell factor, FLT-3 ligand, interleukin-6, thrombopoietin and TEPA. Ten patients with advanced hematological malignancies were transplanted with a CB unit originally frozen in two fractions. The smaller fraction was cultured ex vivo for 21 days and transplanted 24 h after infusion of the larger unmanipulated fraction. All but two units contained <2 x 10(7) total nucleated cells (TNCs) per kilogram pre-expansion. All donor-recipient pairs were mismatched for one or two HLA loci. Nine patients were beyond first remission; median age and weight were 21 years and 68.5 kg. The average TNCs fold expansion was 219 (range, 2-620). Mean increase of CD34+ cell count was 6 (over the CD34+ cell content in the entire unit). Despite the low TNCs per kilogram infused (median=1.8 x 10(7)/kg), nine patients engrafted. Median time to neutrophil and platelet engraftment was 30 (range, 16-46) and 48 (range, 35-105) days. There were no cases of grades 3-4 acute graft-versus-host disease (GVHD) and 100-day survival was 90%. This strategy is feasible.
de Lima
M
M
Department of Stem Cell Transplantation and Cell Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA. mdelima@mdanderson.org
McMannis
J
J
Gee
A
A
Komanduri
K
K
Couriel
D
D
Andersson
B S
BS
Hosing
C
C
Khouri
I
I
Jones
R
R
Champlin
R
R
Karandish
S
S
Sadeghi
T
T
Peled
T
T
Grynspan
F
F
Daniely
Y
Y
Nagler
A
A
Shpall
E J
EJ
D000293:Adolescent; D000328:Adult; D000943:Antigens, Differentiation / Q000378:metabolism; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology*; D002648:Child; D003300:Copper; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D018572:Disease-Free Survival; D005029:Ethylenediamines / Q000494:pharmacology*; D005260:Female; D005312:Fetal Blood; D006085:Graft Survival; D019337:Hematologic Neoplasms / Q000628:therapy; D006412:Hematopoietic Stem Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014019:Tissue Donors
D000943:Antigens, Differentiation; D002614:Chelating Agents; D005029:Ethylenediamines; D003300:Copper; C034269:tetraethylenepentamine