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    • Case report A year old Caucasian

    2019-05-28

    Case report A 76 year-old Caucasian male who was evaluated in an emergency department due to headache in May 2001 and was found to have a right parietal subdural hematoma (SDH). Baseline blood work revealed thrombocytopenia of 50×109/L. His SDH was managed with surgical evacuation with full recovery. He was then referred to our institute for evaluation of persistent thrombocytopenia in August 2001 after recovering from a second SDH that was managed expectantly. His past medical history was limited to hypertension; he was a former smoker and he denied any chemical exposures, allergies or relevant family history. His initial white blood cell (WBC) count was 3.1×109/L, absolute neutrophil count (ANC) of 1.8×109/L, hemoglobin 10.2g/dL and platelets 51×109/L. His anemia work-up, thyroid, liver and renal functions were within normal range. Antinuclear antibodies, hemolysis workup and disseminated intravascular coagulation panel were also negative. A bone marrow biopsy and aspirate showed refractory cytopenia with multilineage dysplasia (RCMD), cellularity of 60% and 2.8% blasts with normal karyotype rendering him an IPSS of 0. The patient was observed until March 2003 without requiring any blood products; however his platelet counts gradually deteriorated to 25×109/L. A repeated bone marrow biopsy and aspirate on 03/08/2003 showed refractory anemia with an excess of blasts -1 with trilineage dysplasia, cellularity 65%, blasts 6.5% and normal male karyotype. It was mutually decided to continue observing until he was placed on erythropoietin 40,000 units subcutaneously weekly on 04/15/2005 for his anemia in addition to intermittent platelets transfusion averaging once a month for his thrombocytopenia. He continued erythropoietin treatment until developing neutropenia with ANC of 0.7×109/L in August 2007; a repeated bone marrow biopsy and aspirate showed refractory anemia with excess of blasts-2 with 60% cellularity and 11% blasts. He was enrolled on protocol PH-93406 consisting of 5-azacitidine 75mg/m2 for seven days with or without AMG 531 (Romiplostim) on 28-day pka inhibitor starting his first on 09/01/2007 (he was randomized to both agents). He received a total of 15 courses of both 5-azacitidine and AMG 531 until the study closed in 12/09/2008. Six months into the study, he was noted to have circulating blasts in the peripheral blood for which he was evaluated for allogeneic stem cell transplant. As he was deemed ineligible to transplant, the study drugs were continued In spite of intermittently noticing circulating blasts ranging between 2 and 7%. The occasional peripheral blood blasts could be explained by the effect of Romiplostim. These blasts did not correlate with the findings on the repeated bone marrow biopsy and even at the end of study biopsy (12/19/2008) that showed persistent MDS with 40% cellularity and only 2% blasts. Due to closure of the study, his therapy was changed to 5-azacitidine 75mg/m2 for five days on 28-day cycle; first dose received on 01/02/2009. He finished 9 cycles by 10/17/2009 with worsening of transfusion requirement (up to twice a week, with Hgb ranges 7.0–8.5g/dL and platelets count between 10 and 20×109/L) and worsening neutropenia (ANC 0.5–0.7×109/L). The patient was enrolled on protocol I-144208 consisting of low dose clofarabine 1mg (fixed dose) orally daily for five days on 28-day cycle. His baseline bone marrow aspirate and biopsy on 11/19/2009 was consistent with persistent MDS with 70% cellularity and 3% blasts. His first cycle was complicated by a one-week admission for neutropenic fever with negative bacterial cultures. After two more cycles (March 2010) he had an episode of Staphylococcus Epidermis and Serratia Liquefaciens bacteremia that was successfully treated with IV antibiotics. His treatment continued for a total of 32 cycles by the time of this report, complicated by grade I transaminitis and grade I rash on lower extremities. He continues to be transfusion-dependent, receiving platelets on average once a week and red blood cells once or twice a month. He has reasonable quality of life and functional capacity with estimated Karnofsky score of 70%.