title: A controlled trial of recombinant human granulocyte-macrophage colony-stimulating factor after total body irradiation, high-dose chemotherapy, and autologous bone marrow transplantation for acute lymphoblastic leukemia or malignant lymphoma.
abstract: Infections during granulocytopenia are major complications of autologous bone marrow transplantation (ABMT). Since recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) has proved to accelerate bone marrow recovery after cytostatic chemotherapy, we studied its effects on hematopoietic regeneration and on infectious complications after total body irradiation (TBI) and high-dose chemotherapy followed by ABMT. Eighty-one patients with acute lymphoblastic leukemia (ALL) in complete remission (CR) or with non-Hodgkin's lymphoma (NHL) in CR or partial remission were randomized in a double-blind, placebo-controlled trial. They received either rhuGM-CSF 250 micrograms/m2 (Escherichia coli-derived) daily by continuous infusion after ABMT, or placebo. Treatment was continued until the neutrophil counts reached greater than 500/microL for 1 week. The maximum treatment duration was 30 days. Thirty-nine patients in the rhuGM-CSF group and 40 patients in the placebo group were evaluable. The median time needed to reach a neutrophil count of 500/microL was 15 days with rhuGM-CSF and 28 days with placebo (P = .0001). Bacterial infections occurred in 14 (35.9%) of the patients with rhuGM-CSF and in 25 (62.5%) of the patients given the placebo (P = .024). Nine of the 14 bacterial infections in the rhuGM-CSF group and 20 of the 25 infections in the placebo group were diagnosed within the first 10 days after ABMT. Capillary leakage and a reversible fluid retention were seen in five of the rhuGM-CSF-treated patients. Patients treated with rhuGM-CSF had lower serum protein and albumin levels than patients in the placebo group. There was no statistically relevant difference in overall survival between the two groups (P = .47). Relapse occurred in 14 (34%) patients with rhuGM-CSF and in 18 (45%) patients with placebo. We conclude that continuous infusion of rhuGM-CSF after ABMT accelerates the regeneration of granulocytes and reduces the number of bacterial infections.
authors.affiliation: Department of Hematology and Oncology, Medizinische Hochschule Hannover, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Link
authors.forename: M A
authors.initials: MA
authors.lastname: Boogaerts
authors.forename: A M
authors.initials: AM
authors.lastname: Carella
authors.forename: A
authors.initials: A
authors.lastname: Ferrant
authors.forename: H
authors.initials: H
authors.lastname: Gadner
authors.forename: N C
authors.initials: NC
authors.lastname: Gorin
authors.forename: I
authors.initials: I
authors.lastname: Harabacz
authors.forename: J L
authors.initials: JL
authors.lastname: Harousseau
authors.forename: P
authors.initials: P
authors.lastname: Hervé
authors.forename: J
authors.initials: J
authors.lastname: Holldack
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001424:Bacterial Infections / Q000209:etiology; D001803:Blood Transfusion; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007958:Leukocyte Count; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000628:therapy*; D008297:Male; D015999:Multivariate Analysis; D010356:Patient Isolation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000628:therapy*; D011336:Probability; D011379:Prognosis; D011994:Recombinant Proteins / Q000627:therapeutic use; D016019:Survival Analysis; D013997:Time Factors; D014182:Transplantation, Autologous; D014916:Whole-Body Irradiation
chemical_list: D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor