It has been suggested that mean platelet volume (MPV) is associated with the risk of venous thromboembolism (VTE) and increased mortality in patients with cancer. We evaluated the association of MPV with VTE and mortality in patients treated for diffuse large B-cell lymphoma (DLBCL). Retrospective analyses were performed on 184 adult patients (median age 59, 55% men), of whom 141 were newly diagnosed, and 43 had relapse/refractory DLBCL. During the observation period (median 499 days), 39 (21.2%) patients developed VTE. Thirty-nine patients died of various causes. In univariate analysis, only the MPV and the treatment line were associated with the occurrence of VTE. In multivariate analysis, MPV ≤10th percentile (odd ratio 1.81; 95% confidence interval 1.06-3.11, p = 0.03) and salvage therapy (odd ratio 2.46; 95% confidence interval 1.66-3.65, p < 0.001) remained significant factors for developing VTE. Other patient-related factors-age, gender, disease-related factors-stage, the International Prognostic Index score, DLBCL subclassification (the germinal centre type and the activated B-cell type), Ki-67 index and VTE risk assessment model failed to be prognostic for VTE. In a Kaplan-Meier analysis, patients with MPV >10th percentile had statistically significantly longer VTE-free survival than patients with lower MPV. In multivariable Cox regression analysis, MPV ≤10th percentile (hazard ratio 5.56, p < 0.001), male gender, age, Ki-67 index, high or high-intermediate International Prognostic Index and VTE development (hazard ratio 7.81, p = 0.029) all significantly correlated with the risk of mortality. The probability of survival was higher in patients with MPV >10th percentile. In conclusion, our results suggest that the pre-chemotherapy MPV value is a cheap and available parameter that may be a useful prognostic marker for a significant risk of VTE and inferior survival rates in patients with DLBCL.
The utility of the venous thromboembolism (VTE) risk assessment model known as the Khorana Risk Score (KRS) in patients with lymphoid malignancies receiving outpatient chemotherapy is not defined. We evaluated the association of the KRS with VTE in patients treated for diffuse large B cell lymphoma (DLBCL) or Hodgkin lymphoma (HL). Retrospective analyses were performed in 428 patients, 241 of whom were newly diagnosed with DLBCL and 187 of whom had HL. During the initial therapy, 64 (15%) patients developed VTE and 56 died during follow-up. More VTE events occurred in patients with DLBCL than in patients with HL. According to the KRS, 364 (85%) and 64 (15%) patients were considered to be at intermediate risk and high risk of VTE development, respectively. The high-risk KRS patients were more often diagnosed with HL than DLBCL (19 vs. 10%, P = 0.0143). The KRS did not discriminate between high- and intermediate-risk patients with respect to VTE occurrence (17 vs. 15%, P = 0.5868). In our patients, the KRS did not adequately predict VTE (positive predictive value 15%, negative predictive value 82% and C statistic 0.51). In the multivariate analysis, bulky disease (OR 2.34; 95% CI 1.62–3.36, P < 0.0001), poor prognostic disease (OR 1.32; 95% CI 1.01–1.74, P = 0.049) and DLBCL histological subtype (OR 1.61; 95% CI 1.17–2.19, P = 0.003) were all significantly associated with the VTE development. In this cohort of patients with lymphoid malignancies, the KRS did not adequately stratify or predict VTE events in patients at a higher risk of VTE. This finding suggests the need for the development of a disease-specific VTE assessment model.
Some cancers treated with allogeneic hematopoietic stem cell transplantation (HSCT) are sensitive to natural killer cell (NK) reactivity. NK function depends on activating and inhibitory receptors and is modified by NK education/licensing effect and mediated by coexpression of inhibitory killer-cell immunoglobulin-like receptor (KIR) and its corresponding HLA I ligand. We assessed activating KIR (aKIR)-based HLA I-dependent education capacity in donor NKs in 285 patients with hematological malignancies after HSCT from unrelated donors. We found significantly adverse progression-free survival (PFS) and time to progression (TTP) in patients who received transplant from donors with NKs educated by C1:KIR2DS2/3, C2:KIR2DS1, or Bw4:KIR3DS1 pairs (for PFS: hazard ratio [HR], 1.70; P = .0020, Pcorr = .0039; HR, 1.54; P = .020, Pcorr = .039; HR, 1.51; P = .020, Pcorr = .040; and for TTP: HR, 1.82; P = .049, Pcorr = .096; HR, 1.72; P = .096, Pcorr = .18; and HR, 1.65; P = .11, Pcorr = .20, respectively). Reduced PFS and TTP were significantly dependent on the number of aKIR-based education systems in donors (HR, 1.36; P = .00031, Pcorr = .00062; and HR, 1.43; P = .019, Pcorr = .038). Furthermore, the PFS and TTP were strongly adverse in patients with missing HLA ligand cognate with educating aKIR-HLA pair in donor (HR, 3.25; P = .00022, Pcorr = .00045; and HR, 3.82; P = .027, Pcorr = .054). Together, these data suggest important qualitative and quantitative role of donor NK education via aKIR-cognate HLA ligand pairs in the outcome of HSCT. Avoiding the selection of transplant donors with high numbers of aKIR-HLA-based education systems, especially for recipients with missing cognate ligand, is advisable.
