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Article ; Online: B-cell and T-cell activation in South African HIV-1-positive non-Hodgkin's lymphoma patients.

Flepisi, Brian T / Bouic, Patrick / Sissolak, Gerhard / Rosenkranz, Bernd

Southern African journal of HIV medicine

2018 Volume 19, Issue 1, Page(s) 809

Abstract: Background: Altered immune mechanisms play a critical role in the pathogenesis of non-Hodgkin's lymphoma (NHL). HIV-1 (HIV) infection is associated with a state of excessive T-cell activation, which can lead to increased T-cell turnover and lymph node ... ...

Abstract	Background: Altered immune mechanisms play a critical role in the pathogenesis of non-Hodgkin's lymphoma (NHL). HIV-1 (HIV) infection is associated with a state of excessive T-cell activation, which can lead to increased T-cell turnover and lymph node fibrosis. Objectives: This study aimed to determine the serum levels of circulating B-cell activation markers, and the expression of T-cell activation and regulatory markers in HIV-positive NHL patients. Method: The serum levels of circulating soluble(s) sCD20, sCD23, sCD27, sCD30 and sCD44 molecules, all of which are biomarkers of B-cell activation, were determined by enzyme-linked immunosorbent assays (ELISA), while biomarkers of T-cell activation (CD8+CD38+) and regulation (FoxP3) were determined by flow cytometry in 141 subjects who were divided into five groups: Combination antiretroviral therapy (ART)-naïve HIV-positive patients; ART-treated HIV-positive patients; HIV-negative NHL patients; HIV-positive NHL patients on ART; and healthy controls. Results: HIV-positive NHL patients had significantly higher serum levels of sCD20, sCD23, sCD30 and sCD44 than HIV-negative NHL patients, while all five biomarkers were significantly elevated in HIV-positive NHL patients when compared with ART-treated HIV-positive patients. HIV-positive NHL patients had higher CD8+CD38+ and lower FoxP3 expression than HIV-negative NHL and ART-treated HIV-positive patients. Conclusion: B-cell activation is increased in HIV-positive NHL patients and is associated with reduced regulatory T-cell populations and increased CD8+ T-cell activation.
Language	English
Publishing date	2018-11-07
Publishing country	South Africa
Document type	Journal Article
ZDB-ID	2259791-8
ISSN	2078-6751 ; 2078-6751
ISSN (online)	2078-6751
ISSN	2078-6751
DOI	10.4102/sajhivmed.v19i1.809
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Article: Burkitt's Lymphoma and B-Cell Lymphoma Unclassifiable With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt's Lymphoma in Patients With HIV: Outcomes in a South African Public Hospital.

Sissolak, Gerhard / Seftel, Matthew / Uldrick, Thomas S / Esterhuizen, Tonya M / Mohamed, Nooroudien / Kotze, Danie

Journal of global oncology

2017 Volume 3, Issue 3, Page(s) 218–226

Abstract: Purpose: Burkitt's lymphoma (BL) is a common HIV-associated lymphoma in South Africa. B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma (BL/DLBCL) also occurs in HIV infection. ... ...

Abstract	Purpose: Burkitt's lymphoma (BL) is a common HIV-associated lymphoma in South Africa. B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma (BL/DLBCL) also occurs in HIV infection. Outcomes of HIV-infected patients with BL or BL/DLBCL in a resource-constrained setting are not defined. Methods: We performed a retrospective study of HIV-positive patients with BL or BL/DLBCL treated from 2004 to 2012 with curative intent at a publically funded academic medical center in South Africa. Differences between BL and BL/DLBCL, survival outcomes, and factors associated with survival were analyzed. Results: There were 35 patients with either HIV-associated BL (24) or BL/DLBCL (11) who met study criteria. Median CD4 Conclusion: Cure of HIV-associated BL and BL/DLBCL with intensive regimens is possible in resource-limited settings, but lower toxicity regimens, improved CNS prophylaxis, and increased resources for supportive care are required.
Language	English
Publishing date	2017-06
Publishing country	United States
Document type	Journal Article
ISSN	2378-9506
ISSN	2378-9506
DOI	10.1200/JGO.2015.002378
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Article: Biomarkers of HIV-associated Cancer.

