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Transplantation of enriched and purged peripheral blood progenitor cells
from a single apheresis product in patients with non-Hodgkin's lymphoma
RS Negrin, CR Kusnierz-Glaz, BJ Still, JR Schriber, NJ Chao, GD Long, C Hoyle, WW Hu, SJ Horning and BW Brown
Department of Medicine, Stanford University School of Medicine, CA, USA.
High-dose chemotherapy with or without radiotherapy followed by autologous
transplantation of hematopoietic progenitor cells is an effective treatment
for patients with high-risk or relapsed non- Hodgkin's lymphoma.
Chemotherapy and/or hematopoietic growth factors have been used to mobilize
progenitor cells in the peripheral blood for transplantation. However, the
mobilized blood cell products have been found to be frequently contaminated
with tumor cells, and techniques have not been developed to purge tumor
cells from these products. In addition, the minimum number of hematopoietic
progenitor cells required for engraftment has not yet been fully
elucidated. We treated 21 patients with a single infusion of
cyclophosphamide (4 g/m2) followed by daily administration of granulocyte
colony-stimulating factor (G- CSF). After recovery of the white blood cell
count, a single 3-hour apheresis collection was performed. The apheresis
product was then applied to a discontinuous Percoll gradient. The
low-density fractions resulting from this separation procedure were
enriched for CD34+ progenitor cells (total cell yield, 19.5%; CD34+ cell
recovery, 81.2%). These enriched cellular products were treated with a
panel of anti-B cell or anti-T cell monoclonal antibodies and complement in
an effort to remove residual tumor cells. After treatment of the patient
with myeloablative therapies, the enriched and purged cells were reinfused.
Hematologic recovery was rapid, with median neutrophil engraftment in 10
days [absolute neutrophil count (ANC), greater than 0.5 x 10(9)/L] and 11
days (ANC, greater than 1.0 x 10(9)/L). Median platelet transfusion
independence required 13 days. The rapidity of multilineage engraftment
correlated with the number of CD34+ cells per kilogram that were infused.
Patients who received more than 2 x 10(6) CD34+ cells per kilogram had
rapid hematologic engraftment, whereas those patients transplanted with
less than 2 x 10(6) CD34+ cells per kilogram had slower platelet recovery.
Modeling studies using a lymphoma cell line with a t(14; 18) chromosomal
translocation demonstrated the successful removal of tumor cells assayed
using the polymerase chain reaction (PCR) after the processing and purging.
Four of the 21 patients had PCR- detectable lymphoma cells in the bone
marrow and peripheral blood; however, the enriched and purged blood
products reinfused in all four did not contain detectable tumor
cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Volume 85,
Issue 11,
pp. 3334-3341,
06/01/1995
Copyright © 1995 by The American Society of Hematology
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