The C3435T polymorphism of the ABCB1/MDR1 gene is not a risk factor for IBD, including UC and CD, in the population coming from central Poland.
on behalf of the Polish Donor-Recipient Matching Study Group Among cancers treated with allogeneic hematopoietic stem-cell transplantation (HSCT), some are sensitive to natural killer (NK) cell reactivity, described as the "missing self" recognition effect. However, this model disregarded the NK cell licensing effect, which highly increases the NK cell reactivity against tumor and is dependent on the coexpression of inhibitory killer cell immunoglobulin-like receptor (iKIR) and its corresponding HLA Class I ligand. We assessed clinical data, HLA and donor iKIR genotyping in 283 patients with myelo-and lymphoproliferative malignancies who underwent HSCT from unrelated donors. We found dramatically reduced overall survival (OS), progression free survival (PFS), and time to progression (TTP) among patients with malignant diseases with the lack of HLA ligand cognate with this iKIR involved in NK cell licensing in corresponding donor (events 83.3% vs. 39.8%, P 5 0.0010; 91.6% vs. 47.7%, P 5 0.00010; and 30.0% vs. 17.3%, P 5 0.013, for OS, PFS, and TTP, respectively). The extremely adverse PFS have withstand the correction when patient group was restricted to HLA mismatched donor-recipient pairs. The incidence of aGvHD was comparable in two groups of patients. In malignant patients after HSCT the missing HLA ligand for iKIR involved in NK cell licensing in corresponding donor ("missing licensing proof") induced extremely adverse survival of the patients due to the progression of malignancy and not to the aGvHD. Avoiding the selection of HSCT donors with the "missing licensing proof" in the malignant patient is strongly advisable.
Mean platelet volume (MPV) is reported to be associated with the risk of venous thromboembolism (VTE) and mortality in patients with cancer.We sought to determine the association of MPV with symptomatic VTE occurrence in patients treated for newly diagnosed Hodgkin lymphoma (HL) and their outcomes. We retrospectively studied 167 consecutive adult patients treated with HL. During first-line treatment 12 (7.2%) patients developed VTE and 14 (8%) died within the observation period. The pre-chemotherapy values of MPV were significantly lower in VTE patients than those without (p=0.0343). Patients with MPV≤25th percentile (6.8 fl) had an increased risk of VTE occurrence (p=0.0244). In multivariate analysis, MPV≤25th percentile (OR 2.21; 95%CI 1.07-4.57, p=0.033), advanced stage (OR 2.08; 95%CI 1.06-4.07, p=0.033) and bulky disease (OR 2.23; 95%CI 1.16-4.31, p=0.016) were significant factors for developing VTE. Only the impact of MPV≤25th percentile on VTE-free survival rates was found. VTE occurred in 43% (n=3) of the high-risk patients of the Thrombosis Lymphoma (ThroLy) score and in 17% (n=2) of the high-risk of the Khorana Risk Score (KRS). Neither the KRS nor the ThroLy score could identify patients at a high risk of VTE with a high degree of accuracy. We expanded the ThroLy score with the addition of the MPV≤25th percentile to more accurately identify HL patients with a higher risk of VTE.Our study indicates that the pre-chemotherapy MPV value, while of no use as an overall prognosis predictor, may still represent a useful prognostic marker for a significant VTE risk especially when incorporated into VTE-risk assessment models.
Point mutations of bcr-abl tyrosine kinase are the most frequent causes of imatinib resistance in chronic myeloid leukaemia (CML) patients. In most CML cases with BCR-ABL mutations leading to imatinib resistance the second generation of tyrosine kinase inhibitors (TKI- e.g. nilotinib or dasatinib) may be effective. Here, we report a case of a CML patient who during imatinib treatment did not obtain clinical and cytogenetic response within 12 months of therapy. The sequencing of BCR-ABL kinase domains was performed and revealed the presence of a F359I point mutation (TTC-to-ATC nucleotide change leading to Phe-to-Ile amino acid substitution). After 1 month of nilotinib therapy a rapid progression of clinical symptoms was observed. In the presence of the F359I point mutation only dasatinib treatment overcame imatinib and nilotinib resistance.
IntroductionSystemic lupus erythematosus (SLE) is a complex, multifactor autoimmune disease. The studies on aetiopathogenesis of autoimmune diseases focus on the impact the genetically conditioned impairment of xenobiotic metabolism may exert. The knowledge of oxidation polymorphism in the course of SLE may be helpful in choosing more efficient and safer therapy. We determined whether there was an association between susceptibility to SLE and particularly to CYP2D6 genotypes.Material and methodsThe study was carried out in 60 patients with SLE and 129 healthy volunteers and all the subjects were of Polish origin. The samples were analysed for two major defective alles for CYP2D6 – CYP2D6*3 and CYP2D6*4 and one wild -type allele CYP2D6*1-by the polymerase chain reaction fragment length polymorphism (PCR-RFLP) metod with DNA extracted from peripheral blood.ResultsNo statistically significant differences in the incidence of CYP2D6 genotypes between the studied groups were found (p = 0.615). Risk (OR) of SLE development was 1.03 for the carriers of CYP2D6*3 allele and 1.48 for the subjects with CYP2D6*4 allele; but it was not statistically significant.ConclusionsIncreased occurrence of mutant alleles of the CYP2D6 gene in SLE patients and the calculated OR values could suggest the effect of these mutations on increased SLE development.
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