Stem cell mobilization in multiple myeloma patients relapsing after previous autologous hematopoietic stem cell transplantation: A multicenter report by the Polish Myeloma Study Group.

Background: Salvage autologous hematopoietic stem cell transplantation (autoHSCT) may be used to treat relapse of multiple myeloma occurring after previous autoHSCT. When insufficient number of hematopoietic stem cells was stored from the initial harvest, remobilization of stem cells is necessary.

Purpose: The analysis of stem cell remobilization after previous autoHSCT.

The efficacy and safety of pomalidomide in relapsed/refractory multiple myeloma in a "real-world" study: Polish Myeloma Group experience.

Background: Patients with relapsed/refractory multiple myeloma (RRMM) have poor prognosis. Pomalidomide is an immunomodulatory compound that has demonstrated activity in MM patients with disease refractory to lenalidomide and bortezomib.

Objectives: Participants of clinical trials are highly selected populations; therefore, the aim of this study was to present observations from real practice that might provide important information for practitioners.

TP53 polymorphism in plasma cell myeloma.

Introduction: Significant and accessible predictive factors for bortezomib treatment in plasma cell myeloma (PCM) are still lacking. TP53 codon 72 polymorphism (P72R) results in proline (P) or arginine (R) at 72 amino acid position, which causes synthesis of proteins with distinct functions. The aims of our study were to: 1) analyze whether this polymorphism is associated with an increased risk of PCM; 2) study whether the P72R polymorphism affects overall survival (OS) among PCM patients; 3) assess the possible association of the P72R polymorphism with sensitivity to bortezomib in cell cultures derived from PCM patients.

Real‑life experience with bortezomib‑based regimens in elderly patients with newly diagnosed multiple myeloma and comorbidities: a Polish retrospective multicenter study.

INTRODUCTION    Bortezomib was the first proteasome inhibitor approved for the therapy of multiple myeloma (MM). Currently, VMP (bortezomib, melphalan, prednisone) is one of the standard regimens recommended as the first‑line therapy for patients with MM ineligible for high‑dose chemotherapy (HDT) with autologous stem‑cell transplantation (auto‑SCT). OBJECTIVES    Participants of clinical trials are highly selected populations; therefore, the aim of this study was to present observations from real practice that might provide important information for practitioners.

Metformin - its potential anti-cancer and anti-aging effects.

The generally accepted mechanism of metformin's effect is stimulation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). AMPK is directly activated by an increase in AMP:ATP ratio in metabolic stress conditions including hypoxia and glucose deprivation. Lately, many novel pathways, besides AMPK induction, have been revealed, which can explain some of metformin's beneficial effects.

Chromosome 1 amplification has similar prognostic value to del(17p13) and t(4;14)(p16;q32) in multiple myeloma patients: analysis of real-life data from the Polish Myeloma Study Group.

The study aimed to assess prognostic significance of del(13q14), del(17p13), t(4;14)(p16;q32), and amp(1q21) in newly diagnosed myeloma patients treated mostly with thalidomide-based therapies. All genetic abnormalities except del(13q14) were independent prognostic factors associated with shortened progression-free survival (PFS) and overall survival (OS). Patients with no abnormalities, one abnormality, and ≥2 abnormalities had a median PFS of 41.

Final overall survival results of a randomized trial comparing bortezomib plus pegylated liposomal doxorubicin with bortezomib alone in patients with relapsed or refractory multiple myeloma.

Background: Previous results from an interim analysis of an open-label, randomized, phase 3 study demonstrated that bortezomib combined with pegylated liposomal doxorubicin (PLD) was superior to bortezomib monotherapy in patients with relapsed/refractory multiple myeloma who had previously received one or more lines of therapy. Protocol-defined final survival data from that study are provided here.

Methods: Patients were randomized (1:1) to receive either bortezomib alone (1.

Danazol induces apoptosis and cytotoxicity of leukemic cells alone and in combination with purine nucleoside analogs in chronic lymphocytic leukemia.

Recently, great progress has been achieved in the treatment of chronic lymphocytic leukemia (CLL). However, some patients, particularly older patients with comorbidities or with relapsed/refractory leukemia, still have limited therapeutic options. There is an urgent need to discover less toxic and more effective drugs for CLL patients.

Efficacy and safety of lenalidomide treatment in multiple myeloma (MM) patients--Report of the Polish Myeloma Group.

Unlabelled: The aim of the multi-centre retrospective study was to evaluate the efficacy and safety of lenalidomide (LEN) therapy in patients with resistant or relapsed multiple myeloma (MM) as well as in patients with stable disease (LEN used due to neurological complications). The primary endpoint of this study was an overall response rate (ORR). The secondary endpoints were as follows: time to progression (TTP), overall survival (OS) and the safety of drug use.

Efficacy, safety and pharmacokinetic profiles of a plasma-derived VWF/FVIII concentrate (VONCENTO®) in subjects with haemophilia A (SWIFT-HA study).

Introduction: VONCENTO® (CSL Behring) is a plasma-derived, high-concentration, low-volume, high-purity concentrate,which contains a high level of von Willebrand factor (VWF) high-molecular-weight multimers and aVWF/factor VIII (FVIII) ratio of ~2.4:1, similar to Haemate® P (CSL Behring).

Methods: The pharmacokinetic, efficacy and safety profiles of VONCENTO® were investigated in this multicentre,double-blind, randomised study.

Thalidomide can promote erythropoiesis by induction of STAT5 and repression of external pathway of apoptosis resulting in increased expression of GATA-1 transcription factor.

Background: Thalidomide was shown to stimulate erythropoiesis and increase hemoglobin level in multiple myeloma patients, but way of such activity remains unclear. The aim of the study was to investigate the mechanisms of thalidomide stimulating effect on erythroid differentiation.

