Polycythemia vera and essential thrombocythemia of intermediate-age: A real-life, multicenter analysis of first-line treatment approach.

BACKGROUND: The treatment of patients with polycythemia vera (PV) and essential thrombocythemia (ET) is conducted according to well-defined risk stratification systems. We hypothesized that adherence to the guidelines, namely the decision to refrain from introducing cytoreduction in non-high-risk patients, is particularly difficult in patients diagnosed when they are between 40 and 59 years of age (intermediate-age group). OBJECTIVES: To evaluate the group of intermediate-age PV and ET patients, focusing on a first-line treatment approach adapted at diagnosis. MATERIAL AND METHODS: The study group consisted of 308 PV and ET patients recruited from 6 Polish Adult Leukemia Group (PALG) Centers. Patients were analyzed with respect to disease phenotype, risk group, treatment approach, cardiovascular (CV) risk factors, and occurrence of bleeding or thrombosis. RESULTS: Overall, 74% of patients in the study group were started on cytoreduction at diagnosis, including 70% of the low-risk PV patients and 85-89% of the non-high-risk ET patients. Factors influencing the decision to start the treatment included higher hemoglobin (Hb) concentration (in PV) as well as higher platelet (PLT) count, and the presence of CV risk factors (in ET). Introducing cytoreduction at diagnosis had no impact on thrombotic events. Patients harboring CV risk factors experienced a higher incidence of complications both at diagnosis and follow-up, independently of the treatment strategy. CONCLUSIONS: We underline the low adherence to recommendations in the treatment of intermediate-age PV and ET patients. Moreover, we emphasize the importance of CV risk factors and stress their impact on disease phenotype in this patient population.

Diagnostic and Prognostic Power of Active DNA Demethylation Pathway Intermediates in Acute Myelogenous Leukemia and Myelodysplastic Syndromes.

Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are characterized by genomic instability, which may arise from the global hypomethylation of the DNA. The active DNA demethylation process may be linked with aberrant methylation and can be involved in leukemogenesis. The levels of 5-methylcytosine oxidation products were analyzed in minimally invasive material: the cellular DNA from peripheral blood cells and urine of patients with AML and MDS along with the control group, using isotope-dilution two-dimensional ultra-performance liquid chromatography with tandem mass spectrometry. The receiver operating characteristic curve analysis was used for the assessment of the ability to discriminate patients' groups from the control group, and AML from MDS. The most diagnostically useful for discriminating AML patients from the control group was the urinary excretion of 5-hydroxymethylcytosine (AUC = 0.918, sensitivity: 85%, and specificity: 97%), and 5-(hydroxymethyl)-2'-deoxyuridine (0.873, 74%, and 92%), while for MDS patients 5-(hydroxymethyl)-2'-deoxycytidine in DNA (0.905, 82%, and 98%) and urinary 5-hydroxymethylcytosine (0.746, 66%, and 92%). Multi-factor models of classification trees allowed the correct classification of patients with AML and MDS in 95.7% and 94.7% of cases. The highest prognostic value of the analyzed parameters in predicting the transformation of MDS into AML was observed for 5-carboxy-2'-deoxycytidine (0.823, 80%, and 97%) and 5-(hydroxymethyl)-2'-deoxyuridine (0.872, 100%, and 75%) in DNA. The presented research proves that the intermediates of the active DNA demethylation pathway determined in the completely non-invasive (urine) or minimally invasive (blood) material can be useful in supporting the diagnostic process of patients with MDS and AML. The possibility of an early identification of a group of MDS patients with an increased risk of transformation into AML is of particular importance.

Autologous stem cell transplantation in the treatment of multiple myeloma with 17p deletion.

