Successful autografting following myeloablative conditioning therapy with blood stem cells mobilized by chemotherapy plus rhG-CSF.
High-dose conditioning therapy followed by autografting with blood stem cells rather than bone marrow has become an increasingly used transplantation modality for patients with chemosensitive malignancies. We treated 10 patients with malignant lymphoma in sensitive relapse with recombinant human granulocyte colony-stimulating factor (rhG-CSF) following salvage therapy. rhG-CSF was given subcutaneously (5 micrograms/kg/day) starting 24 hours after chemotherapy and stem cell collection was performed by repeated leukaphereses during leukocyte recovery. The yield of myeloid progenitors varied between 0.79 and 38.36 x 10(4) CFU-GM/kg body weight (median 4.1 x 10(4). A strong correlation was found between the number of granulocyte-macrophage colony-forming cells (CFU-GM) plus blast-forming erythroid cells (BFU-E) and CD34-positive (CD34+) cells (R = 0.80; p < 0.001). The majority of CD34+ cells (> 95%) strongly coexpressed human lymphocyte antigen-DR (HLA-DR) and CD38, whereas CD33 varied between 20% and 94%. Costaining of CD34+ cells for CD19 above the control level could not be detected, suggesting that early B lymphoid progenitors are not expanded or released into the circulation by rhG-CSF. Following total body irradiation (TBI)/cyclophosphamide or the CBV regimen (cyclophosphamide, BCNU, VP-16), all patients achieved complete engraftment with a median of 14 days for 1.0 x 10(9)/L white blood cells (WBC), 15 days for 0.5 x 10(9)/L polymorphonuclear cells (PMN) and 22 days for 20 x 10(9)/L platelets. The quantity of CFU-GM/kg transplanted was predictive for neutrophil and platelet recovery. The strongest correlation, however, was found between the number of CD34+ cells/kg autografted and platelet recovery (R = -0.86; p < 0.001). The patients transplanted with more than 5 x 10(6)/kg CD34+ cells reached an unsubstituted platelet count > 20 x 10(9)/L within 8 to 12 days. Our data demonstrate that rapid and complete engraftment can be achieved following myeloablative conditioning therapy with rhG-CSF-exposed blood stem cells without the need for additional bone marrow support or growth factor administration posttransplantation.
Hohaus
S
S
Department of Internal Medicine V, University of Heidelberg, Germany.
Goldschmidt
H
H
Ehrhardt
R
R
Haas
R
R
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001773:Blood Cells / Q000637:transplantation; D003131:Combined Modality Therapy; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006410:Hematopoiesis / Q000187:drug effects*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006689:Hodgkin Disease / Q000628:therapy*; D006801:Humans; D007937:Leukapheresis; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D014182:Transplantation, Autologous
D015703:Antigens, CD; D018952:Antigens, CD34; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor