Hemophagocytic lymphohistiocytosis

In this short presentation the most important features of hemophagocytic lymphohistiocytosis in children and adults are presented with pathogenesis, symptoms and treatment

Plasma cell myeloma complicated with hyperviscosity syndrome in a patient with dementia of unknown origin

W pracy przedstawiono przypadek 79-letniego pacjenta z zespołem otępiennym niewiadomego pochodzenia maskującym objawy zespołu nadlepkości (HVS), który rozwinął się w przebiegu szpiczaka plazmocytowego (PCM). Chory dobrze odpowiedział na wdrożone postępowanie terapeutyczne — plazmaferezę i chemioterapię opartą na bortezomibie, osiągając odpowiedź całkowitą. W HVS, który — wskutek zaburzeń mikrokrążenia — pojawia się u 10–30% pacjentów z makroglobulinemią Waldenströma oraz u około 10% chorych na PCM może dochodzić do niebezpiecznych dla życia powikłań narządowych.A case of 79-year-old patient with dementia of unknown origin masking the symptoms of hyperviscosity syndrome (HVS), which developed in the course of plasma cell myeloma (PCM), has been reported. The patient responded well to the implemented treatment — plasmapheresis and chemotherapy regimen based on bortezomib, reaching complete response. In the HVS, which occurs in 10–30% of patients with Waldenström macroglobulinemia and in approximately 10% with PCM, a significant dysfunction of microcirculatory flow may lead to life-threatening organ damage

Autofagia – proces o dwóch obliczach

Autophagy is a process that is involved in the pathogenesis of cancer but also in the development of resistance or sensitivity to cytostatic treatment applied.Until now, the issue is still unresolved if we should stimulate or inhibit the process of autophagy in cancer treatment through the use of appropriate anticancer therapy so that it is beneficial for the patient and induce remission of the disease. On the one hand autophagy as a mechanism of programmed cell death may also cause the death of tumor cells. On the other hand, as a defense mechanism is the process of cell survival strategy in stress situations such as hypoxia in the peripheral parts of the tumor or using cytostatic drugs.It would be good to find an answer if the autophagy is the process increasing the effectiveness of therapy or increasing resistance to treatment in a case of specific tumor

Angiogenesis measured by expression of CD34 antigen in lymph nodes of patients with non-Hodgkin's lymphoma.

Angiogenesis is important in development, maintenance and progression of haematological malignancies. Some clinical observations have indicated that in non-Hodgkin's lymphoma (nHL) tumour microvessel density (MVD) may correlate with tumour staging and outcome. The aim of the study was to examine relationship between MVD as a parameter of tumour angiogenesis measured by expression of CD34 and the grade of nHL histological malignancy as determined by REAL classification. 40 lymph node samples of patients with newly diagnosed nHL (17 women, 23 men; aged 48-70 yrs, median age 64 yrs; stage III and IV) and treated at the Department of Haematology, WrocĹaw Medical University in 1999-2002 were fixed in 10% buffered formalin and embedded in paraffin. In all the studied cases, sections were incubated with antibodies against CD34. The slides were stained with hematoxylin and eosin and evaluated histopathologically. Patients were divided into two groups according to histological malignancy: indolent nHL (19 patients) and aggressive nHL (21 patients). Mean MVD measured by expression of CD34 in aggressive and indolent nHL groups amounted to 19.45 +/- 11.24 vessels/0.375 mm2 and 21.7 +/- 12.4 vessels/0.375 mm2, respectively. Statistical analysis of microvessel staining demonstrated no correlation between tumour MVD and grade of histological malignancy in lymph nodes of nHL patients. Nevertheless, angiogenesis observed in nHL provides rationale for use of angiogenesis inhibitors in lymphoma therapy

Expression of metallothionein (MT) and gluthatione s-transferase pi (SGTP) in the bone marrow of patients with myeloproliferative disorders (MPD)

Overexpression of SGTP and/or MT may contribute to various carcinogenic processes and to resistance to anticancer treatment. The importance of these proteins, although clearly established in solid tumours, has not been fully understood in haematopoietic neoplasm. The aim of this study was to determine the expression of MT and SGTP in the bone marrow of patients with MPD. Twenty paraffin-embedded bone marrow core biopsy specimens from newly diagnosed patients with MPD were evaluated — osteomyelofibrosis (OMF), n = 9 and chronic myelocytic leukaemia (CML), n = 11. We demonstrate increased SGTP and MT expression in the bone marrow of MPD patients. In our study levels of MT in OMF patients were higher than in CML. This suggests that MT expression may correlate with bone marrow fibrosis. These data, although based on a relatively small number of patients, raise the possibility that SGTP and MT may play a role in the pathogenesis of MPD. The clinical significance of this phenomenon needs further investigation

Density of intranodal lymphatics and VEGF-C expression in B-cell lymphoma and reactive lymph nodes.

