Hematologic malignancies developing in previously healthy individuals who received hematopoietic growth factors: Implications for use of colony stimulating factors in healthy volunteers participating in early phase clinical studies and in healthy blood product donors

2559 Background: Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHu-MGDF aka MGDF) and recombinant granulocyte colony stimulating factor (G-CSF) promote the maturation of hematopoietic progenitor cells. Healthy volunteers/donors have received MGDF in phase I/II clinical trials and G-CSF in allogeneic peripheral blood stem cell transplantation procedures. Herein, we review clinical findings for five previously healthy volunteers/donors who developed hematologic malignancies after the use of MGDF or G-CSF. Methods: Clinical information related to hematologic malignancies were reviewed for three volunteers who had participated in a phase I/II clinical trial with MGDF and two donors who underwent G-CSF mobilized peripheral blood stem cell harvesting procedures for sibling allogeneic stem cell transplantation for acute leukemia. Results: Mantle cell, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia were diagnosed three to five years after exposure among three volunteers who received MGDF. For one of these patients, autoimmune thrombocytopenia and antibodies to MGDF that cross-reacted with endogenous thrombopoietin had developed shortly after MGDF administration and persisted until lymphoma chemotherapy was administered. Following chemotherapy, all three achieved complete remission, although one patient subsequently relapsed. Acute myelogenous leukemia was diagnosed four to five years after exposure in two donors who underwent G-CSF primed stem cell harvests prior to their siblings’ allogeneic stem cell transplantation. Following intensive chemotherapy, one of these patients died from acute leukemia and the second is now in complete remission. Conclusion: Controversy exists over the appropriateness of administering hematopoietic growth factors to healthy individuals. While a causal relationship with hematologic malignancies is uncertain, long-term follow-up among healthy individuals who receive hematopoietic growth factors is needed. No significant financial relationships to disclose.