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Mobilization of peripheral blood progenitor cells by chemotherapy and
granulocyte-macrophage colony-stimulating factor for hematologic support
after high-dose intensification for breast cancer
AD Elias, L Ayash, KC Anderson, M Hunt, C Wheeler, G Schwartz, I Tepler, R Mazanet, C Lynch and S Pap
Department of Medicine, Dana-Farber Cancer Institute, Boston, MA.
High-dose therapy with autologous marrow support results in durable
complete remissions in selected patients with relapsed lymphoma and
leukemia who cannot be cured with conventional dose therapy. However,
substantial morbidity and mortality result from the 3- to 6-week period of
marrow aplasia until the reinfused marrow recovers adequate hematopoietic
function. Hematopoietic growth factors, particularly used after
chemotherapy, can increase the number of peripheral blood progenitor cells
(PBPCs) present in systemic circulation. The reinfusion of PBPCs with
marrow has recently been reported to reduce the time to recovery of
adequate marrow function. This study was designed to determine whether
granulocyte-macrophage colony-stimulating factor (GM-CSF)-mobilized PBPCs
alone (without marrow) would result in rapid and reliable hematopoietic
reconstitution. Sixteen patients with metastatic breast cancer were treated
with four cycles of doxorubicin, 5-fluorouracil, and methotrexate (AFM
induction). Patients responding after the first two cycles were
administered GM-CSF after the third and fourth cycles to recruit PBPCs for
collection by two leukapheresis per cycle. These PBPCs were reinfused as
the sole source of hematopoietic support after high doses of
cyclophosphamide, thiotepa, and carboplatin. No marrow or hematopoietic
cytokines were used after progenitor cell reinfusion. Granulocytes greater
than or equal to 500/microL was observed on a median of day 14 (range, 8 to
57). Transfusion independence of platelets greater than or equal to
20,000/microL occurred on a median day of 12 (range, 8 to 134). However,
three patients required the use of a reserve marrow for slow platelet
engraftment. In retrospect, these patients were characterized by poor
baseline bone marrow cellularity and poor platelet recovery after AFM
induction therapy. When compared with 29 historical control patients who
had received the same high-dose intensification chemotherapy using
autologous marrow support, time to engraftment, antibiotic days,
transfusion requirements, and lengths of hospital stay were all
significantly improved for the patients receiving PBPCs. Thus, autologous
PBPCs can be efficiently collected during mobilization by chemotherapy and
GM-CSF and are an attractive alternative to marrow for hematopoietic
support after high-dose therapy. The enhanced speed of recovery may reduce
the morbidity, mortality, and cost of high-dose treatment. Furthermore,
PBPC support may enhance the effectiveness of high-dose therapy by
facilitating multiple courses of therapy.
Volume 79,
Issue 11,
pp. 3036-3044,
06/01/1992
Copyright © 1992 by The American Society of Hematology
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