Flepisi, Brian Thabile / Bouic, Patrick / Sissolak, Gerhard / Rosenkranz, Bernd

Biomarkers in cancer

2014 Volume 6, Page(s) 11–20

Abstract: Cancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as ... ...

Abstract	Cancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities of a myriad of genes, proteins, or other molecular features. Biomarkers can facilitate the molecular definition of cancer, provide information about the course of cancer, and predict response to chemotherapy. They offer the hope of early detection as well as tracking disease progression and recurrence. Current progress in the characterization of molecular genetics of HIV-associated cancers may form the basis for improved patient stratification and future targeted or individualized therapies. Biomarker use for cancer staging and personalization of therapy at the time of diagnosis could improve patient care. This review focuses on the relevance of biomarkers in the most common HIV-associated malignancies, namely, Kaposi sarcoma, non-Hodgkin's lymphoma, and invasive cervical cancer.
Language	English
Publishing date	2014-07-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2592049-2
ISSN	1179-299X
ISSN	1179-299X
DOI	10.4137/BIC.S15056
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Article ; Online: Drug-drug interactions in HIV positive cancer patients.

Flepisi, Brian Thabile / Bouic, Patrick / Sissolak, Gerhard / Rosenkranz, Bernd

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2014 Volume 68, Issue 5, Page(s) 665–677

Abstract: Clinically relevant drug-drug interactions (DDIs) refer to the pharmacological or clinical response to the administration or co-exposure of a drug with another drug that modifies the patient's response. Treatment regimens, which include agents that are ... ...

Abstract	Clinically relevant drug-drug interactions (DDIs) refer to the pharmacological or clinical response to the administration or co-exposure of a drug with another drug that modifies the patient's response. Treatment regimens, which include agents that are involved in the cytochrome P450 (CYP450) enzyme system and transporter systems, such as P-glycoprotein may be associated with higher risk of clinically significant drug interactions. In addition, potential DDIs increase with the increasing number of concomitant drugs. HIV positive cancer patients who receive concomitant chemotherapy and combination antiretroviral therapy (cART) may achieve better response rates and higher rates of survival than those who receive chemotherapy alone, but they may be at increased risk of drug interactions. DDIs in HIV positive cancer patients receiving concomitant chemotherapy and cART may increase or decrease antineoplastic drug concentrations, potentially resulting in life threatening interactions, increased toxicity or loss of efficacy. Avoiding and managing potential interactions between cART and antineoplastic agents is an increasingly important challenge. Based on the current literature, more safety and pharmacokinetic studies are needed with the aim to document a clear survival benefit for patients undergoing chemotherapy and concomitant or sequential administration of cART.
MeSH term(s)	Drug Interactions ; HIV Seropositivity/complications ; HIV Seropositivity/drug therapy ; Humans ; Neoplasms/complications ; Neoplasms/drug therapy
Language	English
Publishing date	2014-06
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2014.04.010
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Article ; Online: Treatment outcomes in AIDS-related diffuse large B-cell lymphoma in the setting roll out of combination antiretroviral therapy in South Africa.

de Witt, Pieter / Maartens, Deborah J / Uldrick, Thomas S / Sissolak, Gerhard

Journal of acquired immune deficiency syndromes (1999)

2013 Volume 64, Issue 1, Page(s) 66–73

Abstract: Background: Long-term survival for patients with AIDS-related diffuse large B-cell lymphoma (DLBCL) is feasible in settings with available combination antiretroviral therapy (cART). However, given limited oncology resources, outcomes for AIDS-associated ...

