Diagnostic and clinical relevance of the number of circulating CD34+ cells in myelofibrosis with myeloid metaplasia

Abstract

The absolute content of CD34 ؉ cells in the peripheral blood of 84 patients with myelofibrosis with myeloid metaplasia (MMM) and 23 patients with other Philadelphia-negative (Ph ؊ ) chronic myeloproliferative disorders (CMDs) was investigated. In MMM, the median absolute number of circulating CD34 ؉ cells was consistently high (91.6 ؋ 10 6 /L; range, 0-2460 ؋ 10 6 /L). Receiver operating characteristic curve analysis showed that 15 ؋ 10 6 /L as a decision criterion for CD34 ؉ cells produced an almost complete discrimination between MMM patients out of therapy and other Ph ؊ CMDs (positive predictive value, 98.4%; negative predictive value, 85.0%). MMM patients with higher numbers of CD34 ؉ cells had a significantly longer disease duration (P ‫؍‬ .019) and higher spleen volume index (P ‫؍‬ .014), liver volume (P ‫؍‬ .000), percentage of circulating immature myeloid cells (P ‫؍‬ .020), and percentage of myeloid blasts (P ‫؍‬ .000). When CD34 ؉ cells were correlated with the use of Dupriez risk stratification, CD34 ؉ cells increased significantly from low-risk (median, 68.1 ؋ 10 6 /L) to intermediate-risk (median, 112.8 ؋ 10 6 /L) and high-risk patients (median 666.1 ؋ 10 6 /L) (F ‫؍‬ 4.95; P ‫؍‬ .009). When CD34 ؉ cells were correlated with a severity score on the basis of both myeloproliferative and myelodepletive characteristics of the disease, only the myeloproliferation index was significantly associated with CD34 ؉ cell level (F ‫؍‬ 5.7; P ‫؍‬ .000). Overall survival and interval to blast transformation from the time of CD34 ؉ cell analysis were significantly shorter in patients with more than 300 ؋ 10 6 /L CD34 ؉ cells (P ‫؍‬ .005 and .0005, respectively). In conclusion, the absolute number of CD34 ؉ circulating cells allows MMM to be distinguished from other Ph ؊ CMDs; it is strongly associated with the extent of myeloproliferation and predicts evolution toward blast transformation. (Blood. 2001;98:3249-3255)

Abnormalities of GATA-1 in Megakaryocytes from Patients with Idiopathic Myelofibrosis

“…They were all chemotherapy-free and 7 of 12 received supportive treatment or low-dose prednisone. They all presented high numbers of circulating CD34 ϩ cells (median, 76.5; range, 27 to 800 ϫ 10 6 /L); in three of them (patients 2, 4, 9), CD34 ϩ count was more than the 300 ϫ 10 6 /L value that has been associated with greater risk of leukemic transformation, 6 yet at 6 to 9 months after blood sampling for this study their disease was still in chronic phase. On histopathological evaluation, all patients were in a typical fibrotic stage of disease.…”

“…The blood film of these patients is characterized by a leuko-erythroblastic picture, with immature myeloid and erythroid cells, and by tear-drop erythrocytes. 4 The CD34 ϩ hematopoietic progenitor cells are constitutively mobilized in the peripheral blood, 5,6 and their number may be related to the severity of the disease and the risk of leukemic transformation; 6,7 the latter occurs in ϳ5 to 20% of patients, 8,9 with a dismal outcome. 8 The changes in bone marrow (BM) stroma are the result of a response of local fibroblasts, that remain polyclonal and do not derive from the neoplastic clone, 10 to cytokines, such as transforming growth factor-␤1, released by the abnormal megakaryocytes.…”

Increased plasma nicotinamide phosphoribosyltransferase is associated with a hyperproliferative phenotype and restrains disease progression in MPN‐associated myelofibrosis

“…White blood cell (WBC) count was corrected for the number of circulating erythroblasts. We also quantified blood hematopoietic CD34-positive cells [31], CXCR4 expression on hematopoietic circulating CD34-positive cells [32], serum cholesterol, and lactic dehydrogenase (LDH) levels in plasma.…”

Allogeneic hemopoietic SCT for patients with primary myelofibrosis: a predictive transplant score based on transfusion requirement, spleen size and donor type

“…The diagnosis of PMF was established according to the Italian Consensus Conference criteria, 17 as per which the diagnosis holds if diffuse BM fibrosis is present. All PMF patients also fulfilled the recent WHO criteria for fibrotic myelofibrosis.…”