Methods: Hematopoietic stem cells were isolated from bone marrow aspirates taken from myeloma patients and cultured with or without thalidomide.

Bortezomib, thalidomide and dexamethasone, with or without cyclophosphamide, for patients with previously untreated multiple myeloma: 5-year follow-up.

This follow-up extension of a randomised phase II study assessed differences in long-term outcomes between bortezomib-thalidomide-dexamethasone (VTD) and VTD-cyclophosphamide (VTDC) induction therapy in multiple myeloma. Newly diagnosed patients (n = 98) were randomised 1:1 to intravenous bortezomib (1·3 mg/m(2); days 1, 4, 8, 11), thalidomide (100 mg; days 1-21), and dexamethasone (40 mg; days 1-4, 9-12), with/without cyclophosphamide (400 mg/m(2); days 1, 8), for four 21-day cycles before stem-cell mobilisation/transplantation. After a median follow-up of 64·8 months, median time-to-next therapy was 51·8 and 47·9 months with VTD and VTDC, respectively.

Assessing the efficacy of allogeneic hematopoietic stem cells transplantation (allo-HSCT) by analyzing survival end points in defined groups of acute myeloid leukemia patients: a retrospective, multicenter Polish Adult Leukemia Group study.

The importance of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for survival outcomes in patients with acute myeloid leukemia (AML) currently remains unclear. The study aimed to compare measures of clinical treatment for patients with AML in CR1 (the first complete remission) with or without being subjected to allo-HSCT. These consisted of leukemia-free survival (LFS), overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality disease (NRM).

The rate of in vitro fludarabine-induced peripheral blood and bone marrow cell apoptosis may predict the chemotherapy outcome in patients with chronic lymphocytic leukemia.

Purpose: The problem of drug sensitivity and predicting the outcome of chemotherapy seems to be of great importance in hemato-oncological disorders. There are some factors that can help to predict effects of chemotherapy in chronic lymphocytic leukemia (CLL), such as presence of del17p, del11q, or TP53 gene mutations, which result in resistance to purine analogues and alkylating drugs. Despite the new therapeutic options introduced recently, purine analogues in combination with cyclophosphamide and the monoclonal antibody rituximab is still the gold standard for the first-line treatment of fit patients with CLL.

Induction therapy alters plasma fibrin clot properties in multiple myeloma patients: association with thromboembolic complications.

Induction therapy in patients with multiple myeloma increases the risk of thromboembolism. We have recently shown that multiple myeloma patients tend to form denser fibrin clots displaying poor lysability. We investigated the effect of induction therapy on fibrin clot properties in multiple myeloma patients.

Cytotoxic activity of valproic acid on primary chronic lymphocytic leukemia cells.

Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in western civilization. The accumulation of CD5+CD19+ B lymphocytes in peripheral blood is due to a defect in the apoptotic pathway rather than excessive proliferation in the bone marrow and lymph nodes. Despite a number of treatments, CLL remains an incurable disease.

The function of a novel immunophenotype candidate molecule PD-1 in chronic lymphocytic leukemia.

Programmed death-1 (PD-1) is a negative receptor expressed on lymphocytes including malignant B cells in chronic lymphocytic leukemia (CLL). In this work, we found that patients with CLL had a higher expression of PD-1 transcript (PDCD1) than healthy volunteers (p < 0.0001).

Treatment of elderly patients with acute myeloid leukemia adjusted for performance status and presence of comorbidities: a Polish Adult Leukemia Group study.

This prospective study estimated outcomes in 509 elderly patients with acute myeloid leukemia (AML) with different treatment approaches depending on Eastern Cooperative Oncology Group (ECOG) performance status and Charlson Comorbidity Index (CCI). Patients were stratified into fit (ECOG 0-2 and CCI 0-2) or frail (ECOG>2 and/or CCI>2) groups. Fit patients with CCI 0 received intensive chemotherapy whilst reduced-intensive chemotherapy (R-IC) was given to those with CCI 1-2.

Safety of bosutinib versus imatinib in the phase 3 BELA trial in newly diagnosed chronic phase chronic myeloid leukemia.

Bosutinib, an orally active, Src/Abl tyrosine kinase inhibitor, has demonstrated clinical activity and acceptable tolerability in chronic phase chronic myeloid leukemia (CP CML). This updated analysis of the BELA trial assessed the safety profile and management of toxicities of bosutinib versus imatinib in adults with newly diagnosed (≤6 months) CP CML after >30 months from accrual completion. Among patients randomized to bosutinib 500 mg/d (n = 250) or imatinib 400 mg/d (n = 252), 248 and 251, respectively, received ≥1 dose of study treatment.

PTK2 expression and immunochemotherapy outcome in chronic lymphocytic leukemia.

Addition of rituximab (R) to fludarabine and cyclophosphamide (FC) has significantly improved patient outcomes in chronic lymphocytic leukemia (CLL). Whether baseline gene expression can identify patients who will benefit from immunochemotherapy over chemotherapy alone has not been determined. We assessed genome-wide expression of 300 pretreatment specimens from a subset of 552 patients in REACH, a study of FC or R-FC in relapsed CLL.

A clinical comparison of the efficacy and safety of biosimilar G-CSF and originator G-CSF in haematopoietic stem cell mobilization.

Background: Recombinant granulocyte colony-stimulating factor (G-CSF) is widely used to mobilize haematopoietic stem cells. We compared the efficacy and safety of a biosimilar G-CSF (Zarzio(®), Sandoz Biopharmaceuticals) with the originator G-CSF (Neupogen(®), Amgen) in patients with haematological malignancies.

Methods: A total of 108 patients were included in this study, 59 of whom were female (49 male), with an overall median age of 51 years (range 19-69).

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.