Circulating CD34+ cells, pulmonary hypertension, and myelofibrosis

Abstract

Response:Deferasirox (ICL670) effectively reduces liver iron concentration, whether assessed by biopsy or SQUIDWe thank Drs Fischer, Harmatz, and Nielsen for their letter and interest in our paper. In this study, liver iron concentration (LIC) was assessed either by biopsy (84% of patients) or superconducting quantum interference device (SQUID; 16%, primarily children and adults with contraindications to biopsy). SQUID assessments were performed at 3 centers (in Italy, Germany, and the US); baseline and end-of-study assessments were always conducted at the same site. We acknowledge that the discrepancy between LIC values obtained from biopsy and SQUID was primarily due to the accepted conversion factor of 3.33 that was used to convert wet-weight into dry-weight values. 1 As discussed in the paper, we opted to present prenormalized LIC values because the discrepancy between values obtained from biopsy and SQUID was only identified late in the trial via a validation study. By this time, most patients had been assigned doses according to baseline LIC and most had completed a large proportion of the study. Subsequently, the more appropriate correction factor noted by Drs Fischer, Harmatz, and Nielsen (5.83 Ϯ 0.60) was determined through an independent study. 2 The effect of deferasirox for reducing iron burden, as measured by LIC, was potentially underreported in our paper because we elected to use prenormalized SQUID data. Although these values are different in absolute magnitude from the prenormalized values, they do not differ in the relative magnitude of response. The inclusion or exclusion of patients whose LIC was assessed by SQUID does not alter the primary outcome of the study, which was to demonstrate that deferasirox is generally well tolerated and effective for reducing body iron burden.Despite the technical limitations of the application in this study, SQUID has made, and is continuing to make, important contributions to the field of iron chelation research. As with all methods that are used in longitudinal assessments, consistency of technique is of utmost importance. For the patients who have access, SQUID will remain an important tool to monitor iron overload and response to chelation therapy. Maria Domenica Cappellini

Pulmonary hypertension in patients with chronic myeloproliferative disorders

“…In this study patients with primary myelofibrosis and PH had higher bone marrow microvessel density and vascular endothelial growth factor levels suggesting the presence of a proangiogenic phenomenon [98,99]. Other studies demonstrated that distinctive features of myelofibrosis associated with PH include normal or low circulating CD34 cell count, polyclonal platelets and granulocytes, absence of peripheral blood dacrocytes and the JAK2 1849G.T(V617F) mutation [100,101].…”

Pulmonary hypertension in patients with chronic myeloproliferative disorders

“…In this study, patients with primary myelofibrosis and PH had higher bone marrow microvessel density and vascular endothelial growth factor levels, suggesting the presence of a pro-angiogenic phenomenon [14,71]. Other studies demonstrated that distinctive features of myelofibrosis associated with PH include normal or low circulating CD34 cell count, polyclonal platelets and granulocytes, the absence of peripheral blood dacrocytes and the JAK2 1849G>T(V617F) mutation [72,73].…”

Angiogenesis in pulmonary hypertension with myelofibrosis

“…2 Distinctive features of MF associated with PAH include normal or low circulating CD34 cell count, polyclonal platelets and granulocytes, absence of peripheral blood dacrocytes and the JAK2 1849G>T(V617F) mutation. 3,4 We have recently shown that there is an overexpression of pericytes around the wide and tortuous capillaries in the bone marrow of patients with PMF, PPMF and PTMF, 5 i.e. the proportion of pericyte covered vessels was significantly higher in these patients as compared to controls.…”