Lymphatic vasculature in solid tumors may serve as the pathway for metastatic spread of the cancer to the regional lymph nodes and to distant organs. Controversy still exists whether tumors metastasize through existing lymphatics or through newly formed vessels (lymphangiogenesis). The role of lymphangiogenesis in lymphoma spread and proliferation is not clearly established. VEGF-C is the most potent inducer of lymphangiogenesis. LYVE-1 was shown to be a specific marker for lymphatic vessels in normal and tumor tissue. The aim of the present study was the evaluation of lymph node LYVE-1-positive lymphatic sinus density (LSD) and VEGF-C expression in patients with non-Hodgkin's lymphoma (nHL) and in reactive lymph nodes. Sixty paraffin-embedded lymph nodes from newly diagnosed patients with B-cell nHL were evaluated. Twelve lymph node biopsy specimens from adult patients with reactive lymphonodulitis were used as controls. Sections of lymph nodes were stained immunohistochemically for LYVE-1 and VEGF-C. VEGF-C expression in lymph nodes of nHL patients was low and not significantly different from that in the control (p = 0.6). Moreover, VEGF-C expression did not differ significantly between aggressive and indolent lymphomas (p = 0.53). Similarly we did not find differences in LSD in aggressive nHL and in indolent nHL (p=0.49). The mean LSD in reactive lymph nodes was higher than in nHL (p = 0.03). Only in 2 out of 12 reactive lymph nodes LYVE-1-positive vessels were absent. In all groups we demonstrated a strong positive correlation between VEGF-C and LYVE-1-expression (p = 0.0001). Higher LSD in reactive lymph nodes as compared to those of nHL patients suggests that lymphoma proliferation leads to the destruction of the existing lymphatics rather than to lymphangiogenesis within lymph nodes. NHL are not associated with increased expression of VEGF-C nor increased LYVE-1-positive lymphatic sinuses density within lymph nodes

Proinflammatory chemokine gene expression influences survival of patients with non-Hodgkin’s lymphoma

Patients with multiple myeloma (MM) treated with conventional chemotherapy have an averagesurvival of approximately three years. High dose chemotherapy followed by autologous stem cell transplantation(ASCT), first introduced in the mid-1980s, is now considered the standard therapy for almost all patientswith multiple myeloma, because it prolongs overall survival and disease free survival. Between November 1997and October 2006, 122 patients with MM (58 females, 64 males, median age 51.0 years [± 7.98] range: 30–66years) were transplanted in the Department of Hematooncology and Bone Marrow Transplantation at the MedicalUniversity of Lublin: 47 patients were in complete remission or in unconfirmed complete remission,66 patients were in partial remission, and nine had stable disease. Of these, there were 95 patients with IgG myeloma,16 with IgA myeloma, one with IgG/IgA, one with IgM myeloma, five with non secretory type, two withsolitary tumor and two with LCD myeloma. According to Durie-Salmon, 62 patients had stage III of the disease,46 had stage II and four had stage I. Most patients (69/122) were transplanted after two or more cycles ofchemotherapy, 48 patients were transplanted after one cycle of chemotherapy, one patient after surgery and rtg--therapy and four patients had not been treated. In mobilisation procedure, the patients received a single infusionof cyclophosphamide (4–6 g/m2) or etoposide 1.6 g/m2 followed by daily administration of G-CSF until theperipheral stem cells harvest. The number of median harvest sessions was 2.0 (± 0.89) (range: 1–5). An averageof 7.09 (± 33.28) × 106 CD34+ cells/kg were collected from each patient (range: 1.8–111.0 × 106/kg). Conditioningregimen consisted of high dose melphalan 60–210 mg/m2 without TBI. An average of 3.04 (± 11.59) × 106CD34+ cells/kg were transplanted to each patient. Fatal complications occured in four patients (treatment--related mortality = 3.2%). In all patients there was regeneration of hematopoiesis. The median number of daysfor recovery to ANC > 0.5 × 109/l was 13 (± 4.69) (range: 10–38) and platelets recovery to > 50 × 109/l was 25days (± 11.65) (range: 12–45). Median time of hospitalization was 22 days (± 7.14) (range: 14–50). Patientswere evaluated on day 100 after transplantation: 74.9% achieved CR and nCR, 14.3% were in PR, 5.4% had SDand 5.4% had progressed. Median of OS was 45 months (± 30.67). OS at 3-years was 84% and at 7-years 59%.Median PFS was 25 months (± 26.13). PFS at 3-years was 68%, and at 7-years was 43%. At present (November2009) 52 patients (42%) are still alive. High-dose chemotherapy followed by autologous stem cell transplantationis a valuable, well tolerated method of treatment for patients with MM that allows the achievement of long--lasting survival

