Granulocyte Colony-Stimulating Factor Induced Differentiation Syndrome Mimicking Acute Myeloid Leukemia and the Unmasking of Chronic Myelomonocytic Leukemia.

In general, the use of granulocyte colony-stimulating factor (G-CSF) has been relatively safe with only occasional reports of inducing adult respiratory distress syndrome. 1 The mechanism for this complication is relatively unknown. A possible mechanism include the superoxide production by G-CSF causing neutrophil leakage resulting in pulmonary epithelial damage. We are reporting a 63 year old woman with a medical history of severe psoriasis and chronic thrombocytopenia with splenomegaly who presented to the emergency room with epistaxis and excessive bruising with a platelet count of 5 x 10 9 /L. She received weekly injections of efalizumab (Raptiva) for six months for treatment of severe psoriasis and was stopped five weeks prior to presentation. Methotrexate and dexamethasone were started approximately one week prior to admission for continued refractory psoriasis. G-CSF was started at 480 mcq subcutaneous once a day on day 4 of admission for neutropenia induced by either efalizumab or methotrexate. When her white blood cell (WBC) count rose from 1.9 x10 9 /L to 6.3 x10 9 /L the G-CSF was stopped on hospital day 8. Her absolute monocyte count also rose from 0 to 3.78 x 10 9 /L (normal range from 0.1 x10 9 /L to 0.9 x10 9 /L) with a left shift in the peripheral blood. The WBC and monocyte counts continued to rise and she was transferred to our hospital for further care on hospital day 11. The WBC count peaked at 147.9 x 10 9 /L on hospital day 12, with a differential of 17% monocytes, 16% metamyelocytes, 4% myelocytes, and 1% promyelocytes. The patient gradually became short of breath at rest, requiring 2–4 liters of oxygen and developed bibasilar crackles on exam. Bibasilar infiltrates were detected on chest radiographs at the outside hospital. Upon arrival to our hospital a CT of thorax showed diffuse bilateral ground glass attenuation. WBC count decreased to 119 x10 9 /L on hospital day 15, with a differential of 47% monocytes, 2% metamyelocytes, 3% myelocytes, and 1% blasts. A bone marrow examination showed morphologic findings consistent with acute monocytic leukemia with monocytoid cells greater than 50%. Since the WBC count continued to decrease with improvement of her respiratory symptoms no chemotherapy was given. When the WBC reached 7.4 x 10 9 /L another bone marrow examination showed a hypercellular marrow with full maturation and no excess of blasts and no evidence of acute leukemia. A background of mature monocytes (12%) and increased reticulin fibers were noted. Chronic myelomonocytic leukemia was her final diagnosis. The laboratory and bone marrow studies while under the effects of G-CSF mimicked those of acute myeloid leukemia. The use of G-CSF in this patient appeared to have unmasked an underlying CMML from an undifferentiated myeloproliferative disorder. Her development of pulmonary infiltrates, hypoxia, leukocytosis and monocytosis after receiving G-CSF appeared to be a differentiation-like syndrome. This resolved after stopping G-CSF and without high dose steroid therapy. Physicians should be aware that G-CSF can cause a syndrome that mimics AML and should refrain from starting cytotoxic chemotherapy based on bone marrow findings under the influence of growth factors.