Pavle Rončević

Role of Plasmapheresis in the Management of Acute Kidney Injury in Patients With Multiple Myeloma: Should We Abandon It?: Plasmapheresis in Myeloma and Kidney

The aim of the current study was to determine whether plasmapheresis in combination with chemotherapy could significantly remove free light chains (FLC) in multiple myeloma (MM) patients with acute kidney injury (AKI) and therefore improve renal recovery and patient survival. During the study period, 29 patients with MM and AKI presented to our unit and were treated with two different therapy modalities (plasmapheresis with chemotherapy or bortezomib). At the end of treatment, a significant decrease of FLCs was present in the group treated with plasmapheresis compared to the bortezomib group. Patients treated with plasmapheresis had similar survival compared to patients treated with bortezomib. There was a significantly higher decrease of FLCs and longer survival in patients treated with three or more plasmapheresis sessions than in patients treated with two plasmapheresis sessions. Plasmapheresis therapy still remains a useful and effective method in the treatment of AKI in MM patients. Plasmapheresis significantly reduces FLCs compared to bortezomib especially with higher number of plasma exchange sessions but it must be combined with other chemotherapy agents in order to prolong renal recovery and therefore patient survival.

Serum chitotriosidase: a circulating biomarker in polycythemia vera

ABSTRACT Objectives: Serum chitotriosidase activity (CHIT1) is a biomarker of macrophage activation with an important role in inflammation-induced tissue remodeling and fibrosis. Macrophages have been described to play a crucial role in regulating pathological erythropoiesis in polycythemia vera (PV). The aim of this study was to evaluate CHIT1 in patients diagnosed with Philadelphia-negative myeloproliferative neoplasms (MPNs). Methods: Using fluorometric assay, we measured CHIT1 in 28 PV, 27 essential thrombocythemia (ET), 17 primary myelofibrosis (PMF), 19 patients with secondary myelofibrosis and in 25 healthy controls. Results: CHIT1 was significantly higher in PV (p < .001) and post-PV myelofibrosis (MF) transformation (post-PV MF) (p = .020), but not in ET (p = .080), post-ET MF transformation (p = .086), and PMF patients (p = .287), when compared to healthy controls. CHIT1 in PV was positively correlated with hemoglobin (p = .026), hematocrit (p = .012), absolute basophil count (p = .030) and the presence of reticulin fibrosis in the bone marrow (p = .023). Discussion: A positive correlation between CHIT1 and these distinct laboratory PV features might imply macrophages closely related to clonal erythropoiesis as cells of CHIT1 origin. In addition, a positive association between CHIT1 and reticulin fibrosis might indicate its potential role in PV progression. Conclusion: CHIT1 might be considered as a circulating biomarker in PV. Additional studies are needed to clarify the role of CHIT1 in promoting disease progression and bone marrow fibrosis in PV.

P019 JAK2 V617F and FLT3 ITD mutation in myelodysplastic syndrome

Molecular basis of myelodysplastic syndrome (MDS) is characterized by a number of frequently occurring abnormalities. Cytogenetic abnormalities in MDS are among the most important routine parts of diagnosis and prognosis, but mutations like internal tandem duplication (ITD) in FLT3 gene and point mutation V617F in JAK2 gene may provide supplementary information. Since some forms of MDS show a significant overlap with chronic myeloproliferative disease (MDS classified as MDS/MPD-U) or acute myeloid leukemia (AML transformed from MDS), this prompted us to determine the prevalence of FLT3 ITD and JAK2 V617F mutations in patients with MDS. The study included a total number od 50 MDS patients classified according to the World Health Organization classification: 4 patients with refractory anemia (RA), 13 patients with myelodysplastic/myeloproliferative disease-unclassifiable (MDS/MPD-U), 4 patients with chronic myelomonocytic leukemia (CMMoL), 8 patients with RA with excess of blasts (RAEB) and 21 patients with secondary AML (AML transformed from MDS, but not therapy-related MDS). Analysis of bone marrow was done by conventional cytogenetic and fluorescence in situ hybridization (FISH) for del(5q), del(7q) and rearrangement of MLL gene. DNA and RNA were isolated from bone marrow cells or peripheral blood cells. The detection of JAK2 V617F was performed by allele specific PCR (Baxter et al, Lancet 2005) and FLT3 ITD by RT-PCR (Nakao et al, Leukemia 1996). Structural and numerical cytogenetic abnormalities were frequent in patients with secondary AML and RAEB as expected. There were no patients with isolated del(5q) or del(7q). Patients with CMMoL did not have any karyotypic abnormalities with exception of one patient with del(20q) and izo(17q). The presence of JAK2 V617F was detected in one of four patients with RA and one out of thirteen patients with MDS/MPD-U. There was no mutation detected in patients with RAEB, CMMoL or secondary AML. On the contrary, the only two positive FLT3 ITD patients were those with secondary AML. In conclusion, there is a need to analyze the mutational status of JAK2 and FLT3 gene in order to properly differentiate MDS/MPD-U and to predict possible transformation of MDS toward AML.