Abstract	Background: Long-term survival for patients with AIDS-related diffuse large B-cell lymphoma (DLBCL) is feasible in settings with available combination antiretroviral therapy (cART). However, given limited oncology resources, outcomes for AIDS-associated DLBCL in South Africa are unknown. Methods: We performed a retrospective analysis of survival in patients with newly diagnosed AIDS-related DLBCL treated at a tertiary teaching hospital in Cape Town, South Africa, with cyclophosphamide, doxorubicin, vincristine, and oral prednisone (CHOP) or CHOP-like chemotherapy (January 2004 until December 2010). HIV-related and lymphoma-related prognostic factors were evaluated. Results: Thirty-six patients evaluated; median age 37.3 years, 52.8% men, and 61.1% black South Africans. Median CD4 count 184 cells per microliter (in 27.8% this was <100 cells/μL), 80% high risk according to the age-adjusted International Prognostic Index. Concurrent Mycobacterium tuberculosis in 25%. Two-year overall survival (OS) was 40.5% (median OS 10.5 months, 95% confidence interval: 6.5 to 31.8). Eastern Cooperative Oncology Group performance status of 2 or more (25.4% vs 50.0%, P = 0.01) and poor response to cART (18.0% vs 53.9%, P = 0.03) predicted inferior 2-year OS. No difference in 2-year OS was demonstrated in patients coinfected with M. tuberculosis (P = 0.87). Conclusions: Two-year OS for patients with AIDS-related DLBCL treated with CHOP like regimens and cART is comparable to that seen in the United States and Europe. Important factors effecting OS in AIDS-related DLBCL in South Africa include performance status at presentation and response to cART. Patients with comorbid M. tuberculosis or hepatitis B seropositivity seem to tolerate CHOP in our setting. Additional improvements in outcomes are likely possible.
MeSH term(s)	Acquired Immunodeficiency Syndrome/drug therapy ; Acquired Immunodeficiency Syndrome/mortality ; Adult ; Anti-HIV Agents/administration & dosage ; Antibodies, Monoclonal, Murine-Derived/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cyclophosphamide/administration & dosage ; Doxorubicin/administration & dosage ; Drug Therapy, Combination ; Female ; Health Services Accessibility ; Humans ; Lymphoma, AIDS-Related/drug therapy ; Lymphoma, AIDS-Related/mortality ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Lymphoma, Large B-Cell, Diffuse/mortality ; Male ; Middle Aged ; Prednisone/administration & dosage ; Prognosis ; Retrospective Studies ; Rituximab ; South Africa/epidemiology ; Survival Analysis ; Time Factors ; Treatment Outcome ; Vincristine/administration & dosage
Chemical Substances	Anti-HIV Agents ; Antibodies, Monoclonal, Murine-Derived ; R-CHOP protocol ; Rituximab (4F4X42SYQ6) ; Vincristine (5J49Q6B70F) ; Doxorubicin (80168379AG) ; Cyclophosphamide (8N3DW7272P) ; Prednisone (VB0R961HZT)
Language	English
Publishing date	2013-06-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	645053-2
ISSN	1944-7884 ; 1077-9450 ; 0897-5965 ; 0894-9255 ; 1525-4135
ISSN (online)	1944-7884 ; 1077-9450
ISSN	0897-5965 ; 0894-9255 ; 1525-4135
DOI	10.1097/QAI.0b013e3182a03e9b
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Article ; Online: Treatment Outcomes in CML Patients Treated With Tyrosine Kinase Inhibitors at a Tertiary Teaching Hospital in South Africa.

Sissolak, Gerhard / Badenhorst, Jacques / Steenkamp, Janami / Heaney, Mark / Louw, Vernon / Schnugh, Desmond / Willem, Pascale

Clinical lymphoma, myeloma & leukemia

2015 Volume 15, Issue 12, Page(s) 803–810

Abstract: Background: Chronic myeloid leukemia (CML) has become one of the most treatable hematologic neoplasms since the advent of the tyrosine kinase inhibitors (TKIs), but it was not known if similar treatment outcomes could be achieved in a resource-limited ... ...

