Usefulness of New Neutrophil-Related Hematologic Parameters in Patients with Myelodysplastic Syndrome.

Myelodysplastic syndromes (MDS) are common malignant disorders with a poor prognosis. It is necessary to search for new rapid diagnostic methods to detect MDS patients with cytogenetic changes. The aim of the study was to assess new hematological neutrophil- and monocyte- related parameters I then bone marrow of MDS patient with and without cytogenetic changes. A total of 45 patients with MDS, including 17 patients with cytogenetic changes, were examined. The study was conducted using the Sysmex XN-Series hematological analyzer. New neutrophil and monocyte parameters, such as immature granulocytes (IG), neutrophil reactivity intensity (NEUT-RI), neutrophil granularity intensity (NEUT-GI), neutrophil size (NE-FSC) and neutrophil/monocyte data relating to granularity, activity and volume (NE-WX/MO-WX, NE-WY/MO-WY, NE-WZ/MO-WZ, MO-X, MO-Y, MO-Z) were evaluated. We observed higher median proportions of NE-WX, NE-WY, NE-WZ, and IG counts in MDS patients with cytogenetic changes than in patients without cytogenetic changes. The NE-FSC parameter was lower in MDS patients with cytogenetic changes than in patients without cytogenetic changes. The combination of new neutrophil parameters was found to be a new successful approach in distinguishing MDS patients with cytogenetic changes from patients without cytogenetic changes. It appears that there may be unique neutrophil parameter signatures associated with an underlying mutation.

A Case of Multifocal Extramedullary and Non-Hepatosplenic Extramedullary Hematopoiesis in a 43-Year-Old Man with a History of Congenital Eisenmenger Syndrome.

BACKGROUND Extramedullary hematopoiesis in organs outside the bone marrow most commonly occurs in the liver and spleen. This report is of a case of multifocal extramedullary and non-hepatosplenic extramedullary hematopoiesis a 43-year-old man with a history of congenital Eisenmenger syndrome. CASE REPORT We present the case of a 43-year-old patient with complex heart disease and full-blown Eisenmenger syndrome associated with ventricular septal defect, bicuspid right ventricle, and pulmonary hypertension. In July 2020, the patient began to report neurological symptoms in the form of lower-limb numbness and weakness of lower-limb strength, with additional increasing lower-limb edema. A CT scan of the abdomen and pelvis revealed a 63×102×103 mm soft-tissue mass in the pelvis, located behind the urinary bladder. Due to the suspicion of proliferative disease, mainly of the lymphatic system, a diagnostic trephine biopsy was performed first, but no tumor cell infiltration was found. Then, the patient was qualified for diagnostic surgery. During the operation, tumor sections were harvested. Histopathological examination of the tissue sections showed extramedullary hematopoiesis in the tumor lining. Hydroxycarbamide was used as first-line treatment. However, it was not effective in controlling clinical symptoms. Therefore, the patient was qualified for radiotherapy as a second-line palliative treatment. CONCLUSIONS This report presents a patient with cyanotic heart disease and extramedullary and non-hepatosplenic hematopoiesis presenting as masses that mimicked malignancy. In this case, palliative radiotherapy effectively reduced the symptoms due to the size of the mass lesion.

Thrombotic activation before and after total hip arthroplasty. A prospective cohort study.

BACKGROUND: Total hip arthroplasty (THA) causes acute blood loss. It may lead to a deficiency in coagulation factors, which, in turn, may lead to increased bleeding during the postoperative period. METHODS: Thirty patients (18 women) with a mean age of 67 years (range: 63-72 years) participated in this prospective diagnostic study. THA was performed without tranexamic acid administration in the perioperative period. Activities of clotting factors II, VIII, X, and fibrinogen concentration were evaluated before surgery, 6 hours after the procedure, 2, 4, and 6 days after the operation. All laboratory tests were performed using ACL TOP 500 CTS analyzer. RESULTS: No thromboembolic complications were noted during hospitalization. Mean fibrinogen concentration was 366 mg/dL before surgery, which decreased to 311 mg/dL 6 hours after the operation and peaked at 827 mg/dL on the 4th day after the procedure. Activities of factors II and X decreased on the second and fourth days after surgery. Although the activity of factor VIII decreased after the procedure, it remained within the normal range. Increased baseline fibrinogen concentrations were observed in 6 out of 30 (20%) patients. Mean blood loss was 1332 mL (range, 183-2479 mL) and did not correlate with changes in clotting factor activities. CONCLUSIONS: In patients undergoing THA, fibrinogen acts as an acute-phase protein. Activities of clotting factors II and X normalize within 6 days, and although the activity of factor VIII decreases, it remains within the normal range. TRIAL REGISTRATION: The study was pre-registered May 1st, 2020 on ClinicalTrials.gov.