INTRODUCTION: Deletion of chromosome 17p [del(17p)] in patients with multiple myeloma is associated with a poor prognosis. High­dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains the standard of treatment in this population. OBJECTIVES: The aim of the study was to compare the treatment outcomes with high­dose chemotherapy and ASCT with standard treatment in patients with del(17p). PATIENTS AND METHODS: We collected data from 12 Polish centers between 2011 and 2017. The records of 97 patients with p53 deletion were assessed, including 29 individuals treated with ACST and 68 receiving standard treatment alone. RESULTS: During the follow­up, 45 patients died and the overall survival (OS) for the whole group was 33 months (range, 1-66 months), with a median progression­free survival (PFS) of 13 months (range, 1-46 months). The prognostic factors of OS in a multivariable analysis were calcium levels at diagnosis within the reference range (hazard ratio [HR], 0.24; 95% CI, 0.12-0.48) and at least partial remission achieved after the first­line treatment (HR, 0.25; 95% CI, 0.12-0.51). Treatment with ASCT was an important factor in improving survival (HR, 3.23; 95% CI, 1.52-6.84). Abnormal kidney function at the time of diagnosis reduced the PFS (HR, 0.46; 95% CI, 0.22-0.94). When the analysis was limited only to patients who could be candidates for ASCT, the survival benefit of the procedure was lost (P = 0.21). CONCLUSIONS: Patients with multiple myeloma with del(17p) do not benefit from high­dose chemotherapy followed by ACST.

18F-fluoro-ethyl-tyrosine (18F-FET) PET/CT as a potential new diagnostic tool in multiple myeloma: a preliminary study.

AIM OF THE STUDY: The aim of this study was to analyse the diagnostic accuracy of "18F-fluoro-ethyl-tyrosine (18F-FET) PET/CT tracer in multiple myeloma. MATERIAL AND METHODS: The analysed group included: patients with newly diagnosed active myeloma (eight patients); in very good partial remission or complete remission (VGPR or CR) after treatment (nine patients); and with active disease after relapse (15 patients). RESULTS: In patients with newly diagnosed myeloma, 64 lesions were found using CT and 83 lesions using 18F-FET. In six patients, the number of lesions using CT and 18F-FET was the same, and two had more lesions with the 18F-FET than with the CT. Patients in VGPR or CR had no FET-positive lesions. Fourteen out of 15 patients with active relapsed myeloma had 47 FET-positive lesions, CT assessment of the same group showed 282 lesions. In one patient with relapse soft tissue mass was found with 18F-FET but not with CT. CONCLUSIONS: 18F-FET can be a promising alternative to 18F-FDG PET/CT for myeloma-related bone disease diagnosis.

Constitutional mutations of the CHEK2 gene are a risk factor for MDS, but not for de novo AML.

CHEK2 plays a key role in cellular response to DNA damage, and also in regulation of mitosis and maintenance of chromosomal stability. In patients newly diagnosed with myelodysplastic syndrome (MDS, n = 107) or acute myeloid leukemia (AML, n = 117) congenital CHEK2 mutations (c.444 + 1G > A, c.1100delC, del5395, p.I157 T) were tested by PCR and sequencing analysis. The karyotype of bone marrow cells of each patient was assessed at disease diagnosis using classical cytogenetic methods and fluorescence in situ hybridization. The CHEK2 mutations were strongly associated with the risk of MDS (p < 0.0001) but not with the risk of de novo AML (p = 0.798). In CHEK2-positive MDS patients, two times higher frequency of aberrant karyotypes than in CHEK2-negative patients was found (71% vs. 37%, p = 0.015). In CHEK2-positive patients with cytogenetic abnormalities, subtypes of MDS: refractory anemia with excess blasts-1 or 2, associated with unfavorable disease prognosis, were diagnosed two times more often than in CHEK2-negative cases with aberrations (78% vs. 44%). In conclusion, the congenital CHEK2 inactivation is strongly associated with the risk of MDS and with a poorer prognosis of the disease. However, the chromosomal instability in AML is not correlated with the hereditary dysfunction of CHEK2.

VEGF-A, sVEGFR-1, and sVEGFR-2 in BCR-ABL negative myeloproliferative neoplasms.

BACKGROUND AND OBJECTIVE: Data from the literature indicate the relationship between the bone marrow microvessel density and the blood parameters of angiogenesis. The aim of this study was to evaluate selected parameters of angiogenesis (VEGF-A, sVEGFR-1, and sVEGFR-2) and their correlations with white blood cells, platelets, and red blood cells. MATERIALS AND METHODS: The study included 72 patients (mean age, 61.84 years) with myeloproliferative neoplasms (MPNs): essential thrombocythemia (ET) (n=46), polycythemia vera (PV) (n=19), and primary myelofibrosis (PMF) (n=7). Serum VEGF-A, sVEGFR-1, and sVEGFR-2 were determined using the ELISA assay. RESULTS: We observed a significantly higher level of VEGF-A and reduced concentrations of sVEGFR-1 and sVEGFR-2 in the whole group of patients with MPNs as compared to controls. Detailed analysis confirmed significantly higher level of VEGF-A and lower concentration of sVEGFR-2 in each subgroups of MPNs patients. However, sVEGFR-1 concentrations were significantly lower only in PV and ET patients. CONCLUSIONS: The study showed an increased level of VEGF-A, which may indicate the intensity of neoangiogenesis in the bone marrow. Decreased sVEGFR-1 and sVEGFR-2 in the blood of patients with MPNs may reflect consumption of these soluble receptors.