Abstract	Background: Chronic myeloid leukemia (CML) has become one of the most treatable hematologic neoplasms since the advent of the tyrosine kinase inhibitors (TKIs), but it was not known if similar treatment outcomes could be achieved in a resource-limited country. We tested the hypothesis that, despite challenges to access to second-generation TKIs, excellent responses could be replicated in the setting of limited resources. Patients and methods: Records of 58 patients with newly diagnosed CML in the chronic phase treated with TKIs at a tertiary teaching hospital in Cape Town, South Africa between 2003 and 2012 were reviewed and assessed according to European LeukemiaNet (ELN) criteria. Results: After a median follow-up of 60.5 months, progression-free survival at 60 and 96 months was 79.98% and 68.4%, respectively. Overall survival at 60 and 96 months was 92.9% and 83.6%, respectively. Progression to blast phase at 60 months was associated with poorer survival (P = .0002) but progression to accelerated phase was not (P = .1456). Attainment of a complete cytogenetic response at 12 months (P = .28) or major molecular response at 18 months (P = .268) did not have prognostic significance. Conclusion: Despite delays in achievement of the target responses defined according to ELN criteria, the use of imatinib mesylate as a first-line treatment can still result in treatment outcomes comparable with those in developed countries. These data suggest opportunities for improvement and success might be even greater with uninterrupted access to second-generation or newer TKIs.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Blast Crisis/drug therapy ; Blast Crisis/mortality ; DNA Mutational Analysis ; Disease-Free Survival ; Female ; Fusion Proteins, bcr-abl/genetics ; Hospitals, Teaching ; Humans ; Kaplan-Meier Estimate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology ; Male ; Middle Aged ; Mutation, Missense ; Protein Kinase Inhibitors/therapeutic use ; Retrospective Studies ; South Africa ; Tertiary Care Centers ; Treatment Outcome ; Young Adult
Chemical Substances	Antineoplastic Agents ; Protein Kinase Inhibitors ; Fusion Proteins, bcr-abl (EC 2.7.10.2)
Language	English
Publishing date	2015-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2540992-X
ISSN	2152-2669 ; 2152-2650
ISSN (online)	2152-2669
ISSN	2152-2650
DOI	10.1016/j.clml.2015.09.006
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Article: Human immunodeficiency and Hodgkin lymphoma.

Sissolak, Gerhard / Sissolak, Dagmar / Jacobs, Peter

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis

2010 Volume 42, Issue 2, Page(s) 131–139

Abstract: Presentation of Hodgkin lymphoma (HL) is distinctive in the infected individual being more advanced, accompanied by B symptoms and the presence of extranodal disease particularly lymphadenopathy of the head and neck. Bone marrow involvement may be found ... ...

Abstract	Presentation of Hodgkin lymphoma (HL) is distinctive in the infected individual being more advanced, accompanied by B symptoms and the presence of extranodal disease particularly lymphadenopathy of the head and neck. Bone marrow involvement may be found in over 50% of cases. Virtually all co express gamma-herpesvirus. Phenotypically there is prominence of the mixed-cellularity and lymphocyte depleted histopathologic subtypes that define an aggressive clinical course in comparison to other variants. Prior to the induction of cART, median survival was only 1-2 years. Notably the first chemotherapy trial using ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in 21 patients, without treating the viral infection, resulted in a 43% complete remission rate accompanied by severe haematological toxicities but did not extend median survival with this being 1.5 years matching the negative cases. Significant change accompanied concomitant anti-retroviral therapy that could be given safely even with dose intensive regimens exemplified by BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) in 12 patients or the Stanford V regimen (doxorubicin, vinblastine, mechlorethamine, etoposide, vincristine, bleomycin, prednisone) coupled with involved-field radiation for bulky disease studied in 59 patients. BEACOPP extended overall survival (OS) to 83% at 2 years. A similar trend was seen when using the Stanford V regimen with an OS rate of 51% at 3 years, disease-free survival (DFS) of 68% and freedom from progression (FFP) in 60%. Additional benefits accrued from supportive care with stimulatory peptides such as G-CSF and when combined with bacterial prophylaxis results approached that found in the uninfected reference group. Current consensus holds this particular lymphoma as still among the non-AIDS defining cancers being lung, stomach, liver or anal despite these having recently gained more attention as several of these neoplasms may be occurring more commonly in the era of cART. While the relative risk of developing a non-AIDS-defining neoplasm in HIV-infected persons on the average is 2-3 times, the risk for developing HL in HIV-infected cases impressively ranges between 5 and 25 times when compared to the general population. Based on the precedent in which Kaposi sarcoma and the non-Hodgkin lymphomas distinctively alter the course of this retroviral infection in a way indistinguishable from concurrent Hodgkin lymphoma we propose that this entity be similarly regarded and the hypothesis tested in large randomised prospective study.
MeSH term(s)	Acquired Immunodeficiency Syndrome/complications ; Acquired Immunodeficiency Syndrome/diagnosis ; Acquired Immunodeficiency Syndrome/epidemiology ; Acquired Immunodeficiency Syndrome/immunology ; Acquired Immunodeficiency Syndrome/therapy ; HIV/immunology ; Hodgkin Disease/complications ; Hodgkin Disease/diagnosis ; Hodgkin Disease/epidemiology ; Hodgkin Disease/therapy ; Humans
Language	English
Publishing date	2010-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2046795-3
ISSN	1878-1683 ; 1473-0502
ISSN (online)	1878-1683
ISSN	1473-0502
DOI	10.1016/j.transci.2010.01.008
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Article: AIDS-related Kaposi's sarcoma: epidemiological, diagnostic, treatment and control aspects in sub-Saharan Africa.

