title: Interleukin-3 followed by GM-CSF for delayed engraftment after autologous bone marrow transplantation.
abstract: Recombinant human interleukin-3 (IL-3) is well-tolerated according to phase I studies, and produces trilineage hematologic responses in patients with normal bone marrow. In addition, promising results have been obtained in a variety of bone marrow failure states. We studied IL-3 in 7 patients with markedly delayed engraftment after autologous bone marrow transplantation (ABMT) for hematologic malignancies (acute myeloid leukemia 4, chronic myeloid leukemia 1, myeloma 1, non-Hodgkin's lymphoma 1). All patients were red blood cell- and platelet transfusion-dependent, had an absolute neutrophil count (ANC) < 0.7 x 10(9)/L and failed to achieve a sustained ANC > 1.0 x 10(9)/L after receiving granulocyte-macrophage colony stimulating factor (GM-CSF) for 28 days. IL-3 was given daily for 21 days at 2 micrograms/kg/d (2 patients) and 5 micrograms/kg/d (5 patients). Toxicity was mild and consisted mostly of low-grade fever and malaise. No changes in platelet, hemoglobin or reticulocyte levels were observed. Four patients had at least a 2-fold increase in ANC at the end of IL-3 treatment. Five patients received GM-CSF 10 micrograms/kg/d subcutaneously for 7 to 10 days immediately after IL-3 and 4 had a further increase in ANC (median 1.7-fold, range 1.6- to 5.8-fold), but no change in platelet transfusion requirements. Hematopoietic colony assays of bone marrow cells obtained before and after treatment showed that granulocyte-macrophage colony-forming cell (CFU-GM) and erythroid blast-forming cell (BFU-E) levels were severely reduced and multilineage progenitors (CFU-GEMM) absent in all patients, and remained low after IL-3 treatment for 21 days. Sequential IL-3 and GM-CSF produced a significant but transient increase in the neutrophil counts of some patients. IL-3 appears to be of limited benefit in patients who are severely aplastic after ABMT and have very low levels of bone marrow progenitors.
authors.affiliation: University of Toronto Autologous Bone Marrow Transplant Program, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Crump
authors.forename: F
authors.initials: F
authors.lastname: Couture
authors.forename: M
authors.initials: M
authors.lastname: Kovacs
authors.forename: R
authors.initials: R
authors.lastname: Saragosa
authors.forename: J
authors.initials: J
authors.lastname: McCrae
authors.forename: J
authors.initials: J
authors.lastname: Brandwein
authors.forename: L
authors.initials: L
authors.lastname: Huebsch
authors.forename: L
authors.initials: L
authors.lastname: Beauregard-Zollinger
authors.forename: A
authors.initials: A
authors.lastname: Keating
mesh_terms: D000208:Acute Disease; D000328:Adult; D001772:Blood Cell Count / Q000187:drug effects; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007377:Interleukin-3 / Q000009:adverse effects / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000601:surgery; D007951:Leukemia, Myeloid / Q000601:surgery; D008228:Lymphoma, Non-Hodgkin / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000601:surgery; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors; D014182:Transplantation, Autologous
chemical_list: D007377:Interleukin-3; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor