Molnupiravir is effective in patients with haematological malignancies.

Patients with hematologic malignancies are particularly vulnerable to severe infectious complications. SARS-CoV-2 infection is associated with a high risk of severe course and death in this patient population. In addition, immune deficits associated with both the blood cancer and the treatment used make vaccination against SARS-CoV-2 less effective than in immunocompetent individuals. Molnupiravir is one of the first oral antiviral drugs to demonstrate a significant benefit in reducing hospitalisation and death in COVID-19 in the general population. In this context, 175 haematology patients with diagnosed COVID-19, and treated with MOL between January and April 2022, came under our scrutiny with a view to defining their clinical characteristics and outcomes. The most common underlying conditions were lymphomas (45%), multiple myelomas (21%) and acute leukaemias or myelodysplastic syndrome (35%). Of all, 77% of the patients were vaccinated, and half of them received a booster. At 28 days after the breakthrough COVID-19 diagnosis, 35 (20%) subjects required hospital admission. Out of those patients, seven (4%) died during the follow-up due to the progression of COVID. Our results corroborate what has been established to date with regard to the positive clinical and safety outcomes of MOL in haematology patients with mild or moderate COVID-19.

Response to anti-SARS-CoV-2 mRNA vaccines in multiple myeloma and chronic lymphocytic leukemia patients.

Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients have increased morbidity and mortality rates of COVID-19 due to immunosuppression associated with the disease and ongoing therapy. The same immune impairment accompanying CLL and MM also affects suboptimal vaccine response. The study assessed the effectiveness of the humoral and T cell-mediated immunity following mRNA COVID-19 vaccination (using either BNT162b2 or mRNA-1273) in short-term (2-5 weeks after second dose) and long-term follow-up (12 weeks after vaccination). Between March and August 2021, blood samples were obtained from 62 CLL and 60 MM patients from eight different hematology departments in Poland. Total anti-RBD antibodies were detected in 37% MM patients before vaccination, increased to 91% and 94% in short- and long-term follow-up, respectively. In CLL, serological responses were detectable in 21% of patients before vaccination and increased to 45% in the short-term and 71% in long-term observation. We detected a tendency to higher frequencies of specific CD8+ T cells against SARS-CoV-2 after vaccination compared to samples before vaccination in MM patients and no changes in frequencies of specific T cells in CLL patients. Our study provides novel insights into mRNA vaccination efficacy in immunocompromised MM and CLL patients, and our findings highlight that specific CD8+ T cells against SARS-CoV-2 might be induced by vaccination but do not correlate positively with serological responses.

Maintaining plasma quality and safety in the state of ongoing epidemic - The role of pathogen reduction.

In the field of transfusion medicine, many pathogen reduction techniques (PRTs) are currently available, including those based on photochemical (PI) and photodynamic inactivation (PDI). This is particularly important in the face of emerging viral pathogens that may pose a threat to blood recipients, as in the case of the COVID-19 pandemic. However, PRTs have some limitations, primarily related to their adverse effects on coagulation factors, which should be considered before their intended use. A comprehensive search of PubMed, Wiley Online Library and Science Direct databases was conducted to identify original papers. As a result, ten studies evaluating fresh plasma and frozen-thawed plasma treated with different PI/ PDI methods and evaluating concentrations of coagulation factors and natural anticoagulants both before and after photochemical treatment were included in the review. The use of PI and PDI is associated with a significant decrease in the activity of all analysed coagulation factors, while the recovery of natural anticoagulants remains at a satisfactory level, variable for individual inactivation methods. In addition, the published evidence reviewed above does not unequivocally favour the implementation of PI/PDI either before freezing or after thawing as plasma products obtained with these two approaches seem to satisfy the existing quality criteria. Based on current evidence, if implemented responsibly and in accordance with the current guidelines, both PI and PDI can ensure satisfactory plasma quality and improve its safety.

No increase in anti-A isohemagglutinin titer after SARS-CoV-2 infection: A retrospective cohort analysis of group O apheresis platelet donors.

The risk of a hemolytic reaction during the transfusion of ABO non-identical PC is determined by the presence of natural anti-A IgM antibodies, the titer of which may increase after infections. The aim of the study was to evaluate the titer of anti-A isohemagglutinins in platelet concentrate (PC) obtained by apheresis from group O donors who experienced SARS-CoV-2 infection, and to compare the titer before and after infection. A retrospective single-center analysis of 21 PC donors with a previous COVID-19 history was performed. The results showed neither a statistically important increase in the anti-A IgM antibody titers nor a significant correlation between the anti-A IgM antibody level and anti-SARS-CoV-2S1 antibody titer in the donors with an asymptomatic or mild COVID-19. Further population-based studies on anti-A titers are necessary for a comprehensive assessment of this phenomenon.

Addition of cladribine to the standard induction treatment improves outcomes in a subset of elderly acute myeloid leukemia patients. Results of a randomized Polish Adult Leukemia Group (PALG) phase II trial.

Intensive induction chemotherapy using anthracycline and cytarabine backbone is considered the most effective upfront therapy in physically fit older patients with acute myeloid leukemia (AML). However, outcomes of the standard induction in elderly AML are inferior to those observed in younger patients, and they are still unsatisfactory. As addition of cladribine to the standard induction therapy is known to improve outcome in younger AML patients. The present randomized phase II study compares efficacy and toxicity of the DAC (daunorubicin plus cytarabine plus cladribine) regimen with the standard DA (daunorubicin plus cytarabine) regimen in the newly diagnosed AML patients over 60 years of age. A total of 171 patients were enrolled in the study (DA, 86; DAC, 85). A trend toward higher complete remission (CR) was observed in the DAC arm compared to the DA arm (44% vs. 34%; P = .19), which did not lead to improved median overall survival, which in the case of the DAC group was 8.6 months compared to in 9.1 months in the DA group (P = .64). However, DAC appeared to be superior in the group of patients aged 60-65 (CR rate: DAC 51% vs. DA 29%; P = .02). What is more, a subgroup of patients, with good and intermediate karyotypes, benefited from addition of cladribine also in terms of overall survival (P = .02). No differences in hematological and nonhematological toxicity between the DA and DAC regimens were observed.

Relationship between tumour necrosis factor-related apoptosis inducing ligand (TRAIL) and vascular endothelial growth factor in human multiple myeloma patients.

Tumour necrosis factor-alfa (TNF-α) is an inflammatory cytokine with a wide spectrum of biological activity, including angiogenesis. Tumour necrosis factor-related apoptosis inducing ligand (TRAIL), which belongs to the TNF family of proteins, plays a role in the regulation of vascular responses, but its effect on the formation of new blood vessels (angiogenesis) is unclear. We analysed TRAIL concentrations in parallel with pro-angiogenic cytokines in serum and their expression in trephine biopsy (TB) in 56 patients with newly diagnosed IgG MM and 24 healthy volunteers. The study showed statistically higher concentrations of TRAIL and TNF-α, as well as of VEGF and its receptor, in MM patients compared to healthy volunteers and patients in advanced stages of the disease. Furthermore, we observed a significant decrease in all studied pro-angiogenic cytokines and significant increase of TRAIL concentration after anti-angiogenic therapy, with meaningful differences between responders (at least partial remission) and patients with progression during the induction treatment. It was also established that TRAIL correlated statistically and negatively with pro-angiogenic cytokines such as VEGF with its receptor and expression of VEGF and syndecan-1 in TB. In summary, our data indicate that in MM patients, both clinical course and treatment responsiveness are associated with dynamic yet corresponding changes of levels of TRAIL parallel pro-angiogenic mediators such as VEGF with its receptor and expression of VEGF and syndecan-1 in TB.

Expression of subtypes of interleukin-17 ligands and receptors in patients with B-cell chronic lymphocytic leukemia.

BACKGROUND: The diversity of biological effects of cytokines from the IL-17 family, as well as the wide range of cells sensitive to their influence, suggests that these molecules might play a significant role in the malignant pro- cess. METHODS: After the cells were initially isolated with Polymorphprep™, they were sorted with a MACS® magnetic separator, CD16 for neutrophils and CD19 for B lymphocytes. The presence of proteins: IL-17A, IL-17E, IL-17F, IL-17D, as well as receptors: IL-17R, IL-17BR, IL-17RC in cell lysates was confirmed by Western blot. The levels of IL-17A, IL-17E, and IL-17F in blood serum were determined with ELISA. RESULTS: The results indicate a lower expression of IL-17A, IL-17E, and IL-17F in PMNs and B lymphocytes of pa- tients with B-cell chronic lymphocytic leukemia compared to cells of healthy subjects. Elevated expression of IL- 17D was observed in the PMNs of patients, with a simultaneous decrease in the expression of this cytokine in leukemic B cells, in comparison to the control group. In patients with B-CLL, there also were observations of decreased expression of IL-17R, IL-17BR, and IL-17RC in leukemic B lymphocytes, compared to their expressions in the cells of healthy subjects. The blood serum of B-CLL patients demonstrated a significantly increased level of IL-17A at stage 0/I, II, and IV of disease; IL-17E at stage 0/I and II; IL-17F at stage 0/I, III, and IV of disease advancement, compared to the data obtained from the control group. CONCLUSIONS: The results clearly support the involvement of the studied proteins from the IL-17 family in the course of B-CLL and indicate that IL-17D may play a significant role in the course of this disease.