Sissolak, Gerhard / Mayaud, Philippe

Tropical medicine & international health : TM & IH

2005 Volume 10, Issue 10, Page(s) 981–992

Abstract: Until the 1980s, little attention had been accorded to endemic Kaposi's sarcoma (KS), a neoplasm noted in several parts of Southern Europe and the African continent but with relatively slow progression, except in children and young adults. Furthermore, ... ...

Abstract	Until the 1980s, little attention had been accorded to endemic Kaposi's sarcoma (KS), a neoplasm noted in several parts of Southern Europe and the African continent but with relatively slow progression, except in children and young adults. Furthermore, therapeutic approaches based on surgery, radiation and topical treatment were of limited efficacy, mostly used to overcome the disabling and stigmatizing effects of the disease. With the emergence of the HIV/AIDS epidemic, and the profound impact of KS on AIDS-related mortality, the pathogenesis of KS has been better studied, and the realisation that a virus (KS-associated Herpesvirus or Human Herpesvirus 8, or KSHV/HHV-8), combined with immunosuppression and cytokine-induced growth, was responsible for the development of this disease has led to novel therapeutic approaches. These are unfortunately still highly toxic, require careful monitoring, and are expensive, thus limiting their use in most parts of Africa. However, the use of highly active antiretroviral therapy (HAART), which has led to a considerable decline in KS incidence in populations of industrialized countries, constitutes the best hope for the control of this stigmatizing and lethal disease in Africa. Trials comparing different regimens of antiretroviral drugs in combination with systemic chemotherapeutic agents are urgently needed.
MeSH term(s)	Acquired Immunodeficiency Syndrome/complications ; Acquired Immunodeficiency Syndrome/drug therapy ; Acquired Immunodeficiency Syndrome/epidemiology ; Adult ; Africa South of the Sahara/epidemiology ; Antineoplastic Agents/therapeutic use ; Antiretroviral Therapy, Highly Active/methods ; Developing Countries/statistics & numerical data ; HIV Infections/complications ; HIV Infections/drug therapy ; HIV Infections/epidemiology ; Herpesviridae Infections/epidemiology ; Herpesviridae Infections/etiology ; Herpesviridae Infections/therapy ; Herpesvirus 8, Human ; Humans ; Interferon-alpha/therapeutic use ; Xeroderma Pigmentosum/epidemiology ; Xeroderma Pigmentosum/etiology ; Xeroderma Pigmentosum/therapy
Chemical Substances	Antineoplastic Agents ; Interferon-alpha
Language	English
Publishing date	2005-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1314080-2
ISSN	1365-3156 ; 1360-2276
ISSN (online)	1365-3156
ISSN	1360-2276
DOI	10.1111/j.1365-3156.2005.01491.x
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Article: Tissue microarray in a subset of South African patients with DLBCL.

