title: Haematological malignancies developing in previously healthy individuals who received haematopoietic growth factors: report from the Research on Adverse Drug Events and Reports (RADAR) project.
abstract: Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) and granulocyte colony-stimulating factor (G-CSF) promote haematopoietic progenitor cell maturation. We reviewed the findings for healthy volunteers/donors who developed haematological malignancies following PEG-rHuMGDF or G-CSF administration. Information was reviewed for three of 538 volunteers who received PEG-rHuMGDF in clinical trials and two of 200 donors who underwent G-CSF mobilised stem cell harvesting procedures for sibling stem cell transplants. Mantle cell, diffuse large B-cell lymphoma and chronic lymphocytic leukaemia were diagnosed 1-5 years after PEG-rHuMGDF exposure among three volunteers. For one patient, thrombocytopenia due to autoantibodies to PEG-rHuMGDF developed shortly after PEG-rHuMGDF administration and persisted until chemotherapy was administered. All three achieved complete remission, although one patient relapsed. Acute myeloid leukaemia was diagnosed 4 and 5 years after G-CSF mobilisation in two donors who underwent peripheral blood stem cell donation for sibling allogeneic haematopoietic stem cell transplantation. Following intensive chemotherapy, one died from acute leukaemia and the second is in complete remission. Controversy exists over the appropriateness of administering haematopoietic growth factors to healthy individuals. While a causal relationship with haematological malignancies cannot be demonstrated, long-term follow-up among healthy individuals who receive haematopoietic growth factors is needed.
authors.affiliation: VA Midwest Center for Health Services and Policy Research, the Jesse Brown VA Medical Center, Chicago, IL, USA. cbenne@northwestern.edu
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bennett
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Evens
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Andritsos
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Balasubramanian
authors.forename: Mark
authors.initials: M
authors.lastname: Mai
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Fisher
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Kuzel
authors.forename: Cara
authors.initials: C
authors.lastname: Angelotta
authors.forename: June M
authors.initials: JM
authors.lastname: McKoy
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Bierman
authors.forename: David J
authors.initials: DJ
authors.lastname: Kuter
authors.forename: Steven M
authors.initials: SM
authors.lastname: Trifilio
authors.forename: Steven M
authors.initials: SM
authors.lastname: Devine
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001323:Autoantibodies / Q000276:immunology; D002986:Clinical Trials as Topic; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics; D016298:Hematopoietic Cell Growth Factors / Q000009:adverse effects*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000209:etiology / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000209:etiology; D007948:Leukemia, Monocytic, Acute / Q000188:drug therapy / Q000209:etiology / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000209:etiology; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D011092:Polyethylene Glycols / Q000009:adverse effects; D011994:Recombinant Proteins / Q000009:adverse effects; D013926:Thrombopoietin / Q000009:adverse effects / Q000276:immunology; D014019:Tissue Donors
chemical_list: D001323:Autoantibodies; D016298:Hematopoietic Cell Growth Factors; D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols; D013926:Thrombopoietin