ICOS gene polymorphisms in B-cell chronic lymphocytic leukemia in the Polish population

There is strong evidence that altered immunological function entails an increased risk of B-cell chronic lymphocytic leukemia (B-CLL). The main mechanism of an anti-tumor response depends on T-cell activation. Unlike the constitutively expressed CD28, inducible costimulatory molecule (ICOS) is expressed on the T-cell surface after activation. ICOS enhances all the basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, the upregulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B cells. ICOS is essential for both efficient interaction between T and B cells and normal antibody responses to T cell-dependent antigens. It does not upregulate the production of interleukin-2, but superinduces the synthesis of interleukin-10. Our previous results indicated the ICOS gene has a role as a susceptibility locus to B-CLL. Therefore an extended study was undertaken to evaluate the association between four ICOS polymorphisms (which were recently described as functional ones) and susceptibility to B-CLL in the Polish population. A case-control study of 296 individuals, including 146 B-CLL patients, was conducted on four polymorphisms in the ICOS gene. Genotyping of the polymorphisms ICOS ISV1+173T>C (rs10932029), ICOSc.1624C>T (rs10932037), ICOSc.2373G>C (rs4675379), and ICOSc.602A>C (rs10183087) was carried out using allelic discrimination methods with the TaqMan® SNP Genotyping Assay. There were no statistically significant differences in the allele, genotype, or haplotype distributions between B-CLL patients and healthy controls for any of the investigated polymorphic markers in the ICOS gene. However, we noted that patients carrying genotype ICOS ISV1+173T>C [TT], ICOSc.602A>C [AA], ICOSc.1624C>T [CC], and ICOSc.2373G>C [GG] have a decreased frequency of progression to a higher Rai stage during 60-month follow-up (21.35% vs. 40.8%, p = 0.013) compared to other individuals. This indicates that the investigated polymorphisms do not modulate the risk of B-CLL in the Polish population, but are associated with disease dynamics, in particular with the time to Rai stage progression. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 49–54

Proinflammatory chemokine gene expression influences survival of patients with non-Hodgkin’s lymphoma

The migration, survival and proliferation of cells is the basis for all physiologic and pathologic processes in the human body. All these reactions are regulated by a complex chemokine network that guides lymphocytes homing, chemotaxis, adhesion and interplay between immunologic system response cells. Chemokines are also responsible for metastatic dissemination of cancers, including Hodgkin&#8217;s and non-Hodgkin&#8217;s lymphomas. The purpose of this study was to determine chemokine gene expression (CXCL8, CXCL10, CCL2, CCL3, CCL4 and CCL5) in lymphoma lymph nodes compared to their expression in reactive lymph nodes. We also analyzed the influence of chemokine gene expression on the survival of lymphoma patients. Chemokine gene expression was evaluated in 37 lymphoma lymph nodes and in 25 samples of reactive lymph nodes. Gene expression of chemokines CXCL8, CXCL10, CCL2, CCL3, CCL4 and CCL5 was measured using the PCR method. Statistical analysis was performed using CSS Statistica for Windows (version 7.0) software. Probability values < < 0.05 were considered statistically significant and those between 0.05 and 0.1 as indicative of a trend. We found lower CXCL8 and CXCL10 gene expression in lymphoma lymph nodes compared to reactive lymph nodes. In the cases of CCL2 and CCL3, expression in lymphomas was higher than in reactive lymph nodes. Patients with high expression of CCL2 and CXCL10 had shorter survival. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 240&#8211;247