Sissolak, Gerhard / Wood, Lucille / Smith, Lynette / Chan, John Wing C / Armitage, James / Jacobs, Peter

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis

2013 Volume 49, Issue 2, Page(s) 120–132

Abstract: Tissue samples from 93 de novo diffuse large B-cell lymphoma patients seen between 1995 and 2009 randomly receiving either standard combination chemotherapy (CHOP, n=48) or the identical program with rituximab (n=45) were subtyped using an ... ...

Abstract	Tissue samples from 93 de novo diffuse large B-cell lymphoma patients seen between 1995 and 2009 randomly receiving either standard combination chemotherapy (CHOP, n=48) or the identical program with rituximab (n=45) were subtyped using an investigational immunohistochemical (IHC) based tissue microarray (TMA) and contrasted to the approximately corresponding categories as defined either by Hans and associates using a three marker panel into germinal or non-germinal centre subtypes or by Choi and colleagues with two additional antibodies into germinal centre (GCB) or activated B-cells (ABC). Each of these primary subdivisions was further evaluated for expression of BCL2 and LMO2 both of which are recognised to predicate response. The addition of rituximab to the uniform drug regimen did not show any significant improvement in 5 years overall (63% versus 59%, p 0.68) or event-free survival (42% versus 39%, p 0.94), for CHOP versus R-CHOP comparisons. Similarly no differences were evident in subtype analysis. Interestingly however, when segregated on the Choi criteria, cytotoxic drugs alone showed a non-significant trend in improved survival (74% versus 55%, p 0.32) as well as event-free survival (44% versus 40%, p 0.42) for the germinal centre as opposed to the activated B-cell subtype. Nevertheless not even a small difference could be demonstrated in the presence of the anti CD 20 monoclonal antibody. According to Choi, both regimens (chemotherapy or immunotherapy antibody) revealed similar results to the Hans algorithm on 5 years OS as well as 3 year EFS when comparing GCB versus ABC or non-GCB subgroups. BCL2 and LMO2 marker expression of the respective immunohistochemical (IHC) subtype, despite small sample size, revealed the following. Analysis by Choi criteria on survival for BCL2, no matter for which subsets (GCB or ABC) or treatment modality (chemotherapy with or without the addition of rituximab) showed no difference in 5 years OS or EFS. In contrast, a significant difference for better EFS (p=0.0015) in the BCL2 positive group of the ABC subgroups subtypes treated with rituximab containing chemotherapy. For LMO2 similar results on survival outcome were seen thus showing no difference in 5 years OS or EFS - regardless of subtype or treatment modality. Also here, this was contrasted by better EFS (p=0.039) in the LMO2 positive group of ABC subtypes when treated with the rituximab containing regimen. The use of the IHC based TMA methodology has shown to be a simple, cost effective and a robust alternative to gene expression profiling (GEP) which is currently regarded as the gold standard for the classification in lymphomas. It provides a useful prognostic tool in stratifying DLBCL or other entities in future, even when frozen tissue samples are not available for GEP analysis. With the current budgetary limitations in South African public hospitals chemotherapy protocols for lymphoproliferative disorders exclude agents such as rituximab. Local therapeutic drug committees consider the approximately 15% overall survival benefit seen at 5 years for DLBCL when rituximab is added to combination chemotherapy as too marginal for justifying the arising additional expenses. Accordingly, demonstration that a specific molecular subtype accounts for superior outcome, when using these regimens, is needed. Such an option would provide convincing evidence for the use of immunochemotherapy in a resource constrained setting.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Biomarkers, Tumor ; Cyclophosphamide/administration & dosage ; Doxorubicin/administration & dosage ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Lymphoma, Large B-Cell, Diffuse/metabolism ; Lymphoma, Large B-Cell, Diffuse/pathology ; Male ; Middle Aged ; Prednisone/administration & dosage ; Retrospective Studies ; Rituximab ; South Africa ; Tissue Array Analysis ; Vincristine/administration & dosage
Chemical Substances	Antibodies, Monoclonal, Murine-Derived ; Biomarkers, Tumor ; R-CHOP protocol ; Rituximab (4F4X42SYQ6) ; Vincristine (5J49Q6B70F) ; Doxorubicin (80168379AG) ; Cyclophosphamide (8N3DW7272P) ; Prednisone (VB0R961HZT)
Language	English
Publishing date	2013-10
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2046795-3
ISSN	1878-1683 ; 1473-0502
ISSN (online)	1878-1683
ISSN	1473-0502
DOI	10.1016/j.transci.2013.07.013
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Article: Lymphoma--emerging realities in sub-Saharan Africa.

