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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

Granulocyte macrophage‐colony‐stimulating factor (GM‐CSF) has shown promise as a means of alleviating leukopenia associated with a wide variety of disorders. It is currently undergoing evaluation as an adjunct to bone marrow transplantation but its use in patients with metabolic disorders, such as Hurler's syndrome (HS), has not been explored. We followed bone marrow morphology in a 2‐year‐old male with HS who received up to 8 μg/kg GM‐CSF per day because of failure of allogeneic bone marrow engraftment. Both premortem and postmortem bone marrow sampling revealed almost complete replacement of the marrow space by sheets of histiocytes demonstrating metachromatic cytoplasmic 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 units/ml. Microscopic examination of these colonies showed a high percent‐age of histiocytes identical to those seen in the patient's bone marrow. These observations suggest that caution should be exercised when considering administration of CSFs to patients with HS and similar metabolic storage diseases. © 1992 Wiley‐Liss, Inc.