Differences and similarities between LC-MS derived serum fingerprints of patients with B-cell malignancies.

Multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) are closely related B-cell non-Hodgkin's lymphomas. MM, a plasma cell malignancy, is the second most common haematopoietic cancer in Western countries, with the median survival time of 3­4 years. CLL, a lymphocyte B malignancy, is the most common leukaemia in Western countries. About 25­30% of all CLL patients do not survive the period of 5 years following diagnosis. Both malignancies are complicated, not fully understood and incurable with the current standard treatment. Biologically, MM and CLL may be preceded by associated precursor conditions, that is, monoclonal gammopathy of undetermined significance for MM and its cellular counterpart and monoclonal B-cell lymphocytosis for CLL. Similarities and differences in the biology of these malignancies prompted us to evaluate their metabolomics in stages requiring chemotherapy. Fingerprinting of serum metabolites by the use of LC-MS has never been applied in studies on MM and CLL patients. Obtained results revealed metabolites common for both malignancies (e.g. fatty acids, acylcarnitines, sphingolipids, phospholipids, phenylalanylphenylalanine and isoprene) as well as those which render them different (e.g. lysophosphatidylcholines, monoacylglycerols, aminocaproic acid, phenylacetylglutamine).

The Association between Immune Checkpoint Proteins and Therapy Outcomes in Acute Myeloid Leukaemia Patients.

The development of novel drugs with different mechanisms of action has dramatically changed the treatment landscape of AML patients in recent years. Considering a significant dysregulation of the immune system, inhibitors of immune checkpoint (ICI) proteins provide a substantial therapeutic option for those subjects. However, use of ICI in haematological malignancies remains very limited, in contrast to their wide use in solid tumours. Here, we analysed expression patterns of the most promising selected checkpoint-based therapeutic targets in AML patients. Peripheral blood of 72 untreated AML patients was used for flow cytometric analysis. Expression of PD-1, PD-L1, CTLA-4, and B7-H3 was assessed within CD4+ (Th) lymphocytes and CD33+ blast cells. Patients were stratified based on therapy outcome and cytogenetic molecular risk. AML non-responders (NR) showed a higher frequency of PD-1 in Th cells compared to those with complete remission (CR). Reduced blast cell level of CTLA-4 was another factor differentiating CR from NR subjects. Elevated levels of PD-1 were associated with a trend for poorer patients' survival. Additionally, prognosis for AML patients was worse in case of a higher frequency of B7-H3 in Th lymphocytes. In summary, we showed the significance of selected ICI as outcome predictors in AML management. Further, multicentre studies are required for validation of those data.

Evaluation of hemostatic balance in blood from patients with polycythemia vera by means of thromboelastography: the effect of isovolemic erythrocytapheresis.

Polycythemia vera (PV) is associated with an increased frequency of thrombotic complications. This study was undertaken to evaluate the hemostatic balance in the blood of PV patients by means of thromboelastography (TEG). The effect of isovolemic erythrocytapheresis (ECP) on the hemostasis of PV patients was also studied. We assessed the coagulation status of 76 PV patients undergoing ECP and 50 of healthy controls. TEG measurements were performed immediately before and after the ECP procedure. Coagulation was triggered by recalcification in freshly collected citrated blood. We recorded clotting time (R), alpha angle, and maximum amplitude (MA) of the clot. The results presented here show that, compared with healthy controls, PV patients demonstrated an increase in alpha angle (p<0.005) and in MA (p=0.14). In the subgroup of PV patients with high (>440 × 10(9)l(-1)) platelet (PLT) count, differences in MA (p<0.01) and alpha angle (p<0.001) were more significant. Following ECP procedure, a significant (p ≤ 0.01) reduction of R time, a rise of alpha angle, and MA were observed, indicating augmentation of a hypercoagulable state. In PV patients, the rise in alpha angle positively correlated (r=0.549) with platelet count but not with the number of erythrocytes and leukocytes. Following ECP, this correlation was reduced (r=0.382). Dilution (with saline) of blood from PV patients and of healthy controls, to a degree similar to that used during the ECP procedure, resulted in reduction of R and rise of the alpha angle. In conclusion, TEG measurements show that the majority of PV patients demonstrate abnormal hemostasis in which a major role is played by platelets rather than plasma factors. The hypercoagulable state in PV patients is significantly augmented following the ECP and may be related to the hemodilution intrinsically included in this procedure. TEG may help to assess the thrombotic risk in individual PV patients.