Sissolak, Gerhard / Juritz, June / Sissolak, Dagmar / Wood, Lucille / Jacobs, Peter

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis

2010 Volume 42, Issue 2, Page(s) 141–150

Abstract: Substantial geographical differences exist for Hodgkin and other lymphoproliferative disorders with these having previously been documented in a report from the lymphoma reclassification project. In the light of rampant human immunodeficiency syndrome, ... ...

Abstract	Substantial geographical differences exist for Hodgkin and other lymphoproliferative disorders with these having previously been documented in a report from the lymphoma reclassification project. In the light of rampant human immunodeficiency syndrome, largely centred in sub-Sahara, this experience is updated in a further 512 consecutive individuals treated over an 8-year period in a privately based academic centre. Median age was 55.2 years 61% were males, 10% had Hodgkin lymphoma and, overall, constitutional symptoms were present in 20%. Prior to referral 19% had received chemotherapy and a further 20% some form of irradiation. Median survival in hairy cell leukaemia (n=14), chronic lymphocytic leukaemia-small lymphocytic lymphoma (n=103), Hodgkin (n=41) and follicular lymphoma (n=59) was not reached at the time of analysis and exceeded 36 months. This was followed by 32 months for those with mantle cell (n=7), splenic (n=2) and extranodal marginal cell (n=11), 24 months for T-cell lymphomas (n=24), 20 months for diffuse large B-cell variants (n=88) but only 12 months for the aggressive tumours exemplified by Burkitt (n=7) and lymphoblastic subtypes (n=6). The remaining 36 patients had to be excluded because numbers were too small for statistical analysis or unreliable staging. Adverse factors were constitutional symptoms, prior treatment with chemotherapy, intermediate or high-risk scores as defined by the international prognostic index, histologic grading and certain anatomical sites of primary tumour. In contrast gender, staging by Rye or Rai classification, retroviral infection and prior treatment with radiotherapy were without effect. Overall survival at 3 years in each category was compared to the curve for the entire cohort and was 100% in hairy cell leukaemia receiving two chlorodeoxyadenosine and greater than 88% in Hodgkin lymphoma treated according to the German study group protocols (p=0.0004). Corresponding figures for chronic lymphocytic leukaemia-small lymphocytic lymphoma were 82% (p=0.0006), follicular lymphoma 71% (p=0.060), peripheral T-cell lymphoma 43% (p=0.0156), diffuse large B-cell lymphoma 39% (p<0.0001), aggressive tumours 25% (p=0.0002) and for the indolent categories including mantle cell, splenic and extra nodal marginal cell lymphomas 22% (p=0.2023). Outcome argues in favour of patient management by a multidisciplinary team implicit in which are standardised protocols for diagnosis, staging and treatment. Under these circumstances the well recognized centre effect applies when results approximate those from first world reference centres. Conversely any deviation from such a disciplined approach is unlikely to achieve comparable benefit and therefore to be strongly discouraged.
MeSH term(s)	Adolescent ; Adult ; Africa South of the Sahara/epidemiology ; Female ; Humans ; Lymphoma/diagnosis ; Lymphoma/epidemiology ; Lymphoma/therapy ; Male ; Middle Aged ; Prognosis ; Survival Rate ; Young Adult
Language	English
Publishing date	2010-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2046795-3
ISSN	1878-1683 ; 1473-0502
ISSN (online)	1878-1683
ISSN	1473-0502
DOI	10.1016/j.transci.2010.01.009
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