T cell-depleted granulocyte colony-stimulating factor (G-CSF) modified allogenic bone marrow transplantation for hematological malignancy improves graft CD34+ cell content but is associated with delayed pancytopenia.
To increase the stem cell content of T cell-depleted bone marrow transplants (BMT), we treated 12 patients with hematological malignancies with BMT from HLA-identical sibling donors given G-CSF 10 microg/kg/day for 5 days before marrow harvest. After CD34+ cell selection, patients received a median of 1.7 (range, 0.82-3.1) x 10(6) CD34+ cells/kg and 2.3 (range, 0.25-4.0) x 10(5) CD3+ cells/kg. All patients had initial engraftment but four developed pancytopenia between days 55-130 post-BMT. In two patients, this required a second infusion of G-CSF-mobilized donor peripheral blood progenitor cells. We observed no delayed pancytopenia in a matched historical group of 24 patients receiving T cell-depleted BMT without prior G-CSF stimulation. Compared to this control group, G-CSF-stimulated marrow recipients showed a significant decline in neutrophil and monocyte counts after 8 weeks. However, outcome after BMT was otherwise comparable, with a similar incidence of acute graft-versus-host disease and transplant-related mortality. Disease-free survival was 63 vs 67% for controls matched for CD34+ cell dose (P = NS). These results indicate that G-CSF stimulation can increase the CD34+ cell content of T cell-depleted marrow but carries a risk of late graft failure.
Mavroudis
D A
DA
Bone Marrow Transplant Unit, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Read
E J
EJ
Molldrem
J
J
Raptis
A
A
Plante
M
M
Carter
C S
CS
Phang
S
S
Dunbar
C E
CE
Barrett
A J
AJ
D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods*; D003587:Cytomegalovirus / Q000254:growth & development; D018572:Disease-Free Survival; D017707:Erythrocyte Transfusion; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D019337:Hematologic Neoplasms / Q000628:therapy*; D006412:Hematopoietic Stem Cells; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy; D010198:Pancytopenia / Q000209:etiology*; D017713:Platelet Transfusion; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D013601:T-Lymphocytes; D019172:Transplantation Conditioning; D014775:Virus Activation
D018952:Antigens, CD34; D016179:Granulocyte Colony-Stimulating Factor