Polycythemia Vera: New Diagnostic Concept and Its Types

Polycythemia vera (PV) is a clonal Ph-negative myeloproliferative disorder characterized by excessive myeloid proliferation of three hematopoietic cell lineages leading to ineffective myelopoiesis. According to WHO classification (2008), hemoglobin and hematocrit values are listed among the major diagnostic criteria. However, in many PV patients the levels may be below the diagnostic level, thus leading to underdiagnosis of PV. At present, three clinical types of the disease are recognized: 1) masked (latent/prodromal), 2) classic (overt), and 3) PV with progression/transformation into myelofibrosis. The masked form is most difficult for diagnosis, being highly heterogeneous with regard to clinical manifestations, laboratory data, medical history, and the course of the disease. It includes early stages, some of them with very high platelet count, imitating essential thrombocythemia, cases with abdominal thrombosis, and latent PV. Bone marrow trephine biopsy appears to be the most reliable method for diagnosis of masked PV. Findings typical for PV are readily visible, including hypercellular bone marrow with three-lineage myeloid proliferation, excess of megakaryocytes with mild to moderate cellular atypia and polymorphism. Gradi ng of reticulin fibrosis has impact on prognosis and reflects the risk of progression into myelofibrosis. In revised edition of WHO classification (2016), the typical bone marrow histopathology will be included among the major criteria for the diagnosis of PV, meaning that bone marrow trephine biops

Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis

Background & Aims. At present, the allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment option with curative potential in patients with myelofibrosis (MF), especially in intermediate and high risk categories. The aim of the study is to perform a retrospective analysis of allo-HSCT outcomes in MF patients. Materials & Methods. Outcomes of allo-HSCT in 11 intermediate-2 (n = 3) and high (n = 6) risk patients (based on Dynamic International Prognostic Scoring Scale, DIPSSplus) performed in the R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation over the period from 2005 till 2015 were analyzed in the study. Two more patients underwent allo-HSCT in MF blast phase. Two patients received ruxolitinib before allo-HSCT and 1 patient before and after allo-HSCT. Reduced intensity conditioning regimen was used in all cases. Results. Primary engraftment was documented in 8 patients. 72 % of patients achieved complete hematological remission. Molecular remission and myelofibrosis regression were confirmed in 5 patients. 5 of 11 patients were still with remission and followed-up by the date of the paper submission. The overall two-year survival was 46 %. Conclusion. Allo-HSCT is an effective treatment option for MF patients. Further trials are required to evaluate an optimal timing for allo-HSCT in MF patients and efficacy of Janus kinase (JAK) inhibitors as pre- and posttransplant therapy in MF

New Сytogenetic Approaches in Patients with Primary Myelofibrosis

Aim. To evaluate the potential of a new cytogenetic technique in patients with primary myelofibrosis (PMF). Materials and methods. 48-hour blood cell cultures (according to Singh et al., 2013) were used for cytogenetic study in 11 PMF patients (5 female, 6 men, aged 32–60 years; median 48.6 years). GTG-banding and different types of fluorescence in situ hybridization (FISH) techniques were used for identification of chromosomal aberrations. Results. The incidence of abnormal karyotypes in blood cultures was significantly higher than that in standard bone marrow cultures (82 vs 27 %; p < 0.01). The polyploid clones were found in blood cultures of 45 % of patients. Structural chromosomal aberrations were found in chromosomes 6, 1, 3, as well as 16 and 17 (in 2 and 1 patients with each aberration, respectively). In all but one patients these abnormalities in diploid and polyploid metaphases were identical. Partial 1q trisomy resulted from adding of additional (1q21–1q44) material translocated to the short arm of chromosome 5 to the material of 2 normal homologue of chromosome 1. It seems that 1q+, i(17q) and some others chromosomal abnormalities were secondary, whereas 6p21 locus involvement may be a primary defect in PMF. The t(3;6)(q25;p21) translocation described for the first time and confirmed by FISH should be considered a variant of well-known translocation t(1;6). Allo-HSCT in 2 patients with 1q+ was successful, whereas there were problems with engraftment in a female patient with prognostically unfavorable t(3;3)(q21;q26) translocation associated with the EVI1 gene overexpression. Conclusion. Cytogenetic examinations in blood cultures provide important additional information about PMF patients