Efficacy and safety of the obinutuzumab-chlorambucil combination in the frontline treatment of elderly CLL patients with comorbidities - Polish Adult Leukemia Group (PALG) real-life analysis.

Introduction Fludarabine- or bendamustine­based upfront immunochemotherapy is the current standard of care in fit patients with chronic lymphocytic leukemia (CLL). These regimens are poorly tolerated by patients with comorbidities, for whom the obinutuzumab-chlorambucil combination became the recommended first­line treatment. Objectives We aimed to analyze real­life experience with the obinutuzumab-chlorambucil combination as the frontline treatment in elderly and unfit patients. Patients and methods The retrospective analysis included 86 elderly patients (median age, 74 years) with CLL and a significant burden of comorbidities, treated with obinutuzumab-chlorambucil as the frontline regimen. All patients had a Cumulative Illness Rating Scale score greater than 6 and/or creatinine clearance of 30 to 69 ml/min. Results Overall response rate at 2 months after treatment completion was 95.3%, with complete remission (CR) rate of 43% and partial remission (PR) rate of 52.3%. Stable disease rate was 4.7%. Progressive disease was not observed after treatment completion. The median progression­free survival (PFS) was not reached after a median follow­up of 18 months; estimated PFS at 30 months was 62%. We observed 6 relapses (7%), 3 (3.5%) in patients obtaining CR, and 3 (3.5%) in those with PR after immunochemotherapy. The most frequent adverse events were neutropenia and infusion­related reactions (IRRs). Grade-3 neutropenia occurred in 11.6% of patients, and grade-3 IRRs, in 2.3%. There were no adverse events of grade 4 or 5. Conclusions Our data confirm that the obinutuzumab-chlorambucil combination is an effective and well­tolerated regimen in untreated CLL patients with comorbidities.

D-dimer Levels are not a Good Marker for Venous Thromboembolism in Patients Before and After Total Hip Replacement.

BACKGROUND: Total hip replacement activates the coagulation and fibrinolysis systems. The aim of this paper is to describe the concentrations of these proteins following elective total hip replacement. MATERIAL AND METHODS: This prospective laboratory study enrolled 30 patients (including 18 women) who had been qualified for primary total hip replacement due to idiopathic osteoarthritis. Mean age was 70 years (range: 45-86 years). All patients received venous thromboembolism (VTE) prophylaxis according to the current guidelines (enoxaparin 40 mg SC s.i.d. from the day of the procedure). An immunoenzymatic assay (ACL TOP 500 CTS analyser, Beckman Coulter, Brea, CA, USA) was used to determine D-dimer levels before the surgical procedure, 6 hours after the procedure, and on the 2nd, 4th, and 6th post-operative day. RESULTS: No patients showed signs and symptoms of VTE during the hospital stay. The mean D-dimer level before the procedure was 1 mg/ml, with a highest mean value of 11.8 mg/ml at 6 hours after the procedure; the levels would then decrease but would remain above the normal range for 6 days after surgery. Elevated baseline D-dimer levels (>0.5 mg/ml) were found in 80% of the study patients. CONCLUSIONS: 1. D-dimers act like acute phase proteins, with levels increasing several-fold following total hip repla-cement. 2. D-dimer levels cannot be used to diagnose venous thromboembolism even before the procedure and hospi-talisation in patients with idiopathic coxarthrosis and no clinical manifestations of thrombosis.

