scholarly journals Atypical hodgkin and reed-sternberg cells in peripheral blood of a patient with advanced stage of Hodgkin's disease - a case report

2003 ◽  
Vol 131 (9-10) ◽  
pp. 400-402 ◽  
Author(s):  
Rajko Milosevic ◽  
Milica Colovic ◽  
Vesna Cemerikic-Martinovic ◽  
Natasa Colovic ◽  
Marina Bogunovic
Keyword(s):  
Bone Marrow ◽  
Lymph Nodes ◽  
Peripheral Blood ◽  
Hodgkin's Disease ◽  
Mononuclear Cells ◽  
Hodgkin’S Disease ◽  
Lymphoid Cells ◽  
High Dose ◽  
Advanced Stage ◽  
Neck Lymph Nodes

The occurrence of abnormal Hodgkin's and Reed-Sternberg cells in the peripheral blood in a patient suffering from Hodgkin's disease has been noticed exceptionally rare in a previous period, and especially rare in last ten years primarily due to successfull treatment of this disease. The presence of atypical mononuclear cells in peripheral blood which cytomorphologically resembled Reed-Sternberg cells was registered in 8 patients till 1966. During the last decade, the presence of atypical mononuclear cells in the peripheral blood was used for their isolation cultivation, and detailed immunophenotypic and genetic analysis. The analysis of mononuclear cells in rare patients with Hodgkin's disease was established that they belong to the B-lymphoid cells with expression of CD30 and CD15 antigens. The examination of presence of Hodgkin's cells in the peripheral blood of patients with Hodgkin's disease is important for patients with advanced stage of the disease in which autologous stem cell transplantation and high dose chmeotherapy is planned. The authors present a 33-year-old patient, who noticed enlarged neck lymph nodes in September 2000, high temperature and loss in weight. On physical examination enlarged neck lymph nodes 5x8 cm and hepatosplenomegaly were found. There was anemia and thrombo-cytopenia, and normal WBC count with 24% of lymphoid elements in differential formula. On histologic examination of lymph nodes Hodgkin?s disease, type nodular sclerosis with mixed cellularity was found. Histology of bone marrow showed nodal lymphomatous infiltration. Immunohistochemistry with monoclonal antibodies of concentrate of peripheral blood cells showed expression of CD30+ and CD15+, immunophenotypically and morphologically matching Reed-Sternberg cells. Cytogentic analysis of mononuclear cells of the bone marrow showed normal karyotype. The patient was in clinical stage IV/V of the disease and chemotherapy with 9 cycles of ABVD+Mp protocol was applied. He is still in remission.

EXTRAVASAL FIBRIN STABILIZATION BY FACTOR XIII IN LYMPH NODES WITH HODGKIN’S DISEASE

1987 ◽  
Author(s):  
R Adày ◽  
A Szegedi ◽  
Z Nemes ◽  
L Muszbek
Keyword(s):  
Lymph Nodes ◽  
Hodgkin's Disease ◽  
Factor Xiii ◽  
Mononuclear Cells ◽  
Hodgkin’S Disease ◽  
Tumor Stroma ◽  
Urea Solution ◽  
Immunoperoxidase Technique ◽  
Long Time ◽  
Covalently Linked

