[High-dose chemotherapy and autologous stem cell transplantation in multiple myeloma patients--single center experience]. / Wysokodawkowana chemioterapia z przeszczepieniem autologicznych komórek macierzystych u chorych na szpiczaka plazmocytowego--wyniki analizy jednoosrodkowej.

Multiple myeloma (MM) is one of the hematologic malignancies in which the impact of dose intensity has been demonstrated. In 2005 it was the most common disease for which autologous stem cell transplantation (ASCT) was performed. However, ASCT is not curative, and most patients relapse within a median of 3 years, the introduction of high-dose therapy resulted in prolonged survival. Novel agents such as thalidomide, bortezomib, or lenalidomide have been introduced to improve high-dose therapy outcome. From April 1998 to December 2008, 65 patients with MM underwent in our Department high-dose chemotherapy supported by autologous transplantation of peripheral blood stem cells (APBSCT). Transplantation of progenitor cells was conducted as consolidation of first line treatment in the majority of patients. Double transplantation was performed in 20 patients (31%). Conditioning regimen consisted of high-dose melphalan (200 mg/m2), in the second procedure the dose of melphalan was reduced to 140 mg/m2. Transplant related mortality was not observed. The duration of hematological recovery after first and second transplantation did not differ significantly. At the time of the analysis (June 2009) 51/65 (78.5%) patients are alive, 14/65 (21.5%) died due to disease progression. Median overall survival (OS) and progression free survival ( PFS) obtained were 86 (range 24-128) and 33 (range 4-110) months respectively. This retrospective analysis confirms the efficacy and safety of APBST in multiple myeloma patients.

[IgA multiple myeloma with adverse prognostic factors--a case report]. / Szpiczak mnogi IgA z niekorzystnymi czynnikami rokowniczymi--opis przypadku.

IgA multiple myeloma is the second most frequent variant of multiple myeloma. The median survival is about 3 years and depends on presence, or not, certain prognostic factors. Cytogenetic status has become the most important of them. The presence of the chromosome 13 deletion is an independent adverse prognostic marker in multiple myeloma and is associated with specific biological features. Patients with the chromosome 13 alterations are less likely to respond to treatment and have a shorter median overall survival. We present a case of IgA multiple myeloma, which was even resistant to new therapeutic strategies (thalidomide, bortezomib).

The use of the Congo red-related dye DBACR to recognize the heavy chain-derived abnormality of myeloma immunoglobulins.

INTRODUCTION: The aim of this study was to differentiate heavy and light chain-derived instability of monoclonal myeloma immunoglobulins by complexation of matched supramolecular dyes. These are composed of several micellar pieces of self-assembled dye molecules which may penetrate the protein interior of the binding locus with polypeptide chains. These dyes were used to elicit, by precipitation, the postulated higher aggregation tendency of the heavy chain derived from its higher hydrophobicity. MATERIALS AND METHODS: Agarose gel electrophoresis was used to create conditions for dye complexation and to reveal the precipitation. RESULTS: Congo red derivatives with aromatic ring substitutes, BACR and DBACR, of increased penetrating capability were chosen to provoke the precipitation of abnormal immunoglobulins by displacing association-prone polypeptide chains from the protein interior. CONCLUSIONS: The results of this study confirm the heavy chain-related propensity of some monoclonal immunoglobulins to aggregate and precipitate. The simplicity of the technique may improve clinical diagnosis and facilitate predictions of disease complications.

[Granulocytic sarcoma with late transformation into acute myeloblastic leukemia--case report]. / Sarcoma granulocyticum z pózna transformacja do pelnoobjawowej ostrej bialaczki szpikowej--opis przypadku.

