TY - JOUR
T1 - Long-term follow-up of patients with breast cancer transplanted with autologous ex vivo expanded peripheral blood progenitor cells
AU - Gutman, Jonathan A.
AU - Shpall, Elizabeth J.
AU - Nieto, Yago
AU - McSweeney, Peter
AU - McNiece, Ian
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006
Y1 - 2006
N2 - Ex vivo expanded peripheral blood progenitor cells (PBPC) have been shown to provide rapid neutrophil engraftment, and in some patients, to eliminate neutropenia after transplantation to support high-dose chemotherapy. However, the effect of expansion culture on stem cell content and potential loss of stem cells caused by induction of differentiation remains a concern. We have transplanted 21 patients with breast cancer with expanded autologous PBPC, with 11 patients receiving expanded PBPC as their sole hematopoietic cell source. In these studies, the CD34+ cells were selected and cultured for 10 days in defined media containing 100 ng/mL each of recombinant human stem cell factor (rhSCF), recombinant human granulocyte colony stimulating factor (rhG-CSF), and recombinant human megakaryocyte growth and developmental factor (rhMGDF) in 1-liter Teflon bags at 20,000 to 50,000 cells/mL. After culture the cells were washed and reinfused after high-dose chemotherapy followed by daily administration of rhG-CSF. Engraftment of neutrophils (absolute neutrophil count [ANC] > 500/μL) occurred in a median of 8 days (range, 4 to 16), with 7 patients engrafting neutrophils in 8 days or less. Of the 11 patients transplanted with only expanded cells, 9 remained alive at more than 24 months, and all had durable engraftment; neutrophil and platelet levels remained stable. At 5 years posttransplant 7 of 11 (64%) patients are alive with no evidence of disease, 2 of 11 (18%) patients have relapsed, and 2 of 11 (18%) patients have died as a result of progressive disease. Late graft failure did not occur in any patients. Because the chemotherapy regimens were myeloablative but may not be stem cell ablative, it is possible that the long-term cell production in these patients resulted from endogenous recovery of stem cells. This study suggests that it is feasible to transplant patients with ex vivo expanded PBPC as the sole autologous hematopoietic support. The expanded products provide (1) rapid neutrophil engraftment, (2) sufficient progenitor cells to bridge the time until stem cells repopulate the hematopoietic system, and (3) possibly sufficient stem cells to enable long-term cell production.
AB - Ex vivo expanded peripheral blood progenitor cells (PBPC) have been shown to provide rapid neutrophil engraftment, and in some patients, to eliminate neutropenia after transplantation to support high-dose chemotherapy. However, the effect of expansion culture on stem cell content and potential loss of stem cells caused by induction of differentiation remains a concern. We have transplanted 21 patients with breast cancer with expanded autologous PBPC, with 11 patients receiving expanded PBPC as their sole hematopoietic cell source. In these studies, the CD34+ cells were selected and cultured for 10 days in defined media containing 100 ng/mL each of recombinant human stem cell factor (rhSCF), recombinant human granulocyte colony stimulating factor (rhG-CSF), and recombinant human megakaryocyte growth and developmental factor (rhMGDF) in 1-liter Teflon bags at 20,000 to 50,000 cells/mL. After culture the cells were washed and reinfused after high-dose chemotherapy followed by daily administration of rhG-CSF. Engraftment of neutrophils (absolute neutrophil count [ANC] > 500/μL) occurred in a median of 8 days (range, 4 to 16), with 7 patients engrafting neutrophils in 8 days or less. Of the 11 patients transplanted with only expanded cells, 9 remained alive at more than 24 months, and all had durable engraftment; neutrophil and platelet levels remained stable. At 5 years posttransplant 7 of 11 (64%) patients are alive with no evidence of disease, 2 of 11 (18%) patients have relapsed, and 2 of 11 (18%) patients have died as a result of progressive disease. Late graft failure did not occur in any patients. Because the chemotherapy regimens were myeloablative but may not be stem cell ablative, it is possible that the long-term cell production in these patients resulted from endogenous recovery of stem cells. This study suggests that it is feasible to transplant patients with ex vivo expanded PBPC as the sole autologous hematopoietic support. The expanded products provide (1) rapid neutrophil engraftment, (2) sufficient progenitor cells to bridge the time until stem cells repopulate the hematopoietic system, and (3) possibly sufficient stem cells to enable long-term cell production.
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U2 - 10.1089/cpt.2006.4.4
DO - 10.1089/cpt.2006.4.4
M3 - Article
AN - SCOPUS:33748762231
SN - 1538-344X
VL - 4
SP - 4
EP - 8
JO - Cell Preservation Technology
JF - Cell Preservation Technology
IS - 1
ER -