The formation of extravasal fibrin deposits in various tumors has been recognized a long time ago and it has been implicated in various aspects of tumor growth. However, no adequate information is available on the nature of intratumoral fibrin. In this study we attempted to find out if fibrin deposit in human lymph nodes with Hodgkin’s disease is stabilized and made resistant to fibrinolysis by factor XIII /FXIII/ of blood coagulation. The two main tasks for FXIII in fibrin stabilization is to attach a^antiplas-min the main phyiological inhibitor of fibrinolysis to fibrin strands and crosslink fibrin chains. By double immunofluorescent labeling for fibrin and α2-antiplasmin a complete colocalization of the two antigens could be observed. A part of fibrin strands also stained for α2-antiplasmin-plasmin-complex-neoantigen revealing that α2-antiplasmin covalently linked to fibrin inhibited intratumoral fibrinolysis. The finding that immunolabeling for fibrin was preserved following the treatment of sections by concentrated urea solution clearly demonstrates that fibrin chains became crosslinked by FXIII. These results were further supported by SDS PAGE analysis of intratumoral fibrin deposits. There are two theoretical possibilities for the appearance of FXIII in the interstitial space: 1/ plasmatic FXIII can get acrossthe vessel wall when increased permeability is induced 2/ FXIII can be produced and released by certain cells of the tumorous tissue. We explored the secondpossibility by various immunomorphological and enzymcytochemical techniques. Alarge number of FXIII positive cells were detected by immunoperoxidase technique in the follicular and interfollicular region of malignant, but not in normal lymph nodes. These relatively large, multipolar, mononuclear cells possesseda macrophage-like appearance and showedANAE-positivity,i.e.,they belong to thegroup of tumor associated macrophages. FXIII containing cells were labeled by monoclonal anti-Leu M3 (a monocyte/macrophage marker), but not by anti-HLA-DR.They were often found in the immediate vicinity of malignant Hodgkin’s cells and also showed an intimate relationshipwith extravasal fibrin formation.lt is suggested that FXIII secreted byintactor released from damaged macrophages might be involved in the stabilization offibrin in the tumor stroma or around tumor cells.

An In Vitro Model of Proliferating CLL Cells for Drug Sensitivity Analysis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2956-2956
Author(s):  
K. Ganeshaguru ◽  
N. I. Folarin ◽  
R. J. Baker ◽  
A. M. Casanova ◽  
A. Bhimjiyani ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Nodes ◽  
Peripheral Blood ◽  
Drug Sensitivity ◽  
In Vitro Model ◽  
Survivin Expression ◽  
Lymphoid Cells ◽  
Malignant Cells ◽  
Vitro Model

Abstract B-cell chronic lymphocytic leukaemia (CLL) is a heterogeneous disease with a variable clinical course. The disease is characterised by the proliferation in the bone marrow and lymph node of a clonal population of CD5+ve cells that accumulates in the peripheral blood. Therefore, the characteristics of the proliferative compartment are important in determining the kinetics of disease progression in CLL and the sensitivity of the malignant cells to cytotoxic drugs. However, laboratory studies on drug sensitivity of CLL have been performed exclusively on resting circulating peripheral blood cells since it is not feasible to obtain cells from the proliferating pool in sufficient numbers for in vitro analysis. CLL cells can be stimulated to proliferate in vitro using CpG oligonucleotides (ODN) and other factors. The aim of the present study was to generate and validate an in vitro model using malignant cells from the peripheral blood of patients with CLL. The expression pattern of proteins eg., survivin in this model should mimic that in proliferating CLL cells in the bone marrow and lymph nodes. Survivin is a member of the family of inhibitor of apoptosis (IAP) proteins with an additional role in cell cycle progression. Survivin has been shown to be expressed in proliferating bone marrow and lymphoid cells. Cells from patients with CLL were activated for 72h with a combination of ODN (1μM), IL-2 (100u/ml) and CD40L (0.5μg/ml) (ODN*). Activated cells retained their characteristic CLL immunophenotype as determined by the continued expression of CD5, CD19, CD23 and CD25 (n=5). Cell proliferation was confirmed by increased incorporation of 3H-thymidine into DNA in activated cells (n=12). Novel findings in the ODN* activated CLL cells were significant increases in expression of CD38 (n=7, p=0.0001) and of T-cell zeta associated protein (ZAP-70) tyrosine kinase (n=14, p=0.0005). The increased expression of both these proteins in circulating peripheral blood CLL cells has been associated with poor prognosis. All six ODN* activated CLL isolates analysed by western blotting showed increased survivin expression with no constitutive expression in the controls. Drug sensitivity was studied in cells from eight patients using the MTT assay. Activated cells showed significantly greater resistance to chlorambucil (median IC50=164.4±28.18μM) compared to control cells (median IC50=93.63±14.96μM, p=0.044). Figure 1 shows representative IC50 curves. The increased resistance of the activated cells to chlorambucil may be a consequence of the upregulation of survivin. In summary, the in vitro model replicates several key features of authentic proliferating CLL cells found in bone marrow and lymph nodes. It also shows increased resistance to the conventional drug chlorambucil. This model may be of value in evaluating novel drugs and drug combinations which may be more effective in killing the proliferating population that maintain the malignant cell population in CLL. Figure Figure

Prognostic factors for response and survival after high-dose cyclophosphamide, carmustine, and etoposide with autologous bone marrow transplantation for relapsed Hodgkin's disease.