Acute Phase Proteins for Monitoring Hematopoietic Recovery After Early Engrafting of CD34+ Peripheral-Blood-Stem-Cells for Autografting or Allografting in Patients with Malignant Diseases.

BACKGROUND Neutropenic fever (NF) is associated with delayed engraftment after peripheral blood stem cell transplantation (PBSCT). MATERIAL AND METHODS We followed the levels of acute-phase proteins (APPs) serially in 60 patients after peripheral blood stem-cell autograft (n=39) or peripheral blood stem-cell allograft (n=21) for hematologic malignancies and germinal tumors; we then examined the correlation of those levels with the presence of fever and with markers of engraftment. RESULTS Fever (present in 60% of patients) was associated with a highly statistically significant delay in reaching conventional engraftment targets (ANC >500/µL [0.5×10^9/L]; platelets >20,000/µL [20×10^9/L]; reticulocytes >20,000/µL [20×10^9/L]) (for all associations, p<0.001). Every 4th day for 24 days, we measured the APPs levels and the number of neutrophils (ANC), platelets (PL), and reticulocytes (RET) to reach the reference values of >0.5 G/L or >1.0 G/L for ANC, >20 G/L or >50 G/L for PL, and >20 G/L for RET, respectively. The presence of NF resulted in longer time to engraft hematopoietic stem cells with ANC, PL, and PET counts statistically significant (range 0.001-0.004). The median day range for NF patients was 21.22-26.89 versus 13.88-19.13 for no NF patients. CONCLUSIONS Our results provide additional information for monitoring hematopoietic engraftment in patients following PBSCT; the presence of NF can be tracked by serial measurements in serum of three investigated APPs throughout an early phase of hematopoietic recovery.

Mobilization of Hematopoietic Stem Cells for Hematopoietic Cells Autologous Transplantation with Use of Plerixafor.

BACKGROUND To increase the number of circulating hematopoietic stem cells (HSC) in the blood, mobilization treatments are currently being used. G-CSF and G-CSF plus chemotherapy are the most common methods of hematopoietic stem cells separation used in Poland. MATERIAL AND METHODS We observed patients who failed an effective hematopoietic stem cell mobilization with G-CSF or with G-CSF plus chemotherapy. The separation was considered unsuccessful if within a period of 4 consecutive days of separation, the number of obtained CD 34+ cells was lower than 2.0×10^6/kg of bodyweight. The study involved 32 patients whose CD34+ cells were collected and the collection for autologous transplantation failed. The study included 20 men and 12 women. Among all 32 patients, 28 had multiple myeloma, 3 had DLBCL lymphoma, and 1 had Hodgkin's disease. RESULTS Separation was unsuccessful in only 3 patients; the remaining 29 achieved an average of 4.83×10^6 CD34+ cells per kg of bodyweight. We conclude that plerixafor is an important tool in obtaining sufficient quantities of cells for hematopoietic stem cells separation. CONCLUSIONS The use of plerixafor is a sufficient and safe option for stem cells mobilization in autologous transplantations.

The evaluation of NT-proCNP, C-reactive protein and serum amyloid A protein concentration in patients with multiple myeloma undergoing stem cell transplantation.

The importance of proinflamatory cytokines and acute phase proteins in pathogenesis and progression of MM is well known. However, there are any studies evaluating the role of NT-proCN in management and treatment of MM. The aim of our study was to evaluate the concentration of NT-proCNP and acute phase proteins in patients with MM before and after stem cell transplantation. We involved 40 newly diagnosed MM patients in stage III according to the Durie-Salmon classification and treated with high dose of melphalan (200mg/m2) prior to ASCT. Concentration of NT-proCNP, hs-CRP and SAA were measured before conditioning treatment and every 4days until the 24th day after stem cell infusion. We observed low NT-proCNP levels before conditioning treatment (0.121±0.04pmol/l), the higher in day on ASCT (0.28±0.14pmol/l). Further we showed significant gradual increase concentration of NT-proCNP up to 12days after stem cells infusion (1.07±0.72pmol/l). The kinetics of hs-CRP and SAA levels were similar to NT-proCNP. We showed positive correlation between NT-proCNP levels and absolute neutrophil and platelets count in patients after ASCT. NT-proCNP can be useful parameter to assess effectiveness of treatment and monitoring of hematopoetic recovery time in patients with MM after stem cell transplantations.

