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The in vivo response to recombinant human granulocyte-monocyte colony-stimulating factor (rHu GM-CSF) in facilitating the reconstitution of granulo-monopoiesis was evaluated in a patient with Graves’ disease who developed severe aplastic anemia during methimazole therapy. After 10 days of treatment with rHu GM-CSF, the neutrophil and monocyte counts rose to 1.65 × 10/l and 0.41 × 10/l, respectively. However, the patient was still dependent on erythrocyte and platelet transfusions. Two days after rHu GM-CSF withdrawal, the neutrophil count dropped off to 0.41 × 10/l. rHu GM-CSF was reinitiated for 2 days along with glucocorticosteroids. With this combined therapeutic approach, the neutrophil count returned to normal and remained stable, and both Hb and platelet values began to improve. It is concluded that the combination of rHu GM-CSF and glucocorticosteroids can be used as a therapeutic option that may lead to beneficial results in drug-induced aplastic anemia. Dr. Xavier López-Karpovitch, Hospital Angeles del Pedregal, Office 243, Camino Real Santa Teresa 1055, Col. Héroes de Padierna, Magdalena Contreras 10700 Mexico, DF (México) The approximate occurrence of agranulocytosis from methimazole, an antithyroid drug, is 1 in 500 as a maximal figure [1]. Apparently, methimazole-induced aplastic anemia (AA) is a rare condition, since information concerning this association has been provided mainly through isolated case reports [2, 3]. In vitro colony-forming assays have provided evidence favoring a humoral, and most probably autoimmune mechanism, rather than a direct toxic effect of methimazole on abnormally sensitive cells as the cause of bone marrow (BM) aplasia [2, 4]. Hence, glucocorticosteroid administration has been the therapeutic approach in antithyroid druginduced AA. However, their use in severely neutropenic patients is often hampered due to bacterial or fungal infections. rHu GM-CSF has been shown to increase neutrophil counts in neutropenic patients with idiopathic AA [5] or AA secondary to accidental heavy irradiation (60Co) [6], and in druginduced agranulocytosis [7, 8]. D ow nl oa de d by : 54 .7 0. 40 .1 1 10 /2 0/ 20 17 7 :4 7: 07 A M This report presents data showing complete, although transient, recovery of granulomonopoiesis with rHu GM-CSF and sustained restoration of BM function soon after glucocorticosteroid treatment in a patient with Graves’ disease who developed severe AA secondary to methimazole ingestion. Case Report Θ rHu GM-CSF □ Glucocorticosteroids 6 4 H 2A 17-year-old female who had been treated with methimazole (45 mg/day for 5 weeks) due to Graves’ disease was admitted with a sore throat, dysphagia, myalgia, arthralgia, and dysuria. Physical examination revealed: fever (39.2°C), tachycardia and functional holosystolic grade II murmur, enlarged and painful thyroid, generalized rash, and oral thrush. Her peripheral blood values were: Hb 12.4 g/dl, 0.16% re-ticulocytes (corrected for PCV), neutrophils 0×109/1, monocytes 0.10x1071, lymphocytes 1.1×109/1, and platelets 233x1071. The BM was hypocellular (cellularity < 25%) with scanty megakaryocytes, 13% late erythroblasts, 79% lymphocytes, 3% lymphoblasts, 2% plasma cells, and 3% granulocytes. The diagnosis of severe AA was based on peripheral blood and BM data (neutrophils < 0.5 × 109/1, re-ticulocytes < 1% and BM cellularity < 30%) [9]. Because of septice-mia and urinary sepsis no glucocorticosteroids were given and the patient was treated with antibiotics. The patient’s clinical status remained stable but the platelet count started to decline (fig. 1). With the patient’s informed consent and after approval of the local Ethic Committee, rHu GMCSF (Scheramex, SA. de C.V., Mexico) was given intravenously in a 2-hour infusion at a daily dose of 10 μg/kg. Moderate anorexia, chills, and fatigue, as well as severe bone pain were noticed and interpreted as side effects of the rHu GM-CSF treatment. At day 4, a second bone biopsy was performed, since both the Hb and platelet values continued to decrease, the neutrophil count remained low and mucocutaneous bleedings appeared, requiring platelet transfusion. Although the BM examination still showed decreased cellularity ( < 30%), incipient signs of haematopoietic recovery were observed, such as the presence of proeryth-roblasts, increase in erythroblasts, megakaryocytes, and granulocyte precursors. Based on these findings the dose of rHu GM-CSF was increased to 12.5 μg/kg and at day 10 the neutrophil and monocyte counts rose to 1.65 × 109/1 and 0.41 × 109/1, respectively. However, the patient was still dependent on erythrocyte and platelet transfusions. rHu GM-CSF was stopped, according to the protocol, and 2 days later, the neutrophil count dropped to 0.41 × 109/1. rHu GM-CSF was resumed for 2 days (12.5 μg/kg) along with glucocorticosteroids (meth-ylprednisolone 2 g daily on days 12-14 and 1.5 g on day 15; prednisone, 75 mg daily, was tapered off during a 3-week period). With this combined therapeutic approach the neutrophil count returned to normal and remained stable. Both the Hb and platelet values gradually improved. Two years after the patient’s discharge her clinical condition and peripheral blood picture remain normal. r14 1 -12 0.5D ow nl oa de d by : 54 .7 0. 40 .1 1 10 /2 0/ 20 17 7 :4 7: 07 A M