Concomitance of monosomal karyotype with at least 5 chromosomal abnormalities is associated with dismal treatment outcome of AML patients with complex karyotype - retrospective analysis of Polish Adult Leukemia Group (PALG).

Monosomal karyotype (MK) and complex karyotype (CK) are poor prognostic factors in acute myeloid leukemia (AML). A comprehensive analysis of cytogenetic and clinical factors influencing an outcome of AML-CK+ was performed. The impact of cladribine containing induction on treatment results was also evaluated. We analyzed 125 patients with AML-CK+ treated within PALG protocols. MK was found in 75 (60%) individuals. The overall complete remission (CR) rate of 66 intensively treated patients was 62% vs. 28% in CK+ MK- and CK+ MK+ group (p = .01). No difference in CR rate was observed between DA and DAC arms. The overall survival (OS) in intensively treated patients was negatively influenced by MK, karyotype complexity (≥5 abnormalities), and WBC >20 G/L in multivariate analysis. The addition of cladribine to DA regimen improved OS only in MK- but not in MK+ group. In conclusion, concomitance of MK with ≥5 chromosomal abnormalities is associated with dismal treatment outcome in AMK-CK+.

Demographic, Hematologic, and Clinical Features of Myelodysplastic Syndrome Patients: Results from the First Polish Myelodysplastic Syndrome Registry.

Epidemiological studies on myelodysplastic syndromes (MDS) in Middle-Eastern Europe are scarce. No data about the demographic, clinical, and laboratory features of Polish MDS patients have been published. The aim of this study was to assess the epidemiological data and toxic exposure of Polish MDS patients and their association with hematological parameters and clinical outcomes. For 15 months, 966 living MDS patients were enrolled at 24 centers (12 university and 12 community hospitals). Follow-up was conducted for the next 55 months. The percentage of patients older than 80 years (16%) was between the values for Eastern and Western countries. In patients younger than 55 years, a female predominance was observed (male/female ratio 0.70:1 vs. 1.29:1; p < 0.001). Female patients had higher platelet counts (160 × 109/l vs. 111 × 109/l; p < 0.001). Patients exposed to chemicals were younger than patients without such exposure; their median age at MDS diagnosis was 66 vs. 70 years (p = 0.037). Smokers had significantly lower hemoglobin concentrations (8.6 vs. 9.1 g/dl; p = 0.032) and lower platelet counts (99 × 109/l vs. 137 × 109/l; p < 0.001) than nonsmokers. We provide the first description of the characteristics of Polish MDS patients. Females predominated in the group aged <60 years and they had higher platelet counts. The course of the disease is affected by toxic exposure and smoking.

Case-adjusted bortezomib-based strategy in routine therapy of relapsed/refractory multiple myeloma shown to be highly effective--a report by Polish Myeloma Study Group.

The observational study was aimed at evaluating response, survival and toxicity of bortezomib-based, case-adjusted regimens in real-life therapy of 708 relapsed/refractory MM patients. Bortezomib was combined with anthracyclines, steroids, thalidomide, alkylators or given in monotherapy. The ORR was 67.9% for refractory and 69.9% for relapsed MM. The median PFS was 14 months and OS 57 months. Patients responding to the therapy had the probability of a 4-year OS at 67.0%. No toxicity was noted in 33.1% of patients. Severe events (grade 3/4) were reported in 35.9% of patients: neurotoxicity (16.7%), neutropenia (9.2%), thrombocytopenia (8.5%), and infections (6.5%). Bortezomib-based, case-adjusted regimens are in real-life practice effective in salvage therapy offering reliable survival with acceptable toxicity for relapsed/refractory MM patients.