American Journal of Hematology 41:280-284 (1992) z Proliferation of Abnormal Bone Marrow Histiocytes, an Undesired Effect of Granulocyte Macrophage-Colony-Stimulating Factor Therapy in a Patient With Hurler’s Syndrome Undergoing Bone Marrow Transplantation Eric Lang, Michael L. Cibull, Vincent S. Gallicchio, P. Jean Henslee-Downey, Diane D. Davey, Michael J. Messino, and Edward J. Harder Departments of Pathology (E.L., M.L.C., D.D.D.) and Medicine (V.S.G., P.J.H.-D., M.J.M., E.J.H.), University of Kentucky Medical Center, Lexington; Department of Hematology/Oncology, St. Joseph Cancer Center, Ashville, North Carolina (M.J.M.) Granulocyte macrophage-colony-stimulating factor (GM-CSF) has shown promise as a means of alleviating leukopeniaassociated with a wide variety of disorders. It is currently undergoing evaluation as an adjunct to bone marrow transplantation but its use in pa- tients with metabolic disorders, such as Hurler’s syndrome (HS), has not been explored. We followed bone marrow morphology in a Byear-old male with HS who received up to 8 pg/kg GM-CSF per day because of failure of allogeneic bone marrow engraftment. Both premortem and postmortem bone marrow sampling revealed almost complete replace- ment of the marrow space by sheets of histiocytes demonstrating metachromatic cyto- plasmic granules. Such cells were present in far greater numbers than are usually seen in untreated patients with HS or patients with HS undergoing successful bone marrow transplantation without GM-CSF. Moreover, the in vitro culture of bone marrow from a second HS patient showed a GM-CSF dose-related increase in colony formation up to a dose of 250 unitsiml. Microscopic examination of these colonies showed a high percent- age of histiocytes identical to those seen in the patient’s bone marrow. These observa- tions suggest that caution should be exercised when considering administration of CSFs to patients with HS and similar metabolic storage diseases. Key words: GM-CSF, leukopenia, metabolic disorders zyxwv o 1992 WileyLiss, zyxwvu Inc. INTRODUCTION zyxwvutsrq Granulocyte macrophage-colony-stimulating factor (GM-CSF) is one of several cloned human hematopoietic growth factors currently undergoing clinical evaluation. GM-CSF has shown promise in alleviating leukopenia associated with a wide variety of disorders, ranging from aplastic anemia to acquired immunodeficiency syndrome [ 1-31, Trials are also underway to evaluate the efficacy of GM-CSF in accelerating engraftment following autolo- gous and allogeneic bone marrow transplantation (BMT) WI. Reported toxicity of GM-CSF appears to be dose de- pendent. Doses of <16 pg/kg/day are generally well tolerated, with a flu-like syndrome and skin rash among the reported side effects. At higher doses, hypotension, renal failure, and thromboembolic complications have zyxwv 0 1992 Wiley-Liss, Inc. occurred. We report a case suggesting that GM-CSF may also be associated with the proliferation of abnormal his- tiocytes in patients undergoing bone marrow transplanta- tion (BMT) for Hurler’s syndrome (HS). This hypothesis is strengthened by the observation that GM-CSF sup- ported the overgrowth of abnormal histiocyte-derived colonies in an in vitro culture of bone marrow obtained from a second patient with HS. CASE REPORT A 2-year-old white male with HS was admitted to the University of Kentucky Medical Center in October, 1989, for allogeneic BMT. The diagnosis was confirmed Received for publication December 23, 1991; accepted May 14, 1992.