Secondary acute lymphoblastic leukaemia in a multiple myeloma patient.

Secondary acute leukaemia (s-ALL) is a destructive complication in patients who have been previously treated for other cancer. Secondary acute lymphoblastic leukaemia is rarely reported whereas secondary acute myeloid leukaemia is much more common. Chromosomal 11q23 abnormality, frequently detected in therapy-related acute myeloid leukaemia, is the most common cytogenetic alteration in secondary ALL too. However, s-ALL cases without 11q23 abnormality have rarely been described. Furthermore, there are only a few published medical reports describing occurrence of acute lymphoblastic leukaemia in multiple myeloma (MM) patients. We would like to present our experience with a patient with MM, who developed ALL without 11q23 abnormality, nine years after alkylating-agent containing treatment. The course of the disease was complicated by thrombosis that obstructed the possibility of effective treatment. In conclusion, it should be kept in mind that the development of a more aggressive neoplasm related to chemotherapy treatment as well as the inherent genetic instability of normal and abnormal lymphoid progenitors may affect overall survival of an indolent lymphoma patient.

A Proliferation-Inducing Ligand and B-Cell Activating Factor Are Upregulated in Patients with Essential Thrombocythemia.

A proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF) are cytokines belonging to the tumor necrosis factor family which play an essential role in B-cell maturation, differentiation, and survival. Recent evidence indicates their importance in hematological disorders; however, their function in essential thrombocytosis (ET) pathogenesis remains elusive. Therefore, we aimed to analyze the role of APRIL and BAFF in megakaryocytopoiesis in ET patients. We observed elevated levels of APRIL and BAFF in the plasma of ET patients compared with healthy controls, while no differences were found among patients with different JAK2(V617F) statuses. In addition, APRIL levels were positively associated with the number of platelets and WBC count. In the bone marrow, APRIL but not BAFF levels were higher in ET patients with the JAK2(V617F) mutation; however, JAK2(V617F)-negative patients showed slightly reduced levels of BAFF. In ET patients, we showed that the differentiation of CD34+ progenitor cells towards megakaryocytes induces the expression of both APRIL and BAFF. More importantly, APRIL neutralization significantly reduced platelet production. In conclusion, our data provide evidence that blocking APRIL signaling, which acts as an autocrine growth factor for terminal megakaryocytopoiesis, inhibits platelet production in ET patients, regardless of the status of JAK2(V617F) mutation.

Cladribine Combined with Low-Dose Cytarabine as Frontline Treatment for Unfit Elderly Acute Myeloid Leukemia Patients: Results from a Prospective Multicenter Study of Polish Adult Leukemia Group (PALG).

Acute myeloid leukemia (AML) in older unfit patients is a therapeutic challenge for clinical hematologists. We evaluated the efficacy and safety of a novel low-intensity regimen consisting of low-dose cytarabine and cladribine (LD-AC+cladribine) in first-line treatment of elderly (≥60 years) AML patients not eligible for intensive chemotherapy (IC) who had either the Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 or the hematopoietic cell transplantation comorbidity index (HCT-CI) score ≥3. The induction phase included two cycles of LD-AC+cladribine. Patients who achieved at least partial remission (PR) received maintenance treatment with LD-AC alone. Overall, 117 patients with a median age of 70 years were enrolled. Adverse cytogenetics, ECOG PS ≥2 and HCT-CI score ≥3 was observed in 43.5%, 60%, and 58% of patients, respectively. The response rate (≥PR) was 54% (complete remission [CR], 32%; CR with incomplete hematologic recovery [CRi], 5%). A median overall survival (OS) was 21 and 8.8 months in CR/CRi and PR group, respectively. Advanced age (≥75 years) and adverse cytogenetics had a negative impact on OS. The 56-day mortality rate was 20.5%. In conclusion, LD-AC+cladribine is a beneficial therapeutic option with a predictable safety profile in elderly AML patients not eligible for IC.

Clinical characteristics of patients with chronic eosinophilic leukaemia (CEL) harbouring FIP1L1-PDGFRA fusion transcript--results of Polish multicentre study.

