Journal of Clinical Oncology, Vol 14, 2521-2526, Copyright © 1996 by American Society of Clinical Oncology
Phase I trial of recombinant fusion protein PIXY321 for mobilization of peripheral-blood cells
MR Bishop, JD Jackson, B O'Kane-Murphy, K Schmit-Pokorny, JM Vose, PJ Bierman, PI Warkentin, JO Armitage, L Garrison and A Kessinger
Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198-3330, USA. MRBishop@mail
PURPOSE: Mobilization of peripheral-blood cells (PBC) with cytokines alone
results in rapid hematopoietic recovery and avoids the potential morbidity
associated with mobilization by chemotherapy. PIXY321, a fusion protein
that consists of granulocyte-macrophage colony- stimulating factor (GM-CSF)
and interleukin-3 (IL-3), has enhanced hematopoietic colony-forming
activity as compared with individual or equimolar combinations of the two
cytokines. A phase I trial of PIXY321 for mobilization of PBC in patients
with malignant lymphoma was performed. PATIENTS AND METHODS: Thirteen
patients with malignant lymphoma who were eligible for high-dose therapy
(HDT) were enrolled onto the trial. All patients were ineligible for
autologous bone marrow transplantation due to overt metastatic disease in
the marrow or to severe marrow hypocellularity. PIXY321 was administered at
three dose levels of 250, 500, and 750 micrograms/m2/d by continuous
infusion until completion of PBC collections. Collections were initiated
when the WBC count was greater than 10 x 10(9)/L or 4 days after the
initiation of PIXY321, whichever came first. Collections were continued
until a minimum of 6.5 x 10(8) mononuclear cells (MNC)/kg patient weight
were obtained. RESULTS: PIXY321 was generally well tolerated. Side effects
associated with PIXY321 administration did not exceed grade 2 and included
fever (85%), chills/sweats (54%), myalgias (38%), fatigue (31%),
nausea/vomiting (31%), headache (31%), edema (23%), and rhinorrhea (23%).
The median numbers of colony-forming units- granulocyte/macrophage (CFU-GM)
in the graft products for the three dose levels were 0.31, 2.94, and 2.88 x
10(4)/kg, respectively; the median numbers of burst-forming units-erythroid
(BFU-e) were 0.20, 6.94, and 12.78 x 10(4)/kg, and the median numbers of
CD34+ cells were 2.30, 0.74, and 0.39 x 10(6)/kg. Following
transplantation, the median times to an absolute neutrophil count (ANC)
> 0.5 x 10(9)/L were 12, 15, and 12 days, respectively, and the median
times to platelet transfusion independence were 30, 19, and 15 days.
CONCLUSION: PIXY321 can be safely administered and effectively mobilizes
PBC in patients with bone marrow defects. PIXY321-mobilized PBC
autotransplants result in rapid and sustained hematopoietic recovery.
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