Case presentation of a 28-year-old patient with acute myeloblastic leukemia (FAB AML-M4), who underwent surgery of an inguinal tumor a year before the diagnosis of leukemia was made. In retrospective assessment a diagnosis of granulocytic sarcoma was made. After induction and consolidation chemotherapy he achieved complete hematological remission and underwent matched unrelated donor bone marrow transplantation. After six months he relapsed. A repeated induction chemotherapy resulted in hematological remission. During maintenance therapy symptoms that appeared suggested an extramedullary relapse.

ABL-kinase domain point mutation as a cause of imatinib (STI571) resistance in CML patient who progress to myeloid blast crisis.

Imatinib mesylate (STI571) is a major therapeutic advance for the management of chronic myeloid leukaemia (CML), however, a proportion of patients are refractory to it, particularly those in more advanced phases of CML. Different mechanisms of resistance to imatinib are suggested, including point mutations within ABL-kinase domains. A point mutation leading to substitution at the ATP binding site of ABL-kinase and insensitivity to imatinib was detected in our patient treated with imatinib, who progressed to blast crisis. Additionally, clonal evolution could lead to BCR-ABL-independent proliferation. Early detection of ABL-kinase mutation could predict the progression of CML treated with imatinib.

[Hepatocyte growth factor: from diagnosis to clinical application]. / Czynnik wzrostu hepatocytów: od diagnostyki do zastosowan klinicznych.

Hepatocyte growth factor (HGF), initially identified and molecularly cloned as potent mitogen of primary cultured hepatocytes, has multiple activities in a variety of tissues during the course of development and also in various disease states. HGF plays key roles in the attenuation of disease progression as an intrinsic repair factor. It is also evident that HGF levels are regulated under different conditions, for example, during the course of pregnancy, aging, and disease. This review focuses on the levels of HGF in normal and pathophysiological situations and examines the relationships between HGF levels and disease, disease stage, and disease prognosis. The clinical potential of HGF as a treatment for subjects with various diseases is also given attention.

[Multiple myeloma: the role of angiogenesis and therapeutic application of thalidomide]. / Szpiczak mnogi--rola angiogenezy i zastosowanie talidomidu.

This article contains biological, epidemiological and clinical data on multiple myeloma and the role of proangiogenetic cytokines in the development of this neoplasm. The role of angiogenesis in the transformation and development of multiple myeloma is a topic which is presently readily studied in leading scientific centres in many parts of the world. Serum and bone marrow levels of cytokines such as VEGF, b-FGF, IL-6, sIL-6R, HGFare raised in patients with multiple myeloma as compared to healthy subjects; their values correlate with the severity of disease and are presently recognised as prognostic factors. Thalidomide has anti-inflammatory, immuno-modulating and antiangiogeneic properties but the mechanism of its action is not yet completely understood. Thalidomide is presently used in therapy of patients with resistant and relapsed multiple myeloma with very promising results.

The efficacy and safety of the low-thalidomide dose CTD (cyclophosphamide, thalidomide, dexamethasone) regimen in patients with multiple myeloma--a report by the Polish Myeloma Study Group.

Multiple myeloma (MM) remains an incurable disease, but response rates to new drugs are promising, offering the majority of patients a significant prolongation of overall survival. The objective of this study was to evaluate time to progression (TTP), event-free survival (EFS), and overall survival (OS) in MM patients treated with a combination of cyclophosphamide (CY), thalidomide (THAL) and dexamethasone (DEX). This study included 132 untreated and relapsing/resistant patients treated with the low-thalidomide dose CTD regimen. The patients received CY 500 mg/m(2)i.v. or 625 mg/m(2) orally at day 1, THAL 100mg/day á la longue and DEX 20mg/day at days 1-4 and 8-11, every 28 days. Patients received 6-9 cycles; ORR by 3 months was 59.1%, by 6 months 65.6% and by 9 months 75.6%. In patients responding to CTD therapy (CR, nCR, PR), the probability of survival for 20 months was 89.3%. The outpatient low-thalidomide dose CTD regimen is well tolerated and produces a significant response rate both in untreated and relapsing/resistant MM patients.