1989 ◽  
Vol 7 (2) ◽  
pp. 179-185 ◽  
Author(s):  
S Jagannath ◽  
J O Armitage ◽  
K A Dicke ◽  
S L Tucker ◽  
W S Velasquez ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Hodgkin's Disease ◽  
Marrow Transplantation ◽  
Hodgkin’S Disease ◽  
Autologous Bone Marrow Transplantation ◽  
Significant Proportion ◽  
Autologous Bone Marrow ◽  
High Dose ◽  
Autologous Bone

Sixty-one patients with relapsed Hodgkin's disease who had failed a mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)- and a doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-like regimen were treated with a high-dose combination chemotherapy containing cyclophosphamide, carmustine, and etoposide (CBV) and autologous bone marrow transplantation (ABMT). Fifty-nine patients were treated in relapse and two were intensified early in third remission. Following therapy, 29 patients (47%) were in complete remission (CR), 18 patients (30%) achieved a partial response (PR), and 14 patients (23%) had progressive disease (PD). Among the partial responders, six patients achieved a CR following addition of local radiation therapy to sites of residual nodal disease. For a minimum follow-up of 2 years, 23 patients (38%) are alive and free of disease. High-dose CBV therapy produced severe myelosuppression, and there were four (7%) treatment-related deaths. A multivariate analysis identified failure of more than two prior chemotherapy treatments and poor performance status as important adverse risk factors for survival. Patients who had no adverse risk factor and/or were intensified with CBV while Hodgkin's disease was still responding to conventional chemotherapy, had a CR rate of 63%, with 77% projected 3-year survival; whereas, all other patients had a CR rate of 31%, and a projected 3-year survival of only 18%. Our results demonstrated that CBV and ABMT can induce remission duration of 2 years or greater in a significant proportion of patients with relapsed Hodgkin's disease.

scholarly journals Successful treatment of refractory Hodgkin's disease by high-dose combination chemotherapy and autologous bone marrow transplantation

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 340-344 ◽  
Author(s):  
JG Gribben ◽  
DC Linch ◽  
CR Singer ◽  
AK McMillan ◽  
M Jarrett ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Complete Remission ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
High Dose ◽  
Dose Combination ◽  
Autologous Bone

Abstract Forty-four patients with refractory Hodgkin's disease were treated with high-dose combination chemotherapy followed by autologous bone marrow rescue. Twenty-two patients (50%) entered complete remission within 6 months of the procedure and four other patients are free of disease progression. Only two patients have subsequently relapsed from complete remission (CR). Bone marrow suppression was the predictable major toxicity of this procedure, and two patients (4.5%) died of sepsis during the aplastic phase. High-dose therapy with autologous bone marrow transplantation (ABMT) appears to be an effective salvage regimen for patients with refractory Hodgkin's disease.

scholarly journals Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3787-3794 ◽  
Author(s):  
R Haas ◽  
R Mohle ◽  
S Fruhauf ◽  
H Goldschmidt ◽  
B Witt ◽  
...  
Keyword(s):  
Malignant Lymphoma ◽  
Peripheral Blood ◽  
Hodgkin's Disease ◽  
Poor Prognosis ◽  
Collection Efficiency ◽  
Hodgkin’S Disease ◽  
Cytotoxic Chemotherapy ◽  
Large Field ◽  
High Dose ◽  
Cd34 Cells

