PMC4706408_01
Chronology of Bone Marrow Studies. Top Row: Initial BM sampling from 2001 shows a hypercellular marrow with expansion of maturing myeloid elements and abundant large polylobated megakaryocytes in a minimally fibrotic stroma, as demonstrated with a reticulin stain depicted on the right. Middle Row: After 12 years of initial presentation, there is evidence of histologic progression to MDS/AML characterized by further increase in cellularity, noticeable increase in left-shifted dyspoietic myeloid precursors, erythroid precursors with 53% ringed sideroblasts (see iron stain on aspirate smear, middle picture inset), and dyspoietic megakaryocytes. Myeloblasts accounted for 26% of cells (300-cell count differential) as illustrated by flow cytometric analysis and CD34 immunostain of biopsy section (right image and inset; color code for inset: Red: Myeloblasts, Blue: Monocytes, Green: Maturing myeloid precursors). Bottom Row: After 6 months of initial therapy with Decitabine and maintenance with Anagrelide, aberrant myeloid, and erythroid precursors have greatly decreased with cellularity consisting mostly of large polylobated megakaryocytes, compatible with blossoming ET. There is a persistent population of aberrant CD34(+) myeloblasts (4.3%; right picture and inset) with similar karyotypic abnormalities seen in the t-MDS/AML clone.
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Bone-marrow sampling showed moderate expansion of maturing myeloid precursors and megakaryocytes in a minimally fibrotic stroma (Fig. 1, top). By late September 2013, no response could be appreciated and a new bone marrow sampling was performed (Fig. 1, middle). Astonishingly, bone marrow biopsy revealed >90% infiltration by megakaryocytes and only 4.3% CD34(+) myeloblasts (Fig. 1, bottom).
Platelet Count Through Disease Progression and Treatment. Circulating platelet levels at different time-points during the progression of this patient's ET, first to MDS and eventually to AML, and in response to various treatments. D1, D2, D3, D4 correspond to the Decitabine cycles; An, anagrelide; RS, ringed sideroblasts; BM, bone marrow; MK, megakaryocytes. X-axis labels are month-year.
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Not surprisingly, the platelets increased to 996 x 109/L in June 2013 and subsequently to 1500 x 109/L in July 2013 (Fig. 2).