A small subgroup of patients with hypereosinophilic syndrome (HES) demonstrates imatinib-sensitive fusion transcript-the FIP1L1-PDGFRA (F/P+). These cases are currently diagnosed as chronic eosinophilic leukaemia (CEL). In this paper, we screened 77 patients to estimate the frequency of FIP1L1-PDGFRA transcript among patients with unexplained, long-term hypereosinophilia exceeding 1.5 x 10(9)/L and to analyse the clinical and serological features in F/P+ CEL population. The FIP1L1-PDGFRA chimeric protein was detectable in 16 (14 males and 2 females) out of 77 examined HES patients (20%) by RT-PCR. Two patients suffered from cough at diagnosis. Three out of 16 (18%) patients had no organ involvements, in 5-one organ was affected and in the remaining eight cases-at least two. Eosinophilic organ damage/dysfunction identified splenomegaly in the majority of studied patients. We compared clinical and serological features between CEL F/P+ (n = 16) and HES (n = 61) patients. F/P+ cases had significantly increased WBC and absolute eosinophil count (AEC) at diagnosis (p = 0.008 and 0.02), whereas platelet count was decreased in this population (p = 0.03). Serum B12 and tryptase levels were increased (p = 0.002 and 0.004) in CEL F/P+ patients when compared to HES cases whereas serum IL-5 levels were significantly increased in the latter group (p = 0.01). Male gender and splenomegaly occurred more frequent in CEL F/P+ population (p = 0.002 and 0.0007, respectively). Additionally, patients with F/P+ CEL (n = 16) were compared with F/P- CEL (n = 8). The latter group, was significantly older, had lower AEC and higher platelet count. In conclusion, significant clinical symptoms are infrequent present and splenomegaly remains the most common organ involvement in patients with CEL expressing F/P fusion transcript. Our study confirmed the long-term remission on imatinib in this patient population.

Activation of platelets and fibrinolysis induced by saturated air dives.

INTRODUCTION: The Doppler technique is currently the usual method for detection of bubbles in the circulation following decompression. However, cases of decompression sickness (DCS) frequently occur in the absence of detectable bubbles, so that other markers for increasing risk of DCS would be welcome. This study assessed the hemostatic effects of compressed-air saturation dives that conformed to the "safe" limits of accepted decompression tables. METHODS: We measured coagulation times, thrombin generation, platelets, and fibrinolysis in 21 male divers who were subjected to saturated hyperbaric exposures to 0.28-0.3 MPa (corresponds to 18-20 msw). Each diver did one dive. RESULTS: Pooled before- and after-dive data for all exposures showed after decompression, statistically significant changes included decrease of the mean platelet count after, increased induced platelet aggregation and number of platelet aggregates, increased number of P-selectin (CD62P) positive platelets and CD62P density on platelets, increase of platelet derived microparticles in the blood of the divers, decrease of factor XII, X, and fibrinogen concentrations, and marked increase of plasmin-antiplasmin complex concentration. Thrombin activation markers and coagulation times did not change significantly. CONCLUSIONS: Saturated hyperbaric exposures followed by nominally safe decompression led to activation of platelets and the fibrinolytic system. The probable mechanism for the activation of platelets and fibrinolysis is contact with the surface of evolved bubbles in the divers' circulation.

Thrombocytopenia associated with TAVI-The summary of possible causes.

Thrombocytopenia (TP) following transcatheter aortic valve implantation (TAVI) procedure is a common phenomenon but the underlying mechanisms are neither well known nor described. Postinterventional severe TP is related to worse early and late outcome. Moreover, the statement of enhanced platelet and coagulation activation might justify even stronger antiplatelet and anticoagulation therapy following TAVI procedure. Thus, the examination of the pathomechanisms responsible for TP post TAVI seems to be crucial. Several hypotheses have been raised. TP can be caused by insufficient production or impaired platelet renewal. On the other hand, increased platelet activation, consumption and destruction might also be responsible for TP. These findings, mostly related to the procedure alone, need further investigation. Here, we summarize the potential multifactorial causes of post TAVI thrombocytopenia.

The causes of thrombocytopenia after transcatheter aortic valve implantation.