Abstract For patients with advanced-stage or poor-prognosis malignant lymphoma, high-dose therapy with peripheral blood progenitor cell (PBPC) support may become a first-line treatment. The duration of severe cytopenia in this setting is inversely related to the number of PBPCs autografted. In a retrospective analysis, we therefore looked for factors influencing the yield of PBPCs in 61 patients (16 with high-grade and 29 with low-/intermediate-grade non-Hodgkin's lymphoma [NHL], and 16 with Hodgkin's disease) who received cytotoxic chemotherapy and filgrastim (R-metHuG-CSF, 300 micrograms/d; median, 4.2 micrograms/kg/d; range, 2.7 to 6.6 micrograms/kg/d; subcutaneously). Sixteen patients had active disease, while 45 were in partial remission (PR) or complete remission (CR) after conventional therapy. A median of three leukaphereses (range, one to 10) resulted in a median of 5.7 x 10(6) CD34+ cells/kg (range, 0.03 to 31.1 x 10(6)). Previous cytotoxic chemotherapy and irradiation adversely affected the yield of CD34+ cells. Each cycle of chemotherapy is associated with an average decrease of 0.2 x 10(6) CD34+ cells/kg per leukapheresis in nonirradiated patients, while large-field radiotherapy reduces the collection efficiency by an average of 1.8 x 10(6)/kg CD34+ cells. The collection efficiency was also significantly lower in patients with Hodgkin's disease. However, except for one, all had been previously irradiated. In contrast, age, sex, disease status, bone marrow involvement during mobilization, and the time since the last chemotherapy or radiotherapy were not significantly related to the collection efficiency. Following high-dose conditioning therapy, 42 patients were autografted with filgrastim-mobilized PBPCs. Hematological recovery (neutrophils > or = 0.5 x 10(9)/L and an unsupported platelet count > or = 20 x 10(9)/L) within 2 weeks was observed in patients autografted with > or = 2.5 x 10(6) CD34+ cells/kg. In seven patients, the quantity of CD34+ cells reinfused was below this threshold. They required a median of 17 days (range, 11 to 34) and 31 days (range, 13 to 141) for neutrophil and platelet recovery, respectively. If autografting with PBPCs in malignant lymphoma with poor prognosis is being considered, mobilization and harvesting should be planned early after initial diagnosis to avoid exhaustion of hematopoiesis by cumulative toxicity.

scholarly journals Peripheral blood mononuclear cells of a patient with advanced Hodgkin's lymphoma give rise to permanently growing Hodgkin-Reed Sternberg cells

Blood ◽  
1996 ◽  
Vol 87 (8) ◽  
pp. 3418-3428 ◽  
Author(s):  
J Wolf ◽  
U Kapp ◽  
H Bohlen ◽  
M Kornacker ◽  
C Schoch ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Hodgkin's Disease ◽  
Gene Rearrangement ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Hodgkin’S Disease ◽  
Chain Gene ◽  
Peripheral Blood Mononuclear ◽  
Light Chain Gene ◽  
B Lymphoid

A novel Hodgkin's disease (HD) derived cell line, L1236, was established from the peripheral blood of a patient with advanced Hodgkin's disease. Analysis of immunoglobulin (Ig) gene rearrangements revealed a biallelic Ig heavy chain and a monoallelic Ig kappa light chain gene rearrangement, pointing to a B-lymphoid origin of these cells. No DNA of Epstein-Barr virus was detected in L1236. The cells expressed the HD-associated surface antigens CD30 and CD15 as well as the transferrin receptor (CD71). Cytogenetic analysis of early passages of L1236 cells revealed a grossly disordered karyotype including cytogenetic aberrations described previously in other HD-derived cell lines. The Hodgkin/Reed-Sternberg (H-RS) cell origin of L1236 cells is further confirmed by Kanzler et al (Blood 87:3429, 1996), who found identical Ig gene rearrangement sequences in L1236 cells and H-RS cells of the same patient's bone marrow. L1236 cells expressed antigens necessary for efficient antigen presentation to T cells including HLA class I and II, B7.1 and B7.2, as well as adhesion molecules ICAM 1 and LFA 3. The cells secreted the interleukins (IL)-6, -8, -10, tumor necrosis factor (TNF) alpha, interferon (IFN) gamma, transforming growth factor (TGF) beta, and the granulocyte-macrophage colony stimulating factor (GM-CSF). After subcutaneous inoculation into SCID mice, a necrotic regression of initially growing tumors at the injection site was followed by disseminated intralymphatic growth. Our findings, together with the results of Kanzler et al, demonstrate that H-RS cells of B-lymphoid origin were present in the peripheral blood of a patient with advanced HD. These cells exerted a malignant phenotype with regard to their in vitro and in vivo characteristics.

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