Polymyalgia rheumatica in a patient with splenic marginal zone lymphoma - a case report.

Polymyalgia rheumatica (PMR) is a common inflammatory disease in elderly people. We present a case of a 49-year-old woman diagnosed with PMR. The treatment with prednisone resulted in a rapid resolution of clinical symptoms. However, inflammatory markers remained elevated. Ultrasonography and computed tomography revealed the presence of a large splenic lesion. A cyst was suspected but, because of the high risk of splenic rupture, a splenectomy was performed. The histopathological examination revealed the presence of splenic marginal zone lymphoma. Inflammatory markers returned to normal after splenectomy. Prednisone was tapered but clinical symptoms of PMR reappeared after lowering the dose of prednisone <10 mg/day. Thus, treatment with methotrexate was started, which allowed for further tapering of prednisone.

Infectious complications in patients with acute myeloid leukemia treated according to the protocol with daunorubicin and cytarabine with or without addition of cladribine. A multicenter study by the Polish Adult Leukemia Group (PALG).

OBJECTIVES: The addition of cladribine to the standard regimen consisting of daunorubicin and cytarabine has been reported to increase the efficacy of induction therapy in acute myeloid leukemia (AML). The goal of this study was to determine the effect of this modification on the incidence and spectrum of infectious complications. METHODS: Case report forms of 309 patients with newly diagnosed AML who had been enrolled in the prospective, randomized 'DAC-7 vs. DA-7' trial were reviewed. The frequency, etiology, localization, severity, and outcome of infections were compared for patients receiving only daunorubicin and cytarabine (DA-7) and those additionally treated with cladribine (DAC-7). RESULTS: A total of 443 febrile episodes were reported with no significant difference between the treatment groups. A trend towards a higher frequency of bacteremias was observed among DA-7 patients compared to those in the DAC-7 group (31% vs. 21%; p=0.08). The treatment arms did not differ in terms of the distribution of the isolated Gram-positive, Gram-negative, fungal, and viral organisms. However, when bacteremias were considered, Gram-positive blood cultures tended to be more frequent in the DA-7 compared to the DAC-7 group (16% vs. 8.5%; p=0.07). This difference reached statistical significance when major blood bacteremias were analyzed separately (13% vs. 5%; p=0.02). Complete recovery from infections was observed in the majority of patients across both treatment arms and no significant difference was noted regarding infection-related mortality. CONCLUSIONS: The addition of cladribine to standard induction chemotherapy has no impact on the incidence and spectrum of infectious complications in newly diagnosed AML patients.

Cladribine in a weekly versus daily schedule for untreated active hairy cell leukemia: final report from the Polish Adult Leukemia Group (PALG) of a prospective, randomized, multicenter trial.

Cladribine (2-chlorodeoxyadenosine, 2-CdA) treatment-associated infections may shorten potentially long-term survival in hairy cell leukemia (HCL). In search of the optimal mode of 2-CdA administration, 132 patients with untreated HCL were randomized to receive either standard 5-day 2-CdA protocol or a novel schedule of 6 weekly 2-CdA infusions suggested to be less toxic. Analysis of treatment response confirmed similar complete remission rates, overall response rates, progression-free survival, and overall survival in both 2-CdA protocols. However, we did not observe lower toxicity in the weekly schedule. Of special interest, no significant differences were found in the rate of grade 3/4 infections (18% for daily and 26% for weekly protocol, difference -8.2%; 95% confidence interval [CI] -23.2% to 6.9%; P = .28) and the rate of septic deaths (3% for daily and 2% for weekly protocol, difference 1.4%; 95% CI -4.3% to 7.0%; P = .64). In conclusion, HCL treatment with weekly 2-CdA infusions is equally effective but no safer than the standard 5-day 2-CdA protocol.