INTRODUCTION: Even though thrombocytopenia following transcatheter aortic valve implantation (TAVI) has been described, further investigation of this phenomenon is needed. AIMS: To determine which factors may explain the fall in platelet count that occurs after implantation of a TAVI device, including markers of platelet and blood coagulation activation. MATERIAL AND METHODS: 32 patients without previous indications for dual antiplatelet therapy (mean age 78.5±7.9 years, 62% females) with severe aortic valve stenosis (mean gradient 54.6±16.9mmHg) who qualified for TAVI procedure (Edwards Sapien XT) were prospectively analyzed. Platelet counts were analyzed before the surgery, on the day of the procedure and for the three following postoperative days (POD 1 to 3). To assess platelet activation P-selectin (PS, serum) and platelet factor 4 (PF-4, CTAD plasma) were measured, whereas for the evaluation of coagulation activation prothrombin fragments 1+2 (F1+2, plasma) were assessed before the procedure, on POD-1 and POD-3 (ELISA). RESULTS: During the postoperative period a significant platelet count drop, the most evident on POD-2, was observed followed by a platelet count raise. The platelet count drop correlated directly with the amount of iodinated contrast agent (r=0.42, p=0.016) and inversely with baseline mean platelet volume (r=-0.37, p=0.046). Neither clinical nor perioperative parameters, except contrast medium, influenced platelet count decrease. No significant differences regarding the concentration of the evaluated markers in patients with and without thrombocytopenia were found. PF-4 and F1+2 significantly changed during the study (p<0.05). Greater acute PF-4 decrease correlated with greater acute platelet count drop (r=0.48, p=0.043), and during the study slower PF-4 increase correlated with higher platelet count increase on POD-3 (r=-0.505, p=0.032). Lower baseline PS correlated with lower baseline platelet count and higher platelet count increase on POD-3 (r=0.45, p=0.04 and =-0.55, p=0.02, respectively). No significant correlations between F1+2 concentrations and platelet count changes have been found. CONCLUSIONS: Platelet reduction shortly after TAVI procedure is related to the amount of contrast agent applied during the procedure. Platelet activation and blood coagulation along with impaired baseline platelet renewal might be the mechanisms of thrombocytopenia following TAVI procedure.

To treat or not to treat: metabolomics reveals biomarkers for treatment indication in chronic lymphocytic leukaemia patients.

In chronic lymphocytic leukaemia (CLL), the clinical course of patients is heterogeneous. Some present an aggressive disease onset and require immediate therapy, while others remain without treatment for years. Current disease staging systems developed by Rai and Binet may be useful in forecasting patient survival time, but do not discriminate between stable and progressive forms of the disease in the early stages. Recently ample attention has been directed towards identifying new disease prognostic markers capable of predicting clinical aggressiveness at diagnosis. In the present study serum samples from stable (n = 51) and progressive (n = 42) CLL patients and controls (n = 45) were used with aim to discover metabolic indicators of disease status. First an LC-MS based metabolic fingerprinting method was used to analyse selected samples in order to find a potential markers discriminating aggressive from indolent patients. Ten of these discovered markers were validated on the whole set of samples with an independent analytical technique. Linoleamide (p = 0.002) in addition to various acylcarnitines (p = 0.001-0.000001) showed to be significant markers of CLL in its aggressive form. Acetylcarnitine (p = 0.05) and hexannoylcarnitine (p = 0.005) were also distinguishable markers of indolent subjects. Forming a panel of selected acylcarnitines and fatty acid amides, it was possible to reach a potentially highly specific and sensitive diagnostic approach (AUC = 0.766).

Expression of IL-1 and IL-6 and their natural regulators in leukocytes of B-cell chronic lymphocytic leukaemia patients.

PURPOSE: The purpose of the study was the assessment of the expression of IL-1ß and IL-6, and the proteins regulating their biological activity, namely IL-1RII, IL-1Ra, as well as sIL-6Rα, sgp-130 in leukemic lymphocytes and autologous neutrophils of B-CLL patients. MATERIAL/METHODS: The study involved a group of B-cell chronic lymphocytic leukemia patients and healthy volunteer blood donors. The presence of chosen proteins and their natural regulators was confirmed by Western blot. RESULTS: Western blot analysis showed a decreased expression of IL-1ß and IL-6 in the leukocytes of B-CLL patients. Decreased expression of sIL-6Rα has been observed in lymphocytes, with a simultaneous increase of expression in PMNs. Lower expression of sgp-130 was found in B cells while its expression was elevated in the neutrophils of patients in early stages of the disease. CONCLUSIONS: The changes observed in the expression of IL-1 and IL-6 seem to exclude their immediate involvement in the progress of B-CLL. However, the presented changes in the expression of proteins regulating IL-1ß and IL-6 in PMNs indicate a potential role of early immune response cells also in advanced stages of the disease.